Depression Flashcards
Epidemiology
Major public health burden - 8th most disability adjusted life years lost in UK, 11th in world
2-3 times more common in women than men, 50% will relapse after a 1st episode, 75% after a second, 90% after a third.
Untreated episodes last 6-24 months, treatment more effective early on.
Dunedin cohort - 1 in 5 people have a major depressive episode before age 18
Simon et al 1995 - All cohorts were most likely to report their first episode in the last 5 years, suggesting that prevalence is increasing over time.
BUT Patten et al 2000 - this cohort effect is an artefact of poor recall of depression - only 3% of cohort need to forget their depression to produce the cohort effect
Stirling County study 2000 - prevalence of depression in 1952, 1970 and 1992 was all 5%.
Diagnostic Criteria
On of three major symptoms: -persistent low mood -anhedonia -fatigue/low energy Other symptoms: -change in movement (agitation or slow movement) -change in sleep patterns -change in appetite -feelings of guilt or worthlessness -suicidality or self-harm -trouble concentration or indecision -low self-confidence
Beck’s cognitive triad
Negative feelings about self, the world, and the future
The psychological account - Beck 1967
Beck’s triad maintained by negative schemata
Negative schemata make and are in turn maintained by cognitive biases
Cognitive biases:
-Magnification and minimalisation
-Arbitrary inference (drawing illogical conclusions)
-Personalisation (It’s all my fault)
-Overgeneralisation and oversimplification
Cognitive effects - cold cognition
~basically, deficient~
Depressed people are worse at the Tower of London and DMTS tasks
Murphy et al 2003 - In a probabilistic reversal learning task, subjects were given accurate feedback 80% of the time and inaccurate 20% of the time. Depressed patients were worse at the task, because as soon as they got any negative feedback they switched to the ‘incorrect’ response. So perhaps depressed patients are more sensitive to negative feedback, and less to positive.
Elliott et al 1996 - depressed patients were more likely to fail if they had failed the preceding problem - perhaps they ‘catastrophise’ and give up after a failed attempt. Exaggerated punishment processing.
Norman et al 2002 - depressed patients had diminished memory when measured using a dementia rating scale.
E.g.s of negative schemata
‘ineptness schemata’, ‘self-blaming schemata’, ‘negative self-evaluation schemata’.
evidence:
Bradley and Matthews 1982 - depressed patients recall more negative than positive self-referant adjectives
Evans et al 2005 - women who hold negative self-schema are more likely to go on to develop depression, even after adjustment for baseline depressive symptoms and previous history of depression.
Cognitive effects - hot cognition
~basically, negatively biased~
Bradley and Matthews 1982 - depressed patients recall more negative than positive self-referant adjectives, though response times did not differ
Erikson et al 2005 - quicker response time to sad than happy words
Worse at recognising happy than negative facial expressions
‘depressive realism’ (Alloy and Abramson)
PFC in depression
Smith et al 2011 - medial PFC and cingulate cortices active in induced sadness
- subgenual PFC hyperactive in depression and reduced activity in spontaneously recovered depressives
- CBT-induced recovery associated with increased activity in rostral subgenual cortex (CBT has robust effects on mood, unknown effects on hot cognition)
- Venlafaxine-induced recovery associated with reduced activity in caudal subgenual cortex
- Deep brain stimulation of subgenual cortex reduces activity and can decrease time taken to endorse happy words and proportion of negative words endorsed as self-descriptive
- Overactivation of subgenual cortex increases bias away from punishment (when monkeys can choose between a probablistic vs always-reward stimulus)
Monoaminergic hypothesis - evidence for
-Acute tryptophan depletion (drink containing amino acids but no tryptophan triggers protein synthesis, available tryptophan used up, less serotonin made in brain) induces negative bias (slower to respond to happy words) in healthy volunteers and depressed individuals in remission or partial remission. No effect on executive function e.g. in Tower of London task
-We treat depressed patients using SSRIs, sometimes it works. SSRIs introduce positive biases, but little effect on cold cognition. One dose of citalopram improves happy (and fearful) face recognition
-Reboxetine (NRI) increases rats’ time spent climbing (vs immobility) in inescapable water tank
-After 5-HT based treatment for 2-3 weeks until ‘feeling well’, patients went on a low Trp diet then ATD. Depressive symptoms recurred within hours, and after return to normal diet these subsided within 24 hours
Note that the reduction in negative biases doesn’t necessarily correlate with mood improvement!
Glutamatergic hypothesis - evidence for (3)
Ketamine is a fast-acting, ‘emergency’ anti-depressant
Nowak et al 1993 - antidepressants modulate NMDARs
Bonnano et al 2005 - chronic SSRI application reduced depolarisation-induced release of glutamate in hippocampus, by reducing SNARE complex formation. Acute did nothing.
glutamate antagonists rescue stress-induced plasticity chanes
Now moving towards a ‘neuroplasticity hypothesis’ - the volumetric changes found in limbic and cortical areas of depressed subjects are due to synaptic remodelling and loss of dendritic spines (Baram et al 2012 - rats with developmental stress had reduced arborisation in CA1, Izquierdo et al 2006 - rats with uncontrolled stress had reduced arborisation in infralimbic cortex)
Monoamine hypothesis - evidence against
-SSRIs affect monoamine availability within minutes to hours, whereas their effects on mood take weeks. (some have proposed that this is because they have transcription effects, or impact synaptic plasticity.)
-Indeed, the prevalent effect of antidepressants is to reduce hippocampal LTP after acute (Shakesby et al 2002) and chronic application (Stewart et al 2000), but we know that LTP is mediated by glutamate and NMDARs.
Lau et al 2009 - Adults with a serotonin transporter allele polymorphism have less 5-HTT (so theoretically more serotonin around), but have greater amygdala response to fearful faces and increased incidence of anxiety and depression (but conflicting results characterise younger samples, and this may be due to an early developmental role of the receptor)
Social risk factors
Being separated, widowed or divorced Lack of social support History of physical or sexual abuse Low socioeconomic status Low social capital
Biological risk factors
Female sex Poor neurodevelopment Genetic risk factors (twin studies suggest heritability 40-50%, but no specific genes found) substance abuse low birth weight systemic inflammation
