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Abstract: I provide a brief and subjective view of where the field of imaging genetics is heading. After recapitulating early debates between imagers and geneticists revolving around the topic of candidate gene studies, I point out the importance of genome-wide significant, rare and common variants. I propose that the next stages will be dominated by large-scale multi-site studies that will enable the examination of rare-high penetrance variants and methodological developments that will be required to properly assess the effects of pleiotropy, epistasis, and gene-by environment interactions. The incorporation of new sources of biological information such as whole genome sequencing, proteomic, lipidomic and expression profiles and cellular models derived from induced pluripotent stem cells opens new vistas for imaging genetics in a translational enterprise that is ultimately hoped to improve and create therapeutic options for psychiatric disorders. [Copyright &y& Elsevier]

Abstract: The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using “pharmacological fMRI” and “imaging genetics”, respectively. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. [Copyright &y& Elsevier]

The evolutionarily highly conserved neuropeptide oxytocin is a key mediator of social and emotional behavior in mammals, including humans. A common variant (rs53576) in the oxytocin receptor gene (OXTR) has been implicated in social-behavioral phenotypes, such as maternal sensitivity and empathy, and with neuropsychiatric disorders associated with social impairment, but the intermediate neural mechanisms are unknown. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to identify structural and functional alterations in OXTR risk allele carriers and their link to temperament. Activation and interregional coupling of the amygdala during the processing of emotionally salient social cues was significantly affected by genotype. In addition, evidence for structural alterations in key oxytocinergic regions emerged, particularly in the hypothalamus. These neural characteristics predicted lower levels of reward dependence, specifically in male risk allele carriers. Our findings identify sex-dependent mechanisms impacting the structure and function of hypothalamic-limbic circuits that are of potential clinical and translational significance. [ABSTRACT FROM AUTHOR]

Abstract: In the past decade, imaging genetics has evolved into a highly successful neuroimaging discipline with a variety of sophisticated research tools. To date, several neural systems mechanisms have been identified that mediate genetic risk for mental disorders linked to common candidate and genome-wide-supported variants. In particular, the examination of intermediate connectivity phenotypes has recently gained increasing popularity. This paper gives an overview of the scientific methods and evidence that link indices of neural network organization to the genetic susceptibility for mental illness with a focus on the effects of candidate genes and genome-wide supported risk variants on brain structure and function. [Copyright &y& Elsevier]

Abstract: Schizophrenia is a chronic, severe, and disabling brain disorder arising from the adverse interaction of predisposing risk genes and environmental factors. The psychopathology is characterized by a wide array of disturbing cognitive, emotional, and behavioral symptoms that interfere with the individual''s capacity to function in society. Contemporary pathophysiological models assume that psychotic symptoms are triggered by a dysregulation of dopaminergic activity in the brain, a theory that is tightly linked to the serendipitous discovery of the first effective antipsychotic agents in the early 1950s. In recent years, the availability of modern neuroimaging techniques has significantly expanded our understanding of the key mediator circuits that bridge the gap between genetic susceptibility and clinical phenotype. This paper discusses the pathophysiological concepts, molecular mechanisms and neuroimaging evidence that link psychosis to disturbances in dopamine neurotransmission. [Copyright &y& Elsevier]

The rs1625579 variant near the microRNA-137 (MIR137) gene is one of the best-supported schizophrenia variants in genome-wide association studies (GWAS), and microRNA-137 functionally regulates other GWAS identified schizophrenia risk variants. Schizophrenia patients with the MIR137 rs1625579 risk genotype (homozygous for the schizophrenia risk variant) also have aberrant brain structure. It is unclear if the effect of MIR137 among schizophrenia patients is due to potential epistasis with genetic risk for schizophrenia or other factors of the disorder. Here, we investigated the effect of MIR137 genotype on white matter fractional anisotropy (FA), cortical thickness (CT), and surface area (SA) in a sample comprising healthy control subjects, and individuals with familial risk for psychosis (first-degree relatives of patients with schizophrenia or bipolar disorder; N=426). In voxel-wise analyses of FA, we observed a significant genotype-by-group interaction (PFWE<0.05). The familial risk group with risk genotype had lower FA (PFWE<0.05), but there was no genetic association in controls. In vertex-wise analyses of SA, we also observed a significant genotype-by-group interaction (PFWE<0.05). Relatives with MIR137 risk genotype had lower SA, however the risk genotype was associated with higher SA in the controls (all PFWE<0.05). These results show that MIR137 risk genotype is associated with lower FA in psychosis relatives that is similar to previous imaging-genetics findings in patients with schizophrenia. Furthermore, MIR137 genotype may also be a risk factor in a subclinical population with wide reductions in white matter FA and cortical SA. [ABSTRACT FROM AUTHOR]