No abstract

Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor gene HTR2A in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semi-structured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. HTR2A genotype and methylation of HTR2A was measured at two CpG sites (−1420 and −1224) from saliva DNA. HTR2A genotype was associated with HTR2A methylation at both CpG sites. HTR2A genotype also moderated associations of contextual stress exposure and HTR2A methylation at site −1420. Contextual stress was positively associated with −1420 methylation among A homozygotes, but negatively associated with −1420 methylation among G homozygotes. PTSD and MDD symptoms were negatively associated with methylation at −1420, but positively associated with methylation at −1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, and HTR2A methylation may be a mechanism by which early adversity is biologically encoded.

Background: Anhedonia is one of the defining features of depression but it remains difficult to target and treat. Transcranial magnetic stimulation (TMS) is a proven treatment for depression, but its effects on anhedonia and whether anhedonia can be used as a predictive biomarker of response is not well known.Methods: Snaith-Hamilton Pleasure Scale was administered to patients with depression before and after a standard course of TMS in a naturalistic outpatient setting.Results: 144 patients were analyzed. There was an overall significant improvement in anhedonia from pre-to post-treatment (7.69 ± 3.88 vs. 2.96 ± 3.45; p < .001).Significant correlations between improvements in anhedonia and other depressive symptoms were present (r = 0.55, p < .001). Logistic regression revealed that baseline anhedonia severity was not a significant predictor of clinical outcome. Conclusion:This is the first large, naturalistic study examining the effects of standard, non-research TMS on anhedonia. Among depressed patients, TMS resulted in significant improvements in anhedonia. Patients with severe baseline anhedonia had an equal chance of achieving clinical response/remission. Patients with anhedonia should not be excluded from treatment if they are safe for outpatient care and otherwise appropriate candidates for treatment.