Search for genetic and environmental factors predictive of adult psychopathy in a clinical sample of callous-unemotional youths with conduct disorder as compared to populations of incarcerated adolescents and adults

Psychopathy has been conceptualized as a constellation of traits that can be differentiated into interpersonal (e.g., manipulative personality, pathological lying), affective (e.g., callousness/lack of empathy), lifestyle (e.g., irresponsibility, poor behavioral control), and antisocial (e.g., early behavioral problems) dimensions. Though psychopathy has been primarily studied in adult samples, one of the main goals of the current psychiatric research is to identify early signs in youths useful to predict psychopathy in adulthood. Many core features of psychopathy, indeed, as for example low empathy, are often related to behavioral problems and aggression in children. This field of research primarily focuses on children with conduct disorder (CD), who are known to be at risk of developing life-course-persistent antisocial problems, mostly if they show callous-unemotional (CU) traits that are cognitive, affective, social, and personality characteristics resembling the adult affective dimension of psychopathy. My PhD work focused on the investigation of the genetic and environmental correlates of psychopathy from childhood to adulthood with the aim of identifying genetic biomarkers that could be early predictors of psychopathy. To this aim, 14 polymorphisms belonging to the serotonergic (5-HTR1B rs13212041, 5-HTR2A rs6314, MAOA uVNTR, 5-HTTLPR, TPH2 rs4570625), dopaminergic (ANKK1 rs1800497, COMT rs4680, DRD4 exonIII VNTR, DRD4 rs1800955, TH rs6356, SLC6A3 40bp VNTR), and oxytonergic (OXTR rs53576, rs1042778, rs237885) pathways were genotyped in three groups of subjects, each of them representative of a different age of life: a) 985 White male incarcerated adults (19-65 years old) that are the largest sample of criminals studied so far; b) 180 White male incarcerated adolescents (14-18 years old); and c) 120 White male youths with CD (7-16 years old). Psychopathic traits were assessed in incarcerated adults by the Psychopathy Checklist-Revised (PCL-R) questionnaire, in incarcerated adolescentsby the Psychopathy Checklist:Youth Version (PCL:YV), and in CD youths by the Antisocial Process Screening Device (APSD). Youths were also assessed for CU traits by the APSD-CU subscale. Finally, in a subgroup of 247 incarcerated adults, the Measure of Parental Style (MOPS) questionnaire was used to measure the perceived behavior of their parents during the first 16 years of life, while, in CD youths, maltreatment data were collected by the Maltreatment Index (MI) scale. The results of my thesis work showed that the 5-HTR1B rs13212041 T/T genotype increased the risk of psychopathy in both incarcerated adults and incarcerated adolescents; in incarcerated adults, childhood paternal maltreatment positively correlated with psychopathy scores and this correlation was stronger in interaction with the 5-HTR1B rs13212041 T/T genotype, the ANKK1 rs1800497 T allele, the OXTR rs53576 A allele, or the TH rs6356 G/G genotype; specific combinations of these risk alleles, such as 5-HTR1B rs13212041 T/T by ANKK1 rs1800497 T allele by TH rs6356 G/G and 5-HTR1B rs13212041 T/T by TH rs6356 G/G by OXTR rs53576 A allele, synergistically increased the correlation between paternal maltreatment and high psychopathy scores. Interestingly, in children exposed to active maltreatment, the ANKK1 rs1800497 T allele, both per se and in interaction with the 5-HTR1B rs13212041 T/T genotype, was associated with CU trait scores that exceeded the diagnostic cut-off of the APSD-CU subscale. The scientific literature suggests that the identified risk alleles are associated with an increased dopamine and serotonin release. We hypothesized that a greater availability of these neurotransmitters modulated by genetics, make children more receptive to maltreatment, increasing further their risk of developing psychopathy. In conclusion, my Ph.D. work indicates that interaction among the 5-HTR1B rs13212041 T/T genotype, the ANKK1 rs1800497 T allele, and childhood maltreatment is a significant correlate of psychopathic traits from childhood to adultness, thus proposing these two genetic variants as potential biomarkers of developmental life-lasting psychopathy. These findings might help improve the success rate of preventing youths with CD from developing psychopathy as adults throught more intense preventive behavioral treatments tailored to increase the child’s empathic abilities and re-educate parental behavior.