week 13

Question 1

What are some myths around mental illnesses? And what is true?

Answer 1

People with mental illness are violent and dangerous
More likely to be a victim
People with mental illness are poor or less intelligent
Most ppl with mental illness tend to be about avg, in intelligence
Mental illness is caused by a personal weakness
Not ture
Mental illness is a single, rare disorder
Not a single disease, many subcategories

Question 2

How does Walter Cannon understand Fight or Flight?

Answer 2

Fight or flight response is a physiological response to an acute threat

Question 3

How does Hans Selye explain “stress”? And what is General Adaptation Syndrome?

Answer 3

“Stress” is a non-specific physiological response to demand made on the organism
General Adaptation Syndrome; provides an outline of the htee difference stages in which an organism may go through when exposed to prolong periods of stress, 3 phases; alarm, resistance and exhaustion

Question 4

Describe the 3 phases of genera l adaptation Syndrome.

Answer 4

alarm; heart rate and blood pressure rise, manage what the threat is
resistance ; maintain high level heart rate and blood pressure, survive
exhaustion; all resources are depleted

Question 5

How does Richard Lazarus understand stress? And what is Transactional Model of Stress?

Answer 5

Stress is experienced when one perceives that demands outweigh resources
Transactional Model of Stress: three process; primary appraisal (appraise environment, is it a pos. or neg. situation? A threat?), secondary appraisal (how am i gonna cope with this situation?) third appraisal (is this working?)

Question 6

How did Bure McEwen explain the biological parameters of managing a changing environment?

Answer 6

Allostatic Load is the wear and tear of the organism due to repeated allostasis
Allostatic Load Index: Neuroendocrine, cardiovascular, metabolic, immune

Question 7

What is the difference between acute and chronic stress? And Absolute and relative Stress?

Answer 7

Acute (good stress, to ensure survival, able to habituate to stressful situations) vs. Chronic Stress (unable to habituate)
Absolute(we would respond similarly e.g., car crash) vs. Relative Stress (singulalry responsing, e.g., neg. Self talk)

Question 8

What is Chronic Stress associated with?

Answer 8

Cardiovascular disease
Metabolic disorder
Poor Sleep
Depression
Anxiety
Cognitive impairment
Accelerated biological aging

Question 9

What was Schizophrenia originally called? and what was it orgnailly thought to be?

Answer 9

Originally called Dementia Praecox (Emile Kraepein, 1883).
Was Seen as cognitive deterioration
We know its not dementia now

Question 10

Who coined the term Schizophrenia? and how did he explain it?

Answer 10

Schizophrenia “Split mind”, a split between the emotional and intellectual aspects of experience (Eugen Bleuler

Question 11

Are the symptoms of Schizophrenia the same across all types of Schizophrenia? Are the symptoms immediate? Is the prevalence higher in men or women? And is it easy to diagnose?

Answer 11

Symptoms vary, depending on type of schizophrenia you have.
Symptom onset is gradual and insidious.
Prevalence higher in men than women (7: 5 ratio)
Difficult to diagnose – need for differential diagnosis

Question 12

What are Positive Symptoms(should be absent) of Schizophrenia?

Answer 12

Disorganized speech
Disorganized behavior
Hallucinations
Delusions

Question 13

What are Negative Symptoms: (expect to see but not shown) of Schizophrenia?

Answer 13

Flattened affect and /or anhedonia
Speech minimized
Lack of motivation
Social withdrawal

Question 14

What are Cognitive Symptoms of Schizophrenia?

Answer 14

Poor sustained attention
Low psychomotor speed /catatonia
Poor learning and memory
Poor abstract thinking and problem solving

Question 15

What is Complex Syndrome in respect to Schizophrenia?

Answer 15

Psychosis
Emotional/Affective Symptoms
Motivational impairment
Cognitive impairment

Question 16

Who is Louis Wain?

Answer 16

Around his 50s his paintings started to take this delirious turn when we started to show signs of Schizophrenia, paintings started to look less and less like cats

Question 16

What are some Etiological Theories of Schizophrenia?

Answer 16

Genetic Theories
Twin studies
Adoption studies
Gene mutation

Neurodevelopment Hypotheses
Seasonal effects
Neurology of Schizophrenia

Dopamine & Glutamate Hypothesis
looking at chemical imbalance in brain

Question 17

What does utero environment tell us about Schizophrenia?

