James Greenblatt, MD

Integrative Psychiatry

Aired on: December 13, 2019

Episode Description
Dr. Greenblatt explains his integrative as well as a functional medicine approach to depression. This combines traditional medical science with nutritional and metabolic therapies. There are many contributing factors to depression including metabolic, physical illnesses, the immune system, hormones, genetics, and psychological factors such as stress. He looks at these factors as well as the uniqueness of each person’s metabolic and nutrition abnormalities that may contribute to depression. This approach can successfully treat many individuals suffering from depression. This book offers hope and treatment models that are simple, safe, and effective. He has been using these therapies for more than thirty years and has seen thousands of patients improve and recover from depression

  • 120 million people worldwide; 15 M in US
  • 7 % older than 18
  • 2x as many females
  • One in 8 teens equal sex
  • 1/33 kids
  • Runs in families 3 x as likely to have it
  • Hx increases risk;
    • 50 % if one episode
    • 90 % if had several episodes
  • Over next 20 years, projected to be #1 cause
    disability in hi income countries and #2 world wide
  • Annual cost 30 – 44 billion.
  • Every person is different- biochemically unique

Suicide

  • 8th leading cause death in US 32K
    deaths Q year
  • 15 % untxed suicide
    • More than 2/3 suicides caused by depression
    • Women 2-3 x more likely SA
    • Men more than 4 x women to die of suicide
    • Risk
      • Family hx, impulsive drugs, separation, divorce,
        family violence, impulsive
    • Times
      • Anxiety, anniversaries, drug /etoh abuse, untx
        derpession
  • He uses integrative psychiatry
  • Factors contributing to depression are unique
  • THE ZEBRA
  • Nutrition important
    • 1601 Capt James Lancaster discovered that lemon
      juice prevented scurvy
    • British government waited 264 years after it was
      proven
    • Just be cause MDs ignore does not mean not true
    • Tomato Effect Dr. James Goodwin `984 JAMA
      efficacious tx for certain ds is ignored or rejected because does not make
      sense
      • Named tomato effect because 16 th – 19 th
        century believed tomatoes were poisonous..
  • Longer one suffers, more difficult it is to
    recover

Meds

  • James Watson winner of Nobel Prize ifor
    determining the structure of   DNA urged
    doctors to have better understanding of mental illness and develop tx based on
    their results
  • Prescribe carefully

Stigma

  • We are more than our experience and genes

Symptoms

  • Also stomach ache, irritability, work too much
  • Aches and pains,
  • Etoh and drug abuse
  • Chain smoking
  • Constant exhaustion
  • Crying a lot
  • Decreased physical activity QD
  • Reckless doing risky things
  • Difficulty getting up in am
  • Irritability, frustration
  • Lack of energy or motivation
  • Reduced sex drive
  • Working long hours long term difficulty sleeping

Results

  • Hard to work, loss relationships
  • No energy to take care of self
  • 4 x risk MI
  • More likely to abuse etoh or drugs

Types

  • Major depressive disorder MDD
    • Depressin, anhedonia and five other
    • Worthless common
    • Not grief or sadness
  • Persistent depressive disorder dysthmica
    • Most of days more often or not for 2 years.
    • If start before age 21, more likely co occurring
      personality disorder or substance abuse
  • Disruptive Mood Dysregulation Disorder kids
    • Chronic, sever, persistent irritability
    • Can be temper outburst, aggression out of
      proptortion in intensity
    • Over at least one year in two settings (home,
      work)
    • Developmentally in appropriate.
    • Have low frustration tolerance
    • Family lie disrupted
  • Premenstrual dysphoric disorder
    • Premenstrual dysphoric disorder is sever form of
      pMS
    • Most cycles, sx must be present in final week
      before period then better
    • At least one of following
      • Emotional changes (mood swings)
      • Irritability, anger, increased conflicts
      • Depressed mood, hoplessnes, self deprecating
      • Anxiety, tension, feeling on edge
    • One or more of following total five
      • Decreased interest in usual activities
      • Difficulties concentrating
      • Lack eergy
      • Change appetite
      • Difficulty sleeping
      • Feeling overwhelmed or out of control
      • Physical sx such as breast tenderness, swelling,
        jt pain, muscle pain, bloating or wt gain
    • Lead to distress or interference with work,
      school, social, relationship
  • Substance/ medication induced depressive
    disorder
    • Depressive sx associated with substance
    • Typically starts within first fee weeks or one
      month after start
    • Stop, get better
  • Depressive disordered due to another medical
    condition
    • CVa, HD, PD, TBI, Cushings, hypothyroid
  • Depression with Anxious Distress
    • Hi anxiety linked to higher suicide risk, longer
      length of illness, greater likelihood of not responding to tx
    • At least tow during most days
      • anxious, tense
      • Unusually restless
      • Difficulties concentrating because of worry
      • Fear that something awful may happen
      • Feeling one might lose control
  • Depression with atypical Features
    • Mood
      reactivity can be cheered up
      • Can be euthymic if environment positive
      • Weight gain or inc appetite
      • Sleep at least ten hours per day
      • Leaden paralysis
      • Rejection sensitivity
  • Post partum Depression
    • 70 % have baby blues
      • Short term worry, unhappiness, fatigue  2 weeks
    • Post partum depression `6 %
      • For 4 weeks
        • Sluggishness, fatigue
        • Sad, hopeless, helpless or worthless
        • Change sleep
        • Change appetite
        • Difficulty concentration, confusion
        • Crying for no reason
        • Lack of interest in baby or family
        • Fear of harming baby or self
        • Difficulties bonding with baby
      • Often have anxiety or panic attacks
      • Rapid changed in hormones or thyroid after
        delivery may contribute
      • Lack of sleep, stress, family hx depression,
        lack support may play rold
  • Depression with a seasonal Pattern (seasonal
    affective disorder
    • Relationship between the start of depressive
      episodes and time of hear
      • Seasonal
        • Loss energy, sleep too much, overeat, wt gain,
          carb craving
        • Linked to biochemical imbalance caused by
          shorter daylight hours
        • More common far from equator
        • Less commonly occurs in summer
        • Possibly in response to hi heat and humidity
        • More likely insomnia, dec appetite, wt loss,
          agitation, anxiety
        • Younger adults and women higher risk
        • Average age onset is 18 – 30 years.

CAUSES

  • Biochemical
    • Neurotransmitters
      • Serotonin,
        • Lack sleep problems, binge eating, irritability
      • norepinephrine,
        • too little low mood and fatigue
      • dopamine
        • due to too little or too much
      • lack due to
        • lack amino acids, vitamins, minerals
        • breaking down neurotransmitters too quickly
  • Physical
    • Illnesses
      • 25 % cancer, 94 % eating disorders
      • 20- 40 % heart attack, 10 – 20 % HIV
      • 50 % HD, 30 % chronic long term pain
      • 50 % PD
      • 25-50 % stroke
      • 60 % disabling tinnitus
      • 27 % drug or etoh
      • 30 – 35 % AD
      • Anxiety disorder, tobacco addiction
      • Depressed people more likely to have DM2 and HD
  • Meds
    • Antipsychotic,
    • antihistamine,
    • beta blockers,
    • birth control pills,
    •  htn,
    • anti inflammatory meds,
    • adrenal hormone agents and
    • corticosteroids
    • Etoh, amphotericin B, bismuth nitrate,
      carbamazepine, cis-retinoic acid, cyloserine
    • Cyclosporine, digitalis
    • Estrogen therapy, flunarizine, h2 blockers
      (cimetidine, ranitidine)
    • Interferon, levodopa, methyldopa mazindol,
      mercury
    • Methylxantines (caffeine, theophylline),
      metoclopramide (reglan)
    • Metronidazole, nifedipine, organic nitrates
    • Phenytoin
    • Psychostimulants (fenfluramine, methylphenidate,
      permoline, phenylpropanolamine)
    • Reserpine
    • Sedative hypnotics (barbiturates,
      benzodiazepines, methaqualone)
    • Thallium
    • Thiazide diuretics
    • Vinblastine and vincristine
  • Overactive
    immune system
    • Sickness behavior normal reaction to infection
      • Poor sleep, concentration, lack of desire
      • Pro inflammatory chemicals inflammatory
        cytokines cause changes in neurotransmitters
      • Depression has changed in cytokines
      • High levels of inflammatory cytokines
      • Low levels of anti inflammatory cytokines
      • Anti inflammatory IL 4 and TGF b1 were lower
      • Sertraline decrease pro inflammatory and
        increase anti inflammatory
      • Depressed with inc inflammatory biomarkers less
        likely to respond to antidepressants
      • Pt with hx no response to antidepressants have
        inc inflammation
  • Inflammatory brain illnesses linked to
    depression
    • Areas of brain dealing with mood regulation  inflammation was 30 % higher in depressed
    • 2017 Manchester MDD have inc microglial
      activation
      • BiolPysch Krystal , J
  • Hormones
    • Estrogen
      • Teen girls = teen boys in depression
      • In women short depression 7 – 10 days before
        period
      • Baby blues
    • Testosterone
      • Men low testosterone may be linked to depression
      • Men may not respond with low testosterone
    • Thyroid sub clinically low in mood disorders
      • Women depressed hi TSH
      • Low thyroid 
        poorer response
      • Give thyroid better response to antidepressants
  • Genetics
    • Tendency to have is inherited not ds
      • Family hx depression 3 x risk
      • Twins
        • Other one depressed 27 %
        • Raised separately risk 67 %
  • Psychological
    factors
    • Stress
    • Aging

KEY POINTS

  • GP. 62 % scripts for depression’ 65 % for
    anxiety
  • Depression, 4 x likely to have MI than no hx
  • s/p MI, chance another higher
  • depressed more likely to abuse drugs, etoh

Treatment

  • 2/3 
    effectively tx have sx that impair
    • 28 % mild impairment
    • 23 % moderate impairment
    • 12 % severe impairment; 4 % very severe impairment
  • Research show 94 % meds work closer to 51 %
    • 1/3 studies showing antidepressants don’t work
      submitted to FDA don’t work not published
    • ½ studies failed to show any benefit other than
      placebo
  • Studies only short term 6 weeks
  • based on symptoms and vulnerabilities. Severity

What is missing in psych eval

  • diet, toxins nutrition, allergies

Drug tx don’t work

Research

  • drug companies sponsoring research have conflict
    of interest
    • 4.9 x likely to report med works
  • Direct advertising to consumer spend billions
  • People not depressed account for 94 % new
    antidepressant use
  • JAMA 2010 antidepressants don’t work  for less severe forms depression
  • Paxil and imipramine do not reduce sx in mild,
    moderate or severe depression
  • Antidepressants only work in severe depression
  • by Vittengl at Truman U; Pt who took
    antidepressants more sx at 9 years
  • Robert Whitaker Anatomy of an Epidemic 50 yrs
    data;  over time, people not on meds do
    better than those who are.
    • Since 1987, 
      3x more on disability
    • Only 15 % 5x with meds remained healthy over
      time
      • The other 85 % have chronic depression
  • Yale found that universities hire to perform
    drug research were part owners
  • Studies more likely to prove if funded by drug
    industry or researchers have financial interest
  • British Psych Joanna Moncrieff paper, “There are
    no signs that the rapidly escalating use antidepressants reduces burden of
    depressive disorders
  • JAMA found standard antidepressants no more
    effective than placebo for people  with
    less severe forms of depression

Bioindividuality

  • Only speciality where no measurements
  • Side
    effects
    • Agitation,
    • Blurred vision, constipation, dec sex drive, dry
      mouth
    • Erectile dysfunction, fatigue, insomnia, nausea
    • Osteoporosis, wt gain risk SI
    • SRRI
      • Sexual
      • St gain
      • Physical
        • Headache, nausea, stomach problems
  • mEd withdrawal 
    like flu
    • Irritability, agitation, restlessness, insomnia
    • Migraines, headaches, not able to focus,
      depression
    • Physical
      • Sweat, palpitation, B &V, difficulties
        breathing, sensory dist
    • Reason: body/ brain no time to adjust to change

Brain and body. Influence each other

  • Brain 3 pounds uses 20 % energy
  • Scars in Brodmann
    area 25 BA 25
    hyperactive in depressed people
    • Activity normalized when depressive sx relieved
    • Does not matter if relieved by tx or meds
    • Is directly linked to amygdala which processes
      anxiety, fear and the hypothalamus 
      (important in stress)
    • Generous supply of special transporter
      molecules. Serotonin
  • Serotonin gene coding for serotonin transporter
    molecule comes in long and short
    • Long triggers production of more transporter
      molecules
    • Short gene have smaller BA 25 and does not act
      with amygdala and other brain areas
    • Is sped up activity in BA 25 the cause or result
      of depression?

Genes

  • Some contribution 37 %
  • Epigenetics
    • Methylation
    • Causes
      • Stress
        • Study mice remove from mothers 3 hrs QD x 10
          days epigenetic changes last a week
        • Mice of good mothers exchanged with bad mothers,
          stress handling abilities of foster 
          mothers.
          • Same for monkeys
    • Good nutrition etc best hope
    • Makes each person unique
  • Genetic testing, twice as likely to be
    prescribed the correct med

IDeal

  • Diet meds, supplements, family hx
  • Labs
  • Vitamin deficiencies, toxic metals, hormone
    imbalances
  • Vitamin levels, amino acid and fatty acid
    imbalances
  • Hi or low minerals
  • Celiac disease and other food sensibilities
  • Imbalanced levels of digestive enzymes
  • Disbiosis, parasites
  • Focus on individual unique
  • Care for how pt, not just ds
  • Understand how body and mind are connected
  • Restore health instead of reducing sx
  • Increase boy nutrients to promote long term
    health

T take care of yourself

H hormones and herbs

E exclude

Z zinc and other minerals

E essential fatty acids and cholesterol

E exercise and energy

B and other vitamins

R restore

A amino acids and proteins

T take care of yourself

  • Link betn mental and psyical vauge
  • Diet
    • Studies
      • 2010 AJP unhealthy diet more depressed
      • 2010 teens unhealthy diet more likely depressed
      • 2014 Iranian children
    • Diets hi in saturated fats and refined carbs can
      affect proteins important in brain development such as BDNF
  • Digestion
    • HCl
      • Dissolve food into parts
      • To absorb vit B12, minerals
      • Make enzyme pepsin necessary in digestion of
        protein
    • In SI sodium bicarbonate neutralizes HCL
      • Fat and protein and carbs broken down
      • Digestive enzymes
        • Need zinc, protein, vitamin c
        • Good nutrition leads to good digestion
        • Good digestion ensures all necessary nutrients
          are absorbed
        • Poor digestion=poor nurtition
      • Gut bacteria
        • Probiotics help digest
  • Sleep
    • POOR SLEEP RISK FOR DEPRESSION 2.5 TIMES FOR
      TWINS
    • Brain dev needs sleep for brain dev. 
    • Sleep problems predict  GAD, depression, and other behavioural d/0
    • Poor sleep caused by
      • Sleep apnea 5 x depression
        • Tx sleep apnea can tx depression
        • Sx tired in am and day
        • Memory problems
        • Toss, turn, choke, asp, snore
        • Headaches in am
        • Bathroom > once or twice
        • Swelling legs
        • c/p sweat during sleep
      • stress, caffeine, etoh , drugs, OTC, allergies,
        asthma, hyperthyroid, chronic pain nutritional deficiencies Mg, zn
      • restless legs
    • sleep hygience
      • sleep same time
      • avoid caffeine after lunch
      • comfortable bed
      • thermostat cool
      • dark
      • use bed for sleep and sex
      • no work, TV in bed
      • ritual
      • no computers, games,
      • don’t ty to hard
    • sleep remedies
      • melatonin,
        • pineal body clock. 1 – 3 mg sleep in 30 min
      • Mg, 200- 300 mg
        • Works c Ca for muscle relax, contract
        • Anti-stress. 
          Reduce cortisol, muscle cramps
        • First mineral to disappear with processed foods
        • First mineral to leave when body stressed
        • Depleted by etoh, caffeine, meds
      • valerian,
        300- 500 mg
        • Does not work right away
        • Side effects h/a, restlessness, sleeplessness,
          irregular heart beat
        • Sleep anti anxiety
      • inositol,
        • made by body and intestinal bactiera
        • helps transmit nerve signals
        • prevents buildup of fat in liver and other
          organs
        • 1t 8 PM helps with obcessive thought
      • 5 HTP, 50
        – 200 mg
        • Reduce anxiety
      • glycine, 3 g
        • inh neurotransmitter
        • helps relax blood vessels
        • lower core body temperature
      • GABA
        • Low GABA anxiety, depression, irritability,
          headache, htn
    • Sugar
      • Glucose,
      • Fructose cant be absorbed by cellsà goes to liver
      • Sucrose homes- fructose and glucose
      • Dextrose from corn identical to glucose
      • Galactose in milk
      • Lactose glucose and galactose
      • Maltose in barley – is two glucose
      • Xylose in wood or straw
      • Low sugar in brain weak, irritability, anxiety,
        headaches, faint, depression
      • Hi insulin an d sugar inc negatively affects
        kidney function, inc blood fats, TG, cholesterol
      • Sugar substitute. Xylitol, cinnamon, cardamom,
        ginger, nutmeg
    • Stress
      • Inc inflammation ~ depressive sx
      • Activate inactive genes that affect future
        generations
        • Inc maternal stress in pregnancy ~ inc risk mod
          to severe depression in offspring
        • Stressed ma -kids depressed 11 years later
    • Key Points
      • AJP study unhealthy dietà more depressive and anxiety
      • Diets 13,486 Iranian kids inc junk food ~
        psychiatric stress
      • Survey, 40 % uS less than 8 hours sleep
      • Met analysis 23 studies adolescents 12- 20 with
        mdd more sleep disturbances
      • 2015 study consistently poor sleep inc
        depression by 2.5
      • More soft drinks higher levels depression,
        hopelessness and aggression
      • 72 % of people with daily stress and anxiety
        claim interferes with lives

