Depression (wk 6)

Question 1

delusion

Answer 1

A belief that is clearly false and indicates an abnormality in content of thought
False belief cannot be explained by the person’s cultural or religious background or intelligence level
Belief is held despite being presented with evidence against it (“fixed” – firmly maintained)
Patient is convinced the delusion is real

Question 2

causes of delusion

Answer 2

Can be due to: mental disorder, neurological or medical disorder

Examples: schizophrenic, substance abuse, bipolar disorder, major depressive disorder (MDD), delirium and dementia

Question 3

hallucination

Answer 3

“A sensory perception in the absence of a corresponding external or somatic stimulus and described according to the sensory domain in which it occurs”
Not under voluntary control
Vivid, clear, full force and impact of normal perceptions
Visual, auditory, tactile, olfactory, gustatory, nociceptive, thermoceptive, proprioceptive, equilibrioceptive
Formed (i.e. voice making a command) or unformed (i.e. non- specific sound)
With insight – px is aware that its not real only hallucination OR without insight – px is unaware and accepts the experience as reality

Question 4

hallucination vs delusion vs psychosis

Answer 4

hallucination: “A sensory perception in the absence of a corresponding external or somatic stimulus and described according to the sensory domain in which it occurs”

delusion: A belief that is clearly false and indicates an abnormality in content of thought

psychosis: Hallucination (without insight), delusion OR hallucination (without insight) and delusion

Question 5

psychosis

Answer 5

Hallucination (without insight), delusion OR hallucination (without insight) and delusion
Loss of contact with external reality
Central component: Impaired reality testing
Can occur in psychiatric and neurological disorders Additionally:
Disorganized thoughts and impairment in cognitive function (i.e. reduced verbal fluency)
Mood changes
Reduced attention and concentration Sleep disturbances

Question 6

what is the central component in psychosis?

Answer 6

impaired reality testing

Question 7

delirium

Answer 7

Acute, fluctuating change in attention (reduced) and consciousness including disorganized thoughts
Altered consciousness: hypervigilant, unresponsive, near-coma, severe agitation
May include: psychosis; delusions and hallucinations, altered mood

Question 8

how long does delirium last and what is it triggered by

Answer 8

Can vary in duration: days (typically) or months
Triggered by: change in medication, infection, surgery, trauma, stroke, withdrawal, very extensive list

Question 9

depressive episode

Answer 9

Experience of low or depressed mood Loss of interest in most activities Additional possible symptoms:
Fatigue
Changes in appetite (and weight)
Feelings of worthlessness
Recurrent thoughts of death
Unexplained physical ailments unresponsive to treatment (i.e. digestive problems, pain)

can be seen in MDD< anxiety, bipolar, schizo, post stroke..

Question 10

mania

Answer 10

Characteristics: increased talkativeness, rapid speech, decreased need for sleep, racing thoughts, distractibility, increase in goal-direct activity, psychomotor agitation
May include: elevated mood, mood lability, impulsivity, irritability, grandiosity

seen in bipolar, meds or substance, brain tumor

Question 11

how long must mania last vs hypomania

Answer 11

Duration: 1 week or more OR if severity of symptoms warrants hospitalization

hypomania is 4 days

Question 12

main dif between mania and hypomania

Answer 12

Differentiating factors from mania:
Duration: at least 4 days (rather than at least 1 week)
Does NOT cause major deficit in social or occupational functioning

Conditions: bipolar disorder, substances, neurological causes (i.e. encephalitis, dementia, lupus)

Question 13

MDD risk factors

Answer 13

trauma, chronic pain or chronic disorders, low income, family history

Question 14

mood physical and cognitive symptoms of MDD

Answer 14

Mood Symptoms
Physical Sx
Cognitive Sx
Feeling sad/ low
Lack of energy / tired
Slow thinking
Lack of interest in general
Difficulty sleeping; waking early
Difficulty concentrating
Anhedonia
Restless/ agitated
Slow movement
Low self-esteem
Weight loss
Forgetfulness
Lacking confidence
Low libido
Difficulty planning
Feelings of guilt or worthlessness
Low appetite/ overeating
Difficulty making decisions
Suicidal thoughts

Question 15

which 2 components must be included in MDD

Answer 15

Depressed mood (subject report of observations of others) Anhedonia – loss of interest/ pleasure in almost all activities