Answer 17

Assuming that Schizophrenia plays a part in the utero environment b/c twins have the highest risk of developing Schizophrenia
Monozygotic twin with the same placenta(monochronic) vs. two different placentas (diachronic) has a higher association of risk of developing Schizophrenia

Question 18

What happens in the Study (Tienari et al 2004)?

Answer 18

Finnish National Sample: Investigated adopted offspring of mothers with and without schizophrenia
Study Design: 21-year follow-up
Measured family environmental factors
Question: What is the contribution of family predisposition (genetic risk) vs. environment (adoptive rearing) on development of schizophrenia?
Study Results: Decreased risk of diagnosis in predisposed kids living on healthy environment vice versa for unhealthy environment

Question 19

What is DISC1 protein important for?

Answer 19

DISC1 protein is important for neurodevelopment

Question 20

What Animal studies show the mutations of DISC1 protein in people with Schizophrenia?

Answer 20

Animal studies:
Mutant mice with no DICS1 in brain stem cells show behaviors that mimic schizophrenia
Down regulation of DISC1 in dentate gyrus leads to schizo-typo behaviors
Transgenic mice expressing DISC1 mutation display enlarged lateral ventricles

Question 21

What is Neuregulin 1 (NRG1 ) important for?

Answer 21

Neuregulin 1 protein important for neurodevelopment

Question 22

What is the association study between Neuregulin 1 (NRG1 ) and Schizophrenia?

Answer 22

Association studies:
Icelandic population - gene doubles the risk of schizophrenia (Steffanson et al., 2002)
Extended to Scottish, Swedish and Chinese populations (Li, Collier He, 2006)
NRG1 also associated with creativity, independent of schizotypal traits (Kéri, 2019) Yayoi Kusama

Question 23

What is a Recent popular hypothesis about Schizophrenia regarding genes?

Answer 23

Recent popular hypothesis: not just one gene, but new mutations in any one of hundreds of genes

Microdeletions and microduplications
Found in 15% schizophrenia patients; 20% if onset before 18 years. Compared to 5% in control group.
Not random, but selective for genes that are important for production of proteins involved in neurodevelopment and cognitive function

Question 24

What is the Neurodevelopmental Hypothesis?

Answer 24

The neurodevelopmental hypothesis suggests abnormalities in the neonatal development of the nervous system leads to mild abnormalities of brain anatomy and major abnormalities in behavior Abnormalities could result from genetics or other influences (e.g., intrauterine environment) Environmental influences later in life aggravate the symptoms ?( eg.,high school or uni) E.g., onset after stress Risk of schizophrenia by population density (e.g., big vs small city) more prevalent in high-density cities

Question 25

What is Season-of-birth-effect onto schizophrenia?

Answer 25

Babies born in late winter and early spring months are at higher risk of “positive” schizophrenia

Question 26

What infects in the mother can lead to a development of schizophrenia?

Answer 26

Increase cytokines in the mother that impair brain development of fetus Cause fever that damages the fetal brain Research evidence: Babies born from mother who contracted flu in 1st trimester 7x more likely to develop schizophrenia Increased schizophrenia rates among people born 2-3 months after major influenza epidemic

Question 27

What are Risk factors that increase the likely hood of developing schizophrenia?

Answer 27

Poor nutrition of the mother during pregnancy Premature birth Low birth weight Complications during delivery Extreme stress of mother during pregnancy Immunological rejection e.g., Rhesus factor(Rh) incompatible Other infections during pregnancy (Toxoplasma gondii) Postnatal stressors

Question 28

how is brain of people with schizophrenia different from a healthy brain?

Answer 28

Enlarged lateral ventricle and prominent sulci Decreased tissue - cerebral gray matter Smaller cell bodies in PFC and hippocampus Reduced cortical connectivity and activity Glial reductions (glial theory) : oligodendrocytes and myelin integrity (DISC1); altered microglia in temporal and frontal lobes; astrocyte glutamate transporters in PFC Brain “insults” may not be apparent until later - clear effect of injury is not prevalent till later

Question 29

What is the Dopamine Hypothesis?

Answer 29

Dopamine Hypothesis: comes from drug studies that showed that antipsychotic effects of certain drugs has an effect of patients with schizophrenia, decrease positive symptoms positive symptoms are caused by over-activity of synapses between DA neurons of the ventral tegmental area and nucleus accumbens and amygdala (Mesolimbic)

Question 30

How do Antipsychotic drugs effect the brains of people with Schizophrenia?

