Abstract
Our recent study has demonstrated that increased connectivity in the cerebello-thalamo-cortical (CTC) circuitry is a state-independent neural trait that can potentially predict the onset of psychosis. One possible cause of such “trait” abnormality would be genetic predisposition. Here, we tested this hypothesis using multi-paradigm functional magnetic resonance imaging (fMRI) data from two independent twin cohorts. In a sample of 85 monozygotic (MZ) and 52 dizygotic (DZ) healthy twin pairs acquired from the Human Connectome Project, we showed that the connectivity pattern of the identified CTC circuitry was more similar in the MZ twins (r = 0.54) compared with that in the DZ twins (r = 0.22). The structural equation modeling analysis revealed a heritability estimate of 0.52 for the CTC connectivity, suggesting a moderately strong genetic effect. Moreover, using an independent schizophrenia cotwin sample (10 discordant MZ cotwins, 30 discordant DZ cotwins, and 32 control cotwins), we observed a significant linear relationship between genetic distance to schizophrenia and the connectivity strength in the CTC circuitry (i.e., schizophrenia MZ cotwins > schizophrenia DZ cotwins > control twins, P = 0.045). The present data provide converging evidence that increased connectivity in the CTC circuitry is likely to be a heritable trait that is associated with the genetic risk of schizophrenia.
Highlights
Psychotic disorders such as schizophrenia possess a strong genetic basis
This study tested the hypothesis that the CTC hyperconnectivity is related to genetic predisposition to schizophrenia using two independent twin data sets
We observed a relatively high heritability of CTC connectivity in the HCP twin sample and a significant association between CTC hyperconnectivity and genetic proximity to schizophrenia. These findings provide converging evidence that CTC hyperconnectivity is likely to be a heritable trait that is related to the genetic risk of schizophrenia
Summary
Psychotic disorders such as schizophrenia possess a strong genetic basis. Empirical data from research on twins and relatives have revealed an estimated heritability of ~80% and a 10-fold increase of risk in first-degree relatives of patients[1,2], making the study of genetic mechanisms critically important to understand such complex disorders. Our recent study has demonstrated that increased connectivity in the cerebello-thalamo-cortical (CTC) circuitry is a state-independent “trait” alteration that may potentially predict the onset of psychosis and distinguish the patients from the healthy population[6] Such alteration can be reliably detected across multiple functional magnetic resonance imaging (fMRI) paradigms in individuals both at clinical high risk (CHR) and with chronic illness, suggesting a “trait” brain functional abnormality that is robustly present across the entire course of psychotic disorders. These findings highly suggest that increased connectivity in the CTC circuitry may be caused by genetic predisposition to psychosis
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