Neurobiological roots of psychopathy

Abstract

Psychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general population, and 10-30% among incarcerated criminal offenders. Although the heritability of severe antisocial behavior is up to 50%, the genetic background is unclear. The underlying molecular mechanisms have remained unknown but several previous studies suggest that abnormal glucose metabolism and opioidergic neurotransmission contribute to violent offending and psychopathy. Here we show using iPSC-derived cortical neurons and astrocytes from six incarcerated extremely antisocial and violent offenders, three nonpsychopathic individuals with substance abuse, and six healthy controls that there are robust alterations in the expression of several genes and immune response-related molecular pathways which were specific for psychopathy. 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. Expression of aforementioned genes explained 30-92% of the variance of psychopathic symptoms. The gene expression findings were confirmed with qPCR. These genes may be relevant to the lack of empathy and emotional callousness seen in psychopathy, since several studies have linked these genes to autism and social interaction.

A Systematic Literature Review of Neuroimaging of Psychopathic Traits

“…Furthermore, identifying genes may reveal viable biomarkers for psychopathy. Recently psychopathy was also associated with upregulation of Ribosomal protein L10 Pseudogene 9 (RPL10P9), Zinc finger protein 132 (ZNF132), and downregulation of Cadherin-5 (CDH5) and Opioid receptor Delta 1 (OPRD1) genes, which explained 30% to 92% of the variance in psychopathic symptoms in a stem cell derived study by Tiihonen et al (185). Identifying more genes and examining their relationship to brain structure and function might provide useful information of the neurobiological etiology of psychopathy.…”

Mental health dished up—the use of iPSC models in neuropsychiatric research

“…There is currently only one published study using iPSC-based models to investigate PD pathomechanisms. Tiihonen et al (2019) focused on antisocial personality disorder (ASPD), of which no underlying molecular pathways are known. It is characterised by aggression, hostility, callousness, manipulativeness, deceitfulness, impulsivity, and its most severe symptom; psychopathy (Tiihonen et al 2019).…”

“…Tiihonen et al (2019) focused on antisocial personality disorder (ASPD), of which no underlying molecular pathways are known. It is characterised by aggression, hostility, callousness, manipulativeness, deceitfulness, impulsivity, and its most severe symptom; psychopathy (Tiihonen et al 2019). ASPD has a prevalence rate of 1-3% in the general population, which increases to 40-70% in prison populations.…”

Forensic psychiatry in Finland: an overview of past, present and future

“…More recently, there has been an increasingly wide array of contributions by Finnish forensic psychiatrists to the scientific literature, ranging from biological psychiatry [24][25][26][27][28][29] and pharmacological interventions [30][31][32] to the psychiatric epidemiology of violence [33,34] and forensic nursing and rehabilitation [35][36][37][38][39], to mention but a few.…”