Multimodal Associations of FKBP5 Methylation With Emotion-Regulatory Brain Circuits.

BACKGROUND: Understanding the biological processes that underlie individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. However, it remains unclear how FKBP5 DNA methylation in peripheral blood is related to individual differences in measures of neural structure and function and their relevance to daily-life stress responsivity. METHODS: Here, we characterized multimodal correlates of FKBP5 DNA methylation by combining epigenetic data with neuroimaging and ambulatory assessment in a sample of 395 healthy individuals. RESULTS: First, we showed that FKBP5 demethylation as a psychiatric risk factor was related to an anxiety-associated reduction of gray matter volume in the ventromedial prefrontal cortex, a brain area that is involved in emotion regulation and mental health risk and resilience. This effect of epigenetic upregulation of FKBP5 on neuronal structure is more pronounced where FKBP5 is epigenetically downregulated at baseline. Leveraging 208 functional magnetic resonance imaging scans during a well-established emotion-processing task, we found that FKBP5 DNA methylation in peripheral blood was associated with functional differences in prefrontal-limbic circuits that modulate affective responsivity to daily stressors, which we measured using ecological momentary assessment in daily life. CONCLUSIONS: Overall, we demonstrated how FKBP5 contributes to interindividual differences in neural and real-life affect regulation via structural and functional changes in prefrontal-limbic brain circuits.

Fear, depression, and well-being during COVID-19 in German and South African students: A cross-cultural comparison.

Various studies have shown a decrease in well-being and an increase in mental health problems during the COVID-19 pandemic; however, only a few studies have explored fear, depression, and well-being cross-culturally during this time. Accordingly, we present the results of a cross-cultural study that (1) compares these mental health scores for German and South African students, (2) compares the correlations among them, and (3) identifies COVID-19 fear, well-being, and depression predictors. German and South African societies differ from each other socio-culturally, politically, and economically. Their university systems also differ to a large extent. University students in both countries completed the Fear of COVID-19 Scale, the World Health Organization-Five Well-Being Index (WHO-5), and the Patient Health Questionnaire-9 (PHQ-9). Welch's t-test, correlation, and multiple regression analyses were performed. (1) German students were found to have statistically lower levels of COVID-19 fear and depression, but lower levels of general well-being than South African students. (2) In both samples, fear of COVID-19 was negatively correlated with well-being and positively associated with female gender and depression. (3) Additionally, female gender, depression, and lower well-being were identified as predictors of COVID-19 fear in both samples. The findings indicate that the fear of COVID-19 is associated with and varies according to gender, depression, and well-being across cultures, and that the difference in the intensity of fear between German and South African students may be partly explained by cultural and contextual differences. These findings can create a deeper understanding of the pandemic's impact on student communities and may be used by mental health practitioners and researchers to develop and apply culture-specific interventions.