These 2 sx must be present most of day, every day for at least 2 weeks in a row

Question 16

how many symptoms for MDD total

Answer 16

at least 5ot

Question 17

components of MDD

Answer 17

Category A – must include the first two components and a total of 5 or more components:
Depressed mood (subject report of observations of others) Anhedonia – loss of interest/ pleasure in almost all activities
These 2 sx must be present most of day, every day for at least 2 weeks in a row

Unintentional weight loss or gain (>5% in 1 mo) or significant change in appetite
Sleep disturbance (insomnia/ hypersomnia)
Psychomotor changes (agitations/ retardation)
Fatigue, low energy, decreased efficiency with routine tasks
Sense of worthlessness or excessive/ inappropriate guilt (i.e. guilt about being sick)
Impaired ability to think/ concentrate/ make decisions Recurrent thoughts of death, suicide ideation or attempts

Additional diagnostic requirements:
These sx must cause significant distress OR impair social, occupational or other important areas of function
Sx are not due to direct physiological effects of a substance (i.e. meds, drug abuse) OR medical condition (i.e. hypothyroidism)
Px has never experienced a manic or hypomanic episode
This condition is not better explained by schizophrenia spectrum or other psychotic disorders

Question 18

leading theories of MDD

Answer 18

Monoamine hypothesis
Stress-induced depression hypothesis
Neurotrophic / Neuroplasticity hypothesis
Cytokine hypothesis/ Neuroinflammation hypothesis Circadian hypothesis of depression GABA-glutamate-mediated depression hypothesis

Question 19

monoamine hypothesis of depression

what is it based on

Answer 19

Altered levels of monoamine neurotransmitters, specifically serotonin and noradrenaline, and/or dopamine cause depression

Based on antidepressant therapies that increase the presence/ function of one or more neurotransmitter resulting in reduced depression

Critiqued in that abruptly decreasing serotonin and/or dopamine doesn’t cause depression in a healthy person

Other neurochemicals are implicated in depression beyond these

Probable causes: genetics, environment, stress

Question 20

stress induced depression hypothesis

which system on the body is impacted

Answer 20

HPA axis

Question 21

stress induced depression hypothesis

Answer 21

Chronic stress leads to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis
Prolonged, moderate stress is the problems, versus minor daily stresses OR one strong stressor
Examples: maternal stress, maternal smoking, early grave loss, child abuse
Early trauma may have more sig impact than in adult life (impact how HPA is developed in utero)
Chronic HPA activation leading to: excess cortisol secretion and pro-inflammatory agents that damage glia and neurons, interfere with neurogenesis and reduce glutamate and GABA

Clinical studies support this in some patients with severe depression: measurable increase in cortisol which is not reduced through negative feedback (also increased CRH)
Resistance of the glucocorticoid receptor (GR)
Antidepressants appear to restore the functioning of the GR and thus improve negative feedback and normalize cortisol levels
Critique: hypercortisolism is not a feature of all MDD cases AND not clear what causes HPA dysregulation (i.e. loss of GR sensitivity)

Question 22

what does chronic HPA acitvation cause

Answer 22

excess cortisol secretion and pro-inflammatory agents that damage glia and neurons, interfere with neurogenesis and reduce glutamate and GABA

Question 23

which receptor does cortisol bind to

Answer 23

glucocorticoid receptor –> for stress induced depression hypothesis and HPA dysregulation

Question 24

what factor promotes neurogenesis

Answer 24

BDNFn

Question 25

neurotrophic and neuroplasticity hypothesis of depression

Answer 25

Brain-derived neurotrophic factor (BDNF) promotes neurogenesis, regulates differentiation and growth of neurons Neurogenesis may offer resilience against stress by enhancing the negative feedback loop with HPA Observations: Decreased BDNF gene expression, decreased BDNF levels and receptors in MDD patients Increased cortisol can inhibit BDNF Same triggers that elevated cortisol appear to block neurogenesis Antidepressants Have been demonstrated to stimulate neurogenesis in adult hippocampus (animal studies) – takes 4 weeks Correlates with the 3-4 week expectation of achieve improvement in mood

