The association between delinquent peer affiliation and disruptive behavior interacts with functional brain correlates of reward sensitivity: a biosocial interaction study in adolescent delinquents.

BACKGROUND: Affiliating with delinquent peers may stimulate the development of antisocial behavior, especially for adolescents who are sensitive to social rewards. The current study examines whether the association between delinquent peer affiliation (DPA) and disruptive behavior interacts with functional brain correlates of reward sensitivity in early onset male adolescents delinquents. METHODS: Childhood arrestees (n = 126, mean age = 17.7 [s.d. 1.6]) completed a DPA questionnaire, and participated in an fMRI study in which reward sensitivity was operationalized through responsiveness of the ventral striatum (VS), amygdala, and medial prefrontal cortex (mPFC) during the monetary incentive delay paradigm (reward anticipation and outcome). Symptoms of disruptive behavior disorders (DBD) were assessed through structured psychiatric interviews (Diagnostic Interview Schedule for Children) with adolescents. RESULTS: DPA had a main effect on DBD symptoms. Adolescents with high VS reward responses showed a stronger significant positive association between DPA and DBD symptoms compared to low VS responders. No evidence for an interaction effect was found for the amygdala and mPFC. Post-hoc analyses revealed the positive association between DPA and DBD was only present in males, with a diminishing effect as age increased. CONCLUSIONS: We found evidence for a biosocial interaction between DPA and reward sensitivity of the VS in relation to DBD symptom severity. This study provides the first evidence of an interaction effect between a brain mechanism and an environmental factor in relation to DBD symptoms, implying that susceptibility to influences of delinquent peers may intertwine with individual biological differences.

Resisting aggression in social contexts: The influence of life-course persistent antisocial behavior on behavioral and neural responses to social feedback.

Early adulthood has long been recognized as a potential turning point for the development of antisocial behavior, due to changes in social contexts and ongoing psychological and neurobiological maturation. However, it remains unclear how different developmental trajectories of antisocial behavior, their neural underpinnings, and individual differences in psychopathic traits may help explain the distinct developmental outcomes of individuals who persist in or desist from antisocial behavior in early adulthood - such as how they respond to others in social contexts. Therefore, in the current study, young adults (aged 18-30, 68% male) with a persistent or desistant antisocial trajectory (N = 54), as well as healthy controls (N = 39), completed the Social Network Aggression Task, during which they received positive, neutral, or negative feedback on a personal profile and got the opportunity to retaliate by blasting a loud noise. On a behavioral level, results indicated that in all groups, negative peer feedback evoked higher retaliatory aggression, compared to positive and neutral feedback. On a neural level, when receiving social feedback, individuals with persistent or desistent trajectories showed both similar and dissociable patterns of neural activity; desisting and persisting trajectory groups showed higher activity in the Insula, and the desisting trajectory group showed higher activity in dlPFC. Finally, when participants retaliated, they showed increased dlPFC and ACC activity following positive relative to neutral and negative feedback, where ACC activity correlated most strongly with inhibition of retaliatory responses in the desisting trajectory group. Together, these findings provide novel insights in dissociable patterns of brain activity that may increase our understanding of the mechanisms underlying different developmental trajectories of antisocial behavior.

Effect of Methylphenidate on Resting-State Connectivity in Adolescents With a Disruptive Behavior Disorder: A Double-Blind Randomized Placebo-Controlled fMRI Study.

