Brain dysconnectivity, white matter patterns in children may show future of mental illness

A recent study published in the January issue of JAMA has shown that dimensional and heritable cognitive and psychopathology factors are associated with white matter patterns in the brain apparent in adolescents diagnosed with mental illness or who show symptoms.  

After analyzing MRI brain scans (46 percent female, 54 percent male) of the 748 study participants (all between the ages of eight and 21 years old) collected from the Philadelphia Neurodevelopmental Cohort, researchers found that general psychopathology is a heritable trait during youth. In other words, brain dysconnectivity as a "transdiagnostic phenotype" can be detected early in children who may be susceptible to mental illness. The study was conducted over a two-year time frame.  

"Independent component analysis was used to drive dimensional psychopathology scores, and genome-wide complex trait analysis was used to estimate its heritability," said lead author of the study Dag Alnæs, PhD, from Oslo University Hospital in Norway. "Multimodal fusion simultaneously modeled contributions of the diffusion magnetic resonance imaging metrics fractional anisotropy, mean diffusivity, radial diffusivity, L1 (the principal diffusion tensor imaging eigen value), mode of anisotropy, as well as dominant and secondary fiber orientations, and structural connectivity density, and their association with general psychopathology and cognition."  

According to study results, researchers found that all 729 participants showed relationships between general psychopathology levels and cognition, which are both are heritable and showed a negative genetic correlation by, through using machine learning and 10-fold cross validation and permutation testing.   

"The present findings show that such abnormalities are present also in youth who do not have a diagnosis but are at risk for psychiatric disease," Alnæs said.  

The cognitive associations were specifically observed for mental illnesses such as anxiety, antisocial behavior, conduct disorder and schizophrenia. The team also found that the most common feature for general psychopathology levels and cognition was brain white matter reflecting frontotemporal connectivity and crossing fibers in the uncinate fasciculus.  

"We have shown that general factors of cognition and symptoms of psychopathology in children and adolescents are heritable traits that show partly overlapping genetic architecture," Alnæs and his team wrote. "Further, we demonstrated that these behavioral phenotypes, which are likely to represent proxies of critical adult-life indicators, including educational attainment and mental health, are associated with brain white matter characteristics as revealed using advanced multivariate analysis of diffusion MRI metrics."