Question 26

which pro inflammatory markers are increased in MDD

Answer 26

TNFalpha, IL6, IL1, CRP, macrophage /monocyte activation

Question 27

cytokine and neuroinflammation hypothesis

Answer 27

MDD px have increased levels of pro-inflammatory markers: TNFalpha, IL-1, IL-6, C-reactive protein (CRP) vs healthy px, as well as increased level of macrophage/monocyte activation Frequent correlation b/w MDD and inflammatory conditions such as asthma, diabetes, arthritis, obesity, CAD Animal studies: injecting pro-inflammatory cytokines induces depressive sx Some antidepressants have anti-inflammatory properties Earlier case reports observed improvement in mood in patients with treatment resistant MDD treated with anti- inflammatory medications, particularly in context of other inflammatory conditions (like IBD)

Question 28

what produces melatonin and what regulated melatonin and what inhibits the production of melatonin

Answer 28

Light inhibits pineal gland from producing melatonin (by activating neurons with suprachiasmatic nucleus (SNC) of the hypothalamus) SCN regulates production of melatonin throughout the body Melatonin production increases at night during conditions of dark

Question 29

circadian hypothesis of MDD

Answer 29

Stressful events lead to changes in diurnal molecular rhythms in cells that in vulnerable px triggers MDD Bidirectional link with sleep disturbance and depression Insomnia is a predisposing factor Sleep deprivation therapy – reduces MDD sx (may resent the circadian clock) Genes controlling circadian rhythms in anterior cingulate cortex are dysregulated in depression Phase advance in cortisol rhythm and reduced amount of melatonin production seen in some patients with MDD Altered circadian rhythms can also affect reward systems, particularly social interaction Same 5-HT receptors have been implicated in both sleep rhythms and depression; serotonin is involved in phosphorylation of CLOCK protein, which regulate suprachiasmatic circadian rhythms Sleep disturbances have also been correlated with pro- inflammatory cytokines

Question 30

what excitatory neurotransmitter has a hypothesis for MDD

Answer 30

glutamate

Question 31

excitatory neurotransmitter hypothesis of MDD

Answer 31

Glutamate may cause excitotoxicity resulting in neuronal atrophy and reduced synaptic connectivity Stress induced changes may be accelerated in the presence of elevated Glu Reduced GABA in CSF of MDD px – may be d/t change in serotonin which modulates GABA, which in turn modulates glutamate Reduced GABA and glutamate within glial cells and neurons of the prefrontal cortex (PFC) Astrocytes recycle glutamate and transport to presynaptic neurons Elevated metabolism of glucose within same areas of PFC, and reduction of the gray matter in this region Ketamine – modulates glutamate transmission Approved for tx of treatment resistant MDD

Question 32

what drug modulate glutamate

Answer 32

ketamine

Question 33

too much glutamate.....

Answer 33

fries the brain circuitry

Question 34

glutamate hypotheiss

Answer 34

Excessive accumulation of glutamate within synaptic cleft results in over stimulation of postsynaptic glutamate receptors Via NMDA receptor glutamate promotes calcium influx increased calcium in the cytosol can cause necrosis via NOS, ROS, pore in mitochondria so cant make ATP

Question 35

clinical features of bipolar

Answer 35

Mania Hypomania Depression (most of time spent in depressive state) Cyclical changes between these states a common to be part of the disorder Manic psychosis, which may include delirium

Question 36

bipolar 1 vs bipolar 2

Answer 36

Bipolar 1 At least 1 manic episode and usually depressive episodes Bipolar 2 Major depressive episodes with at least 1 hypomanic episode

Question 37

what's more severe bipolar 1 or 2

Answer 37

1 (mania)

Question 38

what must you exclude when diagnosis bipolar

Answer 38

Exclusion of hyperthyroidism (TSH and T4) Exclusion of stimulant drug abuse (blood/urine)

Question 39

how many mania symptoms does bipolar 1

Answer 39

3+

Question 40

DSM5 of bipolar

Answer 40

At least 1 episode of mania/hypomania lasting for at least 4 consecutive days AND be present most of the day, almost every day 3 or more symptoms (representing sig change from norm) of mania Cause significant impairment or necessitates hospitalization

Question 41

symptoms of mania

Answer 41

Inflated self-esteem or grandiosity Decreased need for sleep (feels rested after 3 hours of sleep) More talkative than usual or pressure to keep talking Flight of ideas or subjective experience that thoughts are racing Distractibility (i.e. attention too easily drawn to unimportant / external stimuli) Increase in goal-directed activity (purposeful) or psychomotor agitation (purposeless) Excessive involvement in activities that have a high potential for painful consequences (i.e. foolish business investments, unrestrained buying sprees)

