Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder.

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.

Resilience in mental health: linking psychological and neurobiological perspectives.

OBJECTIVE: To review the literature on psychological and biological findings on resilience (i.e. the successful adaptation and swift recovery after experiencing life adversities) at the level of the individual, and to integrate findings from animal and human studies. METHOD: Electronic and manual literature search of MEDLINE, EMBASE and PSYCHINFO, using a range of search terms around biological and psychological factors influencing resilience as observed in human and experimental animal studies, complemented by review articles and cross-references. RESULTS: The term resilience is used in the literature for different phenomena ranging from prevention of mental health disturbance to successful adaptation and swift recovery after experiencing life adversities, and may also include post-traumatic psychological growth. Secure attachment, experiencing positive emotions and having a purpose in life are three important psychological building blocks of resilience. Overlap between psychological and biological findings on resilience in the literature is most apparent for the topic of stress sensitivity, although recent results suggest a crucial role for reward experience in resilience. CONCLUSION: Improving the understanding of the links between genetic endowment, environmental impact and gene-environment interactions with developmental psychology and biology is crucial for elucidating the neurobiological and psychological underpinnings of resilience.

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

Positive affect (PA) has an important role in resilience against depression and has been shown to increase with mindfulness-based cognitive therapy (MBCT). To elucidate the underlying mechanisms of change in PA as well as develop insights that may benefit personalized medicine, the current study examined the contribution of genetic variation to individual differences in change in PA in response to MBCT. Individuals (n=126) with residual depressive symptoms were randomized to either an MBCT group or treatment as usual. PA was assessed using experience sampling methodology (ESM). Single-nucleotide polymorphisms (SNPs) in genes known to be involved in reward functioning were selected. SNPs in the genes for brain-derived neurotrophic factor (BDNF), the muscarinic acetylcholine receptor M2 (CHRM2), the dopamine receptor D4 (DRD4) and the µ1 opioid receptor (OPRM1) significantly moderated the impact of treatment condition over time on PA. Genetic variation in the genes for CHRM2 and OPRM1 specifically had an impact on the level of PA following MBCT. The current study shows that variation in response to MBCT may be contingent on genetic factors associated with the regulation of PA. These findings contribute to our understanding of the processes moderating response to treatment and prediction of treatment outcome.

Imported cases of chloroquine-resistant falciparum malaria in Iran.

Six imported cases of chloroquine-resistant Falciparum malaria have been studied since October 1984. In five cases including two Iranian men, returned from India, two Afghan and one Bengalee immigrants came to Iran through Pakistan, recrudescence occurred following treatment with chloroquine. In these five cases resistance of P. falciparum to chloroquine was clinically (by the in vivo test) at R1 level in all patients. The resistance was also confirmed by the macro in vitro susceptibility test which was carried out in four of them. These five chloroquine-resistant cases were treated, one with Sulfadiazine-Pyrimethamine, three with Quinine-Sulfadiazine-Pyrimethamine and one with Sulfadoxine-Pyrimethamine (Fansidar) successfully. In the sixth case who was a Pakistani tourist the parasites showed resistance in the macro in vitro test, but apparently responded to chloroquine treatment in three days. It seems the resistance in this case was also at R1 level as other cases.