Polygenic risk score for schizophrenia and structural brain connectivity in older age: A longitudinal connectome and tractography study

&NA; Higher polygenic risk score for schizophrenia (szPGRS) has been associated with lower cognitive function and might be a predictor of decline in brain structure in apparently healthy populations. Age‐related declines in structural brain connectivity—measured using white matter diffusion MRI —are evident from cross‐sectional data. Yet, it remains unclear how graph theoretical metrics of the structural connectome change over time, and whether szPGRS is associated with differences in ageing‐related changes in human brain connectivity. Here, we studied a large, relatively healthy, same‐year‐of‐birth, older age cohort over a period of 3 years (age ˜ 73 years, N = 731; age ˜76 years, N = 488). From their brain scans we derived tract‐averaged fractional anisotropy (FA) and mean diffusivity (MD), and network topology properties. We investigated the cross‐sectional and longitudinal associations between these structural brain variables and szPGRS. Higher szPGRS showed significant associations with longitudinal increases in MD in the splenium (&bgr; = 0.132, pFDR = 0.040), arcuate (&bgr; = 0.291, pFDR = 0.040), anterior thalamic radiations (&bgr; = 0.215, pFDR = 0.040) and cingulum (&bgr; = 0.165, pFDR = 0.040). Significant declines over time were observed in graph theory metrics for FA‐weighted networks, such as mean edge weight (&bgr; = −0.039, pFDR = 0.048) and strength (&bgr; = −0.027, pFDR = 0.048). No significant associations were found between szPGRS and graph theory metrics. These results are consistent with the hypothesis that szPGRS confers risk for ageing‐related degradation of some aspects of structural connectivity.

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