Abstract
The Disrupted-in-Schizophrenia 1 (DISC1) gene has been thought as a putative susceptibility gene for various psychiatric disorders, and DISC1 Ser704Cys is associated with variations of brain morphology and function. Moreover, our recent diffusion magnetic resonance imaging (dMRI) study reported that DISC1 Ser704Cys was associated with information transfer efficiency in the brain anatomical network. However, the effects of the DISC1 gene on functional brain connectivity and networks, especially for thalamic-prefrontal circuit, which are disrupted in various psychiatric disorders, are largely unknown. Using a functional connectivity density (FCD) mapping method based on functional magnetic resonance imaging data in a large sample of healthy Han Chinese subjects, we first investigated the association between DISC1 Ser704Cys and short- and long-range FCD hubs. Compared with Ser homozygotes, Cys-allele individuals had increased long-range FCD hubs in the bilateral thalami. The functional and anatomical connectivity of the thalamus to the prefrontal cortex was further analyzed. Significantly increased thalamic-prefrontal functional connectivity and decreased thalamic-prefrontal anatomical connectivity were found in DISC1 Cys-allele carriers. Our findings provide consistent evidence that the DISC1 Ser704Cys polymorphism influences the thalamic-prefrontal circuits in humans and may provide new insights into the neural mechanisms that link DISC1 and the risk for psychiatric disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-013-0640-5) contains supplementary material, which is available to authorized users.
Highlights
The Disrupted-in-Schizophrenia 1 (DISC1) gene (Millar et al 2000) first identified in a large Scotland pedigree study (Blackwood et al 2001) is well established as a genetic risk factor for multiple psychiatric disorders (Chubb et al 2008; Bradshaw and Porteous 2012)
Using a functional connectivity density (FCD) mapping method based on functional magnetic resonance imaging data in a large sample of healthy Han Chinese subjects, we first investigated the association between DISC1 Ser704Cys and short- and long-range FCD hubs
Using data-driven methods based on functional magnetic resonance imaging (fMRI) data in a large sample of healthy Han Chinese subjects, our findings have provided consistent evidence that the DISC1 Ser704Cys polymorphism influences the thalamic-prefrontal circuits in humans
Summary
The Disrupted-in-Schizophrenia 1 (DISC1) gene (Millar et al 2000) first identified in a large Scotland pedigree study (Blackwood et al 2001) is well established as a genetic risk factor for multiple psychiatric disorders (Chubb et al 2008; Bradshaw and Porteous 2012). One common missense variant in the DISC1 gene, Ser704Cys (rs821616), has been independently reported by several groups as associated with an increased risk for various psychiatric disorders (Hashimoto et al 2006; DeRosse et al 2007; Palo et al 2007; Qu et al 2007; Kim et al 2008), a meta-analysis has recently questioned this claim (Mathieson et al 2012) The associations between this genetic variant and changes in brain morphology and function have been reported (Callicott et al 2005; Hashimoto et al 2006; Di Giorgio et al 2008; Prata et al 2008; Takahashi et al 2009; Johnstone et al 2011; Raznahan et al 2011; Sprooten et al 2011; Trost et al 2013). A relevant question was whether the functional connectivity of the brain, especially in specific circuits, was measurably influenced by the DISC1 Ser704Cys polymorphism
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