Some studies suggest that methylphenidate (MPH) might be an effective treatment for antisocial and aggressive behavior in adolescence. However, little is known about the mechanism of action of MPH in adolescents with this kind of psychopathology. MPH is a dopamine and norepinephrine reuptake inhibitor and thus it is likely to affect dopaminergic mesocorticolimbic pathways. This is the first study to investigate the effect of MPH on resting-state connectivity of three mesolimbic seed regions with the rest of the brain in clinical referred male adolescents with a disruptive behavior disorder (DBD). Thirty-six male DBD adolescents and 31 male healthy controls (HCs) were included. DBD subjects were randomly allocated to a single dose of MPH (DBD-MPH, n = 20) or placebo (DBD-PCB, n = 16). Seed-based resting-state functional connectivity of the nucleus accumbens (NAcc), amygdala, and ventral tegmental area (VTA) with the rest of the brain was compared between groups. The NAcc seed showed increased connectivity in DBD-PCB compared to HC with the occipital cortex, posterior cingulate cortex (PCC), precuneus, and inferior parietal lobule (IPL) and increased connectivity in DBD-PCB compared to DBD-MPH with occipital cortex, IPL, and medial frontal gyrus. The amygdala seed showed increased connectivity in DBD-PCB compared to HC with the precuneus and PCC. The VTA seed showed increased connectivity in the DBD-MPH compared to the DBD-PCB group with a cluster in the postcentral gyrus and a cluster in the supplementary motor cortex/superior frontal gyrus. Both NAcc and amygdala seeds showed no connectivity differences in the DBD-MPH compared to the HC group, indicating that MPH normalizes the increased functional connectivity of mesolimbic seed regions with areas involved in moral decision making, visual processing, and attention.

Amygdala functioning during threat acquisition and extinction differentiates antisocial subtypes.

Extensive work implicates abnormal amygdala response during threatening stimuli in youth with antisocial behaviour. However, no research has examined whether youth identified in Primary and Secondary psychopathy subtypes would show differences in amygdala activity in response to threat acquisition and extinction. Latent profile analysis (LPA) was used to identify distinct antisocial groups based on participants' scores on callous-unemotional (CU) traits, anxiety, and familial abuse in a sample of 136 high-risk adolescents (mean age = 17.7, SD = 1.6; 86% male). Functional MRI was then used to assess amygdala activation patterns during a classical differential delay threat-conditioning task. In addition to the Primary and Secondary subtypes, we identified groups mainly high on anxiety and others who were mainly high on abuse. Participants in the Primary group showed lower right amygdala activity in response to neutral male faces compared to the low, Anxious, and Secondary groups, whereas participants in the group with history of abuse exhibited higher right amygdala activity during threat acquisition compared to the rest of the groups. During threat extinction, the Primary group showed lower right amygdala activity compared to the Secondary and abuse groups. This is the first study to reveal amygdala activation in identified psychopathy-related variants during threat conditioning. We found that stratifying the sample based on the identified variants revealed amygdala functioning patterns that furthered our understanding of emotion-based deficits among high-risk adolescents.

Effects of Methylphenidate During Fear Learning in Antisocial Adolescents: A Randomized Controlled fMRI Trial.

OBJECTIVE: Although the neural underpinnings of antisocial behavior have been studied extensively, research on pharmacologic interventions targeting specific neural mechanisms remains sparse. Hypoactivity of the amygdala and ventromedial prefrontal cortex (vmPFC) has been reported in antisocial adolescents, which could account for deficits in fear learning (amygdala) and impairments in decision making (vmPFC), respectively. Limited clinical research suggests positive effects of methylphenidate, a dopamine agonist, on antisocial behavior in adolescents. Dopamine is a key neurotransmitter involved in amygdala and vmPFC functioning. The objective of this study was to investigate whether methylphenidate targets dysfunctions in these brain areas in adolescents with antisocial behavior. METHOD: A group of 42 clinical referred male adolescents (14-17 years old) with a disruptive behavior disorder performed a fear learning/reversal paradigm in a randomized double-blinded placebo-controlled pharmacologic functional magnetic resonance imaging study. Participants with disruptive behavior disorder were randomized to receive a single dose of methylphenidate 0.3 to 0.4 mg/kg (n = 22) or placebo (n = 20) and were compared with 21 matched healthy controls not receiving medication. RESULTS: In a region-of-interest analysis of functional magnetic resonance imaging data during fear learning, the placebo group showed hyporeactivity of the amygdala compared with healthy controls, whereas amygdala reactivity was normalized in the methylphenidate group. There were no group differences in vmPFC reactivity during fear reversal learning. Whole-brain analyses showed no group differences. CONCLUSION: These findings suggest that methylphenidate is a promising pharmacologic intervention for youth antisocial behavior that could restore amygdala functioning. CLINICAL TRIAL REGISTRATION INFORMATION: Fear Conditioning During Specific Conditions in Antisocial Adolescents: A Neuroimaging Study. http://www.trialregister.nl/trialreg/index.asp; NTR4088.

