Depression and Mental

Health
A journey from serotonin to spirit
Depression
 Balance the fundamental of
wellbeing
 Health is the consequence of balance
 Of toxic with nurturing influences
 Of minerals eg Na/K ,Ca/Mg

 Of hormones eg progesterone/oestrogen

 Of anabolism/ catabolism

 Of energy input and output

 Of oxidative phosphorylation and antioxidants

 Of excitatory and inhibitory neurotransmitters

 Balance in health
 Sleep wake cycles
 Cell growth and death
 Bacterial flora
 Immune stimulation and inhibition
 Inflammatory and anti-imflammatory cytokines
 Acid Base and fluid status
 Balance between and within systems
 Imbalance or disequilibrium results in suboptimal
health and eventually in disease
Homeostasis and control systems
 Physiological parameters
 Optimal range vs “normal”
 Exist in balance

 eg zinc/copper

 Progesterone and oestrogen levels

 Regulation requires feedback

 Disease results from failure of
control
 Optimal disease management
 Requires understanding of control mechanisms and
their breakdown
 Toxic factors overwhelm nurturing factors
 Emotional and physical factors
 No system exists in isolation
 Imbalance in one system will effect all others
 Division of body and mind is arbitrary
 Practice of NEM
 Requires the identification of the cause of
illness
 Understand the mechanisms
 Promoting wellness
 Reduce environmental toxins (physical/emotional)
 Providing nutritional resources to restore balance

 Addressing all levels of causation

 Resource the system to restore itself

 Depression as a syndrome
 Cluster of symptoms
 Not a physiological diagnosis
 Multiple associations
 Multiple contributory factors
 Genetic predisposition
 Environmental promoters and triggers
 Causation a complex interplay of these factors
 Multiple effective interventional strategies
 Depressive Causal Factors
 Genetics
 Nutrition
 Toxins
 Neuronal Damage
 Neuronal Dysfunction
 Psychosocial and Environmental Factors
 Hormonal Balance
 Neurogenesis Synaptogenesis
 Cellular Energetics
 Nutritional Factors
 Protein (mehtionine, Tryptophan Tyrosine)
 EFA
 Vitamin B1, B3, B6 B12 Folate
 Zn
 Mg
 Iodine
 Iron
 Vitamin D
 Toxins
 Endotoxins (Gut/ Dysbiosis)
 Heavy Metals
 Chemicals
 Pesticides
 Drugs
 Medications
 Genes
 Gene Polymorphisms
 Epigenetic Changes
 Gene Environment Interaction
 MTHFR
 COMT
 Serotonin Reuptake
 Dopamine receptor and Trransport
 Neuronal Dysfunction and Damage
 Inflammation and Cytokines
 Infection Drugs AID
 Food Allergens
 Oxidation
 Toxins/ heavy metals
 Exorphins
 Excitoxicity ( MSG Food additives)
 Homocysteine
 Stress
 Hormonal Imbalance and Receptor Expression
 Eg thyroid
 Hypothesis re pathogenesis of
depression
 Impaired cellular signalling
 Neurotransmitter
 Neuroendocrine
 Symptoms depend upon
 Neurotransmitters and Neurons involved
 May results from abnormal
 1. Action potential /cellular energetics
 2. Neurotransmitter synthesis, release, metabolism
 3. Receptor function, membrane physiology, second
messenger signalling
 4. Neurogenesis/ synaptogenesis
 Neurotransmitter Balance
 Glutamate 50-60%  Neuropeptides
excitatory  Opioids
 GABA inhibitory  Enkephalin Dynorphin
 Glycine inhibitory  B endorphin
 Monoamines  Balance critical for
 Serotonin mood
 Dopamine  Excess and
 Noradrenaline excitotoxicity
 Histamine
 Ach (quatenary amine)
 Serotonin deficiency
 Aggression, bad temper, irritability
 Anxiety and panic
 Carbohydrate and alcohol cravings and slow BMR
 Depression (mild to moderate)
 Eating Disorders
 Seasonal affective disorder
 Low self esteem
 Poor dream recall
 Low pain threshold
 Easy to tears
 Serotonin synthesis² ³
 Precursor Tryptophan
 Source meats turkey eggs dairy and E Coli
 Cofactors
 Zinc Magnesium Calcium Iron
 B6 ( activated by B2), Folic Acid

