oxytocin and Conduct-Disorder

This study systematically reviewed available evidence regarding associations between polymorphisms of the oxytocin receptor (OXTR) gene and socio-emotional and behavioral functioning in children and adolescents. The search yielded 69 articles, which were grouped into nine categories: depression, anxiety, and internalizing symptoms, alcohol abuse, borderline personality disorder, conduct disorder symptoms or diagnosis, autism spectrum disorder, attention deficit hyperactivity disorder, early childhood attachment and behavior, pro-social skills, and resilience. Direct and/or gene x environment interactions were identified in over half of the studies. ASD and conduct disorder (including callous unemotional traits) were the diagnoses that were most studied and for which there was the strongest evidence of direct links with OXTR polymorphisms. In most studies identifying gene x environment interactions, the candidate OXTR polymorphism was rs53576. Results suggest that OXTR polymorphisms are associated with social, emotional or behavioural functioning in children and adolescents. The mixed findings do, however, highlight the need for further research.

Topics: Adolescent; Autism Spectrum Disorder; Child; Child, Preschool; Conduct Disorder; Emotions; Humans; Oxytocin; Polymorphism, Single Nucleotide; Receptors, Oxytocin; Social Behavior

Callous-unemotional (CU) traits in children and adolescents are an important risk factor for forensic behaviors in youth and in adulthood. There is a strong biologic basis in CU traits, offering the possibility to design biological interventions to address this risk factor. This paper advances the hypothesis that the administration of exogenous oxytocin is a biological intervention worthy of further investigation to address CU traits and moderate future risk factors for forensic behaviors. The evidence for this assertion rests in the empiric evidence that social cognitive deficits play a major role in child and adolescent CU traits and psychopathy. Simultaneously, emerging evidence suggests that youth with CU traits have defined neuroendocrinological correlates within the oxytocin system. A review of the normal neurohormonal physiology of this system is presented to provide a groundwork for the delineation of these correlates. That deficits in this system are found in alternate psychopathologies that present with deficits in social cognition serves as the basis for the hypothesis that these deficits may play a key role in the development and manifestation of CU traits. Their correction through psychopharmacologic and alternate means may provide a future route to addressing a central area of adolescent forensic psychiatry.

Topics: Aggression; Conduct Disorder; Emotions; Humans; Hypothalamo-Hypophyseal System; Oxytocin; Pituitary-Adrenal System; Risk Factors

Conduct disorder (CD) involves aggressive and antisocial behavior and is associated with blunted cortisol stress response in male youths. Far less is known about cortisol stress responsivity in female youths with CD or other neuroendocrine responses in both sexes. Although CD is linked to early adversity, the possibility that neuroendocrine alterations may mediate the relationship between early adversity and CD has not been systematically investigated.. Within the European FemNAT-CD multi-site study, salivary cortisol, testosterone, the testosterone/cortisol ratio, oxytocin, and psychological stress response to a standardized psychosocial stress test (the Trier Social Stress Test [TSST]), together with common pre- and postnatal environmental risk factors, were investigated in 130 pubertal youths with CD (63% female, 9-18 years of age) and 160 sex-, age-, and puberty-matched healthy controls (HCs).. The TSST induced psychological stress in both CD and HCs. In contrast, female and male youths with CD showed blunted cortisol, testosterone, oxytocin, and testosterone/cortisol stress responses compared to HCs. These blunted stress responses partly mediated the relationship between environmental risk factors and CD.. Findings from this unique sample, including many female youths with CD, provide evidence for a widespread attenuated stress responsivity of not only stress hormones, but also sex hormones and neuropeptides in CD and its subgroups (eg, with limited prosocial emotions). Results are the first to demonstrate blunted neuroendocrine stress responses in both female and male youths with CD. Early adversity may alter neuroendocrine stress responsivity. Biological mechanisms should be investigated further to pave the way for personalized intervention, thereby improving treatments for CD.

Topics: Adolescent; Child; Conduct Disorder; Female; Humans; Hydrocortisone; Male; Oxytocin; Saliva; Stress, Psychological; Testosterone

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9-18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.

