Genetic and Neurodevelopmental Markers in Schizophrenia-Spectrum Disorders: Analysis of the Combined Role of the CNR1 Gene and Dermatoglyphics

<b>Background:</b> Dermatoglyphic pattern deviances have been associated with schizophrenia-spectrum disorders (SSD) and are considered neurodevelopment vulnerability markers based on the shared ectodermal origin of the epidermis and the central nervous system. The endocannabinoid system participates in epidermal differentiation, is sensitive to prenatal insults and is associated with SSD. <b>Objective:</b> We aimed to investigate whether the Cannabinoid Receptor 1 gene (<i>CNR1</i>) modulates the dermatoglyphics-SSD association. <b>Methods:</b> In a sample of 112 controls and 97 patients with SSD, 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 <i>CNR1</i> polymorphisms were genotyped: rs2023239-T/C and rs806379-A/T. We tested: (i) the <i>CNR1</i> association with SSD and dermatoglyphic variability within groups; and (ii) the <i>CNR1</i> × dermatoglyphic measures interaction on SSD susceptibility. <b>Results:</b> Both polymorphisms were associated with SSD. The polymorphism rs2023239 modulated the relationship between PII and SSD: a high PII score was associated with a lower SSD risk within C-allele carriers and a higher SSD risk within TT-homozygotes. This result indicates an inverse relationship between the PII and the SSD predicted probability conditional to the rs2023239 genotype. <b>Conclusions:</b> These novel findings suggest the endocannabinoid system's role in the development and variability of dermatoglyphic patterns. The identified interaction encourages combining genetic and dermatoglyphics to assess neurodevelopmental alterations predisposing to SSD in future studies.