HORMONES

  • Low
    thyroid
    • Anxiety , memory, hi cholesterol, constipation,
      gum disease, fat, hypoglycemia, muscle aches and pains, acne, exzema, hair
      loss, recurrent infections, pMS, irregular menstrual, ovarian cysts,
      endometriosis, fluid retention, fatigue
    • Faulty testing à
      faulty dx
    • TSH only show pituitary asks for correct amount
      thyroid
      • But body might not be using it properly
    • Taking imipramine  plus T 3 faster recovery
    • Replacing missing thyroid relieves depression
    • Metanalysis T3 increased improvements seen with
      antidepressants for tx resistant depression
    • 2014, T3 and T4 were both predictors of the
      level of improvement in depression sx.
    • T3 works better for depression
      • Better for women
    • Thyroid needs iodine, tyrosine, zinc and iron
    • Toxins get in the way
      • Plastics, air fresheners
      • Polychlorinated biphenyls, dioxin, phthalates,
        and polybrominated diphenyl ether (PBDE)
        • Upset ratios in diff T hormone
        • Interfere with thyroid hormone synthesis
        • Suppress production thyroid hormone receptors
          and binding thyroid hormone transport proteins.
  • DHEA
    • Produced by adrenals
      • When stressed , makes more
        • Changes in liver to dHEA S which is measured
    • Antiaging supplement controversial
    • For depression
      • 60 % depressed respond
      • Maybe works better for men
    • Makes testosterone and estrogen and all steroid
      hormones
      • Need cholesterol
    • Highest in mid 20s
  • Testosterone
    •  Made in
      testes, ovaries, adrenal glands, liver, skin and brain
    • Responsible for protein synthesis
    • Maintenance of bone mineral density
    • Lean body mass, muscle strength
    • Sensitization or serotonin recptors
    • Physiologic processes that contribute to sex
      appeal
    • Decreases with age
      • Diet, exercise
      • Sleep quality
      • Endocrine do
      • Low testosterone
        • Dec strength, fatigue,
        • poor libido,
        • htn, inc CV risk,
        • loss lean body mass inc fat
      • lowers depression with (and without?) meds
      • lowest testosterone group (age 71-89)2 x
        depression
      • 11/18
        JAMA significant reductions in depressive sx          d
      • Low
        testosterone levels are linked to depression
      • In some
        men depression cannot be relived until testosterone raised to a normal level
      • Antidepressants
        cannot raise testosterone to a normal level
      • Other
        ways to raise testosterone
        • Zinc
        • Exercise
          to strengthen muscles
        • Reduce
          stress to reduce cortisol (which breaks down muscle
        • Cut or
          avoid soy. Phytoestrogens which can counteract testosterone
        • Eat
          plenty EPA and DHA in salmon and other cold water fish
        • Monitor
          cholesterol and DHEA (needed to make testosterone
        • Supplement
          with tribulus, herb than enhances testosterone synthesis
  • Estrogen
    and Progesterone
    • 2014 study estrogen affects brain derived
      neurotrophic factor (BDNF)
      • BDNF support survival of neurons and growth of
        new neurons and their connections
    • Estrogen
      can affect mood by degrading or reducing levels of MAO (which breaks down
      serotonin.
  • Herbs
    • St John’s
      Wort 300 mg po TID
      • Anti depressant mild to moderate depression
      • Germany licensed for anxiety,d epression, sleep
        disorder
      • Pain disorder
      • Cochrane 
        mild to moderate for 4 – 12 weeks did better than placebo
      • Fewer side effects than antidepressants.
      • Safe long term prevents relapse
      • Has hypericin
        • Antiviral, against cancer and HIV in stored
          blood
      • and hyperforin
        • activates a specific receptor in liver that
          triggers production of an enzyme used to metabolize meds
    • Curcumin
      • For Inflammation
      • Regulates stress response system
      • Degrades MAO which breaks down serotonin and by
        protecting against oxidative stress and mitochondrial damage.
      • Regulates the level of neurotransmitters in body
      • Promotes birth of new neurons in hippocampus
      • Improve cognition
        • Daily improved memory and mood in people with
          mild, age-related memory loss
      • Safe and effective
    • Rhodiola
      • Recognized by Russian ministry of health as med
        and herbal tonic
      • Reduce depressive sx, boost mood diminish
        fatigue, tx opioid addiction
      • Assists in normalizing body stress response by
        increasing body resilience
      • Reduce nicotine withdrawal sx by inc serotonin
        and serotonin receptors
      • Degrades MAO A and MAO B
      • Affects 1062 genes, fifty of which are linked to
        behavior and 62 related to psych d/o
      • Ay improve emotional behavior thru effects of
        transcriptions of certain genes
      • Depression. Rhodiola revolution
      • Can enhance mood, concentration, energy
      • Helps with anxiety and BAD although may be too
        stimulating

Summary

  • Thyroid avoid toxins cleaning products,
    pesticides, eat organic, use glass
    • T3, T 4 predict levels of improvement in
      depression
  • DHEA, testosterone, estrogen, progesterone
    • Archive Gen Psych 2005  DHEA for midlife major and minor depression
    • DHEA decrease with age
    • Australians men with low test 2 x depressed >
      highest test
    • Harvard topical test greater improvements in
      depression > placebo
  • Curcumin, SJW, rhodiola

E exclude harmful foods

  • Celiac ds
    • Body mistakenly mistakes gluten for a dangerous
      toxin
    • Immunity system attacking gluten destroys the
      intestine
    • Absorption vit A, B6, B 12, D, E K,  iron, zn, Mg and ca, essential fats other aa
    • Sx anemia, anorexia, arthritis, dermatitis
      herpetiformis, edema, fatigue, infertility, jt pain, migraines, missed
      menstrual periods, numbing hands
    • Osteoporosis, sz, stunted growth, tooth decay
      and discoloration
    • 1/3 have depression
    • Dx Ab: anti gliadin, anti endomysial, anti tissue
      transglutaminase
    • Will develop nutritional problems
      • Take multivit with iron, EFA, digestive enzymes
      • Test for iron, folate, Mg, amino acids
    • Need HCl
    • Casomorphin,
      gliadorphin
      • Similar to morphine
      • Originally in pee of people with autism
      • Incomplete digestion of proteinsà ADHD, child psychosis,
        dyslexia, down, CD, post partum psychosis, Rett’s ds, severe depression
      • These excess peptides  maybe these are unique carriers of info to
        brain that may worsen many psych d/o
      • Elevated these caused by lack functioning of enzyme
        dipeptidyl peptidase IV (DPP IV) which snips casomorphin and gliadorphin into
        small pieces
        • These absorbed
        • Cause deficiency DDPP IV
          • Lack zn
          • Antibiotics, interferon, gelatin
          • Candida,
          • Hi mercury and heavy metals and pesticides
      • Depression suffered from incomplete digestion of
        casein and gluten
    • Food
      Allergies and depression
      • IgG mediated delayed hypersensitivity rxn
      • Have more depression

Summary

  • 18 studies on depression and 11 on CD depression
    is more common  ore more severe in cD
  • Teens with CD have 31 % risk mde vs 7 % in
    healthy children
  • Correlation CD and depressive disorders
  • 2016 AJ Gastroenterology correlation between
    feelings of depression and Crohns’ ds

Z Zinc and other minerals

  • Zn
  • 200 different reactions
  • In brain
    • Helps make DNA and proteins
    • Helps immune fight off viruses and bacteria
    • Helps wounds heal
    • Regulates neurotransmission in brain
    • Makes it possible to taste and smell
    • Make sex and reproduction possible
    • Helps make all enzymes needed to digest fats,
      carbs and proteins
  • In
    • Oysters, poultry, red meat, beans, whole grains
      and nuts
  • Causes of lack
    • Vegetarians
    • Eating disorders
    • UC, crohns
    • Meds
      • Asa, benazepril, cholestyramine
        • Reduce cholesterol and ofloxacin
  • Results of lack
    • Delayed growth in kids and infants
    • Hair loss
    • Diarrhea
    • Loos appetite
    • Weight loss
    • Difficulty tasting food
    • Acne
    • Fatigue
    • Elevated cholesterol
    • More infections
    • Memory impairment
    • Impotence
    • Anorexia, impaired cognitive, other behavioural
      disturbances
    • Poorer appetite
  • Depression
    • Lower levels in major depression, postpartum
      depression
    • Depression à
      inflammation
      • Lowers albumin which transports zinc thru
        bloodstream
      • Maybe liver snatches up zn to use for
        inflammation
    • Zinc inh NMDA which controls glutamate
      • Glutamate
        • Sends signals between nerve cells
        • Helps learning, memory
        • Too much glutamateà
          overstimulation
          • Progressive damage to nerve function (~
            depression)
    • Zinc can relieve depression’
      • Animals given celexa inc zinc levels
      • Given celexa or imrapmine, inc zinc in
        hippocampus, dec other parts of brain
      • Given ECT inc zinc in hippocampus
      • Zinc antidepressant in lab animals
      • Low doses celexa and imipramine ineffective as
        antidepressants stressed by
      • Chronic tx with antidepressants and ECT causes
        zinc to inc in rat brains
      • Lab, zinc deficient diet à> depressive like sx
        including anorexia and anxiety
      • Zinc improves depression
    • Zinc taste  
      no eat 1 hour before

Copper

  • In liver, heat, brain and kidneys
  • Helps growth , maintenance of TBC, bones,
    nerves, brains
  • Makes prostaglandins needed for heart beat and
    blood pressure
  • Part in getting energy out of fats, protein an
    carbs
  • Helps body fight free radicals
  • Found in
    • Liver, organ meats, shellfish, whole grain
      cereals and bread, dark green leafy veggies, peas, poultry , nuts and beans
  • Comes from
    • Dental fixtures, copperpipes, cookware
    • Copper at work
    • Birth control pills and iUD
  • Results of low copper
    • Anemia, htn, diarrhea, difficulties breathing,
      lowered immune function, EKG abnormalities
  • Causes low copper
    • Poor diet, digestive or intestinal disorders
      that interfere with nutrient absorption
    • Chronic diarrhea and
    • Excess zinc
    • Meds which interfere with cu absorption
      • Delavirdine (resciptor for HIV), ethambutol,
        (TB), penicillamine (for RA)
      • Elderly persons, vegetarians, athletes, pregnant
        women and premature infants likely to lack copper
  • Too much copper and depression
    • Involved in monoamine oxidase, dopamine beta
      hydroxylase and tyrosine hydroxylase all of which stimulate dopamine
    • Hi levels found in depressed

Magnesium

  • 54 % in bones 27 % in muscles
  • 19 % in heart and liver
  • 1 % in blood
  • 300 biochemical reactions
    • Maintain health immune system
    • Keeps bones strong
    • Regulates BP
    • Making proteins
    • Ensuring nerves work properly
    • Keep heart beating steadily
  • Lacks cause
    • Irregular heartbeat, nausea, lack appetite, sz,
      fatigue, muscle weakness, poor coordination, personality changes
    • May worsen depression and apathy, irritability,
      nervousness, anxiety, excessive emotional reactions and frequent mood changes,
      decreased memory and concentration, migraines, fatigue and ADHD
    • Link to depression especially in young adults
  • Risks for low Mg
    • Crohn’s and ds interfere with absorption
    • Etohics, dm senior citizens
    • Meds that interfere with absorption or use
      • Diuretics (Lasix) bumetanide (bumex) antibiotics
        (gentamicin)
    • Stress
  • Symptoms low Mg
    • Insomnia
    • Constipation
    • Anxiety
    • Muscle spasms
  • Mg found in
    • Dark green leafy veggies, nuts, whole grain
      breads, beans, peas
    • One of first minerals stripped with processed
      foods.
  • Most Americans low in Mg
    • Is low in processed foods
  • Lack of Mg can trigger depression
    • In mice inc anxiety and depression like
      behaviours
  • High magnesium also in depressed patients.
  • How Mg works
    • Permits excess of calcium into nervous system
      damaging nerves and causing sx similar to depression
    • Lack Mg may reduce brain levels of serotonin

Lithium 2.5 – 20 mg

  • In every organ
  • Helps stabilize mood
  • Regulate neurotransmitter signaling
  • Protects brain cells from early death
  • Helps with antidepressants
  • Aggression suicide attempts
    • Finnish study with li in water
  • Mechanism
    • Fight inflammation
    • Inc enzymes that produce glutathione
    • Regulates pro inflammatory cytokines
      • Reduce synthesis of proinflammatory cytokines
        which can regulate expression responsible for their production

Chromium

  • In foods
  • Cleared by
    • Infection, exercise, physical trauma, diets with
      large amounts of simple sugars, stress
  • Keeps insulin 
    and blood sugar balance and energy levels
    • Helps insulin sensitivity
  • Lowers Cholesterol levels, body fat, Tg, Low
    density lipoprotein
  • Raises HDL good cholesterol
  • Helps with depression

Iodine

  • Make thyroid hormones
  • Thyroid snatches iodine and incorporates it into
    these hormones
    • Thyroid enlarges as tries to get iodine
  • In ocean water and soil

Iron

  • For regulate cell growth
  • Part of hemoglobin within RBC that carries
    oxygen thru blood
  • Lack of iron
    • Lack of oxygen brought to body
      • Fatigue
      • Weakened immune system
      • Psycho problems
        • Poor attention
    • Sx of lack
      • Weak ess, fatigue, disgestive problems fragile
        bones, difficulties maintaining body temperature
      • Requeent infections
      • Poor performance at school or work
    • Found in red meat, fish, poultry, beans,
      lentils, iron fortified cereals
    • Cause of deficiency
      • Low consumption certain foods
      • Pregnant
      • Older infants, toddlers, teenage girls
      • Women of childbearing age
      • Celiac dx and dx interfere with iron absorption
    • Supplement with ferrous bisglycinate
      • Does not cause side effects of nausea,
        constipation, stomach upset
      • 10 mg ferritin BID til normal

SUMMARY

  • Minerals and other nutrients influence brain
    function and mood
  • Consider hi and low trace minerals
  • Every depressed would asses for lack of trace
    minerals
  • Everyone is unique
  • Taking too much trace mineral can lead to
    imbalance.
  • Zinc
    numerous pathways
    • Risk deficiency zinc vegetarians, etohic, eating disorder, ulcerative colitis,
      crohns, absorption disorders
      • Test zinc taste test
      • Lower zinc in major depressed
      • Zinc helps antidepressants
    • Copper
    • higher in depressed
    • needed for dopamine
    • Mg
      helps in depressed who ar mg deficient
      • 2/3 Americans consume less than RDA Mg
      • Depression inc when Mg low or hi
      • Risk crohns, nutrient absorption, etoh, DM,
        seniors
    • Li
      BJP adding lithium relieved sx depression in 48 hours
      • Finnish 2017 nutritional li highly effective
    • Chromium
      promising in antidepressants
    • Iron
      • lower in depressed; supplement 25 % improvement
  • Iron
    for oxygen
    •  
    • Iodine
      • Thyroid with antidepressants do better

E essential fatty acids and cholesterol

  • Saturated; mono unsaturated let go of one
    hydrogen carbon
    • If on 6th is omega 6
    • If on third carbon is omega 3 FA
    • Recommended omega; 6 / omega 3 is 4:1
  • Depression
    correlated with low omega 3, and DHA
  • BAD lower
    DPA, DHA, and alpha linolenic acid (body uses to make EPA)
  • Suicide
    attempts low DHA, high o6/03
  • Omega 6
    • In corn, soy, sunflower oil, margarine, eggs,
      meat
  • Omega 3
    • Higher o3 consumption linked with lower levels
      of depressionIn fish, fish oil, flaxseed oil and walnuts
    • Kids less likely to sit still or pay
      attention 
    • Risk memory problems, dementia, strokes 
    • Higher levels lower risk depression but in
      depression without anxiety
    • Don’t take too much
  • EPA, DHA fuel the brain
    • Help control chronic inflammation of
      degenerative brains (AD)
  • EFA
    • As RBC EFA dec, severity of depression inc and
      vice versa
    • Low EFA in post partum
  • EPA
    • Can help with inflammation
    • Maintains cell membranes
    • EPA content of RBC decreases, severity epression
      inc
    • Same for EPA and DHA in fat tissue
    • Levels related in post partum depression for
      developing fetus
  • DHA
    • Suicide attempts correlate with low plasma DHA
    • Mildly depressed 34 % less DHA in fat tissue
    • Main fatty acid in brain, grey matter and eye
      retina
    • Improves sending brain signals and brain
      communications
    • Bottle fed baby lacking DHA poor vision or
      cognitive ability
    • LINKED TO DEPRESSION AND BAD
    • Hi amount in brain where brain altering
      neurotransmitters stored
      • Can regulate mood by inc serotonin
    • 3rd trimester taking DHA linked to
      less perceived stress and reduced stress hormones
  • Low cholesterol and depression, suicide

E EXERCISE

  • Less likely depression, anxiety
  • Exercised less likely to have depression reoccur
  • Weight lifting, crew, tai chi
  • Reverse harmful effects of stress
  • Lifts depression
  • Improve learning
  • Builds self esteem and improves body image
  • Feel euphoric or joyful
  • How exercise works
    • Release endorphins
    • Change level or effects norepinephrine,
      serotonin
    • Lower cortisol
    • Inc body temperature
    • Gets mind off activities, improve self esteem,
      self image interaction
    • BDNF
  • Mitochondria
    • Brain has lots of mitochondria
    • Energy
    • Vitamin
      B12
      • With other vit B strengthening nervous and
        immune systems
      • Helps muscle tone and healthy skin
      • Role in energy metabolism
      • Deficiency à
        • Fatigue
        • Inc homocsyteine which can worsen heart disease
      • trouble absorbing vitamins
        • antacids
        • Vegans no animal, dairy no ingest B 12
        • Amoxicillin,
          antibiotics, colestipol to reduce cholesterol
    • Carnitine
      • Made from aa found in meat
        • In meat, milk, poultry, fish
        • Some made in liver and kidneys from aa lysine
          and methionine
      • Produces energy in mitochondria by carrying
        fatty acids into mIT
      • Inc energy and helps with depression
    • Co Q 10
      • Enhances carnitine
      • Antioxidant
      • Boosts energy
      • Ubiquinol
      • In diet
        • Whole grains, salmon, oily fish, organ meats
          such as liver
        • Statins, some beta blockers, imipramine can
          deplete coQ10
    • Rhodiola
      • Boost energy endure exercise
      • Supports exercise program

SUMMARY

  • 60.3 % exercise regularly to have depression,
    anxiety
  • NIH exercised less likely to have depressive
    symptoms
  • Over time, exercise feasible tx for mdd
  • 2008 found weakened mitochondrial activity
    translated to less cellular energy was related to physical discomfort.

