White Matter Microstructure in Schizophrenia Not Related to Polygenic Risk Score

White matter fibers
White matter fibres. Computer enhanced 3D diffusion spectral imaging (DSI) scan of the bundles of white matter nerve fibres in the brain. The fibres transmit nerve signals between brain regions and between the brain and the spinal cord. Diffusion spectrum imaging (DSI) is a variant of magnetic resonance imaging (MRI) in which a magnetic field maps the water contained in neuron fibers, thus mapping their criss-crossing patterns. A similar technique called diffusion tensor imaging (DTI) is also used to explore neural data of white matter fibres in the brain. Both methods allow mapping of their orientations and the connections between brain regions. Data software: NIH Human Connectome Project www.humanconnectomeproject.org).
Investigators assessed the influence of polygenic risk score on white matter microstructure, which is known to be impaired in individuals with schizophrenia, bipolar disorder, and their relatives.

Alterations in white matter integrity were not associated with polygenetic risk profiles for schizophrenia in a recent article published in the Journal of Psychiatric Research.

Investigators assessed the influence of polygenic risk score on white matter microstructure, which is known to be impaired in individuals with schizophrenia or bipolar disorder and their relatives. The researchers examined data from studies conducted from 2006 to 2017 at the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London, United Kingdom, selecting 141 individuals from the studies and categorizing them into 4 groups: schizophrenia (n=21), bipolar disorder (n=25), relatives of individuals with schizophrenia or bipolar disorder (n=27), and healthy controls (n=68).

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Alongside data on polygenic risk scores, the investigators performed analyses on diffusion tensor imaging data. Reduced fractional anisotropy and elevated mean diffusivity of white matter, analyzed through tract-based spatial statistical, were examined as correlates of poor white matter integrity.

Investigators found no significant correlation between polygenic risk score and fractional anisotropy or mean diffusivity, either as a main effect or a diagnosis-dependent effect.

Polygenic risk score, however, was correlated with fractional anisotropy in 5 regions, of which the right cingulum showed the largest cluster. There was a positive trend of polygenic risk score on fractional anisotropy in the anterior thalamic radiation. Investigators noted positive trends with mean diffusivity in 4 equality small clusters/regions and 1 negative trend in the inferior cerebellar peduncle.

“Although a higher [polygenic risk score] for [schizophrenia] may lead to impaired white matter integrity and poorer neural connectivity, the present test would need to be replicated in a more powerful sample, so the detected trends are confirmed,” the investigators concluded, noting that the sample size of the study was relatively small.


Simões B, Vassos E Shergill S, et al. Schizophrenia polygenic risk score influence on white matter microstructure. J Psychiatr Res. 2020;121:62-67.