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 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study received funding provided by: i) the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (co-funded by the European Regional Development Fund (ERDF)/European Social Fund "Investing in your future") through the project PI20/01002 to MF-V, through PFIS predoctoral contracts to MG-R (FI19/0352) and NH (FI21/00093) and, a Miguel Servet contract to MF-V (CP20/00072); ii) a PIF-Salut contract to AS-M (SLT017/20/000233), and; iii) the Comissionat per a Universitats i Recerca del DIUE of the Generalitat de Catalunya (Agencia de Gestio d'Ajuts Universitats i de Recerca (AGAUR), 2021SGR1475). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the Sainte Anne Hospital Research Ethics Committee, and all participants provided written informed consent about the study procedures and implications, which were carried out according to the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the corresponding authors.