Summary: New research finds that psychopathy is associated with altered expression of multiple genes and immune-response pathways in brain cells. In cortical neurons, researchers observed increased expression of RPL10P9 and ZNF132 and decreased expression of CDH5 and OPRD1 in individuals with violent psychopathy. In astrocytes, RPL10P9 and MT-RNR2 were elevated. These gene-expression changes explained a substantial portion of the variation in psychopathic symptoms—up to 92% in some measures—and overlap with genes previously linked to autism spectrum disorders and social interaction deficits, suggesting a possible biological basis for emotional callousness and impaired empathy.
Source: University of Eastern Finland
Overview
A collaborative study carried out by researchers at the University of Eastern Finland, the University of Helsinki and Karolinska Institutet used human induced pluripotent stem cell (iPSC) technology to examine gene and protein expression in neurons and astrocytes derived from skin cells. The goal was to determine whether severe antisocial and violent psychopathy is accompanied by distinct molecular changes in brain cells. The research, published in the journal Molecular Psychiatry, highlights robust differences in gene activity and in molecular pathways related to immune response, glucose metabolism and the opioid system.
Study design and participants
The investigators reprogrammed participants’ skin cells into pluripotent stem cells and then differentiated those cells into cortical neurons and astrocytes for molecular analysis. The study population included six incarcerated individuals characterized as extremely antisocial and violent with psychopathic traits, three non-psychopathic individuals with substance-abuse histories, and six healthy control participants. Including a separate group of substance abusers allowed the team to identify changes that were specific to psychopathy rather than caused by substance misuse.
Key molecular findings
Analysis revealed marked dysregulation of several genes in psychopathy. In neurons, RPL10P9 and ZNF132 showed strong upregulation, while CDH5 and OPRD1 were downregulated. Astrocytes from psychopathic individuals had elevated RPL10P9 and MT-RNR2 expression. These gene-expression differences explained between 30% and 92% of the variance in measured psychopathic traits across study participants. The researchers validated gene-expression results using quantitative PCR.
At the protein level, the study identified altered expression of proteins involved in glucose metabolism and components of the opioid system. These protein-level changes are consistent with previous suggestions that abnormal energy metabolism and altered opioidergic neurotransmission may play a role in violent and antisocial behavior.
Implications and potential clinical relevance
While the findings do not establish direct causation, they provide evidence that psychopathy correlates with specific molecular alterations in brain cells. The overlap between genes implicated in psychopathy and genes previously associated with autism spectrum disorders and social interaction issues raises the possibility that these molecular pathways contribute to deficits in empathy and emotional processing observed in psychopathy.
The observed changes in opioid-related genes and proteins support hypotheses about dysfunctional opioid signaling in psychopathy. Based on this rationale, the authors discuss whether long-acting opioid-modulating treatments such as depot naltrexone or extended-release buprenorphine might merit further study as a therapeutic strategy; however, such applications remain speculative and would require rigorous clinical testing.
Source:
University of Eastern Finland
Media Contacts:
Jari Koistinaho – University of Eastern Finland
Image Source:
The image is in the public domain.
Original Research: Open access. Title: “Neurobiological roots of psychopathy”. Authors include Jari Tiihonen, Marja Koskuvi, Markku Lähteenvuo, Pekka L.J. Virtanen, Ilkka Ojansuu, Olli Vaurio, Yanyan Gao, Ida Hyötyläinen, Katja A. Puttonen, Eila Repo-Tiihonen, Tiina Paunio, Marja-Riitta Rautiainen, Sasu Tyni, Jari Koistinaho and Šárka Lehtonen. Journal: Molecular Psychiatry. DOI: 10.1038/s41380-019-0488-z
Summary of the article’s abstract
Psychopathy affects roughly 1% of the general population and 10–30% of incarcerated offenders. Although severe antisocial behavior shows substantial heritability, the molecular basis has been poorly understood. Using iPSC-derived cortical neurons and astrocytes from psychopathic violent offenders, non-psychopathic substance abusers, and healthy controls, the study identified pronounced alterations in expression of several genes and immune response–related pathways specific to psychopathy. Neuronal upregulation of RPL10P9 and ZNF132 and downregulation of CDH5 and OPRD1, together with astrocytic upregulation of RPL10P9 and MT-RNR2, were among the key findings. These changes explained a large portion of symptom variability and were confirmed by qPCR. The genes implicated may contribute to reduced empathy and emotional callousness, given previous links to autism and social interaction deficits.