B B vitamins that affect mood

Niacin, B 6   make serotonin

  • Vit D, B vitamins, SAMe
  • B
    vitamins
    • Thiamine, riboflavin, niacin, vitamin B 6, B 12,
      folate, inositol work as a team
    • Regulate carb metabolism
    • Stabilize blood sugar
    • Ease mood swings improve sleep
    • Help liver deactivate and dispose of old
      estrogen
    • Critical to energy making  (Krebs)
    • Vitamin B deficiency causes
      • Harm brain leading to depression, anxiety,
        irritability difficulty concentrating
    • Vitamin B 6 and niacin
      • Help make serotonin (help mood, sleep, appetite
  • Thiamine
    (Vitamin B1)
    • Free thiamine crosses BBBHelps convert glucose
      into fuel
    • Stimulates brain action
    • Needed for nervous system health
    • Aids in digestion
    • Brain rapidly loses energy when thiamine in
      short supply
      • Depression, fatigue anxiety irritability,
        insomnia, memory problems
    • Lack
      • Interfere with uptake of glucose in brain
      • Leads to mental fatigue and poorer moods
      • Depression, fatigue anxiety irritability,
        insomnia, memory problems
  • Niacin
    Vitamin B 3)
    • When niacin in short supply, tryptophan goes to
      niacin instead of serotonin
    • Lack niacin can result in depression, agitation
      and anxiety
    • Helps maintain health nervous and digestive
      systems
    • Also stimulates circulation causing blood
      vessels and RBC to become more flexible
      • Easier thru body and brain
    • Lack. Pellagra
  • Pyridoxine
    (Vitamin B 6)
    • Lack depression, confusion and irritability
    • Needed to make neurotransmitters serotonin,
      dopamine and norepinephine, GABA
    • Depressed pts have low B 6
    • Necessary for normal brain function for
      synthesis of RNA and DNA and formation of myelin sheath around nerve cells
  • Inteffering with above B vitamins. Eating simple
    sugar flour, cake, candy pies, etoh
  • Folate (vitamin
    B 9)
    • SOURCES
      • Asparagus, 
        citrus, fortified cereals, green leafy veggies, legumes (peas, beans,
        lentils)
      • Required for Normal cell development and
        manufacture of DNA and RNA
    • Cause lack
      • Birth control pills, anti-sz meds, antacids,
        some antibiotic, etoh, smoking
    • Necessary to make SAMe needed for
      neurotransmitter metabolism
    • May protect against colorectal, breast and
      cervical cancers
    • Protects the heart by breaking down homocysteine
      (linked to HD)
    • Homocysteine
      • Heart disease
      • Poor memory and compromised thinking
    • To protect fetus from fetal brain and spinal
      cord defects
    • Lack
      • Can lead to depression
        • Lower folate
          • Higher likelihood of depression
          • Poor response to antidepressants
          • Higher relapse rate
          • Folate supplementation makes antidepressants
            work better.
        • Depressed have lower folate than normal or other
          psych d/o
        • Antidepressants do not work well I low folate
        • People with low folate more likely to experience
          depression relapse
        • Women (not men) who took folic acid with tx do
          better than placebo
    • FOLate natural form in foods
    • Folic acid man made
    • MTHFR MORE PRONE TO DEPRESSION
    • 5 methyltetrahydrofolate= L methlfolate natural
      active form
      • Used at cellular level for DNA , reproduction,
        regulation of homocysteine.
      • Crosses BBB
  • Vitamin
    B6
    • Necessary to make serotonin and dopamine
    • Lack trigger depression and mental confusion
  • Vitamin B
    12
    • Works with B6, and folic acid to make serotonin
      and dopamine
    • Necessary to make RBC
    •  
    • Lack
      • Problems moving oxygen thru body
      • Can cause fatigue, mood swings, irritability,
        dementia or mania
      • neurological problems including tingling in
        hands
      • difficulties coordination walking
      • psychiatric: depression, anxiety, paranoia, AH,
        memory loss, confusion, outbursts, and behavioural challenges

Inositol (Vitamin B 8)

  • for depression, panic, OCD
  • is carb that can make from glucose
    • too much sugar can disrupt the inositol shuttle
      and other messenger pathways leading to deficiency
  • forms health cell membranes
  • maintains proper electrical energy and nutrient
    transfer between cells
  • changed into substance that regulates action of
    serotonin
    • lack serotonin depression, panic disorder, OCD

Vitamin D

  • from food and sunlight
  • cholesterol is precursor
  • important for absorption and utilization of Ca
    and phosphorus for bone and teeth growth
  • involved in brain function
  • vitamin D receptors in both neurons and glial
    cells in brain
  • forms
    • D2 ergocalciferol made by plants
    • Cholecalciferol made when skin exposed to UV-B
  • Lack related to
    • Psoriasis, muscle pain, weakness, htn, some
      cancer, autoimmune disease
    • Depression, suicide
    • Common in seniors
  • Depression and vitamin D

SAMe. 800 – 1600 mg for depression

  • Made from methionine
  • Helps make neurotransmitters, proteins and
    hormones
  • Helps create mood enhancers
  • Can help relieve depression
    • Response rate 45 %  (30 % for escitalopram and 26 % for placebo
    • Add on for depression vs placebo

SUMMARY

  •  every
    depressed person should take B complex vitamin with L methylfolate
  • Check vitamin B 12 and D
  • Everyone unique
  • Vitamins
    • Make neurotransmitters, stabilize blood sugar,
      ease mood swings, improve sleep, control inflammation
  • Affect mood
    • B vitamins, D, SAMe
  • Deficiency of B
    • Harm brain, leading to depression, anxiety,
      irritability and difficulty concentrating
    • Folate natural
      • Low folate higher likelihood of depression, poor
        response to antidepressants, higher relapse rate
    • Folic acid man made
  • Vitamin B
    12 is
    family of compounds. Psych
    • Lack depression, anxiety, paranoia, AH, memory
      loss, confucsion, outbursts, behavioural changes
    • From beef liver, cheese, eggs, milk, fish,
      yogurt
    • If B 12 low and homocysteine hi recommends B 12
      shot
  • Vitamin D
    eat, sun
    • Linked to depression
  • SAMe
    depression
  • Inositol
    changed to substance that regulates action of serotonin
    • Depression, panic disorder, OCD
    • From inositol from foods including wheat germ,
      brewer’s yeast, grapefruit, liver, raisins, unrefined molasses
  • Thiamine
    • Helps brain change glucose into fuel
    • Brain rapidly loses energy when thiamin low
      leading to depression, fatigue anxiety, irritability, insomnia, memory problems
  • Niacin
    • Lack lead to depression, agitation, anxiety all
      linked to low serotonin
    • Lack pellagra sx depression, anxiety, apathy
  • B vitamins depleted by eating too many simple
    sugar, etoh
  • Folic acid, V12 and vitamin D and other
    nutrients effective tx for depression
  • Folic acid with meds happier for women , not men
  • L methylfolate decrease depression 3 months
    later
  • Elderly with vitamin B 12 deficiency more likely
    to be depressed
  • Duke Seniors lower vitamin D greater likelihood
    of depression
  • Swedish depression improve with vitamin D
  • SAMe large improvement in depression

R RESTORE HEALTHY DIGESTION

  • GUT HOUSES > 70 % IMMUNE SYSTEM
  • SUCROSE ALTERS BACTERIà CANDIDA YEAST
  • Factors that decrease good bacteria
    • Lack zinc, B vitamins, Fatty acid
    • Lack of sun
    • Lack of social support
    • Poor nutrition
    • Poor connection with nature
    • Stress
    • Lots sugar
    • Antibiotics, alcohol , birth control pills
    • Corticosteroids and anti inflammatory drugs
    • Infections, laxatives
    • Excessive use of antibacterial soap
    • Meat from animals with growth hormones or
      antibiotics
    • Gluten containing grains
  • Gut Brain connection 2 way street
    • Enteric thru Vagus nerve ascending
    • Descending ANS
    • Capillaries within epithelial tissues
    • Brain can communicate with enteric nervous
      system both directly (thru capillaries and nerve endings in gut wall) and
      directly thru chemical signaling and hormone secretion
    • Gut communicates directly with the brain

Mood is affected by inflammatory markers in the gut

  • Microbiota
    • Microorganisms in a specific region or location
      • Can be gut, skin, lungs oral mucosa
  • Microbiome
    • Collection within a given microbiota
  • Gut microbiota
    • Associated with BAD, schizophrenia anxiety, OCD
    • Pigs given lactobacillus probiotics healthier
      and more resistant to swine flu
    • Bacterioides
      • hi in depression
      • linked to inflammation
    • depressed
      • hi bacteroides
      • firmicutes, bacteroides, proteobacteria abnormalities
      • inc Enterobacteriaceae and alisitpes
      • reduced faecal bacterium negative correlation
        with depression
      • depression can actually be transmitted thru gut
        microbes
    • To help gut
      • For persons over 40, much depression is related
        to gut
      • He recommends
        • Digestive enzyme with hydrochloric acid
          • Hydrochloric acid important for digesting
            protein
          • Ant-acids especially 24 hour PPI lower stomach
            acid
            • So don’t absorb B 12, digest protein
        • Probiotics 50 billion CFUs
      • Can do these without testing without adverse
        side effects.
    • Disrupting
      Gut function
      • ant acids
        – especially 24 hour PPI lower stomach acid
        • so don’t absorb vitamin b 12 and digest/
          breakdown protein
      • antibiotics
        • can get an overgrowth of yeast, dsybiotic gut
      • stress
      • inflammation
      • bad diet
      • food sensitivities
        • celiac disease abnormal reaction to gluten
          • higher incidence of depression
          • the action of gluten interferes with absorption
            • zinc, folate, amino acids not absorbed
              increasing risk of depression
        • food allergies

Toxins can affect mood

  • Toxins are synergistic
    • BPA and phthalates are in many things
      • Affect metabolism and absorption of zinc
      • Have direct effects on neurons on brain
      • Indirect effects to make trace minerals
        unavailable

Toxins can interfere with the conversion of thyroid hormones T4 to T3   

Role of Inflammation in depression

  • Inflammation is Implicated for Heart Disease,
    arthritis, cancer, Alzheimer’s disease
  • Heavily involved in a subset of depressed
  • Overstimulated immune system produces chemicals
    that go into the brain that affects how we synthesize chemicals to make our
    brain regular
    • Chronic inflammation regardless of cause
      (trauma, stress, infection) affects mood
  • If we have the illness feel depressed.

Medications causing depression

  • Propranolol, beta blockers
  • Steroids
    • Contribute to depression and suicide
  • Hormones
  • Blood pressure medications
  • Chantix increases risk of suicide
  • Antidepressants can contribute to more
    depression of suicidality
    • FDA has put out warnings

To help stress

  • Mindfulness
  • Magnesium
    • Interfere with overactive stress response system

Supplements to help with depression

  • Magnesium
    • Most common nutritional deficiency
    • Inverse relationship with stress
    • Magnesium is repleted in soil, so foods are low
      in magnesium
    • Can lower blood pressure
    • Helps with sleep, anxiety
    • Helps with concentration
    • Helps convert fats into energy
    • In hundreds of reactions for brain function
  • Zinc
    • Commonly deficient because of toxins (BPS,
      phthalates)
    • Is not plentiful in a vegan of vegetarian diet
      • Is most bioavailable in animal products
      • Adolescents commonly have low zinc levels
    • Needed as biopathway to make neurotransmitters
    • Linked to depression
    • Symptoms of low zinc levels
      • Hair loss, diarrhea, white marks on nails, skin
        lesions, acne, less zinc
    • Taking zinc makes antidepressants work better
    • Test for zinc with zinc taste test
      • Have strong bitter taste if have adequate zinc
      • Taste buds are zinc dependent
      • Restore zinc, taste return
  • Vitamin B
    12
  • Vitamin D
    • Recommends testing
    • Take at least 2000 iu per day
  • Omega 3.
    Fish oil
    • Helps with mood
  • 5HTP.
    Precursor to serotonin
  • Don’t take tryptophan by it self
  • SAMe
    can be helpful. Do not take if have bipolar
    • Studies show good results
    • 800 – 1600 mg per day
  • St John’s
    Wort
    • 600 mg 900 mg per day
    • Make sure it comes from a reputable company
  • Rhodiola
    • He has had a lot of success
    • Fewer side effects, fewer interactions with
      drugs
    • Russians used for many years for concentration,
      stamina, energy
    • 100 – 400 mg per day
  • Role of Hormones important
    • Bioidentical hormones
  • Neurotransmitter testing not accurate
    • Can look in urine for break down products of
      serotonin and dopamine 
    • He tests levels of amino acids and supplements
      to give the building blocks to make neurotransmitters      
    • He gives amino acid precursor molecules

Role of trauma

  • Depression from trauma is not as easily treated
    with nutritional supplements
  • Look at therapy and nutritional deficiencies

Summary Points

  • 120 million people worldwide; 15 M in US
  • 7 % older than 18
  • 2x as many females
  • One in 8 teens equal sex
  • 1/33 kids
  • Runs in families 3 x as likely to have it
  • Hx increases risk;
    • 50 % if one episode
    • 90 % if had several episodes
  • Over next 20 years, projected to be #1 cause
    disability in hi income countries and #2 world wide
  • Annual cost 30 – 44 billion.
  • Every person is different- biochemically unique

Suicide

  • 8th leading cause death in US 32K
    deaths Q year
  • 15 % untxed suicide
    • More than 2/3 suicides caused by depression
    • Women 2-3 x more likely SA
    • Men more than 4 x women to die of suicide
    • Risk
      • Family hx, impulsive drugs, separation, divorce,
        family violence, impulsive
    • Times
      • Anxiety, anniversaries, drug /etoh abuse, untx
        derpession
  • He uses integrative psychiatry
  • Factors contributing to depression are unique
  • THE ZEBRA
  • Nutrition important
    • 1601 Capt James Lancaster discovered that lemon
      juice prevented scurvy
    • British government waited 264 years after it was
      proven
    • Just be cause MDs ignore does not mean not true
    • Tomato Effect Dr. James Goodwin `984 JAMA
      efficacious tx for certain ds is ignored or rejected because does not make
      sense
      • Named tomato effect because 16 th – 19 th
        century believed tomatoes were poisonous..
  • Longer one suffers, more difficult it is to
    recover

Meds

  • James Watson winner of Nobel Prize ifor
    determining the structure of   DNA urged
    doctors to have better understanding of mental illness and develop tx based on
    their results
  • Prescribe carefully

Stigma

  • We are more than our experience and genes

Symptoms

  • Also stomach ache, irritability, work too much
  • Aches and pains,
  • Etoh and drug abuse
  • Chain smoking
  • Constant exhaustion
  • Crying a lot
  • Decreased physical activity QD
  • Reckless doing risky things
  • Difficulty getting up in am
  • Irritability, frustration
  • Lack of energy or motivation
  • Reduced sex drive
  • Working long hours long term difficulty sleeping

Results

  • Hard to work, loss relationships
  • No energy to take care of self
  • 4 x risk MI
  • More likely to abuse etoh or drugs

Types

  • Major depressive disorder MDD
    • Depressin, anhedonia and five other
    • Worthless common
    • Not grief or sadness
  • Persistent depressive disorder dysthmica
    • Most of days more often or not for 2 years.
    • If start before age 21, more likely co occurring
      personality disorder or substance abuse
  • Disruptive Mood Dysregulation Disorder kids
    • Chronic, sever, persistent irritability
    • Can be temper outburst, aggression out of
      proptortion in intensity
    • Over at least one year in two settings (home,
      work)
    • Developmentally in appropriate.
    • Have low frustration tolerance
    • Family lie disrupted
  • Premenstrual dysphoric disorder
    • Premenstrual dysphoric disorder is sever form of
      pMS
    • Most cycles, sx must be present in final week
      before period then better
    • At least one of following
      • Emotional changes (mood swings)
      • Irritability, anger, increased conflicts
      • Depressed mood, hoplessnes, self deprecating
      • Anxiety, tension, feeling on edge
    • One or more of following total five
      • Decreased interest in usual activities
      • Difficulties concentrating
      • Lack eergy
      • Change appetite
      • Difficulty sleeping
      • Feeling overwhelmed or out of control
      • Physical sx such as breast tenderness, swelling,
        jt pain, muscle pain, bloating or wt gain
    • Lead to distress or interference with work,
      school, social, relationship
  • Substance/ medication induced depressive
    disorder
    • Depressive sx associated with substance
    • Typically starts within first fee weeks or one
      month after start
    • Stop, get better
  • Depressive disordered due to another medical
    condition
    • CVa, HD, PD, TBI, Cushings, hypothyroid
  • Depression with Anxious Distress
    • Hi anxiety linked to higher suicide risk, longer
      length of illness, greater likelihood of not responding to tx
    • At least tow during most days
      • anxious, tense
      • Unusually restless
      • Difficulties concentrating because of worry
      • Fear that something awful may happen
      • Feeling one might lose control
  • Depression with atypical Features
    • Mood
      reactivity can be cheered up
      • Can be euthymic if environment positive
      • Weight gain or inc appetite
      • Sleep at least ten hours per day
      • Leaden paralysis
      • Rejection sensitivity
  • Post partum Depression
    • 70 % have baby blues
      • Short term worry, unhappiness, fatigue  2 weeks
    • Post partum depression `6 %
      • For 4 weeks
        • Sluggishness, fatigue
        • Sad, hopeless, helpless or worthless
        • Change sleep
        • Change appetite
        • Difficulty concentration, confusion
        • Crying for no reason
        • Lack of interest in baby or family
        • Fear of harming baby or self
        • Difficulties bonding with baby
      • Often have anxiety or panic attacks
      • Rapid changed in hormones or thyroid after
        delivery may contribute
      • Lack of sleep, stress, family hx depression,
        lack support may play rold
  • Depression with a seasonal Pattern (seasonal
    affective disorder
    • Relationship between the start of depressive
      episodes and time of hear
      • Seasonal
        • Loss energy, sleep too much, overeat, wt gain,
          carb craving
        • Linked to biochemical imbalance caused by
          shorter daylight hours
        • More common far from equator
        • Less commonly occurs in summer
        • Possibly in response to hi heat and humidity
        • More likely insomnia, dec appetite, wt loss,
          agitation, anxiety
        • Younger adults and women higher risk
        • Average age onset is 18 – 30 years.

