Genetic and neurodevelopmental markers in schizophrenia-spectrum disorders: analysis of the combined role of the Cannabinoid Receptor 1 gene (CNR1) and dermatoglyphics

The aetiology of schizophrenia-spectrum disorders (SSD) involves genetic and environmental factors impacting neurodevelopmental trajectories. Dermatoglyphic pattern deviances have been associated with SSD and considered vulnerability markers for these disorders based on the shared ectodermal origin of the epidermis and the central nervous system. The endocannabinoid system participates in epidermal differentiation, is sensitive to the prenatal environment and is associated with SSD. We assessed whether the Cannabinoid receptor 1 (CNR1) gene is a common denominator in dermatoglyphic pattern configurations and SSD risk and whether it modulates the dermatoglyphics-SSD association. In a sample of 112 controls and 97 SSD patients, three dermatoglyphic markers were assessed: the total palmar a-b ridge count (TABRC), the a-b ridge count fluctuating asymmetry (ABRC-FA), and the pattern intensity index (PII). Two CNR1 polymorphisms were genotyped: rs2023239-A/G and rs806379-A/T. We tested the CNR1 association with SSD and with the dermatoglyphic variability within diagnostic groups. Secondly, we assessed the CNR1 x dermatoglyphic measures interaction on SSD susceptibility. Both polymorphisms were associated with the risk for SSD, and within controls, rs2023239 and rs806379 modulated the PII and TABRC, respectively. Lastly, our data showed that rs2023239 modulated the relationship between PII and SSD: a high PII score was associated with a lower SSD risk within G-allele-carriers and a higher SSD risk within AA-homozygotes. These novel results highlight the endocannabinoid systems role in the development and variability of dermatoglyphic patterns. The identified interaction encourages combining genetic and dermatoglyphics to assess neurodevelopmental alterations predisposing to SSD.