Question 42

bipolar 2

Answer 42

No/never experienced episode of mania Exclusion of/ not better explained by: schizophrenia, delusional or psychotic disorder or unspecified schizophrenia spectrum Clinically significant distress from symptoms Hypomania episode

Question 43

hypomania episode DSM5

Answer 43

Elevated, expansive or irritable mood with persistently increased activity or energy; 4+ days, most of the day, nearly every day 3 or more additional mania symptoms Episode is different from px regular non symptomatic experience Observes can note change in mood and function Not severe enough to impair functioning or necessitate hospitalization (no psychotic features) Episode is not triggered by substance (drug, medication, other treatment)

Question 44

4 theories of bipolar

Answer 44

Circadian Rhythm Dysfunction Metabolic Dysfunction Mitochondria Dysfunction Glutamate Excitotoxicity

Question 45

bipolar disorder; what changes in sleep hormones and genes that are related to circadian rhythm?

Answer 45

melatonin, cortisol, CLOCK genes

Question 46

circadian rhythm dysfunction in bipolar

Answer 46

During mania there is a reduced need for sleep Observations in patients with bipolar disorders: Changes in melatonin levels Changes in melatonin receptor expression with CNS Changes in cortisol profiles (patterns of release) Sleep deprivation as well as light therapy have been effective as adjunct in some cases of bipolar disorder Correlation between polymorphism in CLOCK genes as well as positive response to lithium therapy (common drug used in bipolar management)

Question 47

what metabolic dysfunction can be sen in bipolar? which hormonee increases?

Answer 47

leptin; obesity, T2D

Question 48

metabolic dysfunction in bipolar dirsoder

Answer 48

Various metabolic abnormalities have been found in patients with bipolar disorder such as: Increased risk of obesity, type 2 diabetes, and reduced longevity due to increased cardiovascular problems Increased amount of leptin secreted in obese patients with bipolar compared to obesity alone Leptin regulated appetite AND sleep duration A hypothesis suggests that the body is forced to compensate for the high metabolic demand of the brain during manic states: Reduced appetite Reduced sleep Increased energy expenditur

Question 49

in bipolar disorder which metabolic pathway gets shifted to due to mitochondrial dysfunction

Answer 49

glycolysis mitochondria uses ETC and Krebs cycles to make lots of ATP but then glycolysis makes way less ATP

Question 50

mitochondrial dysfunction in bipolar disorder

Answer 50

Impairment in mitochondrial function resulting brain metabolism shifting towards glycolysis Observations: Polymorphisms within mitochondrial DNA linked to BD Reduced levels of phosphocreatine within frontal cortex. Phosphocreatine is a reserve for ATP and this implied chronic deficiency in ATP synthesis Evidence of impaired oxidative phosphorylation Increased amounts of alpha-ketoglutarate and pyruvate –review: how do these substrates relate to ATP production? Reduced expression of genes coding for various complexes of the electron transport chain in hippocampus

Question 51

what excitatory neurotransmitter can be increased in bipolar and in which region of the brain

Answer 51

glutamate in frontal cortex

Question 52

glutamate excitotoxicity in bipolar

Answer 52

Observation: increased glutamate in frontal cortex of px with BD Mood stabilizers appear to return glutamate levels to normal Increased levels of excitatory glutamate appear to result an increased energy demand on the neuron Increased glucose consumption in areas of high glutamate synaptic activity Hypothesis: increased shift to glycolysis may be due to increased glutamate stimulation

Question 53

what do neutotramsitters do in depression

Answer 53

low levels of neurotransmitters lead to receptor upregulation

Question 54

what is an antidepressetn action

Answer 54

reuptake inhibitor; increase levels of neurotransmitters at the synapse

Question 55

what is a delayed effect on antidepressants

Answer 55

down regulation of neurotransmitter receptors § Could explain time needed to see antidepressant effects § The 5HT1a receptors are autoreceptors – they inhibit release of NT from presynaptic terminals * If they’re down-regulatedàincreased NT release § Sustained antidepressant therapy is also associated with increased production of BDNF, which is likely linked to efficacy

Question 56

antidepressant suciide risk

Answer 56

increased suicide risk in children, adolescents and young adults upto 24 years of age when taking antidepressants.