CAUSES

  • Biochemical
    • Neurotransmitters
      • Serotonin,
        • Lack sleep problems, binge eating, irritability
      • norepinephrine,
        • too little low mood and fatigue
      • dopamine
        • due to too little or too much
      • lack due to
        • lack amino acids, vitamins, minerals
        • breaking down neurotransmitters too quickly
  • Physical
    • Illnesses
      • 25 % cancer, 94 % eating disorders
      • 20- 40 % heart attack, 10 – 20 % HIV
      • 50 % HD, 30 % chronic long term pain
      • 50 % PD
      • 25-50 % stroke
      • 60 % disabling tinnitus
      • 27 % drug or etoh
      • 30 – 35 % AD
      • Anxiety disorder, tobacco addiction
      • Depressed people more likely to have DM2 and HD
  • Meds
    • Antipsychotic,
    • antihistamine,
    • beta blockers,
    • birth control pills,
    •  htn,
    • anti inflammatory meds,
    • adrenal hormone agents and
    • corticosteroids
    • Etoh, amphotericin B, bismuth nitrate,
      carbamazepine, cis-retinoic acid, cyloserine
    • Cyclosporine, digitalis
    • Estrogen therapy, flunarizine, h2 blockers
      (cimetidine, ranitidine)
    • Interferon, levodopa, methyldopa mazindol,
      mercury
    • Methylxantines (caffeine, theophylline),
      metoclopramide (reglan)
    • Metronidazole, nifedipine, organic nitrates
    • Phenytoin
    • Psychostimulants (fenfluramine, methylphenidate,
      permoline, phenylpropanolamine)
    • Reserpine
    • Sedative hypnotics (barbiturates,
      benzodiazepines, methaqualone)
    • Thallium
    • Thiazide diuretics
    • Vinblastine and vincristine
  • Overactive
    immune system
    • Sickness behavior normal reaction to infection
      • Poor sleep, concentration, lack of desire
      • Pro inflammatory chemicals inflammatory
        cytokines cause changes in neurotransmitters
      • Depression has changed in cytokines
      • High levels of inflammatory cytokines
      • Low levels of anti inflammatory cytokines
      • Anti inflammatory IL 4 and TGF b1 were lower
      • Sertraline decrease pro inflammatory and
        increase anti inflammatory
      • Depressed with inc inflammatory biomarkers less
        likely to respond to antidepressants
      • Pt with hx no response to antidepressants have
        inc inflammation
  • Inflammatory brain illnesses linked to
    depression
    • Areas of brain dealing with mood regulation  inflammation was 30 % higher in depressed
    • 2017 Manchester MDD have inc microglial
      activation
      • BiolPysch Krystal , J
  • Hormones
    • Estrogen
      • Teen girls = teen boys in depression
      • In women short depression 7 – 10 days before
        period
      • Baby blues
    • Testosterone
      • Men low testosterone may be linked to depression
      • Men may not respond with low testosterone
    • Thyroid sub clinically low in mood disorders
      • Women depressed hi TSH
      • Low thyroid 
        poorer response
      • Give thyroid better response to antidepressants
  • Genetics
    • Tendency to have is inherited not ds
      • Family hx depression 3 x risk
      • Twins
        • Other one depressed 27 %
        • Raised separately risk 67 %
  • Psychological
    factors
    • Stress
    • Aging

KEY POINTS

  • GP. 62 % scripts for depression’ 65 % for
    anxiety
  • Depression, 4 x likely to have MI than no hx
  • s/p MI, chance another higher
  • depressed more likely to abuse drugs, etoh

Treatment

  • 2/3 
    effectively tx have sx that impair
    • 28 % mild impairment
    • 23 % moderate impairment
    • 12 % severe impairment; 4 % very severe impairment
  • Research show 94 % meds work closer to 51 %
    • 1/3 studies showing antidepressants don’t work
      submitted to FDA don’t work not published
    • ½ studies failed to show any benefit other than
      placebo
  • Studies only short term 6 weeks
  • based on symptoms and vulnerabilities. Severity

What is missing in psych eval

  • diet, toxins nutrition, allergies

Drug tx don’t work

Research

  • drug companies sponsoring research have conflict
    of interest
    • 4.9 x likely to report med works
  • Direct advertising to consumer spend billions
  • People not depressed account for 94 % new
    antidepressant use
  • JAMA 2010 antidepressants don’t work  for less severe forms depression
  • Paxil and imipramine do not reduce sx in mild,
    moderate or severe depression
  • Antidepressants only work in severe depression
  • by Vittengl at Truman U; Pt who took
    antidepressants more sx at 9 years
  • Robert Whitaker Anatomy of an Epidemic 50 yrs
    data;  over time, people not on meds do
    better than those who are.
    • Since 1987, 
      3x more on disability
    • Only 15 % 5x with meds remained healthy over
      time
      • The other 85 % have chronic depression
  • Yale found that universities hire to perform
    drug research were part owners
  • Studies more likely to prove if funded by drug
    industry or researchers have financial interest
  • British Psych Joanna Moncrieff paper, “There are
    no signs that the rapidly escalating use antidepressants reduces burden of
    depressive disorders
  • JAMA found standard antidepressants no more
    effective than placebo for people  with
    less severe forms of depression

Bioindividuality

  • Only speciality where no measurements
  • Side
    effects
    • Agitation,
    • Blurred vision, constipation, dec sex drive, dry
      mouth
    • Erectile dysfunction, fatigue, insomnia, nausea
    • Osteoporosis, wt gain risk SI
    • SRRI
      • Sexual
      • St gain
      • Physical
        • Headache, nausea, stomach problems
  • mEd withdrawal 
    like flu
    • Irritability, agitation, restlessness, insomnia
    • Migraines, headaches, not able to focus,
      depression
    • Physical
      • Sweat, palpitation, B &V, difficulties
        breathing, sensory dist
    • Reason: body/ brain no time to adjust to change

Brain and body. Influence each other

  • Brain 3 pounds uses 20 % energy
  • Scars in Brodmann
    area 25 BA 25
    hyperactive in depressed people
    • Activity normalized when depressive sx relieved
    • Does not matter if relieved by tx or meds
    • Is directly linked to amygdala which processes
      anxiety, fear and the hypothalamus 
      (important in stress)
    • Generous supply of special transporter
      molecules. Serotonin
  • Serotonin gene coding for serotonin transporter
    molecule comes in long and short
    • Long triggers production of more transporter
      molecules
    • Short gene have smaller BA 25 and does not act
      with amygdala and other brain areas
    • Is sped up activity in BA 25 the cause or result
      of depression?

Genes

  • Some contribution 37 %
  • Epigenetics
    • Methylation
    • Causes
      • Stress
        • Study mice remove from mothers 3 hrs QD x 10
          days epigenetic changes last a week
        • Mice of good mothers exchanged with bad mothers,
          stress handling abilities of foster 
          mothers.
          • Same for monkeys
    • Good nutrition etc best hope
    • Makes each person unique
  • Genetic testing, twice as likely to be
    prescribed the correct med

IDeal

  • Diet meds, supplements, family hx
  • Labs
  • Vitamin deficiencies, toxic metals, hormone
    imbalances
  • Vitamin levels, amino acid and fatty acid
    imbalances
  • Hi or low minerals
  • Celiac disease and other food sensibilities
  • Imbalanced levels of digestive enzymes
  • Disbiosis, parasites
  • Focus on individual unique
  • Care for how pt, not just ds
  • Understand how body and mind are connected
  • Restore health instead of reducing sx
  • Increase boy nutrients to promote long term
    health

T take care of yourself

H hormones and herbs

E exclude

Z zinc and other minerals

E essential fatty acids and cholesterol

E exercise and energy

B and other vitamins

R restore

A amino acids and proteins

T take care of yourself

  • Link betn mental and psyical vauge
  • Diet
    • Studies
      • 2010 AJP unhealthy diet more depressed
      • 2010 teens unhealthy diet more likely depressed
      • 2014 Iranian children
    • Diets hi in saturated fats and refined carbs can
      affect proteins important in brain development such as BDNF
  • Digestion
    • HCl
      • Dissolve food into parts
      • To absorb vit B12, minerals
      • Make enzyme pepsin necessary in digestion of
        protein
    • In SI sodium bicarbonate neutralizes HCL
      • Fat and protein and carbs broken down
      • Digestive enzymes
        • Need zinc, protein, vitamin c
        • Good nutrition leads to good digestion
        • Good digestion ensures all necessary nutrients
          are absorbed
        • Poor digestion=poor nurtition
      • Gut bacteria
        • Probiotics help digest
  • Sleep
    • POOR SLEEP RISK FOR DEPRESSION 2.5 TIMES FOR
      TWINS
    • Brain dev needs sleep for brain dev. 
    • Sleep problems predict  GAD, depression, and other behavioural d/0
    • Poor sleep caused by
      • Sleep apnea 5 x depression
        • Tx sleep apnea can tx depression
        • Sx tired in am and day
        • Memory problems
        • Toss, turn, choke, asp, snore
        • Headaches in am
        • Bathroom > once or twice
        • Swelling legs
        • c/p sweat during sleep
      • stress, caffeine, etoh , drugs, OTC, allergies,
        asthma, hyperthyroid, chronic pain nutritional deficiencies Mg, zn
      • restless legs
    • sleep hygience
      • sleep same time
      • avoid caffeine after lunch
      • comfortable bed
      • thermostat cool
      • dark
      • use bed for sleep and sex
      • no work, TV in bed
      • ritual
      • no computers, games,
      • don’t ty to hard
    • sleep remedies
      • melatonin,
        • pineal body clock. 1 – 3 mg sleep in 30 min
      • Mg, 200- 300 mg
        • Works c Ca for muscle relax, contract
        • Anti-stress. 
          Reduce cortisol, muscle cramps
        • First mineral to disappear with processed foods
        • First mineral to leave when body stressed
        • Depleted by etoh, caffeine, meds
      • valerian,
        300- 500 mg
        • Does not work right away
        • Side effects h/a, restlessness, sleeplessness,
          irregular heart beat
        • Sleep anti anxiety
      • inositol,
        • made by body and intestinal bactiera
        • helps transmit nerve signals
        • prevents buildup of fat in liver and other
          organs
        • 1t 8 PM helps with obcessive thought
      • 5 HTP, 50
        – 200 mg
        • Reduce anxiety
      • glycine, 3 g
        • inh neurotransmitter
        • helps relax blood vessels
        • lower core body temperature
      • GABA
        • Low GABA anxiety, depression, irritability,
          headache, htn
    • Sugar
      • Glucose,
      • Fructose cant be absorbed by cellsà goes to liver
      • Sucrose homes- fructose and glucose
      • Dextrose from corn identical to glucose
      • Galactose in milk
      • Lactose glucose and galactose
      • Maltose in barley – is two glucose
      • Xylose in wood or straw
      • Low sugar in brain weak, irritability, anxiety,
        headaches, faint, depression
      • Hi insulin an d sugar inc negatively affects
        kidney function, inc blood fats, TG, cholesterol
      • Sugar substitute. Xylitol, cinnamon, cardamom,
        ginger, nutmeg
    • Stress
      • Inc inflammation ~ depressive sx
      • Activate inactive genes that affect future
        generations
        • Inc maternal stress in pregnancy ~ inc risk mod
          to severe depression in offspring
        • Stressed ma -kids depressed 11 years later
    • Key Points
      • AJP study unhealthy dietà more depressive and anxiety
      • Diets 13,486 Iranian kids inc junk food ~
        psychiatric stress
      • Survey, 40 % uS less than 8 hours sleep
      • Met analysis 23 studies adolescents 12- 20 with
        mdd more sleep disturbances
      • 2015 study consistently poor sleep inc
        depression by 2.5
      • More soft drinks higher levels depression,
        hopelessness and aggression
      • 72 % of people with daily stress and anxiety
        claim interferes with lives

HORMONES

  • Low
    thyroid
    • Anxiety , memory, hi cholesterol, constipation,
      gum disease, fat, hypoglycemia, muscle aches and pains, acne, exzema, hair
      loss, recurrent infections, pMS, irregular menstrual, ovarian cysts,
      endometriosis, fluid retention, fatigue
    • Faulty testing à
      faulty dx
    • TSH only show pituitary asks for correct amount
      thyroid
      • But body might not be using it properly
    • Taking imipramine  plus T 3 faster recovery
    • Replacing missing thyroid relieves depression
    • Metanalysis T3 increased improvements seen with
      antidepressants for tx resistant depression
    • 2014, T3 and T4 were both predictors of the
      level of improvement in depression sx.
    • T3 works better for depression
      • Better for women
    • Thyroid needs iodine, tyrosine, zinc and iron
    • Toxins get in the way
      • Plastics, air fresheners
      • Polychlorinated biphenyls, dioxin, phthalates,
        and polybrominated diphenyl ether (PBDE)
        • Upset ratios in diff T hormone
        • Interfere with thyroid hormone synthesis
        • Suppress production thyroid hormone receptors
          and binding thyroid hormone transport proteins.
  • DHEA
    • Produced by adrenals
      • When stressed , makes more
        • Changes in liver to dHEA S which is measured
    • Antiaging supplement controversial
    • For depression
      • 60 % depressed respond
      • Maybe works better for men
    • Makes testosterone and estrogen and all steroid
      hormones
      • Need cholesterol
    • Highest in mid 20s
  • Testosterone
    •  Made in
      testes, ovaries, adrenal glands, liver, skin and brain
    • Responsible for protein synthesis
    • Maintenance of bone mineral density
    • Lean body mass, muscle strength
    • Sensitization or serotonin recptors
    • Physiologic processes that contribute to sex
      appeal
    • Decreases with age
      • Diet, exercise
      • Sleep quality
      • Endocrine do
      • Low testosterone
        • Dec strength, fatigue,
        • poor libido,
        • htn, inc CV risk,
        • loss lean body mass inc fat
      • lowers depression with (and without?) meds
      • lowest testosterone group (age 71-89)2 x
        depression
      • 11/18
        JAMA significant reductions in depressive sx          d
      • Low
        testosterone levels are linked to depression
      • In some
        men depression cannot be relived until testosterone raised to a normal level
      • Antidepressants
        cannot raise testosterone to a normal level
      • Other
        ways to raise testosterone
        • Zinc
        • Exercise
          to strengthen muscles
        • Reduce
          stress to reduce cortisol (which breaks down muscle
        • Cut or
          avoid soy. Phytoestrogens which can counteract testosterone
        • Eat
          plenty EPA and DHA in salmon and other cold water fish
        • Monitor
          cholesterol and DHEA (needed to make testosterone
        • Supplement
          with tribulus, herb than enhances testosterone synthesis
  • Estrogen
    and Progesterone
    • 2014 study estrogen affects brain derived
      neurotrophic factor (BDNF)
      • BDNF support survival of neurons and growth of
        new neurons and their connections
    • Estrogen
      can affect mood by degrading or reducing levels of MAO (which breaks down
      serotonin.
  • Herbs
    • St John’s
      Wort 300 mg po TID
      • Anti depressant mild to moderate depression
      • Germany licensed for anxiety,d epression, sleep
        disorder
      • Pain disorder
      • Cochrane 
        mild to moderate for 4 – 12 weeks did better than placebo
      • Fewer side effects than antidepressants.
      • Safe long term prevents relapse
      • Has hypericin
        • Antiviral, against cancer and HIV in stored
          blood
      • and hyperforin
        • activates a specific receptor in liver that
          triggers production of an enzyme used to metabolize meds
    • Curcumin
      • For Inflammation
      • Regulates stress response system
      • Degrades MAO which breaks down serotonin and by
        protecting against oxidative stress and mitochondrial damage.
      • Regulates the level of neurotransmitters in body
      • Promotes birth of new neurons in hippocampus
      • Improve cognition
        • Daily improved memory and mood in people with
          mild, age-related memory loss
      • Safe and effective
    • Rhodiola
      • Recognized by Russian ministry of health as med
        and herbal tonic
      • Reduce depressive sx, boost mood diminish
        fatigue, tx opioid addiction
      • Assists in normalizing body stress response by
        increasing body resilience
      • Reduce nicotine withdrawal sx by inc serotonin
        and serotonin receptors
      • Degrades MAO A and MAO B
      • Affects 1062 genes, fifty of which are linked to
        behavior and 62 related to psych d/o
      • Ay improve emotional behavior thru effects of
        transcriptions of certain genes
      • Depression. Rhodiola revolution
      • Can enhance mood, concentration, energy
      • Helps with anxiety and BAD although may be too
        stimulating

Summary

  • Thyroid avoid toxins cleaning products,
    pesticides, eat organic, use glass
    • T3, T 4 predict levels of improvement in
      depression
  • DHEA, testosterone, estrogen, progesterone
    • Archive Gen Psych 2005  DHEA for midlife major and minor depression
    • DHEA decrease with age
    • Australians men with low test 2 x depressed >
      highest test
    • Harvard topical test greater improvements in
      depression > placebo
  • Curcumin, SJW, rhodiola

E exclude harmful foods

  • Celiac ds
    • Body mistakenly mistakes gluten for a dangerous
      toxin
    • Immunity system attacking gluten destroys the
      intestine
    • Absorption vit A, B6, B 12, D, E K,  iron, zn, Mg and ca, essential fats other aa
    • Sx anemia, anorexia, arthritis, dermatitis
      herpetiformis, edema, fatigue, infertility, jt pain, migraines, missed
      menstrual periods, numbing hands
    • Osteoporosis, sz, stunted growth, tooth decay
      and discoloration
    • 1/3 have depression
    • Dx Ab: anti gliadin, anti endomysial, anti tissue
      transglutaminase
    • Will develop nutritional problems
      • Take multivit with iron, EFA, digestive enzymes
      • Test for iron, folate, Mg, amino acids
    • Need HCl
    • Casomorphin,
      gliadorphin
      • Similar to morphine
      • Originally in pee of people with autism
      • Incomplete digestion of proteinsà ADHD, child psychosis,
        dyslexia, down, CD, post partum psychosis, Rett’s ds, severe depression
      • These excess peptides  maybe these are unique carriers of info to
        brain that may worsen many psych d/o
      • Elevated these caused by lack functioning of enzyme
        dipeptidyl peptidase IV (DPP IV) which snips casomorphin and gliadorphin into
        small pieces
        • These absorbed
        • Cause deficiency DDPP IV
          • Lack zn
          • Antibiotics, interferon, gelatin
          • Candida,
          • Hi mercury and heavy metals and pesticides
      • Depression suffered from incomplete digestion of
        casein and gluten
    • Food
      Allergies and depression
      • IgG mediated delayed hypersensitivity rxn
      • Have more depression

Summary

  • 18 studies on depression and 11 on CD depression
    is more common  ore more severe in cD
  • Teens with CD have 31 % risk mde vs 7 % in
    healthy children
  • Correlation CD and depressive disorders
  • 2016 AJ Gastroenterology correlation between
    feelings of depression and Crohns’ ds

