Genes and Neuroimaging: Advances in Psychiatric Research

Abstract

Major psychiatric disorders, including schizophrenia, bipolar disorder and substance addiction, are partly heritable and show a multifactorial pattern of heredity. Although the introduction of explicit diagnostic criteria has improved clinical research on psychiatric disorders, the concept is only of limited use for exploring their genetic underpinnings. On the behavioral level, psychopathological symptoms can hardly separate the many pathophysiological subgroups. Contrary to nosological categories, biologically based phenotypes – referred to as intermediate phenotypes – consisting of neuropsychological, electrophysiological, functional and structural brain imaging parameters, could represent the genetic basis more directly. Thus intermediate phenotypes are being targeted in current molecular genetic investigations. In this article, we review existing data on the effects of genetic variation in the dopamine and serotonin systems (catechol-O-methyltransferase, the serotonin-transporter-linked polymorphic region) on the morphometric, metabolic and functional characteristics of the cerebral cortex and limbic structures. The gene-driven modulation of these brain circuits is discussed with regard to their behavioral correlates and their role for psychiatric diseases. Furthermore, recently identified putative susceptibility genes for schizophrenia (neuregulin 1, dysbindin, G72) are briefly discussed.

Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application

“…Most of the current information comes from postmortem studies. 44,88,89 One limitation of postmortem tissue investigation is that the tissue is usually obtained after a person died or at the end stage of the disease. Despite the potential to understand BD noninvasively and therefore in a highly relevant milieu in human subjects, BD has received only limited attention in molecular imaging studies.…”

Functional Brain Imaging in Schizophrenia: Selected Results and Methods

“…Schizophrenia investigators have argued that both magnitude activation data and connectivity data might serve as useful intermediate phenotypes (Turner et al 2006;Whalley et al 2009). 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).…”

Effects of aCACNA1Cgenotype on attention networks in healthy individuals

“…Because impaired attention can also be found to a lesser degree in relatives of psychotic patients, attention deficits are thought to index genetic liability (Cornblatt & Keilp, 1994 ;Chen & Faraone, 2000 ;Sitskoorn et al 2004 ;Snitz et al 2006 ;Gallinat et al 2008). The mechanisms regarding how genetic variation leads to attention deficits on a neural network level remain unclear but might be elucidated by functional imaging studies.…”