Depression Flashcards
Krishnan and Nester, 2008
Review of the molecular neurobiology of depression
Cause of depression is not just monoamine deficiency - MAOI’s and SSRI’s take effect on monoamine concentration in the synaptic cleft almost immediately but it takes 2 weeks to take effect
Knol et al., 2006
Ppl with MDD are more likley to be diagnosed with coronary artery disease or Type 2 diabetes
Pittenger and Duman, 2008 (Hormones)
The monoamine hypothesis
Lopez-Leon et al., 2008 (Genes)
Meta-analysis of genetic heritability studies in MDD and found 6 genes that may increase susceptibility -
No strong and consistent genetic risk modifiers
Ruhe et al., 2007 (Hormones)
Experimental depletion of monoamines in healthy controls does not effect their mood
Duman and Monteggia, 2006 (Neurotrophins/Neurogenesis)
BDNF hypothesis - Neurodevelopmentally expressed growth factors (like BDNF) regulate plasticity in the adult brain
Stress reduces the expression of BDNF whereas chronic use of antidepressants increases it
Brain Derived Neurotrophic Factor
A growth factor that is expressed in limbic areas
Groves, 2007 (Neurotrophins/neurogenesis)
Research has not been able to replicate the stress/chronic antidepressant use effect on BDNF
Some studies have found the opposite effect
Pezawas et al., 2008 (Neurotrophins/Neurogenesis)
Complex interactions between a BDNF polymorphism, a serotonin transporter gene polymorphism and stressful life events exists
BDNF hypothesis is too simplistic
Kemperman, 2008 (Neurotrophins/Neurogenesis)
Antidepressant treatment is shown to increase the levels of growth factors in the hippocampus that influence neurogenesis - This may allow hippocampal networks to adapt and learn new experiences
In tact neurogenesis during a stressful life-event may create maladaptive learning and subsequently depression
Peters et al., 2003
Pps w depression reported average unpleasant experiences but less than average positive experiences
Papakostas, 2014
Cognitive symptoms of MDD are associated with earlier illness onset and longer episode duration
Can have adverse effects of treatment and recovery
Caspi et al., 2003 (Genetics)
Pps who had 2 long copies of the 5-HTTLPR gene had a 40% increased risk of MDD after a stressful life event, pps with a copy of the long and short gene had a 30% and pps with two copies of the short gene have a 18% risk
5-HTTLPR could magnify response to stressful life events
Still a 5-10% risk of MDD even with no stressful life events
Risch et al., 2009 (Genetics)
Could not recreate the results of Caspi et al., 2003
Wray et al., 2009 (Genetics)
Inaccuracy of biological gene tracking methods may explain Caspi et al., 2003
Parker et al., 2003 (Hormones)
40-50% MDD patients have cortisol hypersecretion
Gibney and Drexhage, 2013 (Hormones)
Dysregulated immune system is an underlying mechanism of depression - this is linked to thyroid hormone function
Berent et al, 2014 (Hormones)
Found low concs of free thyroid hormone to increase depression severity and reduce positive treatment outcomes
von Wolff et al., 2013 (Tricyclics)
Meta-analysis of tricyclics - efficacious in increasing response rates compared to placebo
SSRI’s had fewer drop out rates indicating better acceptability
Most evidence came from patients with dysthymia, not MDD
Qin et al., 2014 (Tricyclics)
Found SSRI’s improved depression rating scale scores and response in symptoms than ppl of tricyclics
More patients on tricylics discontinued their treatment
Barth et al., 2016 (SSRI’s)
Although people on SSRI’s reported more adverse effects than people of placebo, this was not shown to effect treatment
Jakubovski et al., 2016 (SSRI’s)
High doses of SSRI’s work better for people with sever MDD - however the effect is counteracted by the lack of tolarablitity to the high dose
Chuicariello et al., 2014 (MAOI’s)
MAO-A is elevated in the PFC and anterior cingulate cortices during a depressive episode
Elevated MAO-A levels were associated with more sever and reversed neurovegetative symptoms
Zajecka and Zajecka, 2014 (MAOI’s)
Second gen MAOI’s have reduced safety concerns surrounding diet and medication interactions - less restrictive diet
Pherson et al., 2015 (MAOI’s)
MAOI’s can induce improved cognitive functioning in MDD patients
Gibson et al., 2016
56% people have a positive experience with antidepressants, 28% have a mixed experience - antidepressants seen as necessary, life saving, helping them to meet social obligations and is a stepping stone for further help
16% have a negative experience with antidepressants as they provide a lack of control and emotional authenticity, unbearable side effects and they mask real problems
McGrath et al., 2013
6 limbic and cortical regions were identified as biomarkers for treatment options
Insula hypometabolism favoured CBT > escitalopram
Insula Hypermetabolism favoured escitalopram > CBT
