Exam 4 - Affective disorders Flashcards
DSM criteria for diagnosis of depression:
- must experience at least 5 of these symptoms for 2 weeks
- depressed/irritable mood
- diminished interest and pleasure in activities
- change in appetite and weight
- insomnia/hypersomnia
- motor agitation or retardation
- fatigue/diminished energy
- diminished ability to think
- helplessness/worthlessness/guilt
- thoughts of suicide/attempted suicide
Do genetics predispose an individual to depression, what about psychosocial factors? What is the rate for twins?
yes to both, 65%
Monoamine hypothesis
- abnormalities (low levels) in the serotonergic and/or noradrenergic systems underline severe depression
- drugs that deplete NT availability could cause symptoms
Neurotrophic hypothesis
- stress-induced hippocampal cell loss caused by deficits in neurotrophics (important for brain development and survival of neurons)
BDNF (brain-derived neurotrophic factor) levels are _____ in depressed pts
low
The neurotrophic hypothesis proposes that:
stress -> increased glucocorticoids -> decreased BDNF -> atrophy of neurons, increased vulnerability
Hypothalamic pituitary axis
- physiological stress response
- depressed pts have:
- elevated cortisol
- hypersecretion of ACTH
- abnormal circadian rhythm
- failure to respond to dexamethasone challenge (artificial cortisol given, and pt responds negatively by releasing even more cortisol)
How does depression alter sleep?
- long period before onset
- decrease in slow-wave sleep
- REM sleep occurs earlier
- skip phase 3&4 (slow-wave) of sleep, results in decreased restorative sleep
- increase in actual eye movements during REM
What is the animal model for depression?
- forced swim test: put mice in small container filled with water, depressed rats will swim around until they realize that there is no way out, and will just float (learned helplessness)
What are the affects of antidepressants on serotonergic cells?
- increase the amount of serotonin by blocking reuptake at the synaptic cleft
- can cause the downregulation of serotonin autoreceptors over time
Tricyclic antidepressants
- relieve symptoms of depression and have anxiolytic and analgesic actions
- half life - 7-28 hours, takes couple of weeks to show results
- originally released to treat schizophrenia
What is the mechanism of action of tricyclic antidepressants?
- block presynaptic norepi reuptake transporter
- block presynaptic serotonin reuptake transporter
- block postsynaptic histamine receptors
- block postsynaptic ACH receptors
- block postsynaptic norepi receptors
Side effects of tricyclic antidepressants
- drowsiness and sedation (blockage of histamine receptors)
- confusion, memory/cognitive impairments, dry mouth, blurred vision, increased HR and urinary retention (blockage of ACH receptors)
- blood pressure effects, can lead to seizures (blockage of norepi receptors)
Monoamine oxidase inhibitors (MAOIS)
- regulates amount of serotonin, dopamine, norepi.
- blockage causes NT buildup in terminals
- originally released to treat TB
Side effects of MAOIS
- potentially fatal interactions w/ other medications (nasal sprays w/ adrenaline, antiasthma, cold medications, foods that include tyramine like cheese/wines/beans)
SSRIs
- works on all serotonin receptors, inhibits reuptake
- prozac
- less side effects b/c it only acts on serotonin
Side effects of SSRIs
- sexual dysfunction in males, decreased libido, agitation
- serotonin syndrome
- increased risk of suicide ideation and suicidality in children and adolescents
- decreased appetite, insomnia, agitation
Serotonin syndrome
caused by taking medications or eating foods w/ serotonin in them and SSRIs, have too much serotonin in the body
- disorientation/confusion, seizures, manic episodes, sensory (visual) disturbances
Serotonin discontinuation syndrome
- occurs after abrupt cessation of SSRIs, pts must be weaned off of SSRIs to avoid this condition
- persists for 3-4 weeks
- disequilibria, GI symptoms (nausea, vomiting, diarrhea), flu-like symptoms, sensory disturbances
Serotonin-norepi reuptake inhibitors SNRIs
- blocks reuptake of serotonin and norepi
- dual action is to evade receptor effects
Atypical antidepressants
not acting on only serotonin
How effective are antidepressants?
- 40% of pts will not respond to initial treatment, but do eventually, and effectiveness can diminish over time
- many placebo-treated pts improve throughout their initial treatment period
Bipolar disorder
presence of depressive and manic/hypomanic episodes
- BPD1: manic and depressive episodes
- BPD2: hypomanic and depressive episodes
- exhibited for at least 4 days-1weeks
Manic episodes can also be characterized by ___________ features like:
psychotic
- delusional beliefs and hallucinations
Diagnostic criteria for manic episodes
- abnormally elevated, expansive, or irritable mood lasting at least one week
- inflated self-esteem or grandiostiy, excessive talking, racing thoughts or ideas, excessive involvement in pleasurable activities
Genetic determination of BPD
70% chance w/ identical twins
- occur more frequently when theres family history
Anatomical determinants of BPD
- significantly enlarged lateral ventricles
- decreased levels of BDNF
- atrophy in certain areas of brain
- low serotonin and noerpi
Lithium
- mood stabilizer
- easily absorbed into blood stream but crosses BBB slower
- not metabolized by liver or kidneys
- MOA:
- can cause weight gain, kidney dysfunction, can increase serotonin and BDNF
Valproic acid
- anticonvulsant used to treat seizure disorders, acute mania, and migraine headaches
- stimulates BDNF and works on GABA and dopamine (major inhibitory NT)
Gabapentin
- popular alternative to valproic acid and lithium for the treatment of mania
- designed to structurally and functionally mimic GABA
