Anxiety and Depression I Cellular Basis Flashcards
what occurs first? anxiety or depression
depression is predominant then anxiety/schizophrenia/bipolar disorder
major depressive disorder stats
17% prevalence 2:1 females 50% severe
slow/gradual onset
episodic disorder (chronic&recurrent)
moderate genetic disorder (30-40%) vs ASD 60-70%
comorbid (anxiety disorder/diabetes/CV diabetes) - difficult to separate anxiety and depression
criteria for major depressive disorder diagnosis
low mood (irritable)
loss of interest/pleasure (anhedonia)
anxiety stats
2:1 females
29% prevalence
acute/rapid onset (panic disorder)
episodic disorder (chronic & recurrent)
moderate genetic influence (30-40%)
comorbid with depression (differentiated by non-shared environment)
age of onset earlier for anxiety than depression
types of anxiety
GAD
panic
phobia
fear based: OCD/PTSD
anxiety diagnosis
excessive worry/anxiety
difficulties in diagnosis
diagnosis is complex because no objective biomarkers (with significant genetic overlap)
challenge: differences in patients - hard to diagnosis
nature and nurture
influence of each depends on trait/condition being studied
interplay - phenotype = genotype X environment X time
genetics
simple trait - mendelian - one change in gene causes the disorder
multiple genes affected
<0.01% contribution to overall variants
some genes are very common but have little contribution to overall effect e.g. SNP
Genome wide complex trait analysis
30-40% heritability for depression and GAD
challenge: poor replication
genes for GAD & depression could be the same distress vs fear
hypothesis: GWAS (more likely to uncover biology)
environmental challenge
more complex than genetics because it is dynamic
conditions: family/school/pre&post natal/work/home/social influences
shared and non shared environment
proximal (close) and distal (far) environment
social interactions
important but difficult to measure
stress/life events/family history/lower socio-economic status/loneliness
stress is an established factor (80%) but not necessary or sufficient cause
stress being necessary/sufficient
necessary - 20% develop a/d without stress
sufficient - not all stressed develop a/d
correlations and interactions
correlations - genetics predispose you to a personality
interactions - genetics interact with the environment
alleles
Caspi et al., 2003
short allele - reduced expression of gene
long allele - increased expression of gene
SS - increased risk of major depressive disorder LL-decreased risk of major depressive disorder
studies have been replicated
neurochemical theories behind a and d
- GABAergic neurotransmission - modules emotional responses to stimuli
- monoamine neurotransmission - increased NA activity in LC induces fear/increased 5-HT in raphe induces fear
- HPA axis - stress response
- circadian rhythm - altered sleeping/eating
- neuroimmune process - cytokines are transmission molecules
limbic system
hippocampus (neurogenesis=new neurons), parahippocampal gyrus,cingulate gyrus,hypothalamus, amydgala (fear)
cerebral cortex - orbital and mPFC
areas affected by depression
limbic system (hippocampus)
prefrontal cortex - regulates worthlessness and guilt (depression)
monoamine hypothesis (depression)
imbalance of 5-HT and NA neurotransmission - reduced monoamine metabolites
drugs: imipramine/iproniazid (increase monoamines)
MAOIs improve mood
reserpine (depletes monoamine stores) causes depressive symptoms
limitations of antidepressants
antidepressants take 2-3 weeks for affect
depleting monoamines have no effect in healthy controls, mild mood in unmedicated depressed patients
increased DA/NA in animals is maladaptive in models of stress related disorders
antidepressants are dirty - cause unwanted side effects
what does an increase in synaptic monoamine cause
secondary neuroplastic changes
longer timescale
HPA axis
chronic stress is a pre-disposing factor
depressed patients have a disturbed HPA axis
abnormal pattern of cortisol release (negative feedback)
abnormal response to synthetic glucocorticoid drug - dexamethasone
circadian rhythm
disturbances to sleep/wake cycles/appetite/social rhythms
features of manic & depressive episodes
dinural variation
bipolar disorder patients: mania episodes/stabilising CR causes mood stabilisation
genes which produce proteins which regulate CR: clock/PER3/BMAL1/TIMELESS
neuroimmune function
cytokines modulate mood
lipopolysaccharide produces ‘sickness behaviour’ in rodents (social withdrawn/decreased exploration)
pro-inflammatory cytokines: interferon-a/TNF-a/IL-6/IL-B (active HPA/central monoamine systems)
30% individuals treated with recombinant interferons develop depression
early life activation of immune system
