Neurobiology of mood disorders Flashcards
What is the function of the appetitive system?
Mediate seeking and approach behaviours (incl. pleasure)
Reward system
What does the appetitive/ reward 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 function of the aversive system?
Promote survival in the event of threat (fear/ pain)
What does the aversive system involve?
Ascending serotonin pathways NA/CRF/ peptide transmitters Central nucleus of amygdala Hippocampus Ventral Anterior and medial hypothalamus Periaquaductal grey matter
What is the main neurotransmitter involved in the aversive system?
Serotonin
What is depression due to?
Altered sensitivity/ accuracy of brain systems evaluating rewards and cues predicting reward within the brain
What is anxiety due to?
Altered sensitivity/ accuracy of brain systems evaluating threat and cues predicting threat within the environment
Why are mood disorders recurrent?
Abnormal brain development
Genetic and developmental effects
Endocrine/metabolic; thyroid, kidney and liver
Adverse life events; lowers resilience levels
Cultural aspect
Which neurotransmitters are deficient in depression?
Serotonin
NA
Dopamine
Which neurotransmitters are in excess in depression?
ACh (toxic)
Substance P
CRH; stress hormone
What is the pathogenesis of reduced serotonin and depression?
Decrease in receptor binding through cortical and subcortical regions
Reduction in reuptake sites
5-HT mediated endocrine responses blunted
What is the pathogenesis of reduced NA in depression?
Decreased neurotransmission (MFB) leading to anergia, anhedonia and decreased libido
What is the pathogenesis of reduced dopamine in depression?
Hypoactive D1 receptor
Increased binding of D2/3 receptors in striatal regions
Consistently low CSF levels of HVA
What is the pathogenesis of GABA in anxiety?
Primary neurotransmitter mediating neural inhibition
Reductions in GABA observed in plasma and CSF
GABA receptors upregulated by antidepressants
How do benzos assist in anxiety?
Increase levels of GABA
Describe the HPA axis in depression?
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
Describe how adverse childhood experiences impact on depression in later life?
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
Which receptor for serotonin is implicated in depression?
5HT1A
Which system is dopamine involved in?
Mesolimbic; control of motivation and rewarding experiences
Which neurotransmitter is involved in bipolar disorder?
Deficient serotonergic neurotransmission in mania and depression
Contributed to GABA deficit
Are there physical changes in a chronically depressed brain?
Yes; reduced blood flow to frontal lobes
What nT is implicated in the appetitive system?
Dopamine
What nT is implicated in the aversive system?
5-HT
