Neurobiology of mood disorders Flashcards
What are some appetitive/approach systems in the brain and what is their function?
Function: seeking/approach behavior
- ascending dopamine systems (mesolimbic/cortical projections)
- ventral striatum
- dorsal striatum (movement)
- amygdala (conditioning/learning)
- anterior cingulate (attention/conflict/response selection)
- orbitofrontal cortex (relative reward preference/rule learning)
What are some aversive/defensive systems in the brain and what is their function
Function: promote survival in event of threat (fear/pain)
- ascending serotonin systems
- Na/CRT/Peptide transmitters
- central nucleus of amygdala
- hippocampus
- ventroanterior and medial hypothalamus
- periaqueductal gray matter
Describe what happens when there’s disordered appetitive functioning in depression?
difficulty identifying rewarding stimuli
= decreased contact with previously rewarding stimuli = increased contact with adversive stimuli = overall reduction behavior
= move less/ eat less/ lose weight/ less sexual behavior
= inactivity/anhedonia/wt change/loss libido
Describe what happens when there’s disordered appetitive functioning in (hypo)mania?
Previously neutral stimuli become rewarding
=increase in exploration/overall activity
= increased appetite for food/sex/activity
= intolerant to boredom/aversion/frustration
leads to
=increased interest distractability
= overactivity/lose need for sleep/disinhibition/risk taking/poor judgement/irritability/dysphoria
describe the familial factors of depression
increase risk if 1st deg. relative has MDD (3X) or BPD (2X)
heritabilitiy of MDD 70%
How do life events impact on depression
Onset 1st episode assoc. with excess of adverse life events
exit events - losses/separations
adverse early experiences increase risk MDD
Describe the assoc. of childbirth and depression
7X risk psych. admission in the first 30days following childbirth (no assoc. with hormonal change ever demonstrated)
75% women experience ‘blues’ within 2 weeks
10% women develop MDD within 3-6mths
puerperal psychosis - 1/500 deliveries with risk recurrence 1-3 with subsequent deliveries
Describe how the serotonin transporter gene is implicated in depression
5-HTT gene
-implicated to moderate effect of life stress on depression
(if have 2 short alleles = increases chance of having MDD after 2+ major stressful life events)
-implicated to moderate probability of having major depressive episode after maltreatment in childhood
Describe the changes in the H-P axis for cortisol in MDD
- increase in secretion of ACTH and therefore cortisol
-level of ACTH blunted to CRH (from hypothalamus) causing enlarged adrenal glands
-50-70% pts. fail to suppress cortisol in a dexamethason suppression test
?chronic secretion of CRH from hypothalamus
Describe the changes in the HPA for thyroxine in MDD
20-30% MDD pts show some dysfunction
-increase in TRH in CSF, TSH response to TRH is blunted in 20-25% pts despite normal basal TSH,T3 and T4
?chronic secretion of TRH from hypothalamus
How does MDD affect the hippocampus
depression has a negative effect on hippocampal volume and longer duration of depression the smaller the total hippocampal volume`
what is the anterior insular cortex (AIC) - how is this related to MDD?
-this is a region of the brain that has dense connectivity with the anterior cingulate cortex (ACC) and has been long considered as a visceral sensory region
- coactivation of the ACC and the AIC during almost all studies of emotion
- they have parallel descending projections to sensory and motor nuclei in the brain stem
They have been proposed to:
-be limbic motor (ACC) and limbic sensory (AIC) cortices that cause the feeling and motivation assoc. with emotion
- in MDD cognitive and emotional functions assoc. with the AIC are adversely affected and they have decreased amounts of regional grey matter in the AIC
in MDD overall what are the main neurobiological changes
- changes in reward sensitivity
- changes in cognitive attunement
- changes in reward processing
- changes in strength of funtional connectivity
- changes in macro/micro architecture
- altered hormonal regulation
What are the main neurobiological changes in BPD?
- decrease grey matter volume/functional activity in the anterior cingulate cortex
- decreased metabolism in orbitofrontal cortex and medial ventral prefrontal cortex
- increased activity in amygdala correlates with outcome
- decreased glial cell no. with normal neuron no. in ACC and orbitofrontal cortex
