Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders.
In anorexia nervosa (AN), volitional inhibition of rewarding behaviors, such as eating, involves a conflict between the desire to suppress appetite and the inherent motive to consume. This conflict is thought to have costs that carry over into daily life, e.g., triggering negative affect and/or recurring ruminations, which may ultimately impact long term outcome. Hence, increasing research effort is being dedicated to understand the link between emotional and ruminative processes in the etiology and maintenance of AN. We investigated whether affective states influence disorder-related rumination in AN applying "ecological momentary assessment", a method which allows the experimenter to gain insight into psychological processes in the natural environment and assess data in real time. Participants (AN = 37, healthy controls = 33) were given a smartphone for 14 days. A ringtone signaled at six random time-points each day to fill in a questionnaire, which gauged disorder-typical thoughts about food and weight as well as affective state. Analyses, applying hierarchical linear models confirmed that AN patients spend more time thinking about food, body shape and weight than controls (p < 0.001). Additionally, the results support the hypothesis that momentary negative affect (but not baseline depression (p = 0.56) or anxiety symptoms (p = 0.60) are positively associated with a higher amount of disorder-related rumination in patients (p < 0.001). Our findings are in line with theories which claim that ruminative thinking induces a vulnerability to negative stimuli which, in turn, fosters heightened negative affect. Thus, therapeutic interventions could be improved by implementing modules that specifically target disorder-related rumination.
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