111 -Addiction and Co-Occurring Disorders Part 2: Physiology of Addiction and Mental Health Issues
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Assessment: Neurobiology of Mental Health and Addiction Issues

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Objectives
~Neurotransmitters
~Sex Hormones
~Thyroid Hormones
~Stress Hormones
~Physiology of Emotion and Motivation
~Physiology of Sleep
~Physiology of Eating
~Physiology of Stimulants
~Physiology of Depressants
Neurotransmitters–Inhibitory
~Serotonin
~Broken down to make melatonin/sleep
~Bowel function
~Anxiety/Aggression
~Impulse control
~Depression?
~Pain control
~Sleep
~Alcohol impairs body’s ability to convert tryptophan to serotonin…
Neurotransmitters–Inhibitory
~GABA
~Sedative/depressive/anti-anxiety neurotransmitter
~Improves concentration by filtering out “background noise”
~Impulse control
~Glucose is necessary for the formation of GABA…hypoglycemia can lead to a reduction in GABA
Neurotransmitters–Excitatory
~Glutamate
~Glutamate is generally acknowledged to be the most important transmitter for normal brain function.
~Excitatory Neurotransmitter
~Learning and Memory
~Norepinepherine/Noradrenaline (Catecholamine)
~Increases arousal and alertness
~Promotes vigilance and focuses attention
~Enhances formation and retrieval of memory
~Restlessness and anxiety.
Neurotransmitters–Excitatory
~Dopamine (Catecholamine)
~Broken down to make norepinehperine
~Motivation chemical (increased arousal and pleasure)
~High levels of free dopamine in the brain generally enhance mood and increase body movement (i.e., motor activity)
~Too much dopamine may produce nervousness, irritability, aggressiveness, and paranoia
Stress/HPA-Axis
~In response to stress, the level of various hormones changes.
~Reactions to stress are associated with enhanced secretion of a number of hormones including glucocorticoids and catecholamines to increase mobilization of energy sources
~The HPA-Axis is activated
~Cortisol (gluticocorticoid) is released
~Chatecholamines (i.e. adrenaline and dopamine) are released
~Gonadotropins are suppressed

Sex Hormones
~Androgen/Testosterone
~Concentration
~Mood (Irritability and depression)
~Increase in belly fat
~Estrogen (neurostimulant)
~Receptors are very abundant in the amygdala (emotion center) and hypothalamus (autonomic nervous system/fight-flight-freeze)
~Estrogen increases serotonin receptor responsivity, increases the number of serotonin receptors and enhances serotonin transport and uptake
~High levels of estrogen associated with anxiety
~Low levels of estrogen associated with depression
Sex Hormones
~Progesterone
~Imbalance in ratio with estrogen is implicated in mood disorders.
~Referred to as the relaxation hormone
~Synthetic progesterone is associated with depression
~Gonadotropins: Hormones synthesized and released by the anterior pituitary, and promote production of sex hormones
~Oxytocin (bonding hormone): Can counteract cortisol and vice versa
Thyroid Hormones
~Thyroxine (T4) and Triiodothyronine (T3)
~Too much thyroid hormone speeds things up and too little thyroid hormone slows things down
~The pituitary gland releases thyroid stimulating hormone to get the thyroid to release T4 and T3
~Majority of thyroid hormones produced by the thyroid are T4, however T3 is the most active useable form
~The conversion of T4 to T3 is a critical element in this puzzle.
~By testing TSH and T4 alone, doctors are assuming that our bodies are properly converting the T4 to active T3.
Thyroid Hormones Cont…
~Over-activity
~Anxiety – a feeling of nervousness, with butterflies, heart racing, trembling, irritability, sleep difficulties
~Under-activity
~Depression – low mood and difficulty enjoying things, tearfulness, loss of appetite and disturbed sleep
~Either over-activity or under-activity
~Mood swings – snappiness or short-temper which people often call ‘moodiness'
~Sleeping difficulties
~What about other cognitive issues?
~Difficulties with concentration
~Short-term memory lapses
~Lack of interest and mental alertness
More Thyroid…
~Serotonin and Thyroid Health
~Hypothyroidism led to a significant decrease of responsiveness of the serotonin system.
~Optimal thyroid function may be necessary for an optimal response to antidepressants
~Hypothyroidism generally increases enzyme activities and GABA levels
~Thyroid hormone plays a role in the output of dopamine (the precursor to norepinepherine our motivation chemical)
Stress Hormones
~Cortisol (Adrenals—Glucose)
~Mental stress leads to chronic activation of the neuroendocrine systems.
~Cortisol triggers a decrease in leptin and an increase in ghrelin, inducing increased appetite and food intake.
~Affects the endocrine system, which produces all hormones, including
~thyroid hormone (which regulates metabolism)
~insulin (which regulates blood sugar)
~sex hormones (estrogen, progesterone, and testosterone)
~Affects the digestive system
~Affects the immune system
~Affects neurotransmitters, the brain chemicals that determine energy, mood, mental clarity, focus, and sleep.

