Cardiff University researchers found that multiple neurobiological pathways can lead to schizophrenia, with a complex relationship between the structural thickness of brain regions and rare risk variants. This is evident from study results published in the British Journal of Psychiatry.
There are limited data on the impact of the genetic risk of schizophrenia on brain anatomy and the neurobiological basis of the disorder. The study researchers tried to analyze the effect of rare copy number variants (CNV) associated with the disorder on the cortical anatomy of the brain in healthy individuals.
The study researchers used data from the British biobank for this regression analysis. Magnetic resonance imaging (MRI) T1 images of the brains of 18,534 subjects were included. Participants also provided genetic samples and had no history of neuropsychiatric disorders or neurological conditions that could affect cortical anatomy.
All participants were white, British, or Irish (53%, women; mean age 55) [standard deviation [SD]7.46 years]). In the study population, gender was evenly distributed between carriers of known schizophrenia variants and non-carriers (c20.78; P> .1). 49% of the carriers had the most common CNV deletion 15q11.2.
The reduction in total brain surface area (b, -0.020 mm²; P <0.001) and the thicker cortex (b, 0.015 mm; P = 0.035) was associated with carrying an established schizophrenia-associated CNV.
Within specific CNVs, deletions 1q21.1 (n = 9; b, -0.011 mm2; P = .006) and 15q11.2 (n = 59; b, -0.016 mm2; P <.001) were significantly associated with the surface Area reductions. The 15q11.2 deletion was also significantly associated with a thicker cortex (b, 0.020 mm; P = 0.006).
The total structural surface covariance did not differ between carriers and non-carriers of schizophrenia-associated CNVs (z, 0.16 versus 0.14; P = 0.239). The structural covariance of cortical thickness was significantly increased among wearers compared to non-wearers (z, 0.31 versus 0.22; P <0.0005); This has been widely observed in gyri.
Despite the large sample size, the penetrance of schizophrenia-associated CNVs limited sample size and performance. The study’s investigators noted that further studies should try to replicate these findings in the future version of the UK Biobank, which is expected to contain MRI data from 100,000 people.
The study’s authors concluded that individuals who wear schizophrenia-associated variants have reduced cortical surface area and increased cortical thickness compared to non-wearers. However, they added that “the heterogeneity seen in the effects of rare risk alleles suggests potentially different neurobiological gates to the schizophrenic phenotype”.
Caseras X, Kirov G., Kendall KM, et al. Effects of Genomic Copy Number Variants Penetrating for Schizophrenia on Cortical Thickness and Surface Area in Healthy Individuals: Analysis of the UK Biobank. Br J Psychiatry. 2020; 1-8. doi: 10.1192 / bjp.2020.139
This article originally appeared on Psychiatry Advisor