 Vitamin C

 Tetrahydrobiopterin ( product of methylation)

3. Visual textbook of nutritional Medicine Dr Igor Tabrizian
 Serotonin deactivation
 Reuptake (presynaptic)
 Blocked by SSRI and MDMA
 Monoamine oxidase
 Receptors 5HT1-7
 1 and 2 in brain ( mood)
 5HT3 promotes nausea blocked by ondanstron

 5HT4 gut motility

 Also platelet function and formation Melatonin

 Dopamine Function²
 Movement
 Emotional response pleasure/pain reward
 Deficiency
 Tremors muscle tightness restless legs
 Stress and mental/ physical exhaustion
 Reduced basal metabolic rate
 Depression
 Amotivation and reduced libido
 Memory impairment Attention Deficit
 ADHD Parkinsons Alzheimers
 Dopamine Synthesis
 Precursors phenylalanine tyrosine
 Cofactors
 Iron Magnesium
 Activated B6 Folic acid

 Tetrahydrobiopterin *requires SAMe

 B3 B12 and copper also effect levels

 Dopamine degradation
 Reuptake
 MAO and COMT
 Produce excitotoxins
 D2 autoreceptor controls release
 Overaction associated with schizophrenia/psychosis
 Acted on by most antipsychotics
 D4 Rc
 Released by stimulants amphetamines cocaine MDMA
 Alcohol etc
 Noradrenaline Function
 Alertness (Reticular activating system)
 Concentration
 Memory
 Mood Drive
 Sympathetic NS
 vasoconstrictor ionotrope chronotrope
 Fight Flight Hide
 Release hormones from thymus
 Noradrenalin imbalance
 Deficiency
 Poor concentration and memory Unreactive to stress
 Excess
 Panic attacks anxiety
 Hypertension esp white coat tachycardia
 Cold hands and feet, Tremor, Sweats
 Insomnia Light Sleep
 Wide eyed
 Hypervigilance
 Noradrenaline Metabolism
 Synthesis from dopamine
 Copper and Vit C dependant
 Excess copper converts dopamine to noradrenaline

 Reuptake
 MAO 1 and 2
 COMT
 Rc alpha 1,2 B1,2,3 ( increased by T3)
 Breakdown products are excitotoxins
 GABA Function
 Inhibitory
 quenches noradrenaline/glutamate
 Anticonvulsant sedative hypnotic
 Deficiency
 Anxiety panic insomnia
 Trembling palpitations cold clammy
 Seizures
 Hypersensitivity to sound light touch
 Cravings carbs alcohol benzos
 Think alcohol withdrawal
 GABA metabolism
 Synthesised from glutamate
 Cofactors B6
 Increased by progesterone
 Dampens excitotoxicity
 Rc GABA A, B, C
 Opioid Deficiency
 Addictions cravings
 Aggression irritability antisocial behaviour
 Pain and Headaches
 Stress
 Depression
 Memory loss /learning disorder
 Diarrhoea
 Glutamate
 Excitatory / excitotoxin in excess
 Functions
 Learning memory
 Antigravity

 NMDA Receptor activity correlate with depression

 NMDA antagonists improve depression

 Antidepressants Magnesium and Zinc block NMDA

 B6 Zinc
 Acetylcholine function
 Memory especially emotional
 Deficiency
 Dementia impaired learning and memory
 Poor sleep