Topics: Adolescent; alpha-Amylases; Biomarkers; Conduct Disorder; Dehydroepiandrosterone; Estradiol; Female; Gonadal Steroid Hormones; Humans; Hydrocortisone; Male; Neuropeptides; Neurosecretory Systems; Oxytocin; Progesterone; Steroids; Testosterone

The aim of the current study was to compare levels of oxytocin, cortisol, and testosterone in adolescents with either autism spectrum disorder (ASD), or oppositional defiant disorder (ODD)/conduct disorder (CD), and in typically developing individuals (TDI), and relate hormone levels to severity and subtype of aggression and callous-unemotional (CU) traits. Saliva concentrations of oxytocin, cortisol, and testosterone were assessed in 114 male participants (N = 49 ASD, N = 37 ODD/CD, N = 28 TDI,) aged 12-19 years (M = 15.4 years, SD = 1.9). The ASD and the ODD/CD groups had significantly lower levels of oxytocin than the TDI group, and the ODD/CD group had significantly higher levels of testosterone than the ASD group. There were no group effects on cortisol levels. Group differences remained for oxytocin after correcting for the influence of CU traits, but were not significant after controlling for aggression. Results for testosterone became non-significant after correction for either CU traits or aggression. Across groups, higher levels of CU traits were related to higher levels of cortisol and testosterone, however, proactive and reactive aggression were unrelated to all three hormonal levels. The current findings show that, regardless of cognitive ability or comorbid disorders, the diagnostic groups (ASD, ODD/CD) differ from each other by their hormonal levels, with the ASD group characterized by relative low level of oxytocin, and the ODD/CD group by a relative low level of oxytocin and high level of testosterone. These group effects were partly driven by differences in CU traits between the groups.

Topics: Adolescent; Aggression; Attention Deficit and Disruptive Behavior Disorders; Autism Spectrum Disorder; Child; Conduct Disorder; Humans; Hydrocortisone; Male; Netherlands; Oxytocin; Saliva; Testosterone; Young Adult

Inconsistent findings have been found on the relation between oxytocin levels and psychopathy or callous-unemotional (CU) traits in humans, potentially because the role of trauma in oxytocin secretion and the distinction between primary and secondary psychopathy have been overlooked so far. Primary psychopathy has a stronger biological background, whereas secondary psychopathy mainly develops due to environmental adversity, such as childhood trauma. This study investigated the interaction effects of CU traits and childhood trauma on daily salivary oxytocin levels in 57 males living in residential youth care facilities. Participants provided six saliva samples (morning, afternoon, and evening for two consecutive days) and completed self-report questionnaires on CU traits and childhood trauma. A mean daily oxytocin and an oxytocin pattern across the day were examined. A significant interaction between CU traits and one trauma category (emotional neglect) on mean daily oxytocin was observed, demonstrating that subjects with high CU traits and low levels of emotional neglect (primary psychopathy) exhibited lower daily oxytocin secretion compared to subjects with high CU traits and high levels of emotional neglect (secondary psychopathy). There were no significant interactions with the other trauma types or in daily oxytocin patterns. Our findings provided a first insight into the potentially distinct oxytocin concentrations in primary and secondary psychopathy, suggesting that primary psychopathy might be linked to lower daily oxytocin output. Future longitudinal studies are required to unravel the developmental patterns of oxytocin secretion and determine whether lower oxytocin output might be a biomarker of primary psychopathy.

Topics: Adolescent; Adverse Childhood Experiences; Aggression; Child Abuse; Conduct Disorder; Emotions; Humans; Male; Oxytocin; Personality Disorders; Residential Facilities; Saliva; Self Report; Surveys and Questionnaires; Young Adult

The present study aimed to investigate serum cortisol, dehydroepiandrosterone (DHEA), and oxytocin levels of children with attention-deficit/hyperactivity disorder (ADHD) combined presentation and those diagnosed with ADHD combined presentation and coexisting conduct disorder. A total of 74 drug-naive children with ADHD combined presentation alone, 32 children with ADHD combined presentation + conduct disorder, and 42 healthy controls were included. The severities of ADHD and conduct disorder symptoms were assessed via parent- and teacher-rated questionnaires. The severity of aggression, anxiety, and depression symptoms of the children were assessed by the self-report inventories. Independent of potential confounders, including age, sex, pubertal stage, and severity of depression and anxiety, serum oxytocin levels of the ADHD combined presentation + conduct disorder group were significantly lower than those of both the ADHD combined presentation alone and control groups. There was also a trend for the ADHD combined presentation + conduct disorder group to show lower serum DHEA levels than that of the ADHD combined presentation alone group. However, serum cortisol levels did not show significant alterations among the groups. These findings suggest that oxytocin and DHEA may play a role in the pathophysiology of conduct disorder, at least in the presence of ADHD combined presentation.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Conduct Disorder; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Male; Oxytocin; Parents; Self Report; Surveys and Questionnaires

