Influence of Translocator Protein (TSPO) and rs6971 Variant on Methamphetamine Addiction and Methamphetamine-Associated Psychosis in Turkish Population

Background: Translocator Protein (TSPO) is a transmembrane protein located in the mitochondrial outer membrane and highly expressed in the brain, which makes it a potential biomarker for microglial activation and neuroinflammation in neurodegenerative diseases. However, its role in neuropsychiatric disorders and its contribution to methamphetamine (METH) addiction (MA) remain unclear. Here, we aimed to investigate the association of the TSPO rs6971 with susceptibility to MA and METH-associated psychosis (MAP) and to evaluate its effect on TSPO expression. Methods: We investigated the association of TSPO/rs6971 (Ala147Thr) with susceptibility to MA and METH-associated psychosis (MAP). Genotyping was performed on 300 individuals, including 200 diagnosed with METH use disorder, with 100 of these exhibiting MAP, along with 100 healthy controls (HCs). We explored how different genotypes influence TSPO expression at both the transcript and protein levels using RT-qPCR and ELISA. Results: Age- and sex-adjusted logistic regression analysis revealed nominal associations between the rs6971 AA genotype and MAP under the recessive and co-dominant genetic models, with stronger associations observed after excluding individuals with a family history of psychiatric disorders. Within the MAP group, carriers of the A allele exhibited increased circulating TSPO levels compared to those with the GG genotype. Additionally, higher protein concentrations (p = 0.036) were observed in heterozygous individuals with MAP, compared to METH users without psychosis. Conclusions: Our findings suggest that the expression of TSPO may be influenced by genotype, with A allele carriers showing elevated TSPO expression. Overall, these exploratory findings suggest potential for TSPO-based translational strategies for patients with MA, and highlight the need for more comprehensive evaluations in future research.