 Mania

 Synthesis
 B5, choline, acetyl carnitine
 Contributory imbalances
 Nutrition/Physiology
 Minerals
 Vitamins
 Amino acids
 Endocrine
 Neurotransmitters
 Chronobiology
 Genetics/epigenetics
 Cellular energetics
 Exercise/physical activity
 Social support
 Spiritual connection
 Environemental/toxins
 Heavy metals
 Organic chemicals
 Drugs (prescribed/illicit)
 EMF ionising radiation
 Trauma
 Chronic disease/disability
 Inflammation
 Social stressors
 Spiritual disconnection
 Minerals
 Cofactors in
 neurotransmitter/hormone synthesis/degradation/release
 Cellular energetics
 (glycolysis, citric acid cycle, mitochondrial function)
 Neurogenesis synaptogenesis neural migration
 Intracellular 2nd messengers
 Membrane potential/action potential
 Oxygen carrying
 DNA replication/expression
 pH/oxidation status
 Mineral imbalances
 Zinc
 Copper (excess/deficiency/bio-unavaailability)
 Iron
 Chromium (BSL)
 Magnesium (energy and relaxation)
 Calcium (hypercalcaemia)
 ? Sodium/ potassium (intracellular hair analyses)
 Iodine (thyroid, oestrogen, myelination)
 Zinc
 Neurogenesis and neuronal migration
 Synaptogenesis
 Converts glutamate to GABA
 Synthesis serotonin and dopamine
 Inhibits NMDA
 Cognition memory learning abstraction
 Clinical Zinc Deficiency
 Poor short term memory
 Difficulty concentrating
 Frequent infections
 Poor wound healing
 Prefer spicy food
 Halitosis
 Growing pains
 Reactive
Hypoglycaemia
 White spots on finger
nails/ weak fragile nails
 Stretch marks
 Acne
 Hair loss
 Coated Tongue
 Perifollicular
Hyperkeratosis
PMS and Postnatal Depression
 Copper Overload
 Premenstrual Syndrome
 Irritability/ teariness
 Carbohydrate cravings
 Migraine
 Acne
 Insomnia/ light sleeper
especially premenstrually
 Intolerance to OCP
 Post natal depression
 Reactive Hypoglycaemia
 ADHD
 Easy hair loss
 React to cheap jewellery
 Metallic taste in the mouth
 Feeling wired and tired
 Intuitive
 Cold hands and feet
 Low blood pressure
 High blood pressure only
with stress ( white coat
hypertension)
 Copper Overload
 Diagnosis
 Clinical
 Serum Copper >18.5
 High Free Copper
 High Hair Copper
 Altered hair Molybdenum
and Zinc
 Management
 Reduce Oestrogen
 Increase Progesterone
 Zinc titrate slowly 75mg
 B6 300mg mane
 Vitamin C and E
 Molybdenum 200 mic bd
 Manganese 25mg
 Magensium
 GABA
 Iron
 Myelination
 Synthesis serotonin and dopamine
 Energy production in mitochondria
 Hb synthesis
 Cytochromes and detox
 Dopamine receptor function
 Vitamins
 B Group Vitamins
 B1, B2, B3, B6 B12, folate
 Vitamin C and E
 Vitamin D
 Pyrrole disorder
 B6 / pyridoxine
 Synthesis of dopamine serotonin and GABA
 Synthesis of H2S neuromodulator
 NMDA function in hippocampus for memory
 Poor activation in Autism
 Synthesis of glutathione
Pyrrole Disorder
 Pyrrole Disorder
 Functional Zn B6 Deficiency
 Depletion of Antioxidants EFA Biotin and impaired energetics
 Triggered and Exacerbated by stress, alcohol
 Diagnosis Clinical +Urine Hydroxyhaemopyrrolin > 15
 Common In
 Depression
 Behavioural disorders
 Schizophrenia
 Bipolar disorder
 Downs Syndrome
 Alcoholism
 Autism
 Obesity
 Pyrrole Disorder
 Intolerant to stress build up
 Weight gain depression triggered  Poor Dream Recall
by stress  Weight gain around middle
 Irritable Moody or known for  Early greying
temper
 Paranoia
 Grey hair/ hair loss triggered by
stress
 Prominent Fears or Phobias  Hair or skin lightening with stress
 Night person not morning person  Fair skin/ easy sunburn ( China
 Poor morning appetite tendency Doll)
to skip breakfast  Childhood ADHD
 Nausea in morning especially  Reading/learning disorder
pregnancy
 Sensitivities: Bright light Sounds
 Delayed puberty
 Motion sickness
 Picky eater
 Short stature
 Pyrrole Treatment (70kg)
 Zinc 80mg at night
 Vitamin B6 (Pyridoxine) 400mg in the morning
 Pyridoxal 5 phosphate ( activated B6/ p5p) 60mg in
morning
 Vitamin C 1000mg twice daily
 Vitamin E 400mg twice daily
 Biotin 1000 microgram twice daily
 Manganese 25 mg (except in undermethylated people)
 Evening Primrose or Borage oil and fish oil
 Amino Acids Balance
 Tryptophan
 Serotonin precursor
 Tyrosine
 Dopamine noradrenaline T3, T4 precursor
 Methionine/SAMe
 Methyl donors in synthesis and degradation of
 Oestrogen dopamine serotonin and noradrenaline
 Branch Chain Amino Acids
 Effect uptake of precursors to monoamines and energy
 Overmethylation Signs/ Symptoms
 Free floating anxiety
 Panic attacks
 Hyperactive mind
 Hallucinations
 Confusion, paranoia
 Agitation, restlessness
 Learning disabilities, memory loss
 Low libido
 Nausea, poor appetite
 Heavy body hair
 Overmethylation
 Diagnosis Low Histamine < 0.3-0.4
 High Dopamine Noradrenaline and Serotonin
 Management
 GABA
 B3 high dose, B6 (p5P), B12
 Zinc
 Folic acid high dose
 Manganese
 Omega 3 oils
 Vitamin C
 Vitamin E
 Undermethylation Histadelia
 Strong willed or determined
 Competitive
 Driven for success
 Driven for reward ( goal
driven)
 A perfectionist
 Obsessive compulsive traits
 Require little sleep
 Easy to tears eg at movie
 Oppositional Defiance
 Internalise anxiety
 Low pain tolerance
 High libido when young
 Addictive behaviours
 History of eating disorder
 Withdrawn when depressed
 All or nothing person
 Headaches
 Good response to
antidepressant
Type A Depression
 Undermethylation
 Diagnosis
 Clinical
 High Histamine > 0.6
 Low Absolute Basophil
 Low Homocysteine
 High Folate
 Trial SAMe titrate to up
to 1600mg usually
800mg
 Management
 SAMe 800mg mane
 Methionine 1000mg bd
 Zinc 50 B6 200-250
 Vitamin C and E
 Calcium Magnesium
1000/500
 Beta Carotene 25000iu
 Essential fatty acids
 EPA DHA and AA primary FA at nerve
terminal
 Effect lipid bilayer flexibility for normal
receptor and membrane function
 Neurotransmitters stored in DHA
 EPA anti inflammatory prostaglandins LTB5
PGE3
 Source of phospholipid second messengers
 Endocrine Balance
 Cortisol/ ACTH/ CRF
 Oestrogen
 increase 5HT1 decreases 5HT2 Rc
 Progesterone
 Modulate Oestrogen
 Post natal depression PMS
 Testosterone
 DHEA
 Melatonin
 Thyroid
 Cortisol
 Decreases
 LH TSH GH
 DHEA Testosterone Oestrogen Progesterone
 Conversion T4 to T3
 High in 50% of depression
 Associated with decrease dopamine and serotonin
 High CRF associated with negative affect in addiction
 Increases gut permeability to toxins and antigens ?
pyrrole
 Neurogenesis and pruning
 Neurogenesis decreases with
 age stress depression and neurodegenerative disease
 Brain derived neurotropic factor
 Reverse atrophy and cell loss in depression
 Metallothionine
 Progesterone
 IGF1
 neuroprotection and neurogenesis, angiogenesis
 Neurogenesis
 Stress physical or psychosocial
 Decreases hippocampal neurogenesis
 Antidepressants and antipsychotics
 increase neurogenesis via BDNF
 Noradrenergic stimulus results in acute stimulus

