What are DSM diagnostic criteria for major depressive disorder?
must have depressed mood OR anhedonia must cause significant distress or impairment and there has never been manic episode 5 or more of the following for > 2 wks - depressed mood - anhedonia = lack of interest - sleep disturbance = in/hypersomnia - change in appetite - low energy - psychomotor agitation or retardation - impaired concentration - guilty feeling/self blame - suicidal/thoughts of death
What is prevalence of major depressive disorder [MDD]?
~15% across different populations
more in women [1 in 4] than men [1 in 8]
pre-pubertal = equal men to women
What is course of MDD?
- may be triggered by event or may have no trigger
- untreated episode lasts 6-13 mo
- treated lasts 3 mo
- chronic with relapses
What percent of untreated MDD attempt suicide?
30%
What are the 4 theories of depression etiology?
- psychodynamic
- cognitive
- neurobiological
- genetics
What is the psychodynamic theory of MDD?
by freud
- depression linked to real or imagined loss of a loved object and resulting damaged self esteem and unresolved conflict
- can be seen as anger turned inward
goal of treatment = promote symptom relief and personality change through understanding of unconscious conlifcts
What is the cognitive theory of depression?
by Aaron beck
- depression from specific cognitive distortions
- cognitive triad
- — negative views of self
- — negative views of environment
- — negative views of future
What are the neurobiological theories of MDD?
many theories from molecular and cellular level to whole brain imaging/neuro circuitry level
- MOA [DA/5HT/NE] deficiency
- glutamate dysregulation [excess glu]
- neuroendocrine [HPA] dysregulation
- structural and functional brain changes
- neuropathological changes
- impairments in neuroplasticity
What is the MOA deficiency hypothesis of depression?
depression is result of deficiecny of MOAs [5HT, DA, NE]
proof: early antidepressants blocked reuptake or degradation 5HT/NE
reality: its a more complicated picture
What is the AA NT system dysregulation theory of depression?
- chronic stress –> excess glutamate
- hyperactivation of NMDA glu receptors –> atrophy and death of neurons/glial cells
treat by ketamine = NMDA antagonist
What is the neuroendocrine dysregulation theory of depression?
- increased cortisol, CRF
- lack of normal cortisol suppression when given dexamethasone suppression test [DST]
- less negative feedback sensitivity
- less glucocorticoid receptor sensitivity
- hippocampus damaged
problem with this theory = no evidence of HPA dysfunction in many pts
hypercholesterolemia may be associated with very severe depression only
What are structural and functional brain changes thought to cause depression?
reduced volume in all the following areas plus:
reduced activity in:
- dlPFC = decision making, judgement
- ACC = motivation, reward, empathy
increased activity in:
- OFC = socially appropriate behavior
- amygdala = memory of emotional events
dlPFC + hippo = cognitive aspects of depression
lack of cortical regulation of limbic system
What neuropathological changes associated with depression?
- reduction glial cell density + number [maybe due to glu toxicity from stress]
What impairments in neuroplasticity associated with depression?
- decrease neurotropic factors
- subsequent failure of neuronal plasticity
decreased BDNF in depressive; inverse correlation level of BDNF and sensitivity to stress in healthy people
What is role of brain derived neurotrophic factor [BDNF]?
imp for axonal growth, neuronal survival, allowing changes in synapses between neurons throughout life
levels of BDNF affected by stress and cortical
What is the final common path for all effective therapies?
enhancement in neural plasticity and cellular resilience
What are genetics of depression?
- heritability
- no single depression gene = multiple genes combined with environmental causes
What is the gene/environment interaction of 5HT transporter gene in depression?
carriers of short allele of 5HT transporter gene can make vulnerable to depression under stress
What is treatment for MDD?
medications like SSRIs, tricyclic antidepressants, MOA inhibitors
psychotherapy
ECT therapy
vagal nerve stimulation
What are diagnostic criteria for manic episode?
- at least 1 wk abnormally and persistently elevated mood PLUS 3-4 of: - inflated self esteem/grandiosity - decreased need for sleep - more talkative - flighty ideas - distractibility - psychomotr agitation - psychotic/impaired functioning - excessive involvement in pleasurable activities with high potential for painful consequence
What are diagnostic criteria bipolar 1 disorder?
- at least 1 manic episode
typically have recurrent episodes both mania/hypomania and depression but not required for diagnosis
What is the prevalence of bipolar 1 disorder?
0.5-1%
equal in men/women
mean age onset = 18-21 yrs
What is course of bipolar disorder?
most have manias + depressions –> 10-20% ONLY manias
long term –> 15% well; 45% well but multiple relapses
more than 90% of individuals who have a single manic episode go on the have recurrent episodes
What is the neurobiology of bipolar disorder?
- dysregulation in limbic and prefrontal cortical circuitry
- HPA axis dysregulation
- decreased neuronal size and density
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