Z Zinc and other minerals

  • Zn
  • 200 different reactions
  • In brain
    • Helps make DNA and proteins
    • Helps immune fight off viruses and bacteria
    • Helps wounds heal
    • Regulates neurotransmission in brain
    • Makes it possible to taste and smell
    • Make sex and reproduction possible
    • Helps make all enzymes needed to digest fats,
      carbs and proteins
  • In
    • Oysters, poultry, red meat, beans, whole grains
      and nuts
  • Causes of lack
    • Vegetarians
    • Eating disorders
    • UC, crohns
    • Meds
      • Asa, benazepril, cholestyramine
        • Reduce cholesterol and ofloxacin
  • Results of lack
    • Delayed growth in kids and infants
    • Hair loss
    • Diarrhea
    • Loos appetite
    • Weight loss
    • Difficulty tasting food
    • Acne
    • Fatigue
    • Elevated cholesterol
    • More infections
    • Memory impairment
    • Impotence
    • Anorexia, impaired cognitive, other behavioural
      disturbances
    • Poorer appetite
  • Depression
    • Lower levels in major depression, postpartum
      depression
    • Depression à
      inflammation
      • Lowers albumin which transports zinc thru
        bloodstream
      • Maybe liver snatches up zn to use for
        inflammation
    • Zinc inh NMDA which controls glutamate
      • Glutamate
        • Sends signals between nerve cells
        • Helps learning, memory
        • Too much glutamateà
          overstimulation
          • Progressive damage to nerve function (~
            depression)
    • Zinc can relieve depression’
      • Animals given celexa inc zinc levels
      • Given celexa or imrapmine, inc zinc in
        hippocampus, dec other parts of brain
      • Given ECT inc zinc in hippocampus
      • Zinc antidepressant in lab animals
      • Low doses celexa and imipramine ineffective as
        antidepressants stressed by
      • Chronic tx with antidepressants and ECT causes
        zinc to inc in rat brains
      • Lab, zinc deficient diet à> depressive like sx
        including anorexia and anxiety
      • Zinc improves depression
    • Zinc taste  
      no eat 1 hour before

Copper

  • In liver, heat, brain and kidneys
  • Helps growth , maintenance of TBC, bones,
    nerves, brains
  • Makes prostaglandins needed for heart beat and
    blood pressure
  • Part in getting energy out of fats, protein an
    carbs
  • Helps body fight free radicals
  • Found in
    • Liver, organ meats, shellfish, whole grain
      cereals and bread, dark green leafy veggies, peas, poultry , nuts and beans
  • Comes from
    • Dental fixtures, copperpipes, cookware
    • Copper at work
    • Birth control pills and iUD
  • Results of low copper
    • Anemia, htn, diarrhea, difficulties breathing,
      lowered immune function, EKG abnormalities
  • Causes low copper
    • Poor diet, digestive or intestinal disorders
      that interfere with nutrient absorption
    • Chronic diarrhea and
    • Excess zinc
    • Meds which interfere with cu absorption
      • Delavirdine (resciptor for HIV), ethambutol,
        (TB), penicillamine (for RA)
      • Elderly persons, vegetarians, athletes, pregnant
        women and premature infants likely to lack copper
  • Too much copper and depression
    • Involved in monoamine oxidase, dopamine beta
      hydroxylase and tyrosine hydroxylase all of which stimulate dopamine
    • Hi levels found in depressed

Magnesium

  • 54 % in bones 27 % in muscles
  • 19 % in heart and liver
  • 1 % in blood
  • 300 biochemical reactions
    • Maintain health immune system
    • Keeps bones strong
    • Regulates BP
    • Making proteins
    • Ensuring nerves work properly
    • Keep heart beating steadily
  • Lacks cause
    • Irregular heartbeat, nausea, lack appetite, sz,
      fatigue, muscle weakness, poor coordination, personality changes
    • May worsen depression and apathy, irritability,
      nervousness, anxiety, excessive emotional reactions and frequent mood changes,
      decreased memory and concentration, migraines, fatigue and ADHD
    • Link to depression especially in young adults
  • Risks for low Mg
    • Crohn’s and ds interfere with absorption
    • Etohics, dm senior citizens
    • Meds that interfere with absorption or use
      • Diuretics (Lasix) bumetanide (bumex) antibiotics
        (gentamicin)
    • Stress
  • Symptoms low Mg
    • Insomnia
    • Constipation
    • Anxiety
    • Muscle spasms
  • Mg found in
    • Dark green leafy veggies, nuts, whole grain
      breads, beans, peas
    • One of first minerals stripped with processed
      foods.
  • Most Americans low in Mg
    • Is low in processed foods
  • Lack of Mg can trigger depression
    • In mice inc anxiety and depression like
      behaviours
  • High magnesium also in depressed patients.
  • How Mg works
    • Permits excess of calcium into nervous system
      damaging nerves and causing sx similar to depression
    • Lack Mg may reduce brain levels of serotonin

Lithium 2.5 – 20 mg

  • In every organ
  • Helps stabilize mood
  • Regulate neurotransmitter signaling
  • Protects brain cells from early death
  • Helps with antidepressants
  • Aggression suicide attempts
    • Finnish study with li in water
  • Mechanism
    • Fight inflammation
    • Inc enzymes that produce glutathione
    • Regulates pro inflammatory cytokines
      • Reduce synthesis of proinflammatory cytokines
        which can regulate expression responsible for their production

Chromium

  • In foods
  • Cleared by
    • Infection, exercise, physical trauma, diets with
      large amounts of simple sugars, stress
  • Keeps insulin 
    and blood sugar balance and energy levels
    • Helps insulin sensitivity
  • Lowers Cholesterol levels, body fat, Tg, Low
    density lipoprotein
  • Raises HDL good cholesterol
  • Helps with depression

Iodine

  • Make thyroid hormones
  • Thyroid snatches iodine and incorporates it into
    these hormones
    • Thyroid enlarges as tries to get iodine
  • In ocean water and soil

Iron

  • For regulate cell growth
  • Part of hemoglobin within RBC that carries
    oxygen thru blood
  • Lack of iron
    • Lack of oxygen brought to body
      • Fatigue
      • Weakened immune system
      • Psycho problems
        • Poor attention
    • Sx of lack
      • Weak ess, fatigue, disgestive problems fragile
        bones, difficulties maintaining body temperature
      • Requeent infections
      • Poor performance at school or work
    • Found in red meat, fish, poultry, beans,
      lentils, iron fortified cereals
    • Cause of deficiency
      • Low consumption certain foods
      • Pregnant
      • Older infants, toddlers, teenage girls
      • Women of childbearing age
      • Celiac dx and dx interfere with iron absorption
    • Supplement with ferrous bisglycinate
      • Does not cause side effects of nausea,
        constipation, stomach upset
      • 10 mg ferritin BID til normal

SUMMARY

  • Minerals and other nutrients influence brain
    function and mood
  • Consider hi and low trace minerals
  • Every depressed would asses for lack of trace
    minerals
  • Everyone is unique
  • Taking too much trace mineral can lead to
    imbalance.
  • Zinc
    numerous pathways
    • Risk deficiency zinc vegetarians, etohic, eating disorder, ulcerative colitis,
      crohns, absorption disorders
      • Test zinc taste test
      • Lower zinc in major depressed
      • Zinc helps antidepressants
    • Copper
    • higher in depressed
    • needed for dopamine
    • Mg
      helps in depressed who ar mg deficient
      • 2/3 Americans consume less than RDA Mg
      • Depression inc when Mg low or hi
      • Risk crohns, nutrient absorption, etoh, DM,
        seniors
    • Li
      BJP adding lithium relieved sx depression in 48 hours
      • Finnish 2017 nutritional li highly effective
    • Chromium
      promising in antidepressants
    • Iron
      • lower in depressed; supplement 25 % improvement
  • Iron
    for oxygen
    •  
    • Iodine
      • Thyroid with antidepressants do better

E essential fatty acids and cholesterol

  • Saturated; mono unsaturated let go of one
    hydrogen carbon
    • If on 6th is omega 6
    • If on third carbon is omega 3 FA
    • Recommended omega; 6 / omega 3 is 4:1
  • Depression
    correlated with low omega 3, and DHA
  • BAD lower
    DPA, DHA, and alpha linolenic acid (body uses to make EPA)
  • Suicide
    attempts low DHA, high o6/03
  • Omega 6
    • In corn, soy, sunflower oil, margarine, eggs,
      meat
  • Omega 3
    • Higher o3 consumption linked with lower levels
      of depressionIn fish, fish oil, flaxseed oil and walnuts
    • Kids less likely to sit still or pay
      attention 
    • Risk memory problems, dementia, strokes 
    • Higher levels lower risk depression but in
      depression without anxiety
    • Don’t take too much
  • EPA, DHA fuel the brain
    • Help control chronic inflammation of
      degenerative brains (AD)
  • EFA
    • As RBC EFA dec, severity of depression inc and
      vice versa
    • Low EFA in post partum
  • EPA
    • Can help with inflammation
    • Maintains cell membranes
    • EPA content of RBC decreases, severity epression
      inc
    • Same for EPA and DHA in fat tissue
    • Levels related in post partum depression for
      developing fetus
  • DHA
    • Suicide attempts correlate with low plasma DHA
    • Mildly depressed 34 % less DHA in fat tissue
    • Main fatty acid in brain, grey matter and eye
      retina
    • Improves sending brain signals and brain
      communications
    • Bottle fed baby lacking DHA poor vision or
      cognitive ability
    • LINKED TO DEPRESSION AND BAD
    • Hi amount in brain where brain altering
      neurotransmitters stored
      • Can regulate mood by inc serotonin
    • 3rd trimester taking DHA linked to
      less perceived stress and reduced stress hormones
  • Low cholesterol and depression, suicide

E EXERCISE

  • Less likely depression, anxiety
  • Exercised less likely to have depression reoccur
  • Weight lifting, crew, tai chi
  • Reverse harmful effects of stress
  • Lifts depression
  • Improve learning
  • Builds self esteem and improves body image
  • Feel euphoric or joyful
  • How exercise works
    • Release endorphins
    • Change level or effects norepinephrine,
      serotonin
    • Lower cortisol
    • Inc body temperature
    • Gets mind off activities, improve self esteem,
      self image interaction
    • BDNF
  • Mitochondria
    • Brain has lots of mitochondria
    • Energy
    • Vitamin
      B12
      • With other vit B strengthening nervous and
        immune systems
      • Helps muscle tone and healthy skin
      • Role in energy metabolism
      • Deficiency à
        • Fatigue
        • Inc homocsyteine which can worsen heart disease
      • trouble absorbing vitamins
        • antacids
        • Vegans no animal, dairy no ingest B 12
        • Amoxicillin,
          antibiotics, colestipol to reduce cholesterol
    • Carnitine
      • Made from aa found in meat
        • In meat, milk, poultry, fish
        • Some made in liver and kidneys from aa lysine
          and methionine
      • Produces energy in mitochondria by carrying
        fatty acids into mIT
      • Inc energy and helps with depression
    • Co Q 10
      • Enhances carnitine
      • Antioxidant
      • Boosts energy
      • Ubiquinol
      • In diet
        • Whole grains, salmon, oily fish, organ meats
          such as liver
        • Statins, some beta blockers, imipramine can
          deplete coQ10
    • Rhodiola
      • Boost energy endure exercise
      • Supports exercise program

SUMMARY

  • 60.3 % exercise regularly to have depression,
    anxiety
  • NIH exercised less likely to have depressive
    symptoms
  • Over time, exercise feasible tx for mdd
  • 2008 found weakened mitochondrial activity
    translated to less cellular energy was related to physical discomfort.

B B vitamins that affect mood

Niacin, B 6   make serotonin

  • Vit D, B vitamins, SAMe
  • B
    vitamins
    • Thiamine, riboflavin, niacin, vitamin B 6, B 12,
      folate, inositol work as a team
    • Regulate carb metabolism
    • Stabilize blood sugar
    • Ease mood swings improve sleep
    • Help liver deactivate and dispose of old
      estrogen
    • Critical to energy making  (Krebs)
    • Vitamin B deficiency causes
      • Harm brain leading to depression, anxiety,
        irritability difficulty concentrating
    • Vitamin B 6 and niacin
      • Help make serotonin (help mood, sleep, appetite
  • Thiamine
    (Vitamin B1)
    • Free thiamine crosses BBBHelps convert glucose
      into fuel
    • Stimulates brain action
    • Needed for nervous system health
    • Aids in digestion
    • Brain rapidly loses energy when thiamine in
      short supply
      • Depression, fatigue anxiety irritability,
        insomnia, memory problems
    • Lack
      • Interfere with uptake of glucose in brain
      • Leads to mental fatigue and poorer moods
      • Depression, fatigue anxiety irritability,
        insomnia, memory problems
  • Niacin
    Vitamin B 3)
    • When niacin in short supply, tryptophan goes to
      niacin instead of serotonin
    • Lack niacin can result in depression, agitation
      and anxiety
    • Helps maintain health nervous and digestive
      systems
    • Also stimulates circulation causing blood
      vessels and RBC to become more flexible
      • Easier thru body and brain
    • Lack. Pellagra
  • Pyridoxine
    (Vitamin B 6)
    • Lack depression, confusion and irritability
    • Needed to make neurotransmitters serotonin,
      dopamine and norepinephine, GABA
    • Depressed pts have low B 6
    • Necessary for normal brain function for
      synthesis of RNA and DNA and formation of myelin sheath around nerve cells
  • Inteffering with above B vitamins. Eating simple
    sugar flour, cake, candy pies, etoh
  • Folate (vitamin
    B 9)
    • SOURCES
      • Asparagus, 
        citrus, fortified cereals, green leafy veggies, legumes (peas, beans,
        lentils)
      • Required for Normal cell development and
        manufacture of DNA and RNA
    • Cause lack
      • Birth control pills, anti-sz meds, antacids,
        some antibiotic, etoh, smoking
    • Necessary to make SAMe needed for
      neurotransmitter metabolism
    • May protect against colorectal, breast and
      cervical cancers
    • Protects the heart by breaking down homocysteine
      (linked to HD)
    • Homocysteine
      • Heart disease
      • Poor memory and compromised thinking
    • To protect fetus from fetal brain and spinal
      cord defects
    • Lack
      • Can lead to depression
        • Lower folate
          • Higher likelihood of depression
          • Poor response to antidepressants
          • Higher relapse rate
          • Folate supplementation makes antidepressants
            work better.
        • Depressed have lower folate than normal or other
          psych d/o
        • Antidepressants do not work well I low folate
        • People with low folate more likely to experience
          depression relapse
        • Women (not men) who took folic acid with tx do
          better than placebo
    • FOLate natural form in foods
    • Folic acid man made
    • MTHFR MORE PRONE TO DEPRESSION
    • 5 methyltetrahydrofolate= L methlfolate natural
      active form
      • Used at cellular level for DNA , reproduction,
        regulation of homocysteine.
      • Crosses BBB
  • Vitamin
    B6
    • Necessary to make serotonin and dopamine
    • Lack trigger depression and mental confusion
  • Vitamin B
    12
    • Works with B6, and folic acid to make serotonin
      and dopamine
    • Necessary to make RBC
    •  
    • Lack
      • Problems moving oxygen thru body
      • Can cause fatigue, mood swings, irritability,
        dementia or mania
      • neurological problems including tingling in
        hands
      • difficulties coordination walking
      • psychiatric: depression, anxiety, paranoia, AH,
        memory loss, confusion, outbursts, and behavioural challenges

Inositol (Vitamin B 8)

  • for depression, panic, OCD
  • is carb that can make from glucose
    • too much sugar can disrupt the inositol shuttle
      and other messenger pathways leading to deficiency
  • forms health cell membranes
  • maintains proper electrical energy and nutrient
    transfer between cells
  • changed into substance that regulates action of
    serotonin
    • lack serotonin depression, panic disorder, OCD

Vitamin D

  • from food and sunlight
  • cholesterol is precursor
  • important for absorption and utilization of Ca
    and phosphorus for bone and teeth growth
  • involved in brain function
  • vitamin D receptors in both neurons and glial
    cells in brain
  • forms
    • D2 ergocalciferol made by plants
    • Cholecalciferol made when skin exposed to UV-B
  • Lack related to
    • Psoriasis, muscle pain, weakness, htn, some
      cancer, autoimmune disease
    • Depression, suicide
    • Common in seniors
  • Depression and vitamin D

SAMe. 800 – 1600 mg for depression

  • Made from methionine
  • Helps make neurotransmitters, proteins and
    hormones
  • Helps create mood enhancers
  • Can help relieve depression
    • Response rate 45 %  (30 % for escitalopram and 26 % for placebo
    • Add on for depression vs placebo

SUMMARY

  •  every
    depressed person should take B complex vitamin with L methylfolate
  • Check vitamin B 12 and D
  • Everyone unique
  • Vitamins
    • Make neurotransmitters, stabilize blood sugar,
      ease mood swings, improve sleep, control inflammation
  • Affect mood
    • B vitamins, D, SAMe
  • Deficiency of B
    • Harm brain, leading to depression, anxiety,
      irritability and difficulty concentrating
    • Folate natural
      • Low folate higher likelihood of depression, poor
        response to antidepressants, higher relapse rate
    • Folic acid man made
  • Vitamin B
    12 is
    family of compounds. Psych
    • Lack depression, anxiety, paranoia, AH, memory
      loss, confucsion, outbursts, behavioural changes
    • From beef liver, cheese, eggs, milk, fish,
      yogurt
    • If B 12 low and homocysteine hi recommends B 12
      shot
  • Vitamin D
    eat, sun
    • Linked to depression
  • SAMe
    depression
  • Inositol
    changed to substance that regulates action of serotonin
    • Depression, panic disorder, OCD
    • From inositol from foods including wheat germ,
      brewer’s yeast, grapefruit, liver, raisins, unrefined molasses
  • Thiamine
    • Helps brain change glucose into fuel
    • Brain rapidly loses energy when thiamin low
      leading to depression, fatigue anxiety, irritability, insomnia, memory problems
  • Niacin
    • Lack lead to depression, agitation, anxiety all
      linked to low serotonin
    • Lack pellagra sx depression, anxiety, apathy
  • B vitamins depleted by eating too many simple
    sugar, etoh
  • Folic acid, V12 and vitamin D and other
    nutrients effective tx for depression
  • Folic acid with meds happier for women , not men
  • L methylfolate decrease depression 3 months
    later
  • Elderly with vitamin B 12 deficiency more likely
    to be depressed
  • Duke Seniors lower vitamin D greater likelihood
    of depression
  • Swedish depression improve with vitamin D
  • SAMe large improvement in depression