 Prolonged Serotonergic stimulus required for effect

 Serotonin importance in kids adolescence

 (level 2x adult)
 Chronobiology
 Sleep disorders (Anabolic)
 Sleep apnoea
 Sleep deprivation (environemntal)

 Restless legs

 Seasonal Affective Disorder

 Premenstrual dysphoric disorder
 Sleep and light
 Sleep
 Neurotransmitters synthesis
 Cellular repair, Synaptogenesis
 ? Frequency Energetics ( alpha delta wave etc on EEG)
 Disordered REM sleep in depression (reduced latency)
 REM deprivation may help major depression
 Light
 melatonin/ cortisol circadian rhythm
 Vitamin D synthesis
 Light therapy effective in seasonal affective disorder
 Genetics and polymorphisms
 Methyltetrahydrofolate reductase
 Depression BPD
 COMT
 OCD Schizophrenias BPD Anxiety panic ADHD
 Novelty seeking; reward dependance
 Dopamine Receptor genes
 D2 OCD Schizophrenia reward dependance
 D4 novelty seeking reward dependance
 Prodynorphin
 Cocaine and amphetamine abuse
 Polymorphisms
 Serotonin Transporter Gene
 BPD Schizophrenia
 Trytpophan Hydroxylase
 BPD, schizophrenia alcohol abuse
 Serotonin Receptor genes
 1b substance abuse and depression, 1a/2a panic, 2c
reward dependance
 Cellular Energy
 Mitochondrial dysfunction
 Lack of mitochondrial nutrients
 Heavy metals