Deficits in empathy, the ability to share an emotion of another individual, constitute a hallmark of several psychopathological conditions, including conduct disorder. The co-occurrence of excess rates of aggression, general violation of societal norms and callous-unemotional traits confers specific risk for adult psychopathy. In the present study, we relied on a recently devised experimental model of conduct disorder in mice to test the potential efficacy of intranasal oxytocin administration. Two subgroups of BALB/cJ male mice exhibiting opposite profiles in emotional contagion (i.e. socially transmitted adoption of another's emotional states) underwent a series of tests mapping onto reactive aggression, information processing, perseverative behaviour, punishment-related emotional memory, physiological arousal and hormonal stress reactivity, with or without intranasal oxytocin administration (5.0 or 20.0 μg/kg). Collectively, our data indicate that a trait of markedly reduced emotional contagion is associated with a behavioural syndrome of sensorimotor gating deficits, impaired emotional memory, increased aggression and stereotyped behaviours, dysregulations in the circadian rhythms of activity and body temperature and dampened physiological reactivity to external stressors. Moreover, in the absence of changes in oxytocin receptor density in the neural network involved in empathy-like behaviour, we showed that oxytocin administration normalised emotional contagion, aggression and behavioural stereotypies, thereby ameliorating the phenotype of mice characterised by deficient empathy-like behaviour. Besides, oxytocin led to a lower, more prolonged neuroendocrine response of the HPA-axis to stress in all mice. Ultimately, current data support the notion that oxytocin may constitute a valid therapeutic approach in disturbances characterised by abnormal aggression and excess callousness.

Topics: Administration, Intranasal; Aggression; Animals; Brain; Conduct Disorder; Disease Models, Animal; Emotions; Empathy; Individuality; Male; Memory; Mice, Inbred BALB C; Oxytocin; Psychotropic Drugs; Punishment; Random Allocation; Receptors, Oxytocin; Social Behavior; Stress, Psychological

The present study evaluated the self-report version of the Inventory of Callous-Unemotional Traits (ICU-SR) in terms of reliability, concurrent validity, and correlation with salivary oxytocin levels, a potential biomarker of CU traits. 67 socially at-risk male adolescents (mean 16.2 years) completed the ICU-SR, ICU teacher-version (ICU-TR), Strengths and Difficulties Questionnaire, and their medical files were coded for previous antisocial acts using Brown-Goodwin Lifetime Aggression Scale. Salivary samples were assayed for oxytocin. The reliability of ICU-SR was lower (α = 0.71) than ICU-TR (α = 0.86). ICU-SR mean score was significantly lower than ICU-TR (M = 25.29, SD = 8.02; M = 33.14, SD = 9.47). ICU-TR but not ICU-SR, significantly correlated with history of antisocial acts (r = 0.40). Two-way analysis of variance showed a significant effect of conduct disorder and oxytocin on ICU-TR but not ICU-SR [F(1,59) = 6.53; F(1,59) = 6.08], and a significant interaction only for ICU-TR [F(1,59) = 2.89]. Subjective self-reports of CU traits may be less reliable and valid than teachers' reports.

Topics: Adolescent; Adolescent Behavior; Antisocial Personality Disorder; Conduct Disorder; Emotions; Humans; Male; Oxytocin; Personality Inventory; Reproducibility of Results; Saliva; Self Report; Young Adult

Callous-unemotional (CU) traits correlate with the severity and prognosis of conduct disorder in youth. The neuropeptide oxytocin (OT) has been linked to prosocial behaviors, including empathy and collaboration with others. This study discusses a possible role for OT in the biology of delinquent behavior. We hypothesized that in delinquent youth OT secretion will correlate with the severity of conduct problems and specifically with the level of CU traits. The study group included 67 male adolescents (mean age 16.2 years) undergoing residential treatment, previously assessed by an open clinical interview and history for the psychiatric diagnosis. Staff based Inventory of Callous-Unemotional traits for psychopathy and Strength and Difficulties Questionnaire were administered, and patients' medical and social personal files were systematically coded for previous history of antisocial acts using the Brown-Goodwin Questionnaire. Salivary OT was assayed by ELISA. Salivary OT levels were inversely correlated with conduct problems severity on Strength and Difficulties Questionnaire (r = -0.27; p ≤ 0.01). Recorded history of antisocial acts did not correlate with current OT levels. Odds ratio (OR) for significant CU traits among subjects with conduct problems was increased in low-OT (OR = 14, p ≤ 0.05) but not in high-OT subjects (OR = 6, p ≥ 0.05). Children with conduct problems and low levels of salivary OT are at risk for significant CU traits. These results suggest a possible role for salivary OT as a biomarker for CU traits and conduct problems severity.

