Age specific interregional cortical thinning indicated similar molecular pathways in multiple psychiatric disorders, according to findings from a multicohort study published in JAMA Psychiatry.

Researchers sought to understand the potential neurodevelopmental underpinnings of psychiatric disorders, which often emerge in adolescence. They combined data from 3 community-based studies (Saguenay Youth Study from Canada, IMAGEN cohort from 8 European cities, and The Brazil High Risk Cohort Study) for a total of 3596 adolescents ages 9 to 21 years. All data were collected between 2003 and 2015.

Magnetic resonance imaging scans were used to estimate age associated thinning of 34 cortical regions aligned with gene expression data from the Allen Human Brain Atlas. Patients were tested by 3 gene expression panels (dendrite, spine, and myelin) to assess alteration in expression patterns.

The sample was 50.1% women and had a mean age of 15.2±2.6 years. Most cortical regions (88.5%) exhibited cortical thinning. The temporal and frontal lobes had the greatest variation in thickness during maturation. Moreover, the inferior temporal gyrus thinned at a rate of -0.071 mm per year at 9 years of age and decelerated to -5.63×10-3 mm per year at 19 years. At 19 years of age, the thinning rate of the pars triangularis was -0.038 mm per year.


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The correlation between gene expression and cortical thinning varied over gene panel and age. The variance in thinning explained by gene expression of myelin-related genes was 0.19% to 26.39%, dendrite-related genes was 0.45% to 10.55%, and spine-related genes was 0.00% to 9.98%. The spine panel was more associated with late childhood (9-12 years), the myelin panel with midadolescence (12-15 years), and the dendrite panel with late adolescence (17-19 years).

Correlations between expression and thinning and their co-expression networks were tested for enrichment with psychiatric disorders. The myelin panel had an enrichment for schizophrenia at 15 years old. The spine and dendrite panels had enrichments for autism spectrum disorder, bipolar disorder, and schizophrenia during midadolescence. The dendrite panel was also moderately enriched for attention deficit/hyperactivity disorder and major depressive disorder. No enrichment for obsessive-compulsive disorder was observed.

A limitation of this study is that all gene expression data for brain regions were based on the Allen Human Brain Atlas. These data were generated from 6 adult donors, and it remains unclear whether brain-related expression patterns are significantly different among adults and children. To address this potential problem, the investigators concentrated on genes with a reliable spatial gradient and applied 2 filters for consistency.

The researchers concluded that the correlation between interregional cortical thinning during maturation and expression patterns of genes associated with multiple psychiatric disorders suggested a common molecular process. They noted that this “genetic similarity suggests overlapping molecular pathways that modify susceptibility to psychiatric disorders during maturation.”

Reference

Parker N, Patel Y, Jackowski A P, et al. Assessment of neurobiological mechanisms of cortical thinning during childhood and adolescence and their implications for psychiatric disorders [published online June 17, 2020]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2020.1495.