16 Dec Gene Linked To Methamphetamine Addiction Identified
MedicalResearch.com Interview with:
Camron D. Bryant, Ph.D.
Laboratory of Addiction Genetics
Department of Pharmacology and Experimental Therapeutics & Psychiatry
Boston University School of Medicine
Boston, MA 02118
Medical Research: What is the background for this study? What are the main findings?
Dr. Bryant: The addictions, including addiction to psychostimulants such as methamphetamine and cocaine, are heritable neuropsychiatric disorders. However, the genetic factors underlying these disorders are almost completely unknown. We used an unbiased, discovery-based genetic approach to fine map a novel candidate genetic factor influencing the acute stimulant response to methamphetamine in mice. We then directly validated the causal genetic factor using a gene editing approach. The gene – Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) – codes for an RNA binding protein that is involved in alternative splicing of hundreds of genes in the brain. Based on a genome-wide transcriptome analysis of differentially expressed genes within the striatum – a crucial brain region involved in the stimulant properties of amphetamines – we predict that Hnrnph1 is essential for proper neural development of the dopamine circuitry in the brain. These findings could have implications for understanding not only the addictions but also other neuropsychiatric disordersthat involve perturbations in the dopaminergic circuitry. (e.g., ADHD and schizophrenia) as well as neurodegenerative disorders such as Parkinson’s disease.
Medical Research: What should clinicians and patients take away from your report?
Dr. Bryant: Genome-wide asssociation studies in humans are currently under powered to detect the majority of common and rare genetic variation that influences the addictions and other neuropsychiatric disorders. As researchers continue to increase their sample sizes in human genetic studies, HNRNPH1 may one day be identified as a key polymorphic genetic factor underlying certain neuronal disorders.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Bryant: We are currently investigating the contribution of Hnrnph1 to methamphetamine addictive behaviors in mice. Furthermore, because Hnrnph1 is involved in alternative splicing of the mu opioid receptor, we are also investigatingHnrnph1 in opioid behaviors. Finally, because Hnrnph1 is an RNA binding protein, we are developing research tools to identify the direct binding targets of Hnrnph1 with the hope of identifying therapeutic targets for treating methamphetamine addiction – a neuropsychiatric disorder for which there is no FDA-approved drug.
Camron Bryant, PhD et al. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity. PLOS Genetics, December 2015 DOI:10.1371/journal.pgen.1005713
Camron D. Bryant, Ph.D. (2015). Gene Linked To Methamphetamine Addiction Identified