Topics: Adolescent; Antisocial Personality Disorder; Child; Conduct Disorder; Emotions; Female; Humans; Male; Oxytocics; Oxytocin

Child conduct problems (CPs) are a robust predictor of adult mental health; the concurrence of callous-unemotional (CU) traits confers specific risk for psychopathy. Psychopathy may be related to disturbances in the oxytocin (OXT) system. Evidence suggests that epigenetic changes in the OXT receptor gene (OXTR) are associated with lower circulating OXT and social-cognitive difficulties. We tested methylation levels of OXTR in 4- to 16-year-old males who met DSM criteria for a diagnosis of oppositional-defiant or conduct disorder and were stratified by CU traits and age. Measures were DNA methylation levels of six CpG sites in the promoter region of the OXTR gene (where a CpG site is a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its lenth, linked together by phosphate binding), and OXT blood levels. High CU traits were associated with greater methylation of the OXTR gene for two cytosine nucleotide and guanine nucleotide phosphate linked sites and lower circulating OXT in older males. Higher methylation correlated with lower OXT levels. We conclude that greater methylation of OXTR characterizes adolescent males with high levels of CU and CPs, and this methylation is associated with lower circulating OXT and functional impairment in interpersonal empathy. The results add genetic evidence that high CU traits specify a distinct subgroup within CP children, and they suggest models of psychopathy may be informed by further identification of these epigenetic processes and their functional significance.

Topics: Adolescent; Age Factors; Antisocial Personality Disorder; Child; Conduct Disorder; DNA Methylation; Empathy; Epigenesis, Genetic; Family; Humans; Male; Oxytocin; Receptors, Oxytocin; Social Environment

Given the known behavior effects of oxytocin,and in particular its putative effect on trust, affiliation and anxiety, we hypothesized that oxytocin may be involved in the development and expression of callous-unemotional traits in children with aggressive antisocial behavior. We recruited 162 children between the ages of 6 and 16. The majority of subjects were Caucasian (84.0%) compared to African-Canadian (4.9%) and others (11.1%). The oxytocin and oxytocin receptor gene polymorphisms were genotyped and analyzed for possible association with child aggression in a case–control study design as well as with callous-unemotional traits in a within cases analysis. We did not have significant findings with our tested OXTR markers in the case–control analysis. We found the OXTR_rs237885 AA genotype carriers to score higher than AC or CC genotype carriers on the callous-unemotional traits. This result remained significant following correction for multiple testing. No other markers were found to be significant. However, the haplotype consisting of the OXTR_rs237885 A allele and OXTR_rs2268493 A allele was associated with significantly higher callous-unemotionals cores than other haplotypes. This is the first known study to show a significant association between callous unemotional traits in children and adolescents with extreme, persistent pervasive aggression and a polymorphism on the oxytocin receptor. Given the small sample size and the possibility of false positive effects, the need to replicate and verify these findings is required.

Topics: Adolescent; Aggression; Alleles; Antisocial Personality Disorder; Anxiety; Canada; Case-Control Studies; Child; Child Behavior Disorders; Conduct Disorder; Emotions; Female; Genetic Markers; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Narcissism; Oxytocics; Oxytocin; Phenotype; Polymorphism, Genetic; Receptors, Oxytocin

Altered stress response is characteristic for subjects with abnormal aggressive and antisocial behavior, but the underlying biological mechanisms are unclear. We hypothesized that autoantibodies (autoAbs) directed against several stress-related neurohormones may exist in aggressive subjects.. Using enzyme-linked immunosorbent assay, we studied whether autoAbs directed against corticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), oxytocin, and vasopressin are present in serum of male subjects with conduct disorder and prisoners with history of violence. Healthy blood donors served as control subjects.. Both conduct disorder and prisoners groups displayed strongly increased levels of ACTH-reactive immunoglobulin G (IgG) and immunoglobulin M (IgM) autoAbs compared with control subjects. Levels of oxytocin-reactive IgM autoAbs were slightly increased in both groups of aggressive subjects, whereas levels of vasopressin-reactive IgG and IgM autoAbs were lower only in conduct disorder. No differences in the levels of alpha-MSH-reactive autoAbs were found between aggressive and control subjects.. High levels of ACTH-reactive autoAbs as well as altered levels of oxytocin- and vasopressin-reactive autoAbs found in aggressive subjects may interfere with the neuroendocrine mechanisms of stress and motivated behavior. Our data suggest a new biological mechanism of human aggressive behavior that involves autoAbs directed against several stress-related neurohormones.

Topics: Adrenocorticotropic Hormone; Adult; Aggression; alpha-MSH; Antisocial Personality Disorder; Autoantibodies; Conduct Disorder; Enzyme-Linked Immunosorbent Assay; Humans; Male; Middle Aged; Neuropeptides; Neurotransmitter Agents; Oxytocin; Prisoners; Psychiatric Status Rating Scales; Stress, Psychological; Vasopressins; Violence