Answer 30

Antipsychotic drugs (chlorpromazine) block DA receptors Block D2 receptors, preventing receptor activation (antagonist) amphetamine psychosis resembles schizophrenia Amphetamines (and cocaine) block DA reuptake thus increase DA levels (agonist). Amphetamines exacerbate symptoms

Question 31

What effect does positive symptoms have on DA?

Answer 31

Hyperactivity of DA projections to nucleus accumbens from VT. Amphetamines exacerbate symptoms.

Question 32

What effect does Negative & Cognitive symptoms have on DA?

Answer 32

Hypofrontality of DA activity of the (dorsolateral) PFC | Perform poorly on neurocognitive tests that are sensitive to frontal lobe damage.

Question 33

How are Positive and Negative/Cognitive Symptoms linked in Schizophrenia?

Answer 33

Evidence indicates these symptoms are linked—prefrontal hypoactivity causes hyperactivity of mesolimbic dopaminergic neurons Glutamate hypothesis: Schizophrenia due to under-stimulation of glutamate receptors. PCP (angel dust) and ketamine (date rape drug) create all symptoms This effect is not observed in preadolescence

Question 34

What are treatments of Schizophrenia?

Answer 34

Glycine or D-serine stimulate NMDA receptors and reduce schizophrenic symptoms – namely, effective in reducing negative symptoms Atypical antipsychotic - Clozapine- increases release of DA in PFC and decreases DA in nucleus accumbens - rids of all symptoms Partial agonist: drug has very high affinity for a particular receptor but activates that receptor less than the normal ligand does; serves as an agonist in regions of low concentration of the normal ligand and as an antagonist in regions of high concentrations

Question 35

What are some Major Affective Disorders?

Answer 35

Includes Major Depressive Disorder (MDD) and Bipolar Disorder MDD (unipolar): unremitting depression Bipolar: cyclical periods of mania and depression BPI: full-blown mania BPII: hypomania

Question 36

What are sympotoms of MDD?

