Anxiety and Depression I Cellular Basis

Question 1

what occurs first? anxiety or depression

Answer 1

depression is predominant then anxiety/schizophrenia/bipolar disorder

Question 2

major depressive disorder stats

Answer 2

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

Question 3

criteria for major depressive disorder diagnosis

Answer 3

low mood (irritable)
loss of interest/pleasure (anhedonia)

Question 4

anxiety stats

Answer 4

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

Question 5

types of anxiety

Answer 5

GAD
panic
phobia
fear based: OCD/PTSD

Question 6

anxiety diagnosis

Answer 6

excessive worry/anxiety

Question 7

difficulties in diagnosis

Answer 7

diagnosis is complex because no objective biomarkers (with significant genetic overlap)
challenge: differences in patients - hard to diagnosis

Question 8

nature and nurture

Answer 8

influence of each depends on trait/condition being studied
interplay - phenotype = genotype X environment X time

Question 9

genetics

Answer 9

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

Question 10

Genome wide complex trait analysis

Answer 10

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)

Question 11

environmental challenge

Answer 11

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

Question 12

social interactions

Answer 12

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

Question 13

stress being necessary/sufficient

Answer 13

necessary - 20% develop a/d without stress
sufficient - not all stressed develop a/d

Question 14

correlations and interactions

Answer 14

correlations - genetics predispose you to a personality
interactions - genetics interact with the environment

Question 15

alleles

Caspi et al., 2003

Answer 15

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

Question 16

neurochemical theories behind a and d

Answer 16

• 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

Question 17

limbic system

Answer 17

hippocampus (neurogenesis=new neurons), parahippocampal gyrus,cingulate gyrus,hypothalamus, amydgala (fear)
cerebral cortex - orbital and mPFC

Question 18

areas affected by depression

Answer 18

limbic system (hippocampus)
prefrontal cortex - regulates worthlessness and guilt (depression)

Question 19

monoamine hypothesis (depression)

Answer 19

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

Question 20

limitations of antidepressants

Answer 20

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

Question 21

what does an increase in synaptic monoamine cause

Answer 21

secondary neuroplastic changes
longer timescale

Question 22

HPA axis

Answer 22

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

Question 23

circadian rhythm

Answer 23

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

Question 24

neuroimmune function

Answer 24

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