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Recent studies have reported altered methylation levels at disorder-relevant DNA sites in people who are ill with Anorexia Nervosa (AN) compared to findings in people with no eating disorder (ED) or in whom AN has remitted. The preceding implies state-related influences upon gene expression in people with AN. This study further examined this notion. We measured genome-wide DNA methylation in 145 women with active AN, 49 showing stable one-year remission of AN, and 64 with no ED. Comparisons revealed 205 differentially methylated sites between active and no ED groups, and 162 differentially methylated sites between active and remitted groups (Q < 0.01). Probes tended to map onto genes relevant to psychiatric, metabolic and immune functions. Notably, several of the genes identified here as being differentially methylated in people with AN (e.g. SYNJ2, PRKAG2, STAT3, CSGALNACT1, NEGR1, NR1H3) have figured in previous studies on AN. Effects also associated illness chronicity and lower BMI with more pronounced DNA methylation alterations, and remission of AN with normalisation of DNA methylation. Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology. [ABSTRACT FROM AUTHOR]

Peers are present for most bullying episodes. Peers who witness bullying can play an important role in either stopping or perpetuating the behavior. Defending can greatly benefit victimized peers. Empathy is strongly associated with defending. Yet, less is known about defenders' neural response to witnessing social distress, and how this response may relate to the link between empathy and defending. Forty-six first-year undergraduate students (Mage = 17.7; 37 women), with varied history of peer defending, underwent fMRI scanning while witnessing a depiction of social exclusion. Functional connectivity analysis was performed across brain regions that are involved in cognitive empathy, empathetic distress, and compassion. History of defending was positively associated with functional connectivity (Exclusion > Inclusion) between the left orbitofrontal cortex (OFC) – medial prefrontal cortex (MPFC), and right OFC – left and right amygdalae. Defending was negatively associated with functional connectivity between the left OFC – anterior cingulate cortex. The relationship between history of defending and empathy (specifically, empathetic perspective taking) was moderated by functional connectivity of the right OFC – left amygdala. These findings suggest that coactivation of brain regions involved in compassionate emotion regulation and empathetic distress play a role in the relationship between empathy and peer defending. [ABSTRACT FROM AUTHOR]

Objectives: About 50% of patients with unipolar depression suffer from treatment-resistant depression (TRD). Animal studies have suggested potential antidepressant properties of valproate (VPA) possibly due to its implication in epigenetic programming.Methods: Fourteen TRD patients (seven males and seven females; age 19–59) received VPA (375–1000 mg/day) in addition to their treatment regimen after previously failing to respond to two or more antidepressant trials and/or different combinations. Clinical response to VPA was investigated prior the treatment (T-0) and after 1 (T-1), 4 (T-4) and 7 (T-7) months of therapy using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI).Results: Compared to T-0, VPA significantly decreased MADRS score at T-1 (P < 0.001), T-4 (P < 0.001) and T-7 (P < 0.001) (partial η2=0.86). Importantly, MADRS score at T-7 (13.6 ± 1.6, mean ± SEM) was closer to the reported value of remission (MADRS <10), and none of the patients relapsed during the observational period. Compared to T-0, VPA also decreased CGI-Severity of illness score at T-1 (p = 0.03), T-4 (p < 0.001) and T-7 (p < 0.001) (partial η2 = 0.74).Conclusions: Antidepressant augmentation with VPA provided substantial clinical improvement and maintenance over a relatively long-term period in a subgroup of patients with severe TRD. VPA thus deserves further exploration in large double-blind clinical trials. [ABSTRACT FROM PUBLISHER]