Differentiating autism spectrum disorder and overlapping psychopathology with a brief version of the social responsiveness scale.

The Social Responsiveness Scale (SRS) is a well-established measure of autism spectrum disorder (ASD), yet it is known to suffer reduced specificity in samples of children with comorbid emotional or behavioural problems. This research examined the specificity of the SRS in children with mixed presentations of internalising and externalising psychopathology and ASD. Participants were 522 (397 male) children aged between 4 and 16 years. The associations between SRS total scores and diagnoses were determined using partial correlations and analyses of variance. A subsample of participants with a single diagnosis was used to identify a subset of questions that distinguished between ASD and all other diagnoses. These items were used to create the 16-item SRS-brief. The SRS was found to have good reliability and sensitivity but poor specificity. The SRS-brief had good psychometric properties and was found to be a more accurate tool for the screening of ASD than the original SRS.

Polymorphisms in the oxytocin receptor gene are associated with the development of 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 rs2268490, rs2254298, rs237889, 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.

Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy.

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.

Revisiting the treatment of conduct problems in children with callous-unemotional traits.

OBJECTIVE: This study examined whether the diminished treatment response previously reported for children with conduct problems and high levels of callous-unemotional (CU) traits is evident when these traits are indexed using multi-informant data collected from mothers, fathers, and teachers. It also tested whether treatment outcomes associated with CU traits are independent of overlap between CU traits and autism spectrum disorder (ASD) symptoms. METHOD: Diagnostic data on oppositional defiant disorder (ODD) severity were collected pre-treatment (time 1) and at 6-month follow-up (time 2) in a sample of children (N = 95; 67 boys, 28 girls) aged 3-9 years with clinic-referred conduct problems and comorbid symptoms in a range of diagnostic domains. Time 1 measures of CU traits and ASD symptoms were tested as predictors of time 2 ODD severity using structural equation modeling, with multi-informant ratings of CU traits modeled as a single latent variable. RESULTS: Compared to children with low levels of CU traits, those with high levels exhibited more severe ODD symptoms at follow-up (ß = 0.33, SE = 0.08, p < 0.05), after controlling for pre-treatment severity, socio-economic status, other demographics (age, gender), and parameters of treatment (number of treatment sessions, medication status). Although CU traits and ASD symptoms were positively correlated, ASD symptoms showed no association with change in ODD severity from pre-treatment to follow-up. Likewise, the association between CU traits and ODD outcomes held when controlling for covariation between CU traits and ASD symptoms. CONCLUSIONS: Our findings replicate previous evidence that CU traits are uniquely associated with poor clinical outcomes among children treated for conduct problems, and show for the first time that this association is not accounted for by symptoms of ASD.

Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial.

The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day 'live-in' intervention using a double-blind randomized control trial. 38 male youths (7-16 years old) with autism spectrum disorders were administered 24 or 12 international units (depending on weight) intranasal placebo or oxytocin once daily over four consecutive days. The oxytocin or placebo was administered during parent-child interaction training sessions. Parent and child behaviours were assessed using parent reports, clinician ratings, and independent observations, at multiple time points to measure side-effects; social interaction skills; repetitive behaviours; emotion recognition and diagnostic status. Compared to placebo, intranasal oxytocin did not significantly improve emotion recognition, social interaction skills, or general behavioral adjustment in male youths with autism spectrum disorders. The results show that the benefits of nasal oxytocin for young individuals with autism spectrum disorders may be more circumscribed than suggested by previous studies, and suggest caution in recommending it as an intervention that is broadly effective.

Replication of a ROBO2 polymorphism associated with conduct problems but not psychopathic tendencies in children.

The co-occurrence of conduct problems (CPs) and high callous-unemotional (CU) traits specifies risk for adult psychopathy and is under a high genetic influence. A previous genome-wide pooled DNA study of 7-year olds identified a set of candidate single-nucleotide polymorphisms (SNPs) that might differentiate high CP+CU children from healthy children. We attempted to replicate an identified subset of these SNP-psychopathy associations. In a case-control design, 210 clinically referred children were partitioned into Comparison, High CP+Low CU, and High CP+CU groups and genotyped. One SNP, rs13064369, differentiated the groups but was associated with high CP, regardless of the level of CU traits, that is, the rare and heterozygote variants CC and CT were significantly more frequent in both CP groups compared with Comparisons but did not differ from each other. We replicated the finding that a polymorphism associated with the ROBO2 gene, which is involved in neurodevelopment, confers risk for the common emotionally reactive, impulsive aspects of conduct disorder, independent of concurrent risk for psychopathy.

Outcomes, moderators, and mediators of empathic-emotion recognition training for complex conduct problems in childhood.

Impairments in emotion recognition skills are a trans-diagnostic indicator of early mental health problems and may be responsive to intervention. We report on a randomized controlled trial of "Emotion-recognition-training" (ERT) versus treatment-as-usual (TAU) with N=195 mixed diagnostic children (mean age 10.52 years) referred for behavioral/emotional problems measured at pre- and 6 months post-treatment. We tested overall outcomes plus moderation and mediation models, whereby diagnostic profile was tested as a moderator of change. ERT had no impact on the group as a whole. Diagnostic status of the child did not moderate outcomes; however, levels of callous-unemotional (CU) traits moderated outcomes such that children with high CU traits responded less well to TAU, while ERT produced significant improvements in affective empathy and conduct problems in these children. Emotion recognition training has potential as an adjunctive intervention specifically for clinically referred children with high CU traits, regardless of their diagnostic status.

A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research.

BACKGROUND: Human research investigating the impact of intranasal oxytocin on psychological processes has accelerated over the last two decades. No review of side effects, subjective reactions and safety is available. METHOD: A systematic review of 38 randomised controlled trials conducted between 1990 and 2010 that investigated the central effects of intranasal oxytocin was undertaken. A systematic search for reports of adverse reactions involving intranasal oxytocin was also completed. RESULTS: Since 1990, research trials have reported on N=1529 (79% male) of which 8% were participants with developmental or mental health difficulties. Dosages ranged from 18 to 40 IU, mainly in single doses but ranged up to 182 administrations. Diverse methods have been used to screen and exclude participants, monitor side effects and subject reactions. Side effects are not different between oxytocin and placebo and participants are unable to accurately report on whether they have received oxytocin and placebo. Three case reports of adverse reactions due to misuse and longer-term use of intranasal oxytocin were reported. CONCLUSIONS: The evidence shows that intranasal oxytocin: (1) produces no detectable subjective changes in recipients, (2) produces no reliable side-effects, and (3) is not associated with adverse outcomes when delivered in doses of 18-40 IU for short term use in controlled research settings. Future research directions should include a focus on the dosage and duration of use, and application with younger age groups, vulnerable populations, and with females.