Answer 36

``` Hopelessness and helplessness Worthlessness, self-hate, guilt Agitation/ irritability Weight loss Concentration Fatigue/lack of energy Isolation/withdrawal Anhedonia Sleep Suicidal thoughts Females> Males ```

Question 37

What are Etiological Theories of MDD?

Answer 37

Genetics Chemical Imbalance Neurogenesis, neurology Neurology of MDD

Question 38

What do twin studies and gene mutations show about MDD?

Answer 38

Concordance in MZ twin is ~ 65% vs 13% in DZ twins Serotonin transporter gene (s/l allele) 2 copies of s allele higher chance of developing MDD Gene-Environment Interaction Being in a stressful environment increases MDD along with the short allele) Increase in developing MDD when you have both an allele and a lot of stressful events

Question 39

What is the Monoamine Hypothesis?

Answer 39

depression is caused by low level of activity of one or more monoaminergic synapses Dopamine, NE, 5HT

Question 40

What is Depletion Studies? tryptophan or tyrosine

Answer 40

Deplete levels of a certain neurotransmitter by depleting the precursor. Tryptophan depletion precursor to serotonin Tyrosine depletion precursory to catecholamine Study: Delgado et al 1999 3 groups: SRI responders; NRI responders; healthy controls Depleted of tryptophan or tyrosine SSRI group: depletion of Tryptophan lead to increase of depression symptoms Depletion of Tyrosine lead to no return of depression symptoms NRI group: Depletion of Tryptophan no impact on symptoms Depletion of Tyrosine lead to return of depression symptoms Depression has underlying mechanisms

Question 41

What is the role of Neurogenesis to MDD? And what is Glucocorticoid cascade hypothesis?

Answer 41

Hypothesis: Stress exposure decreases neurogenesis in the dentate gyrus of the hippocampus which causes depression. (Glococorticoid cascade hypothesis) Glucocorticoid cascade hypothesis: through chronic exposure distress, this has a neurotoxic effect on cells of the hippocampus can lead to depression or cognitive impairment Evidence: Treatment with anti-depressant meds alleviate symptoms at the same time that they facilitate neurogenesis in the rodent HC Evidence: Exercise enhances neurogenesis in the HC of both animals and humans and alleviates depressive symptoms

Question 42

What are the brain abnormality prevalent in people with MDD? Amygdala.

Answer 42

Decreased activity in left and increased activity in right PFC (recall Emotions chapter) Amygdala (applies to bipolar too) 50-70% increased blood flow & metabolism in amygdala Amygdala activity correlated with severity symptoms Faulty amygdala-PFC coupling

Question 43

What are the brain abnormality prevalent in people with MDD? Subgenual Anterior Cingulate Cortex.

Answer 43

Subgenual Anterior Cingulate Cortex important for emotion Smaller volume in MDD and Bipolar In healthy adults: 5HT s allele carriers had 25% reduction in sgACC volume Gotlib et al 2005 - increased activity in depressed patients Coincides with deep brain stimulation studies

Question 44

What are drug treatments for MDD?

Answer 44

Antidepressant drugs MAOIs - enhance monoamines by inhibiting MAO. Interaction effects with food containing tyrosine TCAs - enhance monoamines by blocking reuptake of 5-HT and NE SSRIs and NRIs - enhance 5-HT and NE (respectively) by inhibiting reuptake of the neurotransmitter. Atypical AD - inhibit reuptake of DA

Question 45

What are some forms of treatment that is a 2nd option for a person isn't responding to other therapy?

Answer 45

Transcranial Magnetic Stimulation Pulses of magnetic energy focused over a particular surface along the scalp to inactivate neurons. Electroconvulsive therapy (ECT) An electrically induced seizure used for the treatment of severe depression. For Non-responders or suicidal patients Applied every other day for a period of two weeks Side effects include memory loss Memory loss can be minimized if shock is localized to the right hemisphere Light therapy May be more effective than certain medications (Lam et al 2016 JAMA) Sleep Deprivation - mimics SSRIs Sleep patterns in depression Typically fall asleep but awaken early; unable to get back to sleep Enter REM sleep earlier and have an increased average number of eye movements during REM sleep Reduced time in slow wave sleep A night of total sleep deprivation is the quickest method of relieving depression Benefit is brief, and increases sensitivity to pain As soon as they get a good nights sleeps symptoms will return

Question 46

How does treatment effect the faulty amygdala and PFC connection?

Answer 46

Taking SSRIs can calm down the amygdala, cognitive therapy, strengthening PFC combination of both therapy's heavily surpasses symptoms of MDD

Question 47

Treatment in the brain in non-responsive MDD patients

Answer 47

Deep brain stimulation for non-responsive depressives Deep brain stimulation damping the activity of a part of the brain Mild electrical stimulation through an implanted electrode Premise: increased activity of subgenual ACC in depressed patients more effective than medication

Question 48

What are symptoms of Bipolar

Answer 48

Depressive symptoms (can last 3 times longer than mania) Manic episodes Elevated mood: hyperactive, increased energy, high self-esteem (false), grandiose/delusions Racing thoughts loud-rapid speech Reckless behavior: binging, poor judgment, promiscuity, spending sprees Agitated or irritated Females = males; earlier onset than unipolar

Question 49

What are Etiological Theories of bipolar?

Answer 49

Genetics Concordance in MZ twins is 80% Neurology of Bipolar Overactive Amygdala (see MDD) Overactive subgenual ACC (see MDD) Enlarged lateral ventricles (remember DISC1?

Question 50

What is a first line of treatment for bipolar? and how does it work?

Answer 50

Lithium Stabilizes mood and prevents relapse in mania or depression Exact mechanism is unknown, but shows neurotrophic effects Drug shown to works by: Decreasing glutamate activity Decreases inflammation in the brain inflammation is involved in depression

Question 51

What is Anxiety and what are some common types?

Answer 51

Anxiety = unfounded, unrealistic, chronic fear ``` Common types: Generalized anxiety disorder Panic disorder Specific phobias Obsessive compulsive disorder Post-traumatic stress disorder ```

Question 52

What part of the brain is important for imagined fear?

Answer 52

Amygdala activates in response to threat in the environment, imitate threat Bed nucleus of the stria terminalis (BNST): regulates long-term, generalized emotional arousal, fear of something that might happen BNST activated to impending threat Sexual dimorphic Receptors for 5HT and GABA

Question 53

What is a symptom of GAD? What is it common with? How is it more prevalent in and when does it often begin?

Answer 53

Excessive uncontrollable anxiety and worry Symptoms: fatigue, muscle tension, restlessness, irritability, sleep disturbances concentration problems Common co-morbidity of depression Women > Men; Onset often begins in childhood or adolescence Symptoms exacerbated by stress and can wax and wane throughout a person’ life

Question 54

What is Panic Disorder?

Answer 54

Characterized by repeated and unexpected panic attacks along with worry about future attacks Symptoms of panic attack are similar to those of heart attack and include chest pains, rapid heartbeat, shortness of breath, dizziness, etc. Anxiety sensitivity

Question 55

What is a Phobia?

Answer 55

An unreasonable or excessive fear of an object, situation, or activity Three broad categories: Agoraphobia: fearful of a public place or being outside of the home to the extent that a panic attack or extreme embarrassment is possible Social phobia: a fear of social activity, especially of being scrutinized and embarrassed Specific phobias: exaggerated fear of specific objects/situations not covered by the other two

Question 56

What are risk factors of anxiety disorders?

Answer 56

Genetics Meta-analysis: heritability of 31.6%; 2x more likely to develop GAD if parent has diagnosis Candidate genes that code for the monoaminergic system Personality trait neuroticism, high stress sensitivity Childhood maltreatment Chronic or Traumatic Stress

Question 57

What parts of the brain have increased activation in people with anxiety disorders?

Answer 57

Increased activation of amygdala and decreased activation of prefrontal cortex (PFC) while looking at angry faces In healthy controls, vmPFC decreases activation of amygdala, but not in persons with anxiety High levels of anxiety correlates with increased activation of amygdala, insular cortex and anterior cingulate cortex In anticipation of phobia-related stimuli, patients with specific phobia display enhance activation of the BNST(anticipation of something harming you), ACC(emotion regulation), and insula compared with non-phobia controls (Straube et al. 2007)

Question 58

What is OCD?

Answer 58

Obsessions: thoughts, images, or impulses that are intrusive enough to cause marked rise in anxiety Compulsions: ritualistic behaviours or mental acts that are designed to lower anxiety Usually begins at ages 6-15 for females and 20-29 for males

Question 59

What parts of the brain are connected to people with OCD?

Answer 59

