Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study

Brain Imaging Behav. 2013 Mar;7(1):15-27. doi: 10.1007/s11682-012-9168-1.

Abstract

Individuals with schizophrenia show a broad range of language impairments, similar to those observed in reading disability (RD). Genetic linkage and association studies of RD have identified a number of candidate RD-genes that are associated with neuronal migration. Some individuals with schizophrenia also show evidence of impaired cortical neuronal migration. We have previously linked RD-related genes with gray matter distributions in healthy controls and schizophrenia. The aim of the current study was to extend these structural findings and to examine links between putative RD-genes and functional connectivity of language-related regions in healthy controls (n = 27) and schizophrenia (n = 28). Parallel independent component analysis (parallel-ICA) was used to examine the relationship between language-related regions extracted from resting-state fMRI and 16 single nucleotide polymorphisms (SNPs) spanning 5 RD-related genes. Parallel-ICA identified four significant fMRI-SNP relationships. A Left Broca-Superior/Inferior Parietal network was related to two KIAA0319 SNPs in controls but not in schizophrenia. For both diagnostic groups, a Broca-Medial Parietal network was related to two DCDC2 SNPs, while a Left Wernicke-Fronto-Occipital network was related to two KIAA0319 SNPs. A Bilateral Wernicke-Fronto-Parietal network was related to one KIAA0319 SNP only in controls. Thus, RD-genes influence functional connectivity in language-related regions, but no RD-gene uniquely affected network function in schizophrenia as compared to controls. This is in contrast with our previous study where RD-genes affected gray matter distribution in some structural networks in schizophrenia but not in controls. Thus these RD-genes may exert a more important influence on structure rather than function of language-related networks in schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain / anatomy & histology
  • Brain / physiology*
  • DNA / genetics
  • Dyslexia / genetics*
  • Dyslexia / pathology*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Language*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Nerve Net / pathology
  • Pilot Projects
  • Polymorphism, Single Nucleotide / genetics
  • Principal Component Analysis
  • Rest / physiology*
  • Schizophrenia / genetics*
  • Schizophrenia / pathology*
  • Schizophrenic Psychology*
  • Sex Characteristics
  • Temporal Lobe / pathology
  • Young Adult

Substances

  • DNA