Genetic basis of white matter changes in schizophrenia uncovered
MedWire News: Changes in major white matter pathways in the brain associated with schizophrenia may have a genetic basis that could offer insights into how genes affect brain structure and predispose individuals to schizophrenia, say US scientists.
Identifying endophenotypes in unaffected biological relatives of patients with schizophrenia may highlight specific genetic factors related to the disorder, although findings have so far been conflicting.
Kristi Clark, from the University of California, Los Angeles, and colleagues examined fractional anisotropy (FA) and mean diffusivity (MD) of major white matter pathways in 35 schizophrenia patients, 28 unaffected first-degree patient relatives, 29 community controls, and 28 unaffected community control relatives.
The participants, who were age- and gender-matched, underwent diffusion tensor imaging with high-resolution structural data acquisition to identify differences in FA and MD using a comprehensive atlas-based tract mapping approach.
Compared with community controls, schizophrenia patients had significantly lower FA in the bilateral inferior fronto-occiptal fasciculus (IFO), left inferior longitudinal fasciculus (ILF), left superior longitudinal fasciculus temporal component (tSLF), and bilateral uncinate. Patients also had significantly higher MD in the right anterior thalamic radiation (ATR), forceps minor, bilateral IFO, left tSLF, and bilateral uncinate.
In post-hoc analyses, disparities in FA of the left ILF and IFO, as well as the MD of the right ATR, forceps minor, and bilateral uncinate, remained significant while the other associations became trends, the team notes in the Journal of Psychiatric Research.
Analysis of patients, controls and first-degree unaffected relatives indicated that there were significant genetic liability effects in the FA of the bilateral IFO, bilateral ILF, and left tSLF, with the FA of the ILF remaining significant on post-hoc analysis.
When compared with unaffected relatives, patients had significantly lower FA in the left tSLF, with a trend for a lower FA in the left ILF, and significantly higher MD in the right uncinate.
The researchers conclude: "This study is the first to identify significant indications that these white matter pathways reflect schizophrenia genetic predisposition.
"Thus, FA levels of these three tracts may serve as endophenotypes that may help elucidate the role of specific genetic risk factors in schizophrenia and serve as biomarkers for studies seeking to identify how genes influence altered brain tissue microstructure associated with the disorder."
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By Liam Davenport