Prefrontal gene expression changes in mood disorders and suicide

The research described in this thesis was centered on two questions. Firstly, we investigated whether suicide, as specific entity and as part of the symptomatology of depressive disorder, is characterized by specific neurotransmitter changes in the prefrontal cortex (PFC). To this end, we studied two independent patient cohorts: (i) the Stanley Medical Research Institute (SMRI) cohort, comprising patients who were diagnosed with major depressive disorder (MDD) and who had accomplished suicide, and (ii) a Netherlands Brain Bank (NBB) cohort, consisting of elderly MDD and bipolar disorder (BD) patients who had died of non-suicidal causes. Secondly, we investigated possible differences in molecular changes in the PFC, between Alzheimer’s disease (AD) cases with major depression as comorbidity, and patients suffering from MDD per se. We also used the APP/PS1 double-transgenic mouse model of AD, which overexpresses mutated forms of the human amyloid precursor protein (APP), and presenilin 1 (PS1), to test the hypothesis that molecular changes in the frontal cortex may induce hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in AD. In conclusion, we speculate that mood disorders and suicide are two different entities, while mood disorders per se, and depression in AD are also different when it comes to specific molecular alterations. Later on in the Discussion we will give some suggestions for further research.