DISC1 Ser704Cys impacts thalamic-prefrontal connectivity

Brain Struct Funct. 2015 Jan;220(1):91-100. doi: 10.1007/s00429-013-0640-5. Epub 2013 Oct 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Afferent Pathways / anatomy & histology*
  • Afferent Pathways / blood supply
  • Brain Mapping
  • Chi-Square Distribution
  • Cysteine / genetics*
  • Female
  • Humans
  • Imaging, Three-Dimensional
  • Magnetic Resonance Imaging
  • Male
  • Nerve Tissue Proteins / genetics*
  • Oxygen / blood
  • Prefrontal Cortex / anatomy & histology*
  • Prefrontal Cortex / blood supply
  • Serine / genetics*
  • Thalamus / anatomy & histology*
  • Thalamus / blood supply
  • Young Adult

Substances

  • DISC1 protein, human
  • Nerve Tissue Proteins
  • Serine
  • Cysteine
  • Oxygen