Stress Hormones
~Adrenaline
~Thyroxine (Thyroid—Fatty acids)
~Effects of Chronic Elevated Cortisol
~Impaired cognitive performance
~Dampened thyroid function
~Blood sugar imbalances
~Sleep disruption
~Elevated blood pressure
~Lowered immune function
~Increased abdominal fat
Stress Hormones
~Cortisol—Chronically low levels
~Brain fog, cloudy-headedness and mild depression
~Low thyroid function
~Blood sugar imbalances, such as hypoglycemia (remember GABA??)
~Fatigue – especially morning and mid-afternoon fatigue
~Sleep disruption
~Low blood pressure
~Lowered immune function
~Inflammation

Physiology of Emotion
~In general
~Stimulus received by peripheral nervous system
~Brain responds by triggering
~Amygdala (emotion center)
~Hypothalamus assesses the need for fight or flight
~Emotional memory helps the brain determine the types of neurochemicals to secrete and in what amounts
~What happens if there is
~Too much chemical/hypersensitive receptors
~Too little chemical/ insensitive receptors
Note
~All notations of excess and insufficiency are relative to the proportions of all other hormones and neurotransmitters
Physiology of Emotion
~Anxiety/Irritability/Anger (threat response)
~Serotonin insufficiency
~GABA insufficiency
~Norepinepherine excess
~Estrogen excess
~Testosterone excess
~Thyroid hormone excess
Physiology of Emotion
~Happiness/Excitement
~Dopamine
~Norepinepherine
~Glutamate
~Serotonin (for balance)

Physiology of Emotion
~Depression
~Serotonin insufficiency or excess
~Norepinepherine insufficiency
~Dopamine insufficiency
~Thyroid (T3) insufficiency
~Estrogen insufficiency or excess

Physiology of Depression
~A New England Journal of Medicine review on Major Depression, stated:
~ “… numerous studies of norepinephrine and serotonin metabolites in plasma, urine, and cerebrospinal fluid as well as postmortem studies of the brains of patients with depression, have yet to identify the purported deficiency reliably.”
Physiology of Sleep
~Estrogen and progesterone modulate sleep—too much estrogen can cause insomnia
~Sleep deficiency promotes elevated cortisol and further disrupts ghrelin and leptin (elevated nor-epinpherine and Stress Response Hormones)
~Sleep deficiency is related to a 30% reduction in thyroid hormone levels. (GABA, Serotonin)
Physiology of Eating
~Serotonin suppresses appetite and increases with feeding
~Dopamine is associated with satiety
~Cortisol increases appetite
~Neurons involved in the regulation of feeding are located mainly in the hypothalamus
~Ghrelin & Leptin regulate hunger and satiety
Physiology of Stimulants
~Stimulants
~Set off the Stress Response System
~Thyroid hormones
~Stress hormones
~Suppression of sex hormones
~Excitatory Neurotransmitters
~Dopamine (pleasure/reward)
~Norepinepherine (focus/concentration)

Physiology of Depressants
~Increase GABA
~May increase serotonin (i.e. alcohol)
Summary
~There are a variety of neurotransmitters that are implicated in moods.
~Sex, stress and thyroid hormones, among others modulate the secretion and absorption (i.e. availability) of these neurotransmitters
~Dysphoria is about having an imbalance.  You may have too much X in relation to Y.
~Sleep deprivation directly contributes to alterations in hormone and neurotransmitter levels
~Excessive eating may be caused by high cortisol levels because the brain thinks it needs to store energy for the long fight
Summary
~Sex hormones also impact the availability of serotonin
~One sex hormone, oxytocin, has been shown to inhibit cortisol
~Dysphoric moods are caused by a neurotransmitter imbalance.  What causes that imbalance in each person varies greatly.
~A cascade effect  can happen when one “system” goes offline

References
~Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition
~Serotonin deficiency as cause of depression – is it a myth?
~The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels.
~Too Much Serotonin in Some Brain Regions Causes Depression
~Is Mood Chemistry?
~Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans.