Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.

Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD.

The effect of different psychological profiles and timings of stress exposure on humoral immune response.

The aim of this study was to analyse the effects of different timings of stress exposure on humoral immune response in mice previously distinguished by their own psychological profile. The Swiss mice were submitted to two different protocols of social confrontation, based on the timing of stress exposure in relation to an immune challenge: animals socially confronted daily for 2 weeks (SINT) and another group confronted daily for 3 weeks (LINT). Control groups were individually housed in a different room. All groups were intraperitoneally injected with sheep red blood cells (SRBC). The SINT group was challenged on the 1st and 7th days of confrontation, whereas the LINT group was challenged on the 7th and 14th days. Two days prior to the period of social conflict, the animals were tested in the elevated plus-maze (PM). The SINT protocol caused a more depressed primary immune response in the submissive mice than that observed in the dominants. The LINT protocol induced a marked increase in the primary immune response, which was more evident in the dominant mice, whilst no changes were observed in the secondary immune response. In the control and dominant groups, the correlation analysis attributed a higher anti-SRBC titre to the more anxious animals; by contrast, higher anti-SRBC titres were found in the less anxious submissive mice. These studies show that different physiological and behavioural adaptations to environmental demands over time, as well as different psychological profiles, constitute important factors to a better understanding of neuro-immune interactions.