Neurobiology of Mood Disorders Flashcards
what is the appetitive system?
reward system function is to mediate seeking and approach behaviours (including pleasure)
what does the appetitive system involve?
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 is the aversive system?
functions to promote survival in the event of fear or pain (threat)
what does the aversive system involve?
ascending serotonin systems NA/CRF/peptide transmitters central nucleus of amygdala hippocampus ventroanterior and medial hypothalamus periaqueductal grey matter
how are the systems involved in depression?
altered sensitivity/accuracy of brain systems evaluating rewards and cues predicting reward within the environment
how are the systems involved in anxiety?
altered sensitivity/accuracy of brain systems evaluating threat and cues predicting threat within the environment
how does unipolar depression progress generally across lifetime?
increases over childhood/adolescence, then decreases again, then increases as life stresses increase (job, marriage, finances etc)
why may mood disorders be recurrent through lifetime?
abnormal brain development genetic/development effects endocrine/metabolic causes adverse life events psychological resilience or lack of cultural aspects
what neurotransmitters, if deficient, may contribute to depression?
serotonin
norepinephrine
dopamine
GABA
what neurotransmitters, if in excess, may contribute to depression?
ACh
substance P
corticotrophin releasing hormone
what can low serotonin cause in depression?
decrease in receptor binding through cortical and subcortical areas
reduction in reuptake sites
5HT mediated endocrine responses are blunted
what can low norepinephrine cause in depression?
decreased neurotransmission leading to anergia, anhedonia and decreased libido
what can low dopamine cause in depression?
hypoactive D1 receptor
increased binding of D2/D3 receptors in striatal regions
consistently low CSF level of HVA
how is GABA involved in depression?
principal neurotransmitter mediating neural inhibition
reductions in GABA seen in plasma and CSF
GABA receptors upregulated by antidepressants
how is the HPA axis affected in depression?
the HPA axis is upregulated but with a down-regulation of the negative feedback controls
cortisol in chronic depression?
increased corticotropin releasing factor (CRF) secretion from hypothalamus > induces release of ACTH from pituitary > ACH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands (can also cause adrenal hypertrophy) > impaired negative feedback of cortisol to hypothalamus/immune system/pituitary > continual activation of HPA axis and excess cortisol release > cortisol receptors are desensitized > increased activity of pro-inflammatory immune mediators and disturbances in neurotransmitter transmission
release of cortisol into the circulation has what effects?
elevation of blood glucose
many others
why is treatment (e.g SSRIs) maintained for so long in depression?
serotonin is abnormal before, during and after depression episode
what is the main receptor possibly involved in low serotonin/depression?
5HT1A - plays major role in how 5HT communicates with rest of brain
how is the norepinephrine system involved in mood disorders?
seems hyperactive but since there are fewer neurones, this can lead to a deficiency in norepinephrine when overactive
- depletion of NE causes depression in recovered vulnerable/depressed people
what can cause the lower number of neurones in the norepinephrine system?
adverse childhood experience can produce an over-active responsiveness in this system that persists into adulthood?
how is the dopamine system involved in depression?
mesolimbic dopaminergic system involved in control of motivation and rewarding experiences
therefore, hypofunction of this system may cause loss of pleasure/interest which is seen in depression
how may neurotransmitters be involved in mania?
deficiency in serotonergic neurotransmission may be involved in mania and depression as it contributes to GABA deficit
- GABA deficiency may contribute to mood instability
increased NE and dopamine may also cause mania
