Neurobiology of mood disorders

Question 1

What is the function of the appetitive system?

Answer 1

Mediate seeking and approach behaviours (incl. pleasure)

Reward system

Question 2

What does the appetitive/ reward 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 function of the aversive system?

Answer 3

Promote survival in the event of threat (fear/ pain)

Question 4

What does the aversive system involve?

Answer 4

Ascending serotonin pathways
NA/CRF/ peptide transmitters
Central nucleus of amygdala 
Hippocampus
Ventral Anterior and medial hypothalamus 
Periaquaductal grey matter

Question 5

What is the main neurotransmitter involved in the aversive system?

Answer 5

Serotonin

Question 6

What is depression due to?

Answer 6

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

Question 7

What is anxiety due to?

Answer 7

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

Question 8

Why are mood disorders recurrent?

Answer 8

Abnormal brain development
Genetic and developmental effects
Endocrine/metabolic; thyroid, kidney and liver
Adverse life events; lowers resilience levels
Cultural aspect

Question 9

Which neurotransmitters are deficient in depression?

Answer 9

Serotonin
NA
Dopamine

Question 10

Which neurotransmitters are in excess in depression?

Answer 10

ACh (toxic)
Substance P
CRH; stress hormone

Question 11

What is the pathogenesis of reduced serotonin and depression?

Answer 11

Decrease in receptor binding through cortical and subcortical regions
Reduction in reuptake sites
5-HT mediated endocrine responses blunted

Question 12

What is the pathogenesis of reduced NA in depression?

Answer 12

Decreased neurotransmission (MFB) leading to anergia, anhedonia and decreased libido

Question 13

What is the pathogenesis of reduced dopamine in depression?

Answer 13

Hypoactive D1 receptor
Increased binding of D2/3 receptors in striatal regions
Consistently low CSF levels of HVA

Question 14

What is the pathogenesis of GABA in anxiety?

Answer 14

Primary neurotransmitter mediating neural inhibition
Reductions in GABA observed in plasma and CSF
GABA receptors upregulated by antidepressants

Question 15

How do benzos assist in anxiety?

Answer 15

Increase levels of GABA

Question 16

Describe the HPA axis in depression?

Answer 16

Increased CRF from hypothalamus and therefore increased ACTH from pituitary
Increased cortisol from adrenal glands (increased BG)
Impaired negative feedback to hypothalamus and pituitary and therefore continual activation of HPA axis and excess cortisol release
Cortisol receptors become desensitized leading to increased activity of pro-inflammatory immune mediators and disturbances in neurotransmitter transmission

Question 17

Describe how adverse childhood experiences impact on depression in later life?

Answer 17

Affects NA system
Adverse childhood experiences can produce an over-active responsiveness in this system that persists into adulthood
In situations that most people find unstressful, the vulnerable depression individual depletes NA = depression

Question 18

Which receptor for serotonin is implicated in depression?

Answer 18

5HT1A

Question 19

Which system is dopamine involved in?

Answer 19

Mesolimbic; control of motivation and rewarding experiences

Question 20

Which neurotransmitter is involved in bipolar disorder?

Answer 20

Deficient serotonergic neurotransmission in mania and depression
Contributed to GABA deficit

Question 21

Are there physical changes in a chronically depressed brain?

Answer 21

Yes; reduced blood flow to frontal lobes

Question 22

What nT is implicated in the appetitive system?

Answer 22

Dopamine

Question 23

What nT is implicated in the aversive system?

Answer 23

5-HT