Functional Imaging as a Tool to Investigate the Relationship between Genetic Variation and Response to Treatment with Antipsychotics

Abstract

Recent evidence suggests that genetic variation is associated with individual variability in response to treatment with antipsychotics. Although numerous studies have been performed for identification of potential genetic variants affecting response to treatment, initial enthusiasm has been tempered by inconsistent results. Along with some specific methodological issues, another plausible explanation for such inconsistencies is lack of sensitivity of the phenotype (clinical measures) used to define response. In this paper, we review use of Imaging Genetics, a relatively new approach that combines genetic assessment with functional neuroimaging, to explore in vivo neurobiological effects of genetic variation. Moreover, we propose to use Imaging Genetics as a tool to evaluate and predict response to treatment with antipsychotics based on the individual genetic makeup.

Evidence that hippocampal–parahippocampal dysfunction is related to genetic risk for schizophrenia

“…Patients in this study and in prior samples were mostly on antipsychotic treatment and it has been suggested that such medications may have an effect on the nature of the functional and behavioral abnormalities observed in patients (for a review, see Di Giorgio et al 2009). Patients in this study and in prior samples were mostly on antipsychotic treatment and it has been suggested that such medications may have an effect on the nature of the functional and behavioral abnormalities observed in patients (for a review, see Di Giorgio et al 2009).…”

Catechol-O-methyltransferase Val158Met association with parahippocampal physiology during memory encoding in schizophrenia

“…Moreover, antipsychotics are known to antagonize dopamine transmission whereas our results suggest a shift to the right of the inverted U relationship between dopamine signaling and hippocampal activity, a hypothesis that is consistent with greater levels of dopamine (discussed earlier). Finally, antipsychotic medication may have an effect on the nature of the functional and behavioral abnormalities observed in patients (for a review, see Di Giorgio et al 2009). However, no significant correlations were found between behavioral data or signal change extracted from the significant cluster showing gene by diagnosis interaction and chlorpromazine equivalents.…”

Functional Brain Imaging in Schizophrenia: Selected Results and Methods

“…Imaging studies of genes regulating dopamine and serotonin neurotransmission and genes related to schizophrenia susceptibility are active areas of research (Gallinat et al 2008;Lawrie et al 2008). Functional brain imaging methods are now investigated as potential links to integrate neurogenetic information into drug development and, ultimately, to guide tailored treatment (Di Giorgio et al 2009). Such studies should move the field towards a general neurobiological theory of the complex symptoms that trouble individuals with schizophrenia.…”