Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study.
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.
Olin Neuropsychiatry Research Center, Institute of Living, 200 Retreat Ave, Hartford, CT 06106, USA. sharna.jamadar@monash.edu
Sharna
S
Jamadar
Natalie R
NR
Powers
Shashwath A
SA
Meda
Vince D
VD
Calhoun
Joel
J
Gelernter
Jeffrey R
JR
Gruen
Godfrey D
GD
Pearlson
D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D004247:DNA / Q000235:genetics; D004410:Dyslexia / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007802:Language; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis; D012146:Rest / Q000502:physiology*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D012565:Schizophrenic Psychology; D012727:Sex Characteristics; D013702:Temporal Lobe / Q000473:pathology; D055815:Young Adult
D004247:DNA