White Matter Patterns Associated with Mental Illness, Cognitive Ability Identified

The study finds that general psychopathology is a heritable trait in youth which could be detected early in life through brain structural connectivity.

Dag Alnaes, PhD

A new study, published at the end of January in JAMA Psychiatry suggests cognitive ability and psychiatric conditions that emerge in adolescence can be associated with heritable patterns of white matter in the brain that could be identified in brain scans.

“Using machine learning we were able to estimate both cognitive as well as symptom scores from brain imaging of white matter connections,” Dag Alnaes, PhD, a postdoctoral fellow at the Oslo University Hospital, and lead author of the study told MD Magazine. “This suggests that brain images contain clinically relevant information about susceptibility for psychiatric disease.”

In adolescence, the brain rapidly undergoes a variety of changes. The frontal cortex, which is implicated in reasoning and decision-making, continues developing well into early adulthood. Neurons rapidly make many more connections, building complex circuits. The neuronal axons grow myelin sheaths to improve communication between cells, helping to strengthen these circuits. As the adolescent brain is going through all these changes, many psychiatric disorders such as anxiety and schizophrenia are likely to be first diagnosed. Previous studies have suggested that these disorders may be related to dysfunctional development of white matter during this period.

Suspecting that myelination and connectivity may be transdiagnostic criteria for several psychiatric disorders, researchers at the Oslo University Hospital studied genes, brain scans, symptoms of psychopathology and cognition in adolescents from the Philadelphia Neurodevelopmental Cohort (PNC) a National Institute of Mental Health-funded initiative to elucidate interactions between the brain, behavior and genetics.

Over the course of 2 years, the team studied data on 6487 individuals from the PNC who were between the ages of 8 and 22, of which, 729 had both clinical data and MRI brain scans available. They used diffusion magnetic resonance imaging to investigate the structure of connections in the children’s brains, and machine-learning to associate these structural patterns with behavioral phenotypes such as clinical symptoms and cognitive ability. They also conducted genome-wide complex trait analysis to estimate the heritability of these traits.

They found associations between white matter structure in the frontotemporal cortex and psychopathology and cognitive ability for all 729 participants. Both adolescents who had been diagnosed with mental illnesses and children who were at risk of psychiatric illness but had not developed diagnosable symptoms had distinctive, heritable patterns of white matter visible in their brain scans. Rather than associate these patterns with a specific diagnosis, the team showed that they are common across several clinical domains in psychiatry. The genome-wide complex trait analysis showed that these patterns are likely to be heritable.

The large, population-level study complements previous data that implicate white matter abnormalities in a variety of psychiatric diseases. They also showed that behavioral phenotypes such as educational attainment could be associated with white matter patterns.

Alnaes says that the long-term goal for the field is to be able to identify at-risk youth and prevent illness from developing. For this, we’ll need longitudinal studies; the information from this study is not yet ready to be used as diagnostic criteria for patients.

Nonetheless, in an accompanying editorial, David Roalf, PhD, Research Assistant Professor at the Perelman School of Medicine emphasizes that “This offers a better understanding of the developmental antecedents of mental illness, which may aid in earlier diagnosis and the development of novel therapeutic approaches.”

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