Psychopathy is associated with altered expression of genes and immune responses related to molecular pathways

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The expression of many genes that have previously been associated with autism is abnormal also in violent psychopathy, a new study shows.

The researchers used stem cell technology to analyze the expression of genes and proteins in the brain cells of psychopathic violent offenders.

Published in Molecular Psychiatry, the findings may open up new avenues for the treatment of psychopathy.

The study was carried out in collaboration between the University of Eastern Finland, the University of Helsinki and Karolinska Institutet in Sweden.

Psychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general population, and 10-30% prevalence among incarcerated criminal offenders.

Psychopathy is known to be strongly hereditary, but whether or not it is associated with abnormal expression of genes or proteins in neurons has remained unclear- up until now.

In the newly published study, the researchers used stem cell technology to analyze the expression of genes and proteins that have been associated with psychopathy.

The study participants’ skin cells were used to create pluripotent stem cells, which were then differentiated into cortical neurons and astrocytes.

The study population comprised of psychopathic violent offenders and healthy controls.

Since psychopathy was accompanied by substance abuse, the study population also included non-psychopathic substance abusers.

This made it possible for the researchers to determine which abnormalities were associated exclusively with psychopathy.

This shows DNA

Psychopathy is known to be strongly hereditary, but whether or not it is associated with abnormal expression of genes or proteins in neurons has remained unclear- up until now. The image is in the public domain.

The study shows that psychopathy is associated with robust alterations in the expression of genes and immune-response-related molecular pathways.

Several of these genes have also been linked to autism.

In neurons, psychopathy was associated with marked upregulation of RPL10P9 and ZNF132, and downregulation of CDH5 and OPRD1.

In astrocytes, RPL10P9 and MT-RNR2 were upregulated.

The expression of these genes explained 30-92% of the variance of psychopathic symptoms.

Psychopathy was also associated with altered expression of proteins related to glucose metabolism and the opioid system.

Several earlier studies have suggested that violent and psychotic behavior are associated with alterations in glucose metabolism and opioidergic neurotransmission.

The new findings support the idea of abnormal opioid system function being a factor underlying psychopathy.

This suggests that using long-lasting injections of naltrexone or buprenorphine to balance the opioid system could be a feasible treatment for psychopathy.


The co-occurrence of child conduct problems (CPs) and callous–unemotional (CU) traits confers risk for psychopathy.

The oxytocin (OXT) system is a likely candidate for involvement in the development of psychopathy. We tested variations in the OXT receptor gene (OXTR) in CP children and adolescents with varying levels of CU traits.

Two samples of Caucasian children, aged 4–16 years, who met DSM criteria for disruptive behavior problems and had no features of autism spectrum disorder, were stratified into low versus high CU traits.

Measures were the frequencies of nine candidate OXTR polymorphisms (single nucleotide polymorphisms).

In Sample 1, high CU traits were associated with single nucleotide polymorphism rs1042778 in the 3′ untranslated region of OXTR and the CGCT haplotype of rs2268490rs2254298rs237889, and rs13316193.

The association of rs1042778 was replicated in the second rural sample and held across gender and child versus adolescent age groups. We conclude that polymorphic variation of the OXTR characterizes children with high levels of CU traits and CPs.

The results are consistent with a hypothesized role of OXT in the developmental antecedents of psychopathy, particularly the differential amygdala activation model of psychopathic traits, and add genetic evidence that high CU traits specify a distinct subgroup within CP children.


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
“Neurobiological roots of psychopathy”. 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, Šárka Lehtonen..
Molecular Psychiatry. doi:10.1038/s41380-019-0488-z

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