Schizophrenia is a devastating, highly heritable brain disorder of unknown etiology. Recently, the first common genetic variant associated on a genome-wide level with schizophrenia and possibly bipolar disorder was discovered in ZNF804A (rs1344706). We show, by using an imaging genetics approach, that healthy carriers of rs1344706 risk genotypes exhibit no changes in regional activity but pronounced gene dosage-dependent alterations in functional coupling (correlated activity) of dorsolateral prefrontal cortex (DLPFC) across hemispheres and with hippocampus, mirroring findings in patients, and abnormal coupling of amygdala. Our findings establish disturbed connectivity as a neurogenetic risk mechanism for psychosis supported by genome-wide association, show that rs1344706 or variation in linkage disequilibrium is functional in human brain, and validate the intermediate phenotype strategy in psychiatry.

Detecting and evaluating emotional information from facial expressions as a basis for behavioural adaption belong to the core social-cognitive abilities of mankind. Dysfunctions in emotional face processing are observed in several major psychiatric disorders like depression and schizophrenia. In search for psychiatric disease biomarkers using the imaging genetics approach, serotonergic gene polymorphisms have been associated with altered brain circuit activation during emotional face processing. Especially the 5-HTTLPR gene polymorphism has been extensively investigated in association with emotion regulation processes. In this article, imaging genetics literature on emotional face processing, reporting genetic effects of 5-HTTLPR in healthy volunteers is reviewed. Additionally, these results are regarded in relation to pharmacologic challenge (antidepressants, acute tryptophan depletion) imaging studies and discussed in light of recent neurobiological evidence with a focus on serotonin (5-HT, 5-HT, 5-HT) receptor findings.