Predicting brain structure in population-based samples with biologically informed genetic scores for schizophrenia.

Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non-replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants for schizophrenia belonging to specific biological systems like synaptic function, neurodevelopment, calcium signaling, and glutamatergic neurotransmission. We hypothesized that this "biologically informed" approach would provide the missing link between genetic risk for schizophrenia and brain structural phenotypes. We applied whole-brain voxel-based morphometry (VBM) analyses in two population-based target samples and subsequent regions of interest (ROIs) analyses in an independent replication sample (total N = 2725). No consistent association between the genetic scores and brain volumes were observed in the investigated samples. These results suggest that in healthy subjects with a higher genetic risk for schizophrenia additional factors apart from common genetic variants (e.g., infection, trauma, rare genetic variants, or gene-gene interactions) are required to induce structural abnormalities of the brain. Further studies are recommended to test for possible gene-gene or gene-environment effects. © 2017 Wiley Periodicals, Inc.

Reduced Affective Biasing of Instrumental Action With tDCS Over the Prefrontal Cortex.

BACKGROUND: Instrumental action is well known to be vulnerable to affective value. Excessive transfer of affective value to instrumental action is thought to contribute to psychiatric disorders. The brain region most commonly implicated in overriding such affective biasing of instrumental action is the prefrontal cortex. OBJECTIVE: The aim of the present study was to reduce affective biasing of instrumental action using transcranial direct current stimulation (tDCS) in young healthy human volunteers. METHODS: In a double-blind, randomized between-group design, 120 participants received anodal, cathodal and sham tDCS while at the same time (online) performing a task that assessed affective biasing of instrumental action. We placed tDCS electrodes over the anterior part of the prefrontal cortex based on evidence from brain stimulation work demonstrating the role of this brain region in controlling affective biasing of instrumental action. RESULTS: We showed that prefrontal tDCS reduced affective biasing of instrumental action. Specifically, prefrontal tDCS reduced the degree to which aversive (versus appetitive) cues potentiated instrumental avoidance and suppressed instrumental approach. Contrary to our hypothesis, this effect was seen for cathodal tDCS rather than anodal tDCS. CONCLUSION: The results demonstrate the potential utility of prefrontal tDCS as a tool for reducing affective biasing of instrumental behavior, thus opening avenues for interventional research on psychiatric disorders that implicate excessive transfer of affective value.