Genetic predisposition to impulsive–antisocial behaviour is a frequent topic in criminal proceedings, though it remains uncertain if these factors can truly override an individual's impulse control. Because multiple determinants contribute to antisocial behaviour, the specific role of a person's genotype often remains unclear in legal and clinical contexts. To isolate gene-related effects, this research examines patients with frontotemporal dementia (FTD) and Alzheimer’s disease (AD), clinical conditions that markedly impair the regulation of impulses. This work reports a preliminary  analysis to demonstrate feasibility of a larger project designed to enrol 55 patients with neurodegenerative disorder from two Italian centres: Sapienza University of Rome (S, n=37, 67%) and Università Cattolica del Sacro Cuore (UCSC/C, n=18, 33%). In this preliminary analysis, 31 individuals were sequenced:18 controls (58.1%) and 13 patients (41.9%), 16 with AD and 15 with FTD. Targeted sequencing was performed on the whole sequence of major candidate genes, including MAO‑A, MAO‑B, TPH1, TPH2, SLC6A4, DRD2, COMT and additional modulators of serotonergic and dopaminergic signaling. The overall mean SNPs frequency was 0.342 (SD=0.265), with very similar values between controls (mean 0.338, SD=0.264) and patients (mean 0.348, SD=0.267), suggesting balanced allele distributions and minimal evidence of population stratification in this preliminary dataset. The chromosomal distribution of SNPs was heterogeneous: chromosome X harbored the largest number of variants (44 SNPs, 20.9%), followed by chromosomes 11 and 22 (41 SNPs each, 19.5%), chromosome 17 (36 SNPs, 17.1%), chromosome 5 (23 SNPs, 10.9%), chromosome 9 (17 SNPs, 8.1%), and chromosome 12 (8 SNPs, 3.8%). Chromosome‑level frequency analysis revealed the highest mean SNP frequency on chromosome X (0.599), encompassing the MAO‑A/MAO‑B locus, whereas chromosomes 17 and 5 showed lower mean frequencies (0.252 and 0.205, respectively), suggesting distinct genetic architectures across monoaminergic loci. Chi‑square case–control comparisons of a total of 209 SNPs, identified only one SNP (chr17:28525050-A-C) with nominally significant association to disease status (p=0.0478, χ²=3.916) but the current results are certainly limited by sample size. Future steps will be expand sample sizes and determine whether it is scientifically valid and clinically meaningful to consider genetic variants for forensic or medico legal purpose.

Authors

• Giorgia Leone (Section of Legal Medicine, Department of Health Surveillance and Bioethics - Università Cattolica del Sacro Cuore, Italy)
• Serena Spartano (Section of Genomic Medicine, Department of Life Sciences and Public Health - Università Cattolica del Sacro Cuore, Italy)
• Simone Grassi (Forensic Medical Sciences, Department of Health Science - University of Florence, Italy)
• Stefano Ferracuti (Department of Human Neuroscience - Sapienza University, Italy)
• Fabrizia D'Antonio (Department of Human Neuroscience - Sapienza University, Italy)
• Tommaso Accinni (Department of Human Neuroscience - Sapienza University, Italy)
• Camillo Marra (Neurology Unit, Department of Neurosciences, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Italy)
• Davide Quaranta (Neurology Unit, Department of Neurosciences, Fondazione  Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Italy)
• Antonio Oliva (Section of Legal Medicine, Department of Health Surveillance and Bioethics - Università Cattolica del Sacro Cuore, UOC Legal Medicine, Fondazione  Policlinico Universitario "A. Gemelli" IRCCS, Italy)