 Free radical damage

 Anaemia
 Cerebrovascular disease
 Cellular Hypoxia (acute/chronic) eg pilots
 Exercise physical activity
 Endorphin release
 Increase in brain derived neurotropic factor
 Likley mediated by noradrenergic pathways
 Stimulates
 testosterone;
 cortisol;

 GH
 Medical triggers for depression
 Chronic or life threatening physical illness
 COAD, CCF, IHD, CRF; chronic liver disease,cancer
 Severe physical disability
 Chronic pain/ fatigue or “ hypochondriasis”
 Postpartum
 CNS illness eg parkinsons MS CVA, brain tumours
 Autoimmune Disease RA, SLE
 Obesity
 Endocrine thyroid adrenal parathyroid NIDDM
 Mechanisms
 Inflamatory cytokines
 Neuroendocrine
 Psychological
 Infection and Depression
 AIDS/HIV
 Viral hepatitis
 TB
 EBV
 Syphilis
 Influenza
 Viral pneumonia
 Encephalitis
 Gut and Depression
 Dysbiosis
 Effects amino acids metabloism eg tyrosine trytpophan
and cytokines
 Intestinal candidiasis
 Toxic metabolites
 Food allergies/ intolerances
 Csaomorphin, glutomorphin
 Chemical amines salicylates sulfites
 Excitotoxins glutamates and other food additives
 Cytokines and cortisol
 Gut peptides eg CCK
Toxins
 Heavy Metals
 Mercury
 Astrocyte swelling
 decrease glutamate uptake and excitotoxicity

 Antinutrient blocking iron zinc and selenium

 Cadmium
 Blockade of Mg, Zn, Se
 Lead
 Inhibit serotonin synapse formation
 Heavy metal neurotoxicity
 pH change acidosis with enzymatic inhibition
 Pro-oxidant free radical genesis
 Lipid peroxidation
 Protein oxidation and dysfunction
 Enzymatic hypofunction
 DNA damage
 Pro inflammatory
 Dysregulation of protein turnover
 Mitochondrial dysfunction
 Environmental toxins
 Xeno oestrogens
 Create oestrogen progesterone imbalance
 Effect copper levels

 Organophosphates pesticides
 Deplete liver detoxification pathways
 Deplete transulfuration and methyaltion
 May deplete glutathione

 Effect ph free radical production and energy

production
 Recreational drugs
 Alcohol
 Stimulants especially withdrawal
 MDMA ( ecstasy)
 Amphetamines

 Cocaine
 Electromagnetic frequencies
 Mood changes associated with
 Solar flares
 Hot winds (Sirocco, Santa Anna, Chinock, Sharav)
 Associated with positive ionisation of air
 Improves with negative ionisers

 Lunar Cycles
 Ref: J Pollitt J of Royal Soc Med Jan 1982

 Likely effect action potential

 EMF
 ECT causes changes in theta waves on EEG
 QEEG theta waves are abnormal in uni/bipolar
depression
 Repetitve transcranial magnetic stimulation is
effective in treating depression
 EMF studies on incidence of depression are unclear
 It appears some specific patients are subjectively
effected by EMF with effects including mood fatigue
and headaches
 Management
 History
 Examination
 Ix
 FBC EUC/LFT/TFT B12 Folate Iron studies Ca/Mg /Po4/
PTH; Vit D; Spot urine iodine
 Zinc Copper Caeruloplasmin Histamine Homocysteine
Urinary kryptopyrrole
 Hormonal testing (blood saliva)
 CDSA/ Bioscreen/ OAT Urine/serum amino acid
 Hair minerals TMA Urine Chelation challenge
 ? Elimination diet ? IgG food panel ? Melisa testing
 Management
 Identify and eliminate cause
 Chelation, gut management, treat infections, change medications, remove EMF
 Nutritional
 Diet vitamins minerals amino acids/ Methylation
 Herbal
 Psychotherapies
 Exercise
 Light
 Mindfulness/ Meditation
 Art therapies
 Supportive social/ spiritual
 Drugs
 ECT, negative ionisers