Possible role of a dysregulation of the endogenous opioid system in antisocial personality disorder

Abstract

Around half the inmates in prison institutions have antisocial personality disorder (ASPD). A recent theory has proposed that a dysfunction of the endogenous opioid system (EOS) underlies the neurobiology of borderline personality disorder (BPD). In the present theoretical paper, based on a comprehensive database and hand search of the relevant literature, this hypothesis is extended to ASPD, which may be the predominant expression of EOS dysfunction in men, while the same pathology underlies BPD in women. According to evidence from human and animal studies, the problematic behaviours of persons with antisocial, callous, or psychopathic traits may be seen as desperate, unconscious attempts to stimulate their deficient EOS, which plays a key role in brain reward circuits. If the needs of this system are not being met, the affected persons experience dysphoric mood, discomfort, or irritability, and strive to increase binding of endogenous opioids to receptors by using the rewarding effects of aggression by exertion of physical or manipulative power on others, by abusing alcohol or substances that have the reward system as target, by creating an "endorphin rush" by self-harm, by increasing the frequency of their sexual contacts, or by impulsive actions and sensation seeking. Symptoms associated with ASPD can be treated with opioid antagonists like naltrexone, naloxone, or nalmefene.

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

“…Proteomic analysis showed that the largest effect sizes were observed for opioid-binding protein/celladhesion molecule (OPCML), with the highest expression found in ASPD violent offenders, supporting the OPRD1 transcription data. These results support previous research which suggested that a deficient endogenous opioid system contributes to ASPD (Bandelow and Wedekind 2015).…”

The opioid system and the social brain: implications for depression and suicide

“…In fact, in a PET study, female borderline patients showed higher MOR concentrations at baseline relative to healthy controls, and a sustained sadness state was shown to activate the opioid system more potently in patients (Prossin et al ). Antisocial personality disorder has also been related to opioid system dysfunction in men, symmetrically to what has been reported in borderline females (Bandelow and Wedekind ). Patients with self‐injurious behaviors (a form of self‐aggression that tends to co‐occur with, and may possibly be related to suicidal behaviors) typically report that these behaviors help them decrease their emotional pain, an effect that might be due to the recruitment of endogenous opioid signaling (Kirtley et al ; Sher and Stanley ; Stanley et al ).…”

Neurobiological roots of psychopathy

“…Our results showing a decrease in the expression of opioid delta receptor gene are in line with these previous findings. A recent theory suggests that a deficient endogenous opioid system contributes to antisocial personality, proposing that antisocial individuals attempt to stimulate their dysfunctional opioid system by the rewarding effect of substance abuse, and impulsive, sensationseeking, aggressive, and promiscuous behavior [11]. Our data suggest that dysfunction of the opioid system contributes to the phenotype of psychopathy, supporting the recently presented idea that partial opioid receptor agonists, such as (+)-naloxone might be the first effective treatment for psychopathy [11].…”

“…The gene linked to adult antisocial behavior, ABCB1, is also highly expressed in the brain, and implicated in substance abuse [9]. No underlying molecular pathways of severe antisocial and criminal behavior are known, but there is preliminary evidence on dysregulation of the endogenous opioid system and brain opioid receptors [11][12][13] in antisocial individuals. Also abnormal glucose metabolism leading to hypoglycemia has been observed as the strongest predictor for violent crimes [14].…”