Question 57

SNRIs examples

Answer 57

1. TCAs; amitriptyline 2. venlafaxine “-triptyline” suffix = TCA

Question 58

SSRI examples

Answer 58

fluoxetine “-oxetine” suffix = SSRI

Question 59

other antidepressants

Answer 59

-MAOIs -trazodone -bupropion (Wellbutrin and zyban)

Question 60

why are there adverse effects of TCAs

Answer 60

Many are due to non-therapeutic block of M, alpha 1 and H1 receptors

Question 61

muscarinin receptors

Answer 61

in brainstem or spinal cord, parasympathetic, bound by acetylcholine acts on heart, small muscle, glands

Question 62

alpha 1 receptors

Answer 62

spinal cord, sympathetic, acetylcholine, epinephrin and norepinephrine act of heart, small muscles, glands

Question 63

adverse effets of blocking M receptors (via TCAs)

Answer 63

salivary glands= dry mouth intestine= constipation bladder= urinary retention pupil= dilated

Question 64

advers effects on blocking alpha 1 receptors

Answer 64

vasodilation

Question 65

H1 receptors role

Answer 65

mediate feeding and part of sleep wake cycle

Question 66

effects of blocking M, alpha 1, and H1 receptors

Answer 66

* M-block § Dry mouth § Constipation § Urinary retention § Mydriasis § Blurred vision § Confusion Alpha 1-block Orthostatic hypotension Sedation Sexual dysfunction H1-block Weight gain Sedation/ drowsiness

Question 67

other adverse effects of TCAs

Answer 67

Adverse effects not fully explained by M-, alpha 1 - and H1-blocks are: § Sexual dysfunction * Caused by serotonin acting at 5-HT2a receptors § Antidepressant effect of serotonin is via 5-HT1a receptors § Weight gain * Could also be due to remission of depression and/or direct stimulation of appetite

Question 68

TCA overdose can lead to?

Answer 68

cardiac arythmias alpha 1 and muscarinic receptors cause vasodilation

Question 69

venlafaxine (SNRI) what does it act on

Answer 69

serotonin and norepinephrine § Also weakly inhibits dopamine reuptake § No significant alpha 1, H1 or M-block * Less likely to cause related adverse effects, including sexual dysfunction and weight gain (may cause weight loss)

Question 70

which SNRI has more adverse side effects; TCA or venlafaxine

Answer 70

TCA

Question 71

SSRI adverse effects

Answer 71

* Adverse effects often related to M, α1, H1-block § Receptor blocks less potent than with TCA’s, related adverse effects typically more mild * Exception: sexual dysfunction is typically worse § What is the role of serotonin? § Additional NO (vasodilator) synthesis block * Weight disturbances can include weight loss § Transient, followed by potential long-term weight gain * Does not have the same cardiotoxicity as TCA’s § Does have the potential for serotonin syndrome

Question 72

serotonin syndrome

Answer 72

from increased serotonin from SSRIs agitation sweat, hot fast heart rate, high blood pressure hyperreflexia and clonus

Question 73

what to give to help with serotonin syndrome

Answer 73

cyproheptadine to interfere with serotonin action or symptomatic treatment; treat agitation with benzodiazepines

Question 74

MAOIs mechanism; what neurotransmitter

Answer 74

§ Block monoamine oxidase, the enzyme that metabolizes NE, resulting in higher NE levels

Question 75

if you combine MAOIs with foods containing tyramine what could happen

Answer 75

hypertensive crisis tyramine has synergistic effect on NE levels

Question 76

trazodone acts on which neurotransmitter and which receptors does it block and can cause adverse effets

Answer 76

serotonin H1 and Alpha 1 receptors § Inhibits serotonin reuptake, but not considered an SSRI * Also acts directly as an antagonist at serotonin 5-HT2A receptors § What is the benefit of this antagonist action? § Adverse effects * H1-block and potent alpha 1 block effects § Strong sedative effects * May be useful for patients with anxiety, or for helping with sleep patterns of depressed patients * Weight gain tends to be minimal

Question 77

what are the 2 brands of bupropion and their uses

Answer 77

§ Wellbutrin = antidepressant § Zyban = smoking cessation therapy

Question 78

wellbrutin use

Answer 78

antidepressant

Question 79

zyban use

Answer 79

smoking cessationm

Question 80

mechanism of action of bupropion

Answer 80

weak inhibition of NE and dopamine reupaake

Question 81

adverse effects of bupropion

Answer 81

dose related seizure risk