Block 4 Lecture 6 -- Depression Flashcards
Define unipolar depression.
mental disorder;
- pervasive and persistent low mood
- low self esteem
- loss of interest/self-pleasure
What are the types of unipolar depression?
1) major depressive disorder
2) persistent depressive disorder
3) psychotic depression
4) postpartum depression
5) substance- or med-induced depressive disorder
6) PMDD
7) SAD
What is persistent depressive disorder?
- depressed mood ≥ 2 years
- - episodes of major depression w/ period of less severe sxs
How effective is light therapy in SAD?
50%
What populations are most likely to get depression?
1) females
2) indians, alaskans, whites, hispanics
3) prevalence decreases with age
What are the categories of symptoms of depression?
1) psychological symptoms
2) somatic symptoms
psychological symptoms of depression:
- intense sadness, pessimistic worry, depressed mood, reduced self-esteem
- loss of interest/enjoyment
- suicidal thinking
- impaired cognition, memory
somatic symptoms of depression:
- agitation
- fatigue, loss of drive & libido
- reduced appetite, weight change
- bowel disturbances
- motor retardation
What are the theories for pathology in depression?
1) monoamine hypothesis
2) neurotrophic hypothesis
What is the monoamine hypothesis?
1) deficiency in monoamine signaling: synthesis, storage, or release
2) deficiency in monoamine signaling due to receptor insensitivity
What is the neurotrophic hypothesis?
BDNF is decreased in depression
– decreased neuronal plasticity (dendritic sprouts)
What is the function of BDNF?
regulation of…
1) neuronal plasticity
2) growth
3) resilience
4) neurogenesis
What is CREB?
cAMP response element binding protein
– yields BDNF
What substances affect [CREB]?
increased by:
- monoamines
- Glu
- BDNF
decreased by:
– glucocorticoids
What is the DSM-5 criteria for diagnosis?
5+ symptoms for 2+ weeks
How is mild-moderate depression treated?
CBT
How is MDD treated?
CBT + other things
What non-drug therapies are used for depression?
CBT
exercise, light therapy, group therapy, mediation/yoga
Why is stress implicated in depression?
yields cortisol
– decreased CREB
yields Glu
– acts on NMDAr to result in neural apoptosis
What are the strengths of the monoamine hypothesis re: receptor insensitivity?
1) chronic antidepressant administration causes change in expression/function of receptors
2) receptor plasticity correlates with time course of improvement
What are the weaknesses of the monoamine hypothesis re: receptor insensitivity?
some drugs don’t work on the monoamine system
What are the strengths of the monoamine hypothesis re: synthesis, storage, release?
1) reserpine led to depression
2) most antidepressants work on monoamines
3) studies show change in monoamine function
4) polymorphism in promoter of SERT in depression
What are the weaknesses of the monoamine hypothesis re: synthesis, storage, release?
1) neurochemical effects in 1-2 days, but improvement takes 10-21 days
2) studies show normal monoamine levels in depression
3) some drugs don’t act on monoamines
Describe effect of NE binding receptor in depression?
Gs
– increase CREB
Describe the 5-HT receptor.
Gi
- but, use PLC, IP3, PKC pathway
- yields CREB
5-HT 1A and 1B are presynaptic
Describe the NE receptors involved in monoamine antidepressant signaling.
Gs
– yield CREB
What are the strengths of the neurotrophic hypothesis?
1) antidepressant increase neurogenesis and change synaptic connectivity
2) pain, stress = decreased BDNF
3) structural changes, loss of volume observed in hippocampus
4) BDNF = antidepressant-like effects in rodents
5) BDNF gene mutation = altered anxiety and depressive behavior in animals and humans
Describe weaknesses of the neurotrophic hypothesis.
1) BDNF KO mice don’t exhibit depression/anxiety
2) increased [BDNF] in animals after social stress
What are the effects of increasing NE, 5-HT, BDNF in depression?
1) decrease detrimental gene transcription
2) increase beneficial gene transcription
- - improve neurogenesis
- - inhibit apoptosis
Depression is associated with:
1) shorter life expectancy
- - death 2x
- - suicide 26x
- - susceptibility to other infections
2) recurrence if sxs have not fully resolved (80% of MDD)
