Theory of mind and the social brain: implications for understanding the genetic basis of schizophrenia

Martin, A. K., Robinson, G., Dzafic, I., Reutens, David and Mowry, Bryan (2014) Theory of mind and the social brain: implications for understanding the genetic basis of schizophrenia. Genes, Brain and Behavior, 13 1: 104-117. doi:10.1111/gbb.12066

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Author Martin, A. K.
Robinson, G.
Dzafic, I.
Reutens, David
Mowry, Bryan
Title Theory of mind and the social brain: implications for understanding the genetic basis of schizophrenia
Journal name Genes, Brain and Behavior   Check publisher's open access policy
ISSN 1601-1848
1601-183X
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1111/gbb.12066
Open Access Status DOI
Volume 13
Issue 1
Start page 104
End page 117
Total pages 14
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.
Formatted abstract
Genome-wide association studies in schizophrenia have recently made significant progress in our understanding of the complex genetic architecture of this disorder. Many genetic loci have been identified and now require functional investigation. One approach involves studying their correlation with neuroimaging and neurocognitive endophenotypes. Theory of Mind (ToM) deficits are well established in schizophrenia and they appear to fulfill criteria for being considered an endophenotype. We aim to review the behavioral and neuroimaging-based studies of ToM in schizophrenia, assess its suitability as an endophenotype, discuss current findings, and propose future research directions. Suitable research articles were sourced from a comprehensive literature search and from references identified through other studies. ToM deficits are repeatable, stable, and heritable: First-episode patients, those in remission and unaffected relatives all show deficits. Activation and structural differences in brain regions believed important for ToM are also consistently reported in schizophrenia patients at all stages of illness, although no research to date has examined unaffected relatives. Studies using ToM as an endophenotype are providing interesting genetic associations with both single nucleotide polymorphisms (SNPs) and specific copy number variations (CNVs) such as the 22q11.2 deletion syndrome. We conclude that ToM is an important cognitive endophenotype for consideration in future studies addressing the complex genetic architecture of schizophrenia, and may help identify more homogeneous clinical sub-types for further study
Keyword Behavior
COMT
Copy number variants
DAOA
Endophenotype
Genetics
Mutations, neurexin
Neuroimaging
OXTR, phenotype
Psychiatry
Schizophrenia
Single nucleotide polymorphisms
Social cognition
Theory of mind
22q deletion syndrome, ZNF804A
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID K24 MH094614
K99 MH101367
K23 MH104515
U54 EB020403
R01 HD050735
K01 MH099232
R01 MH101486
Institutional Status UQ
Additional Notes Article first published online: 24 AUG 2013

 
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Created: Fri, 04 Oct 2013, 00:24:02 EST by Debra McMurtrie on behalf of Queensland Brain Institute