``` Orbitofrontal cortex Anterior Cingulate Cortex (ACC) Caudate Nucleus (Basal Ganglia) Important for how the brain learns Cortico-basal ganglia-thalamo-cortical (BGTC) loop Similar to other movement disorders, PD and HD Learned behaviour that is motor Dysfunction in 5HT and DA system ```

Question 60

What is PTSD?

Answer 60

Post-traumatic stress disorder (PTSD) occurs in some people after terrifying experiences and includes the following symptoms: Frequent distressing recollections Nightmares Avoidance of reminders of the event Exaggerated arousal in response to noises and other stimuli

Question 61

What is a treatment used for OCD?

Answer 61

SSRIs | drugs that increase dopamine, minimized symptoms of OCD

Question 62

What parts of the brain are effected in those with PTSD?

Answer 62

The amygdala is essential for the extreme emotional impact that produces PTSD Dysregulation of HPA-axis: Lower than normal cortisol levels and blunted cortisol response to acute stressor Smaller than average hippocampus

Question 63

What happened in the Gilbertson et al. 2002: Chicken or Egg, veteran twin study.

Answer 63

Is it that PTSD leads to shrinking of the hippocampus or did they begin with smaller hippocampus’ Looks at veteran twins, one twin went ot war the other twin did not. Some vets reports PTSD. MZ twins, brain would be similar. Results: going to war with a small hippocampus increases the risk of developing PTSD

Question 64

Briefly state the connection between stress and the brain.

Answer 64

Predisposition to increase stress reactivity - genetics/heredity (e.g., 5HT transporter gene) - personality traits (e.g., neuroticism, very stress reactive) - neurodevelopment (e.g., HCV) Environmental challenges Chronic activation of the stress response Allostatic Load (wear and tear of our interconnected biological systems, fight or flight) Wiring the brain/building circuitry factors that make up our entire and how is that supporting to damaging your wellness

Question 65

What Human studies show the mutations of DISC1 protein in people with Schizophrenia?

Answer 65

High prevalence of “broken copy” in large Scottish family over 5 generations - development of schizophrenia, bipolar & other mood disorders (St. Clair et al, 1990) Meta-analysis confirmed overall association and found strongest estimate in Chinese population (Wang et al., 2018)