R RESTORE HEALTHY DIGESTION

  • GUT HOUSES > 70 % IMMUNE SYSTEM
  • SUCROSE ALTERS BACTERIà CANDIDA YEAST
  • Factors that decrease good bacteria
    • Lack zinc, B vitamins, Fatty acid
    • Lack of sun
    • Lack of social support
    • Poor nutrition
    • Poor connection with nature
    • Stress
    • Lots sugar
    • Antibiotics, alcohol , birth control pills
    • Corticosteroids and anti inflammatory drugs
    • Infections, laxatives
    • Excessive use of antibacterial soap
    • Meat from animals with growth hormones or
      antibiotics
    • Gluten containing grains
  • Gut Brain connection 2 way street
    • Enteric thru Vagus nerve ascending
    • Descending ANS
    • Capillaries within epithelial tissues
    • Brain can communicate with enteric nervous
      system both directly (thru capillaries and nerve endings in gut wall) and
      directly thru chemical signaling and hormone secretion
    • Gut communicates directly with the brain

Mood is affected by inflammatory markers in the gut

  • Microbiota
    • Microorganisms in a specific region or location
      • Can be gut, skin, lungs oral mucosa
  • Microbiome
    • Collection within a given microbiota
  • Gut microbiota
    • Associated with BAD, schizophrenia anxiety, OCD
    • Pigs given lactobacillus probiotics healthier
      and more resistant to swine flu
    • Bacterioides
      • hi in depression
      • linked to inflammation
    • depressed
      • hi bacteroides
      • firmicutes, bacteroides, proteobacteria abnormalities
      • inc Enterobacteriaceae and alisitpes
      • reduced faecal bacterium negative correlation
        with depression
      • depression can actually be transmitted thru gut
        microbes
    • To help gut
      • For persons over 40, much depression is related
        to gut
      • He recommends
        • Digestive enzyme with hydrochloric acid
          • Hydrochloric acid important for digesting
            protein
          • Ant-acids especially 24 hour PPI lower stomach
            acid
            • So don’t absorb B 12, digest protein
        • Probiotics 50 billion CFUs
      • Can do these without testing without adverse
        side effects.
    • Disrupting
      Gut function
      • ant acids
        – especially 24 hour PPI lower stomach acid
        • so don’t absorb vitamin b 12 and digest/
          breakdown protein
      • antibiotics
        • can get an overgrowth of yeast, dsybiotic gut
      • stress
      • inflammation
      • bad diet
      • food sensitivities
        • celiac disease abnormal reaction to gluten
          • higher incidence of depression
          • the action of gluten interferes with absorption
            • zinc, folate, amino acids not absorbed
              increasing risk of depression
        • food allergies

Toxins can affect mood

  • Toxins are synergistic
    • BPA and phthalates are in many things
      • Affect metabolism and absorption of zinc
      • Have direct effects on neurons on brain
      • Indirect effects to make trace minerals
        unavailable

Toxins can interfere with the conversion of thyroid hormones T4 to T3   

Role of Inflammation in depression

  • Inflammation is Implicated for Heart Disease,
    arthritis, cancer, Alzheimer’s disease
  • Heavily involved in a subset of depressed
  • Overstimulated immune system produces chemicals
    that go into the brain that affects how we synthesize chemicals to make our
    brain regular
    • Chronic inflammation regardless of cause
      (trauma, stress, infection) affects mood
  • If we have the illness feel depressed.

Medications causing depression

  • Propranolol, beta blockers
  • Steroids
    • Contribute to depression and suicide
  • Hormones
  • Blood pressure medications
  • Chantix increases risk of suicide
  • Antidepressants can contribute to more
    depression of suicidality
    • FDA has put out warnings

To help stress

  • Mindfulness
  • Magnesium
    • Interfere with overactive stress response system

Supplements to help with depression

  • Magnesium
    • Most common nutritional deficiency
    • Inverse relationship with stress
    • Magnesium is repleted in soil, so foods are low
      in magnesium
    • Can lower blood pressure
    • Helps with sleep, anxiety
    • Helps with concentration
    • Helps convert fats into energy
    • In hundreds of reactions for brain function
  • Zinc
    • Commonly deficient because of toxins (BPS,
      phthalates)
    • Is not plentiful in a vegan of vegetarian diet
      • Is most bioavailable in animal products
      • Adolescents commonly have low zinc levels
    • Needed as biopathway to make neurotransmitters
    • Linked to depression
    • Symptoms of low zinc levels
      • Hair loss, diarrhea, white marks on nails, skin
        lesions, acne, less zinc
    • Taking zinc makes antidepressants work better
    • Test for zinc with zinc taste test
      • Have strong bitter taste if have adequate zinc
      • Taste buds are zinc dependent
      • Restore zinc, taste return
  • Vitamin B
    12
  • Vitamin D
    • Recommends testing
    • Take at least 2000 iu per day
  • Omega 3.
    Fish oil
    • Helps with mood
  • 5HTP.
    Precursor to serotonin
  • Don’t take tryptophan by it self
  • SAMe
    can be helpful. Do not take if have bipolar
    • Studies show good results
    • 800 – 1600 mg per day
  • St John’s
    Wort
    • 600 mg 900 mg per day
    • Make sure it comes from a reputable company
  • Rhodiola
    • He has had a lot of success
    • Fewer side effects, fewer interactions with
      drugs
    • Russians used for many years for concentration,
      stamina, energy
    • 100 – 400 mg per day
  • Role of Hormones important
    • Bioidentical hormones
  • Neurotransmitter testing not accurate
    • Can look in urine for break down products of
      serotonin and dopamine 
    • He tests levels of amino acids and supplements
      to give the building blocks to make neurotransmitters      
    • He gives amino acid precursor molecules

Role of trauma

  • Depression from trauma is not as easily treated
    with nutritional supplements
  • Look at therapy and nutritional deficiencies

Summary Points

  • Look at whole body
  • Look at contributing factors
  • Use integrative approach
  • Nurture brain and mind
    • Mind body approaches,
    • Nature
    • Spirituality helps with resilience and recovery
      • Mindfulness, meditation
        • These can change anatomy and neurochemistry of
          the brain
    • Meaning, gratitude and hope are important parts
      of mental health
  • Look at whole body
  • Look at contributing factors
  • Use integrative approach
  • Nurture brain and mind
    • Mind body approaches,
    • Nature
    • Spirituality helps with resilience and recovery
      • Mindfulness, meditation
        • These can change anatomy and neurochemistry of the brain
    • Meaning, gratitude and hope are important parts of mental health
  • 120 million people worldwide; 15 M in US
  • 7 % older than 18
  • 2x as many females
  • One in 8 teens equal sex
  • 1/33 kids
  • Runs in families 3 x as likely to have it
  • Hx increases risk;
    • 50 % if one episode
    • 90 % if had several episodes
  • Over next 20 years, projected to be #1 cause
    disability in hi income countries and #2 world wide
  • Annual cost 30 – 44 billion.
  • Every person is different- biochemically unique

Suicide

  • 8th leading cause death in US 32K
    deaths Q year
  • 15 % untxed suicide
    • More than 2/3 suicides caused by depression
    • Women 2-3 x more likely SA
    • Men more than 4 x women to die of suicide
    • Risk
      • Family hx, impulsive drugs, separation, divorce,
        family violence, impulsive
    • Times
      • Anxiety, anniversaries, drug /etoh abuse, untx
        derpession
  • He uses integrative psychiatry
  • Factors contributing to depression are unique
  • THE ZEBRA
  • Nutrition important
    • 1601 Capt James Lancaster discovered that lemon
      juice prevented scurvy
    • British government waited 264 years after it was
      proven
    • Just be cause MDs ignore does not mean not true
    • Tomato Effect Dr. James Goodwin `984 JAMA
      efficacious tx for certain ds is ignored or rejected because does not make
      sense
      • Named tomato effect because 16 th – 19 th
        century believed tomatoes were poisonous..
  • Longer one suffers, more difficult it is to
    recover

Meds

  • James Watson winner of Nobel Prize ifor
    determining the structure of   DNA urged
    doctors to have better understanding of mental illness and develop tx based on
    their results
  • Prescribe carefully

Stigma

  • We are more than our experience and genes

Symptoms

  • Also stomach ache, irritability, work too much
  • Aches and pains,
  • Etoh and drug abuse
  • Chain smoking
  • Constant exhaustion
  • Crying a lot
  • Decreased physical activity QD
  • Reckless doing risky things
  • Difficulty getting up in am
  • Irritability, frustration
  • Lack of energy or motivation
  • Reduced sex drive
  • Working long hours long term difficulty sleeping

Results

  • Hard to work, loss relationships
  • No energy to take care of self
  • 4 x risk MI
  • More likely to abuse etoh or drugs

Types

  • Major depressive disorder MDD
    • Depressin, anhedonia and five other
    • Worthless common
    • Not grief or sadness
  • Persistent depressive disorder dysthmica
    • Most of days more often or not for 2 years.
    • If start before age 21, more likely co occurring
      personality disorder or substance abuse
  • Disruptive Mood Dysregulation Disorder kids
    • Chronic, sever, persistent irritability
    • Can be temper outburst, aggression out of
      proptortion in intensity
    • Over at least one year in two settings (home,
      work)
    • Developmentally in appropriate.
    • Have low frustration tolerance
    • Family lie disrupted
  • Premenstrual dysphoric disorder
    • Premenstrual dysphoric disorder is sever form of
      pMS
    • Most cycles, sx must be present in final week
      before period then better
    • At least one of following
      • Emotional changes (mood swings)
      • Irritability, anger, increased conflicts
      • Depressed mood, hoplessnes, self deprecating
      • Anxiety, tension, feeling on edge
    • One or more of following total five
      • Decreased interest in usual activities
      • Difficulties concentrating
      • Lack eergy
      • Change appetite
      • Difficulty sleeping
      • Feeling overwhelmed or out of control
      • Physical sx such as breast tenderness, swelling,
        jt pain, muscle pain, bloating or wt gain
    • Lead to distress or interference with work,
      school, social, relationship
  • Substance/ medication induced depressive
    disorder
    • Depressive sx associated with substance
    • Typically starts within first fee weeks or one
      month after start
    • Stop, get better
  • Depressive disordered due to another medical
    condition
    • CVa, HD, PD, TBI, Cushings, hypothyroid
  • Depression with Anxious Distress
    • Hi anxiety linked to higher suicide risk, longer
      length of illness, greater likelihood of not responding to tx
    • At least tow during most days
      • anxious, tense
      • Unusually restless
      • Difficulties concentrating because of worry
      • Fear that something awful may happen
      • Feeling one might lose control
  • Depression with atypical Features
    • Mood
      reactivity can be cheered up
      • Can be euthymic if environment positive
      • Weight gain or inc appetite
      • Sleep at least ten hours per day
      • Leaden paralysis
      • Rejection sensitivity
  • Post partum Depression
    • 70 % have baby blues
      • Short term worry, unhappiness, fatigue  2 weeks
    • Post partum depression `6 %
      • For 4 weeks
        • Sluggishness, fatigue
        • Sad, hopeless, helpless or worthless
        • Change sleep
        • Change appetite
        • Difficulty concentration, confusion
        • Crying for no reason
        • Lack of interest in baby or family
        • Fear of harming baby or self
        • Difficulties bonding with baby
      • Often have anxiety or panic attacks
      • Rapid changed in hormones or thyroid after
        delivery may contribute
      • Lack of sleep, stress, family hx depression,
        lack support may play rold
  • Depression with a seasonal Pattern (seasonal
    affective disorder
    • Relationship between the start of depressive
      episodes and time of hear
      • Seasonal
        • Loss energy, sleep too much, overeat, wt gain,
          carb craving
        • Linked to biochemical imbalance caused by
          shorter daylight hours
        • More common far from equator
        • Less commonly occurs in summer
        • Possibly in response to hi heat and humidity
        • More likely insomnia, dec appetite, wt loss,
          agitation, anxiety
        • Younger adults and women higher risk
        • Average age onset is 18 – 30 years.

CAUSES

  • Biochemical
    • Neurotransmitters
      • Serotonin,
        • Lack sleep problems, binge eating, irritability
      • norepinephrine,
        • too little low mood and fatigue
      • dopamine
        • due to too little or too much
      • lack due to
        • lack amino acids, vitamins, minerals
        • breaking down neurotransmitters too quickly
  • Physical
    • Illnesses
      • 25 % cancer, 94 % eating disorders
      • 20- 40 % heart attack, 10 – 20 % HIV
      • 50 % HD, 30 % chronic long term pain
      • 50 % PD
      • 25-50 % stroke
      • 60 % disabling tinnitus
      • 27 % drug or etoh
      • 30 – 35 % AD
      • Anxiety disorder, tobacco addiction
      • Depressed people more likely to have DM2 and HD
  • Meds
    • Antipsychotic,
    • antihistamine,
    • beta blockers,
    • birth control pills,
    •  htn,
    • anti inflammatory meds,
    • adrenal hormone agents and
    • corticosteroids
    • Etoh, amphotericin B, bismuth nitrate,
      carbamazepine, cis-retinoic acid, cyloserine
    • Cyclosporine, digitalis
    • Estrogen therapy, flunarizine, h2 blockers
      (cimetidine, ranitidine)
    • Interferon, levodopa, methyldopa mazindol,
      mercury
    • Methylxantines (caffeine, theophylline),
      metoclopramide (reglan)
    • Metronidazole, nifedipine, organic nitrates
    • Phenytoin
    • Psychostimulants (fenfluramine, methylphenidate,
      permoline, phenylpropanolamine)
    • Reserpine
    • Sedative hypnotics (barbiturates,
      benzodiazepines, methaqualone)
    • Thallium
    • Thiazide diuretics
    • Vinblastine and vincristine
  • Overactive
    immune system
    • Sickness behavior normal reaction to infection
      • Poor sleep, concentration, lack of desire
      • Pro inflammatory chemicals inflammatory
        cytokines cause changes in neurotransmitters
      • Depression has changed in cytokines
      • High levels of inflammatory cytokines
      • Low levels of anti inflammatory cytokines
      • Anti inflammatory IL 4 and TGF b1 were lower
      • Sertraline decrease pro inflammatory and
        increase anti inflammatory
      • Depressed with inc inflammatory biomarkers less
        likely to respond to antidepressants
      • Pt with hx no response to antidepressants have
        inc inflammation
  • Inflammatory brain illnesses linked to
    depression
    • Areas of brain dealing with mood regulation  inflammation was 30 % higher in depressed
    • 2017 Manchester MDD have inc microglial
      activation
      • BiolPysch Krystal , J
  • Hormones
    • Estrogen
      • Teen girls = teen boys in depression
      • In women short depression 7 – 10 days before
        period
      • Baby blues
    • Testosterone
      • Men low testosterone may be linked to depression
      • Men may not respond with low testosterone
    • Thyroid sub clinically low in mood disorders
      • Women depressed hi TSH
      • Low thyroid 
        poorer response
      • Give thyroid better response to antidepressants
  • Genetics
    • Tendency to have is inherited not ds
      • Family hx depression 3 x risk
      • Twins
        • Other one depressed 27 %
        • Raised separately risk 67 %
  • Psychological
    factors
    • Stress
    • Aging

KEY POINTS

  • GP. 62 % scripts for depression’ 65 % for
    anxiety
  • Depression, 4 x likely to have MI than no hx
  • s/p MI, chance another higher
  • depressed more likely to abuse drugs, etoh

Treatment

  • 2/3 
    effectively tx have sx that impair
    • 28 % mild impairment
    • 23 % moderate impairment
    • 12 % severe impairment; 4 % very severe impairment
  • Research show 94 % meds work closer to 51 %
    • 1/3 studies showing antidepressants don’t work
      submitted to FDA don’t work not published
    • ½ studies failed to show any benefit other than
      placebo
  • Studies only short term 6 weeks
  • based on symptoms and vulnerabilities. Severity

What is missing in psych eval

  • diet, toxins nutrition, allergies

Drug tx don’t work

Research

  • drug companies sponsoring research have conflict
    of interest
    • 4.9 x likely to report med works
  • Direct advertising to consumer spend billions
  • People not depressed account for 94 % new
    antidepressant use
  • JAMA 2010 antidepressants don’t work  for less severe forms depression
  • Paxil and imipramine do not reduce sx in mild,
    moderate or severe depression
  • Antidepressants only work in severe depression
  • by Vittengl at Truman U; Pt who took
    antidepressants more sx at 9 years
  • Robert Whitaker Anatomy of an Epidemic 50 yrs
    data;  over time, people not on meds do
    better than those who are.
    • Since 1987, 
      3x more on disability
    • Only 15 % 5x with meds remained healthy over
      time
      • The other 85 % have chronic depression
  • Yale found that universities hire to perform
    drug research were part owners
  • Studies more likely to prove if funded by drug
    industry or researchers have financial interest
  • British Psych Joanna Moncrieff paper, “There are
    no signs that the rapidly escalating use antidepressants reduces burden of
    depressive disorders
  • JAMA found standard antidepressants no more
    effective than placebo for people  with
    less severe forms of depression

Bioindividuality

  • Only speciality where no measurements
  • Side
    effects
    • Agitation,
    • Blurred vision, constipation, dec sex drive, dry
      mouth
    • Erectile dysfunction, fatigue, insomnia, nausea
    • Osteoporosis, wt gain risk SI
    • SRRI
      • Sexual
      • St gain
      • Physical
        • Headache, nausea, stomach problems
  • mEd withdrawal 
    like flu
    • Irritability, agitation, restlessness, insomnia
    • Migraines, headaches, not able to focus,
      depression
    • Physical
      • Sweat, palpitation, B &V, difficulties
        breathing, sensory dist
    • Reason: body/ brain no time to adjust to change

Brain and body. Influence each other

  • Brain 3 pounds uses 20 % energy
  • Scars in Brodmann
    area 25 BA 25
    hyperactive in depressed people
    • Activity normalized when depressive sx relieved
    • Does not matter if relieved by tx or meds
    • Is directly linked to amygdala which processes
      anxiety, fear and the hypothalamus 
      (important in stress)
    • Generous supply of special transporter
      molecules. Serotonin
  • Serotonin gene coding for serotonin transporter
    molecule comes in long and short
    • Long triggers production of more transporter
      molecules
    • Short gene have smaller BA 25 and does not act
      with amygdala and other brain areas
    • Is sped up activity in BA 25 the cause or result
      of depression?

Genes

  • Some contribution 37 %
  • Epigenetics
    • Methylation
    • Causes
      • Stress
        • Study mice remove from mothers 3 hrs QD x 10
          days epigenetic changes last a week
        • Mice of good mothers exchanged with bad mothers,
          stress handling abilities of foster 
          mothers.
          • Same for monkeys
    • Good nutrition etc best hope
    • Makes each person unique
  • Genetic testing, twice as likely to be
    prescribed the correct med

IDeal

  • Diet meds, supplements, family hx
  • Labs
  • Vitamin deficiencies, toxic metals, hormone
    imbalances
  • Vitamin levels, amino acid and fatty acid
    imbalances
  • Hi or low minerals
  • Celiac disease and other food sensibilities
  • Imbalanced levels of digestive enzymes
  • Disbiosis, parasites
  • Focus on individual unique
  • Care for how pt, not just ds
  • Understand how body and mind are connected
  • Restore health instead of reducing sx
  • Increase boy nutrients to promote long term
    health

T take care of yourself

H hormones and herbs

E exclude

Z zinc and other minerals

E essential fatty acids and cholesterol

E exercise and energy

B and other vitamins

R restore

A amino acids and proteins

T take care of yourself

  • Link betn mental and psyical vauge
  • Diet
    • Studies
      • 2010 AJP unhealthy diet more depressed
      • 2010 teens unhealthy diet more likely depressed
      • 2014 Iranian children
    • Diets hi in saturated fats and refined carbs can
      affect proteins important in brain development such as BDNF
  • Digestion
    • HCl
      • Dissolve food into parts
      • To absorb vit B12, minerals
      • Make enzyme pepsin necessary in digestion of
        protein
    • In SI sodium bicarbonate neutralizes HCL
      • Fat and protein and carbs broken down
      • Digestive enzymes
        • Need zinc, protein, vitamin c
        • Good nutrition leads to good digestion
        • Good digestion ensures all necessary nutrients
          are absorbed
        • Poor digestion=poor nurtition
      • Gut bacteria
        • Probiotics help digest
  • Sleep
    • POOR SLEEP RISK FOR DEPRESSION 2.5 TIMES FOR
      TWINS
    • Brain dev needs sleep for brain dev. 
    • Sleep problems predict  GAD, depression, and other behavioural d/0
    • Poor sleep caused by
      • Sleep apnea 5 x depression
        • Tx sleep apnea can tx depression
        • Sx tired in am and day
        • Memory problems
        • Toss, turn, choke, asp, snore
        • Headaches in am
        • Bathroom > once or twice
        • Swelling legs
        • c/p sweat during sleep
      • stress, caffeine, etoh , drugs, OTC, allergies,
        asthma, hyperthyroid, chronic pain nutritional deficiencies Mg, zn
      • restless legs
    • sleep hygience
      • sleep same time
      • avoid caffeine after lunch
      • comfortable bed
      • thermostat cool
      • dark
      • use bed for sleep and sex
      • no work, TV in bed
      • ritual
      • no computers, games,
      • don’t ty to hard
    • sleep remedies
      • melatonin,
        • pineal body clock. 1 – 3 mg sleep in 30 min
      • Mg, 200- 300 mg
        • Works c Ca for muscle relax, contract
        • Anti-stress. 
          Reduce cortisol, muscle cramps
        • First mineral to disappear with processed foods
        • First mineral to leave when body stressed
        • Depleted by etoh, caffeine, meds
      • valerian,
        300- 500 mg
        • Does not work right away
        • Side effects h/a, restlessness, sleeplessness,
          irregular heart beat
        • Sleep anti anxiety
      • inositol,
        • made by body and intestinal bactiera
        • helps transmit nerve signals
        • prevents buildup of fat in liver and other
          organs
        • 1t 8 PM helps with obcessive thought
      • 5 HTP, 50
        – 200 mg
        • Reduce anxiety
      • glycine, 3 g
        • inh neurotransmitter
        • helps relax blood vessels
        • lower core body temperature
      • GABA
        • Low GABA anxiety, depression, irritability,
          headache, htn
    • Sugar
      • Glucose,
      • Fructose cant be absorbed by cellsà goes to liver
      • Sucrose homes- fructose and glucose
      • Dextrose from corn identical to glucose
      • Galactose in milk
      • Lactose glucose and galactose
      • Maltose in barley – is two glucose
      • Xylose in wood or straw
      • Low sugar in brain weak, irritability, anxiety,
        headaches, faint, depression
      • Hi insulin an d sugar inc negatively affects
        kidney function, inc blood fats, TG, cholesterol
      • Sugar substitute. Xylitol, cinnamon, cardamom,
        ginger, nutmeg
    • Stress
      • Inc inflammation ~ depressive sx
      • Activate inactive genes that affect future
        generations
        • Inc maternal stress in pregnancy ~ inc risk mod
          to severe depression in offspring
        • Stressed ma -kids depressed 11 years later
    • Key Points
      • AJP study unhealthy dietà more depressive and anxiety
      • Diets 13,486 Iranian kids inc junk food ~
        psychiatric stress
      • Survey, 40 % uS less than 8 hours sleep
      • Met analysis 23 studies adolescents 12- 20 with
        mdd more sleep disturbances
      • 2015 study consistently poor sleep inc
        depression by 2.5
      • More soft drinks higher levels depression,
        hopelessness and aggression
      • 72 % of people with daily stress and anxiety
        claim interferes with lives

HORMONES

  • Low
    thyroid
    • Anxiety , memory, hi cholesterol, constipation,
      gum disease, fat, hypoglycemia, muscle aches and pains, acne, exzema, hair
      loss, recurrent infections, pMS, irregular menstrual, ovarian cysts,
      endometriosis, fluid retention, fatigue
    • Faulty testing à
      faulty dx
    • TSH only show pituitary asks for correct amount
      thyroid
      • But body might not be using it properly
    • Taking imipramine  plus T 3 faster recovery
    • Replacing missing thyroid relieves depression
    • Metanalysis T3 increased improvements seen with
      antidepressants for tx resistant depression
    • 2014, T3 and T4 were both predictors of the
      level of improvement in depression sx.
    • T3 works better for depression
      • Better for women
    • Thyroid needs iodine, tyrosine, zinc and iron
    • Toxins get in the way
      • Plastics, air fresheners
      • Polychlorinated biphenyls, dioxin, phthalates,
        and polybrominated diphenyl ether (PBDE)
        • Upset ratios in diff T hormone
        • Interfere with thyroid hormone synthesis
        • Suppress production thyroid hormone receptors
          and binding thyroid hormone transport proteins.
  • DHEA
    • Produced by adrenals
      • When stressed , makes more
        • Changes in liver to dHEA S which is measured
    • Antiaging supplement controversial
    • For depression
      • 60 % depressed respond
      • Maybe works better for men
    • Makes testosterone and estrogen and all steroid
      hormones
      • Need cholesterol
    • Highest in mid 20s
  • Testosterone
    •  Made in
      testes, ovaries, adrenal glands, liver, skin and brain
    • Responsible for protein synthesis
    • Maintenance of bone mineral density
    • Lean body mass, muscle strength
    • Sensitization or serotonin recptors
    • Physiologic processes that contribute to sex
      appeal
    • Decreases with age
      • Diet, exercise
      • Sleep quality
      • Endocrine do
      • Low testosterone
        • Dec strength, fatigue,
        • poor libido,
        • htn, inc CV risk,
        • loss lean body mass inc fat
      • lowers depression with (and without?) meds
      • lowest testosterone group (age 71-89)2 x
        depression
      • 11/18
        JAMA significant reductions in depressive sx          d
      • Low
        testosterone levels are linked to depression
      • In some
        men depression cannot be relived until testosterone raised to a normal level
      • Antidepressants
        cannot raise testosterone to a normal level
      • Other
        ways to raise testosterone
        • Zinc
        • Exercise
          to strengthen muscles
        • Reduce
          stress to reduce cortisol (which breaks down muscle
        • Cut or
          avoid soy. Phytoestrogens which can counteract testosterone
        • Eat
          plenty EPA and DHA in salmon and other cold water fish
        • Monitor
          cholesterol and DHEA (needed to make testosterone
        • Supplement
          with tribulus, herb than enhances testosterone synthesis
  • Estrogen
    and Progesterone
    • 2014 study estrogen affects brain derived
      neurotrophic factor (BDNF)
      • BDNF support survival of neurons and growth of
        new neurons and their connections
    • Estrogen
      can affect mood by degrading or reducing levels of MAO (which breaks down
      serotonin.
  • Herbs
    • St John’s
      Wort 300 mg po TID
      • Anti depressant mild to moderate depression
      • Germany licensed for anxiety,d epression, sleep
        disorder
      • Pain disorder
      • Cochrane 
        mild to moderate for 4 – 12 weeks did better than placebo
      • Fewer side effects than antidepressants.
      • Safe long term prevents relapse
      • Has hypericin
        • Antiviral, against cancer and HIV in stored
          blood
      • and hyperforin
        • activates a specific receptor in liver that
          triggers production of an enzyme used to metabolize meds
    • Curcumin
      • For Inflammation
      • Regulates stress response system
      • Degrades MAO which breaks down serotonin and by
        protecting against oxidative stress and mitochondrial damage.
      • Regulates the level of neurotransmitters in body
      • Promotes birth of new neurons in hippocampus
      • Improve cognition
        • Daily improved memory and mood in people with
          mild, age-related memory loss
      • Safe and effective
    • Rhodiola
      • Recognized by Russian ministry of health as med
        and herbal tonic
      • Reduce depressive sx, boost mood diminish
        fatigue, tx opioid addiction
      • Assists in normalizing body stress response by
        increasing body resilience
      • Reduce nicotine withdrawal sx by inc serotonin
        and serotonin receptors
      • Degrades MAO A and MAO B
      • Affects 1062 genes, fifty of which are linked to
        behavior and 62 related to psych d/o
      • Ay improve emotional behavior thru effects of
        transcriptions of certain genes
      • Depression. Rhodiola revolution
      • Can enhance mood, concentration, energy
      • Helps with anxiety and BAD although may be too
        stimulating

Summary

  • Thyroid avoid toxins cleaning products,
    pesticides, eat organic, use glass
    • T3, T 4 predict levels of improvement in
      depression
  • DHEA, testosterone, estrogen, progesterone
    • Archive Gen Psych 2005  DHEA for midlife major and minor depression
    • DHEA decrease with age
    • Australians men with low test 2 x depressed >
      highest test
    • Harvard topical test greater improvements in
      depression > placebo
  • Curcumin, SJW, rhodiola

E exclude harmful foods

  • Celiac ds
    • Body mistakenly mistakes gluten for a dangerous
      toxin
    • Immunity system attacking gluten destroys the
      intestine
    • Absorption vit A, B6, B 12, D, E K,  iron, zn, Mg and ca, essential fats other aa
    • Sx anemia, anorexia, arthritis, dermatitis
      herpetiformis, edema, fatigue, infertility, jt pain, migraines, missed
      menstrual periods, numbing hands
    • Osteoporosis, sz, stunted growth, tooth decay
      and discoloration
    • 1/3 have depression
    • Dx Ab: anti gliadin, anti endomysial, anti tissue
      transglutaminase
    • Will develop nutritional problems
      • Take multivit with iron, EFA, digestive enzymes
      • Test for iron, folate, Mg, amino acids
    • Need HCl
    • Casomorphin,
      gliadorphin
      • Similar to morphine
      • Originally in pee of people with autism
      • Incomplete digestion of proteinsà ADHD, child psychosis,
        dyslexia, down, CD, post partum psychosis, Rett’s ds, severe depression
      • These excess peptides  maybe these are unique carriers of info to
        brain that may worsen many psych d/o
      • Elevated these caused by lack functioning of enzyme
        dipeptidyl peptidase IV (DPP IV) which snips casomorphin and gliadorphin into
        small pieces
        • These absorbed
        • Cause deficiency DDPP IV
          • Lack zn
          • Antibiotics, interferon, gelatin
          • Candida,
          • Hi mercury and heavy metals and pesticides
      • Depression suffered from incomplete digestion of
        casein and gluten
    • Food
      Allergies and depression
      • IgG mediated delayed hypersensitivity rxn
      • Have more depression

Summary

  • 18 studies on depression and 11 on CD depression
    is more common  ore more severe in cD
  • Teens with CD have 31 % risk mde vs 7 % in
    healthy children
  • Correlation CD and depressive disorders
  • 2016 AJ Gastroenterology correlation between
    feelings of depression and Crohns’ ds

Z Zinc and other minerals

  • Zn
  • 200 different reactions
  • In brain
    • Helps make DNA and proteins
    • Helps immune fight off viruses and bacteria
    • Helps wounds heal
    • Regulates neurotransmission in brain
    • Makes it possible to taste and smell
    • Make sex and reproduction possible
    • Helps make all enzymes needed to digest fats,
      carbs and proteins
  • In
    • Oysters, poultry, red meat, beans, whole grains
      and nuts
  • Causes of lack
    • Vegetarians
    • Eating disorders
    • UC, crohns
    • Meds
      • Asa, benazepril, cholestyramine
        • Reduce cholesterol and ofloxacin
  • Results of lack
    • Delayed growth in kids and infants
    • Hair loss
    • Diarrhea
    • Loos appetite
    • Weight loss
    • Difficulty tasting food
    • Acne
    • Fatigue
    • Elevated cholesterol
    • More infections
    • Memory impairment
    • Impotence
    • Anorexia, impaired cognitive, other behavioural
      disturbances
    • Poorer appetite
  • Depression
    • Lower levels in major depression, postpartum
      depression
    • Depression à
      inflammation
      • Lowers albumin which transports zinc thru
        bloodstream
      • Maybe liver snatches up zn to use for
        inflammation
    • Zinc inh NMDA which controls glutamate
      • Glutamate
        • Sends signals between nerve cells
        • Helps learning, memory
        • Too much glutamateà
          overstimulation
          • Progressive damage to nerve function (~
            depression)
    • Zinc can relieve depression’
      • Animals given celexa inc zinc levels
      • Given celexa or imrapmine, inc zinc in
        hippocampus, dec other parts of brain
      • Given ECT inc zinc in hippocampus
      • Zinc antidepressant in lab animals
      • Low doses celexa and imipramine ineffective as
        antidepressants stressed by
      • Chronic tx with antidepressants and ECT causes
        zinc to inc in rat brains
      • Lab, zinc deficient diet à> depressive like sx
        including anorexia and anxiety
      • Zinc improves depression
    • Zinc taste  
      no eat 1 hour before

Copper

  • In liver, heat, brain and kidneys
  • Helps growth , maintenance of TBC, bones,
    nerves, brains
  • Makes prostaglandins needed for heart beat and
    blood pressure
  • Part in getting energy out of fats, protein an
    carbs
  • Helps body fight free radicals
  • Found in
    • Liver, organ meats, shellfish, whole grain
      cereals and bread, dark green leafy veggies, peas, poultry , nuts and beans
  • Comes from
    • Dental fixtures, copperpipes, cookware
    • Copper at work
    • Birth control pills and iUD
  • Results of low copper
    • Anemia, htn, diarrhea, difficulties breathing,
      lowered immune function, EKG abnormalities
  • Causes low copper
    • Poor diet, digestive or intestinal disorders
      that interfere with nutrient absorption
    • Chronic diarrhea and
    • Excess zinc
    • Meds which interfere with cu absorption
      • Delavirdine (resciptor for HIV), ethambutol,
        (TB), penicillamine (for RA)
      • Elderly persons, vegetarians, athletes, pregnant
        women and premature infants likely to lack copper
  • Too much copper and depression
    • Involved in monoamine oxidase, dopamine beta
      hydroxylase and tyrosine hydroxylase all of which stimulate dopamine
    • Hi levels found in depressed

Magnesium

  • 54 % in bones 27 % in muscles
  • 19 % in heart and liver
  • 1 % in blood
  • 300 biochemical reactions
    • Maintain health immune system
    • Keeps bones strong
    • Regulates BP
    • Making proteins
    • Ensuring nerves work properly
    • Keep heart beating steadily
  • Lacks cause
    • Irregular heartbeat, nausea, lack appetite, sz,
      fatigue, muscle weakness, poor coordination, personality changes
    • May worsen depression and apathy, irritability,
      nervousness, anxiety, excessive emotional reactions and frequent mood changes,
      decreased memory and concentration, migraines, fatigue and ADHD
    • Link to depression especially in young adults
  • Risks for low Mg
    • Crohn’s and ds interfere with absorption
    • Etohics, dm senior citizens
    • Meds that interfere with absorption or use
      • Diuretics (Lasix) bumetanide (bumex) antibiotics
        (gentamicin)
    • Stress
  • Symptoms low Mg
    • Insomnia
    • Constipation
    • Anxiety
    • Muscle spasms
  • Mg found in
    • Dark green leafy veggies, nuts, whole grain
      breads, beans, peas
    • One of first minerals stripped with processed
      foods.
  • Most Americans low in Mg
    • Is low in processed foods
  • Lack of Mg can trigger depression
    • In mice inc anxiety and depression like
      behaviours
  • High magnesium also in depressed patients.
  • How Mg works
    • Permits excess of calcium into nervous system
      damaging nerves and causing sx similar to depression
    • Lack Mg may reduce brain levels of serotonin

Lithium 2.5 – 20 mg

  • In every organ
  • Helps stabilize mood
  • Regulate neurotransmitter signaling
  • Protects brain cells from early death
  • Helps with antidepressants
  • Aggression suicide attempts
    • Finnish study with li in water
  • Mechanism
    • Fight inflammation
    • Inc enzymes that produce glutathione
    • Regulates pro inflammatory cytokines
      • Reduce synthesis of proinflammatory cytokines
        which can regulate expression responsible for their production

Chromium

  • In foods
  • Cleared by
    • Infection, exercise, physical trauma, diets with
      large amounts of simple sugars, stress
  • Keeps insulin 
    and blood sugar balance and energy levels
    • Helps insulin sensitivity
  • Lowers Cholesterol levels, body fat, Tg, Low
    density lipoprotein
  • Raises HDL good cholesterol
  • Helps with depression

Iodine

  • Make thyroid hormones
  • Thyroid snatches iodine and incorporates it into
    these hormones
    • Thyroid enlarges as tries to get iodine
  • In ocean water and soil

Iron

  • For regulate cell growth
  • Part of hemoglobin within RBC that carries
    oxygen thru blood
  • Lack of iron
    • Lack of oxygen brought to body
      • Fatigue
      • Weakened immune system
      • Psycho problems
        • Poor attention
    • Sx of lack
      • Weak ess, fatigue, disgestive problems fragile
        bones, difficulties maintaining body temperature
      • Requeent infections
      • Poor performance at school or work
    • Found in red meat, fish, poultry, beans,
      lentils, iron fortified cereals
    • Cause of deficiency
      • Low consumption certain foods
      • Pregnant
      • Older infants, toddlers, teenage girls
      • Women of childbearing age
      • Celiac dx and dx interfere with iron absorption
    • Supplement with ferrous bisglycinate
      • Does not cause side effects of nausea,
        constipation, stomach upset
      • 10 mg ferritin BID til normal

