Neurobiology of Mood Disorders

Question 1

what is the appetitive system?

Answer 1

reward system
function is to mediate seeking and approach behaviours (including pleasure)

Question 2

what does the appetitive system involve?

Answer 2

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)

Question 3

what is the aversive system?

Answer 3

functions to promote survival in the event of fear or pain (threat)

Question 4

what does the aversive system involve?

Answer 4

ascending serotonin systems
NA/CRF/peptide transmitters
central nucleus of amygdala
hippocampus
ventroanterior and medial hypothalamus
periaqueductal grey matter

Question 5

how are the systems involved in depression?

Answer 5

altered sensitivity/accuracy of brain systems evaluating rewards and cues predicting reward within the environment

Question 6

how are the systems involved in anxiety?

Answer 6

altered sensitivity/accuracy of brain systems evaluating threat and cues predicting threat within the environment

Question 7

how does unipolar depression progress generally across lifetime?

Answer 7

increases over childhood/adolescence, then decreases again, then increases as life stresses increase (job, marriage, finances etc)

Question 8

why may mood disorders be recurrent through lifetime?

Answer 8

abnormal brain development
genetic/development effects
endocrine/metabolic causes
adverse life events
psychological resilience or lack of
cultural aspects

Question 9

what neurotransmitters, if deficient, may contribute to depression?

Answer 9

serotonin
norepinephrine
dopamine
GABA

Question 10

what neurotransmitters, if in excess, may contribute to depression?

Answer 10

ACh
substance P
corticotrophin releasing hormone

Question 11

what can low serotonin cause in depression?

Answer 11

decrease in receptor binding through cortical and subcortical areas
reduction in reuptake sites
5HT mediated endocrine responses are blunted

Question 12

what can low norepinephrine cause in depression?

Answer 12

decreased neurotransmission leading to anergia, anhedonia and decreased libido

Question 13

what can low dopamine cause in depression?

Answer 13

hypoactive D1 receptor
increased binding of D2/D3 receptors in striatal regions
consistently low CSF level of HVA

Question 14

how is GABA involved in depression?

Answer 14

principal neurotransmitter mediating neural inhibition
reductions in GABA seen in plasma and CSF
GABA receptors upregulated by antidepressants

Question 15

how is the HPA axis affected in depression?

Answer 15

the HPA axis is upregulated but with a down-regulation of the negative feedback controls

Question 16

cortisol in chronic depression?

Answer 16

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

Question 17

release of cortisol into the circulation has what effects?

Answer 17

elevation of blood glucose

many others

Question 18

why is treatment (e.g SSRIs) maintained for so long in depression?

Answer 18

serotonin is abnormal before, during and after depression episode

Question 19

what is the main receptor possibly involved in low serotonin/depression?

Answer 19

5HT1A - plays major role in how 5HT communicates with rest of brain

Question 20

how is the norepinephrine system involved in mood disorders?

Answer 20

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

Question 21

what can cause the lower number of neurones in the norepinephrine system?

Answer 21

adverse childhood experience can produce an over-active responsiveness in this system that persists into adulthood?

Question 22

how is the dopamine system involved in depression?

Answer 22

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

Question 23

how may neurotransmitters be involved in mania?

Answer 23

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