SUMMARY

  • Minerals and other nutrients influence brain
    function and mood
  • Consider hi and low trace minerals
  • Every depressed would asses for lack of trace
    minerals
  • Everyone is unique
  • Taking too much trace mineral can lead to
    imbalance.
  • Zinc
    numerous pathways
    • Risk deficiency zinc vegetarians, etohic, eating disorder, ulcerative colitis,
      crohns, absorption disorders
      • Test zinc taste test
      • Lower zinc in major depressed
      • Zinc helps antidepressants
    • Copper
    • higher in depressed
    • needed for dopamine
    • Mg
      helps in depressed who ar mg deficient
      • 2/3 Americans consume less than RDA Mg
      • Depression inc when Mg low or hi
      • Risk crohns, nutrient absorption, etoh, DM,
        seniors
    • Li
      BJP adding lithium relieved sx depression in 48 hours
      • Finnish 2017 nutritional li highly effective
    • Chromium
      promising in antidepressants
    • Iron
      • lower in depressed; supplement 25 % improvement
  • Iron
    for oxygen
    •  
    • Iodine
      • Thyroid with antidepressants do better

E essential fatty acids and cholesterol

  • Saturated; mono unsaturated let go of one
    hydrogen carbon
    • If on 6th is omega 6
    • If on third carbon is omega 3 FA
    • Recommended omega; 6 / omega 3 is 4:1
  • Depression
    correlated with low omega 3, and DHA
  • BAD lower
    DPA, DHA, and alpha linolenic acid (body uses to make EPA)
  • Suicide
    attempts low DHA, high o6/03
  • Omega 6
    • In corn, soy, sunflower oil, margarine, eggs,
      meat
  • Omega 3
    • Higher o3 consumption linked with lower levels
      of depressionIn fish, fish oil, flaxseed oil and walnuts
    • Kids less likely to sit still or pay
      attention 
    • Risk memory problems, dementia, strokes 
    • Higher levels lower risk depression but in
      depression without anxiety
    • Don’t take too much
  • EPA, DHA fuel the brain
    • Help control chronic inflammation of
      degenerative brains (AD)
  • EFA
    • As RBC EFA dec, severity of depression inc and
      vice versa
    • Low EFA in post partum
  • EPA
    • Can help with inflammation
    • Maintains cell membranes
    • EPA content of RBC decreases, severity epression
      inc
    • Same for EPA and DHA in fat tissue
    • Levels related in post partum depression for
      developing fetus
  • DHA
    • Suicide attempts correlate with low plasma DHA
    • Mildly depressed 34 % less DHA in fat tissue
    • Main fatty acid in brain, grey matter and eye
      retina
    • Improves sending brain signals and brain
      communications
    • Bottle fed baby lacking DHA poor vision or
      cognitive ability
    • LINKED TO DEPRESSION AND BAD
    • Hi amount in brain where brain altering
      neurotransmitters stored
      • Can regulate mood by inc serotonin
    • 3rd trimester taking DHA linked to
      less perceived stress and reduced stress hormones
  • Low cholesterol and depression, suicide

E EXERCISE

  • Less likely depression, anxiety
  • Exercised less likely to have depression reoccur
  • Weight lifting, crew, tai chi
  • Reverse harmful effects of stress
  • Lifts depression
  • Improve learning
  • Builds self esteem and improves body image
  • Feel euphoric or joyful
  • How exercise works
    • Release endorphins
    • Change level or effects norepinephrine,
      serotonin
    • Lower cortisol
    • Inc body temperature
    • Gets mind off activities, improve self esteem,
      self image interaction
    • BDNF
  • Mitochondria
    • Brain has lots of mitochondria
    • Energy
    • Vitamin
      B12
      • With other vit B strengthening nervous and
        immune systems
      • Helps muscle tone and healthy skin
      • Role in energy metabolism
      • Deficiency à
        • Fatigue
        • Inc homocsyteine which can worsen heart disease
      • trouble absorbing vitamins
        • antacids
        • Vegans no animal, dairy no ingest B 12
        • Amoxicillin,
          antibiotics, colestipol to reduce cholesterol
    • Carnitine
      • Made from aa found in meat
        • In meat, milk, poultry, fish
        • Some made in liver and kidneys from aa lysine
          and methionine
      • Produces energy in mitochondria by carrying
        fatty acids into mIT
      • Inc energy and helps with depression
    • Co Q 10
      • Enhances carnitine
      • Antioxidant
      • Boosts energy
      • Ubiquinol
      • In diet
        • Whole grains, salmon, oily fish, organ meats
          such as liver
        • Statins, some beta blockers, imipramine can
          deplete coQ10
    • Rhodiola
      • Boost energy endure exercise
      • Supports exercise program

SUMMARY

  • 60.3 % exercise regularly to have depression,
    anxiety
  • NIH exercised less likely to have depressive
    symptoms
  • Over time, exercise feasible tx for mdd
  • 2008 found weakened mitochondrial activity
    translated to less cellular energy was related to physical discomfort.

B B vitamins that affect mood

Niacin, B 6   make serotonin

  • Vit D, B vitamins, SAMe
  • B
    vitamins
    • Thiamine, riboflavin, niacin, vitamin B 6, B 12,
      folate, inositol work as a team
    • Regulate carb metabolism
    • Stabilize blood sugar
    • Ease mood swings improve sleep
    • Help liver deactivate and dispose of old
      estrogen
    • Critical to energy making  (Krebs)
    • Vitamin B deficiency causes
      • Harm brain leading to depression, anxiety,
        irritability difficulty concentrating
    • Vitamin B 6 and niacin
      • Help make serotonin (help mood, sleep, appetite
  • Thiamine
    (Vitamin B1)
    • Free thiamine crosses BBBHelps convert glucose
      into fuel
    • Stimulates brain action
    • Needed for nervous system health
    • Aids in digestion
    • Brain rapidly loses energy when thiamine in
      short supply
      • Depression, fatigue anxiety irritability,
        insomnia, memory problems
    • Lack
      • Interfere with uptake of glucose in brain
      • Leads to mental fatigue and poorer moods
      • Depression, fatigue anxiety irritability,
        insomnia, memory problems
  • Niacin
    Vitamin B 3)
    • When niacin in short supply, tryptophan goes to
      niacin instead of serotonin
    • Lack niacin can result in depression, agitation
      and anxiety
    • Helps maintain health nervous and digestive
      systems
    • Also stimulates circulation causing blood
      vessels and RBC to become more flexible
      • Easier thru body and brain
    • Lack. Pellagra
  • Pyridoxine
    (Vitamin B 6)
    • Lack depression, confusion and irritability
    • Needed to make neurotransmitters serotonin,
      dopamine and norepinephine, GABA
    • Depressed pts have low B 6
    • Necessary for normal brain function for
      synthesis of RNA and DNA and formation of myelin sheath around nerve cells
  • Inteffering with above B vitamins. Eating simple
    sugar flour, cake, candy pies, etoh
  • Folate (vitamin
    B 9)
    • SOURCES
      • Asparagus, 
        citrus, fortified cereals, green leafy veggies, legumes (peas, beans,
        lentils)
      • Required for Normal cell development and
        manufacture of DNA and RNA
    • Cause lack
      • Birth control pills, anti-sz meds, antacids,
        some antibiotic, etoh, smoking
    • Necessary to make SAMe needed for
      neurotransmitter metabolism
    • May protect against colorectal, breast and
      cervical cancers
    • Protects the heart by breaking down homocysteine
      (linked to HD)
    • Homocysteine
      • Heart disease
      • Poor memory and compromised thinking
    • To protect fetus from fetal brain and spinal
      cord defects
    • Lack
      • Can lead to depression
        • Lower folate
          • Higher likelihood of depression
          • Poor response to antidepressants
          • Higher relapse rate
          • Folate supplementation makes antidepressants
            work better.
        • Depressed have lower folate than normal or other
          psych d/o
        • Antidepressants do not work well I low folate
        • People with low folate more likely to experience
          depression relapse
        • Women (not men) who took folic acid with tx do
          better than placebo
    • FOLate natural form in foods
    • Folic acid man made
    • MTHFR MORE PRONE TO DEPRESSION
    • 5 methyltetrahydrofolate= L methlfolate natural
      active form
      • Used at cellular level for DNA , reproduction,
        regulation of homocysteine.
      • Crosses BBB
  • Vitamin
    B6
    • Necessary to make serotonin and dopamine
    • Lack trigger depression and mental confusion
  • Vitamin B
    12
    • Works with B6, and folic acid to make serotonin
      and dopamine
    • Necessary to make RBC
    •  
    • Lack
      • Problems moving oxygen thru body
      • Can cause fatigue, mood swings, irritability,
        dementia or mania
      • neurological problems including tingling in
        hands
      • difficulties coordination walking
      • psychiatric: depression, anxiety, paranoia, AH,
        memory loss, confusion, outbursts, and behavioural challenges

Inositol (Vitamin B 8)

  • for depression, panic, OCD
  • is carb that can make from glucose
    • too much sugar can disrupt the inositol shuttle
      and other messenger pathways leading to deficiency
  • forms health cell membranes
  • maintains proper electrical energy and nutrient
    transfer between cells
  • changed into substance that regulates action of
    serotonin
    • lack serotonin depression, panic disorder, OCD

Vitamin D

  • from food and sunlight
  • cholesterol is precursor
  • important for absorption and utilization of Ca
    and phosphorus for bone and teeth growth
  • involved in brain function
  • vitamin D receptors in both neurons and glial
    cells in brain
  • forms
    • D2 ergocalciferol made by plants
    • Cholecalciferol made when skin exposed to UV-B
  • Lack related to
    • Psoriasis, muscle pain, weakness, htn, some
      cancer, autoimmune disease
    • Depression, suicide
    • Common in seniors
  • Depression and vitamin D

SAMe. 800 – 1600 mg for depression

  • Made from methionine
  • Helps make neurotransmitters, proteins and
    hormones
  • Helps create mood enhancers
  • Can help relieve depression
    • Response rate 45 %  (30 % for escitalopram and 26 % for placebo
    • Add on for depression vs placebo

SUMMARY

  •  every
    depressed person should take B complex vitamin with L methylfolate
  • Check vitamin B 12 and D
  • Everyone unique
  • Vitamins
    • Make neurotransmitters, stabilize blood sugar,
      ease mood swings, improve sleep, control inflammation
  • Affect mood
    • B vitamins, D, SAMe
  • Deficiency of B
    • Harm brain, leading to depression, anxiety,
      irritability and difficulty concentrating
    • Folate natural
      • Low folate higher likelihood of depression, poor
        response to antidepressants, higher relapse rate
    • Folic acid man made
  • Vitamin B
    12 is
    family of compounds. Psych
    • Lack depression, anxiety, paranoia, AH, memory
      loss, confucsion, outbursts, behavioural changes
    • From beef liver, cheese, eggs, milk, fish,
      yogurt
    • If B 12 low and homocysteine hi recommends B 12
      shot
  • Vitamin D
    eat, sun
    • Linked to depression
  • SAMe
    depression
  • Inositol
    changed to substance that regulates action of serotonin
    • Depression, panic disorder, OCD
    • From inositol from foods including wheat germ,
      brewer’s yeast, grapefruit, liver, raisins, unrefined molasses
  • Thiamine
    • Helps brain change glucose into fuel
    • Brain rapidly loses energy when thiamin low
      leading to depression, fatigue anxiety, irritability, insomnia, memory problems
  • Niacin
    • Lack lead to depression, agitation, anxiety all
      linked to low serotonin
    • Lack pellagra sx depression, anxiety, apathy
  • B vitamins depleted by eating too many simple
    sugar, etoh
  • Folic acid, V12 and vitamin D and other
    nutrients effective tx for depression
  • Folic acid with meds happier for women , not men
  • L methylfolate decrease depression 3 months
    later
  • Elderly with vitamin B 12 deficiency more likely
    to be depressed
  • Duke Seniors lower vitamin D greater likelihood
    of depression
  • Swedish depression improve with vitamin D
  • SAMe large improvement in depression

R RESTORE HEALTHY DIGESTION

  • GUT HOUSES > 70 % IMMUNE SYSTEM
  • SUCROSE ALTERS BACTERIà CANDIDA YEAST
  • Factors that decrease good bacteria
    • Lack zinc, B vitamins, Fatty acid
    • Lack of sun
    • Lack of social support
    • Poor nutrition
    • Poor connection with nature
    • Stress
    • Lots sugar
    • Antibiotics, alcohol , birth control pills
    • Corticosteroids and anti inflammatory drugs
    • Infections, laxatives
    • Excessive use of antibacterial soap
    • Meat from animals with growth hormones or
      antibiotics
    • Gluten containing grains
  • Gut Brain connection 2 way street
    • Enteric thru Vagus nerve ascending
    • Descending ANS
    • Capillaries within epithelial tissues
    • Brain can communicate with enteric nervous
      system both directly (thru capillaries and nerve endings in gut wall) and
      directly thru chemical signaling and hormone secretion
    • Gut communicates directly with the brain

Mood is affected by inflammatory markers in the gut

  • Microbiota
    • Microorganisms in a specific region or location
      • Can be gut, skin, lungs oral mucosa
  • Microbiome
    • Collection within a given microbiota
  • Gut microbiota
    • Associated with BAD, schizophrenia anxiety, OCD
    • Pigs given lactobacillus probiotics healthier
      and more resistant to swine flu
    • Bacterioides
      • hi in depression
      • linked to inflammation
    • depressed
      • hi bacteroides
      • firmicutes, bacteroides, proteobacteria abnormalities
      • inc Enterobacteriaceae and alisitpes
      • reduced faecal bacterium negative correlation
        with depression
      • depression can actually be transmitted thru gut
        microbes
    • To help gut
      • For persons over 40, much depression is related
        to gut
      • He recommends
        • Digestive enzyme with hydrochloric acid
          • Hydrochloric acid important for digesting
            protein
          • Ant-acids especially 24 hour PPI lower stomach
            acid
            • So don’t absorb B 12, digest protein
        • Probiotics 50 billion CFUs
      • Can do these without testing without adverse
        side effects.
    • Disrupting
      Gut function
      • ant acids
        – especially 24 hour PPI lower stomach acid
        • so don’t absorb vitamin b 12 and digest/
          breakdown protein
      • antibiotics
        • can get an overgrowth of yeast, dsybiotic gut
      • stress
      • inflammation
      • bad diet
      • food sensitivities
        • celiac disease abnormal reaction to gluten
          • higher incidence of depression
          • the action of gluten interferes with absorption
            • zinc, folate, amino acids not absorbed
              increasing risk of depression
        • food allergies

Toxins can affect mood

  • Toxins are synergistic
    • BPA and phthalates are in many things
      • Affect metabolism and absorption of zinc
      • Have direct effects on neurons on brain
      • Indirect effects to make trace minerals
        unavailable

Toxins can interfere with the conversion of thyroid hormones T4 to T3   

Role of Inflammation in depression

  • Inflammation is Implicated for Heart Disease,
    arthritis, cancer, Alzheimer’s disease
  • Heavily involved in a subset of depressed
  • Overstimulated immune system produces chemicals
    that go into the brain that affects how we synthesize chemicals to make our
    brain regular
    • Chronic inflammation regardless of cause
      (trauma, stress, infection) affects mood
  • If we have the illness feel depressed.

Medications causing depression

  • Propranolol, beta blockers
  • Steroids
    • Contribute to depression and suicide
  • Hormones
  • Blood pressure medications
  • Chantix increases risk of suicide
  • Antidepressants can contribute to more
    depression of suicidality
    • FDA has put out warnings

To help stress

  • Mindfulness
  • Magnesium
    • Interfere with overactive stress response system

Supplements to help with depression

  • Magnesium
    • Most common nutritional deficiency
    • Inverse relationship with stress
    • Magnesium is repleted in soil, so foods are low
      in magnesium
    • Can lower blood pressure
    • Helps with sleep, anxiety
    • Helps with concentration
    • Helps convert fats into energy
    • In hundreds of reactions for brain function
  • Zinc
    • Commonly deficient because of toxins (BPS,
      phthalates)
    • Is not plentiful in a vegan of vegetarian diet
      • Is most bioavailable in animal products
      • Adolescents commonly have low zinc levels
    • Needed as biopathway to make neurotransmitters
    • Linked to depression
    • Symptoms of low zinc levels
      • Hair loss, diarrhea, white marks on nails, skin
        lesions, acne, less zinc
    • Taking zinc makes antidepressants work better
    • Test for zinc with zinc taste test
      • Have strong bitter taste if have adequate zinc
      • Taste buds are zinc dependent
      • Restore zinc, taste return
  • Vitamin B
    12
  • Vitamin D
    • Recommends testing
    • Take at least 2000 iu per day
  • Omega 3.
    Fish oil
    • Helps with mood
  • 5HTP.
    Precursor to serotonin
  • Don’t take tryptophan by it self
  • SAMe
    can be helpful. Do not take if have bipolar
    • Studies show good results
    • 800 – 1600 mg per day
  • St John’s
    Wort
    • 600 mg 900 mg per day
    • Make sure it comes from a reputable company
  • Rhodiola
    • He has had a lot of success
    • Fewer side effects, fewer interactions with
      drugs
    • Russians used for many years for concentration,
      stamina, energy
    • 100 – 400 mg per day
  • Role of Hormones important
    • Bioidentical hormones
  • Neurotransmitter testing not accurate
    • Can look in urine for break down products of
      serotonin and dopamine 
    • He tests levels of amino acids and supplements
      to give the building blocks to make neurotransmitters      
    • He gives amino acid precursor molecules

Role of trauma

  • Depression from trauma is not as easily treated
    with nutritional supplements
  • Look at therapy and nutritional deficiencies

Summary Points

  • Look at whole body
  • Look at contributing factors
  • Use integrative approach
  • Nurture brain and mind
    • Mind body approaches,
    • Nature
    • Spirituality helps with resilience and recovery
      • Mindfulness, meditation
        • These can change anatomy and neurochemistry of
          the brain
    • Meaning, gratitude and hope are important parts
      of mental health
  • Look at whole body
  • Look at contributing factors
  • Use integrative approach
  • Nurture brain and mind
    • Mind body approaches,
    • Nature
    • Spirituality helps with resilience and recovery
      • Mindfulness, meditation
        • These can change anatomy and neurochemistry of the brain
    • Meaning, gratitude and hope are important parts of mental health