Multidimensional family therapy in adolescents with a cannabis use disorder: long-term effects on delinquency in a randomized controlled trial.

BACKGROUND: Substance use and delinquency are considered to be mutual risk factors. Previous studies have shown that multidimensional family therapy (MDFT) is effective in tackling both conditions on the short term. The current study examines the long-term effects of MDFT on criminal offending. METHODS: 109 adolescents with cannabis use disorder and comorbid problem behavior were randomly assigned to either MDFT or cognitive behavioral therapy (CBT). Police arrest data were collected for 6 years: 3 years prior to and 3 years after treatment entry. Using survival analysis and repeated measure General Linear Models (rmGLM), the two treatment groups were compared on number of arrests, type of offence, and severity of offence. Moderator analyses looking at age, disruptive behavior disorders, history of crimes, family functioning, and (severe) cannabis use were conducted (rmGLM). RESULTS: While police arrest rates increased in the 3 years before treatment, the rates decreased substantially after the start of both treatments. No differences were found between the treatment groups with respect to either time to first offence from the start of the treatment or changes in frequency or severity of offending over time. A treatment effect trend favoring MDFT was found for property offending in the subgroup of adolescents with high baseline-severity of cannabis use. CONCLUSIONS: Across a follow-up period of 3 years, MDFT and CBT were similarly effective in reducing delinquency in adolescents with a cannabis use disorder.Trial registration ISRCTN51014277, Registered 17 March 2010-Retrospectively registered, http://www.isrctn.com/ISRCTN51014277.

Representational Uncertainty in the Brain During Threat Conditioning and the Link With Psychopathic Traits.

BACKGROUND: Psychopathy has repeatedly been linked to disturbed associative learning from aversive events (i.e., threat conditioning). Optimal threat conditioning requires the generation of internal representations of stimulus-outcome contingencies and the rate with which these may change. Because mental representations are imperfect, there will always be uncertainty about the accuracy of representations in the brain (i.e., representational uncertainty). However, it remains unclear 1) to what extent threat conditioning is susceptible to different types of uncertainty in representations about contingencies during the acquisition phase and 2) how representational uncertainty relates to psychopathic features. METHODS: A computational model was applied to functional neuroimaging data to estimate uncertainty in representations of contingencies (CoUn) and the rate of change of contingencies (RUn), respectively, from brain activation during the acquisition phase of threat conditioning in 132 adolescents at risk of developing antisocial personality profiles. Next, the associations between these two types of representational uncertainty and psychopathy-related dimensions were examined. RESULTS: The left and right amygdala activations were associated with CoUn, while the bilateral insula and the right amygdala were associated with RUn. Different patterns of relationships were found between psychopathic features and each type of uncertainty. Callous-unemotional traits and impulsive-irresponsible traits uniquely predicted increased CoUn, while only impulsive-irresponsible traits predicted increased RUn. CONCLUSIONS: The findings suggest that 1) the insula and amygdala differ in how these regions are affected by different types of representational uncertainty during threat conditioning and 2) CoUn and RUn have different patterns of relationships with psychopathy-related dimensions.

Regional grey matter volume and concentration in at-risk adolescents: Untangling associations with callous-unemotional traits and conduct disorder symptoms.

Structural Magnetic Resonance Imaging studies have reported volume reductions in several brain regions implicated in social cognition and emotion recognition in juvenile antisocial populations. However, it is unclear whether these structural abnormalities are specifically related to antisocial features, or to co-occurring callous-unemotional (CU) traits. The present study employed voxel-based morphometry to assess both grey matter volume (GMV) and grey matter concentration (GMC) in a large representative at-risk sample of adolescents (n=134; mean age 17.7yr), characterized by a broad range of CU trait and conduct disorder (CD) symptom scores. There was a significant interaction between CD symptom and CU trait scores in the prediction of GMV in the anterior insula, with a significant positive association between CU traits and GMV in youth low on CD symptoms only. In addition, we found a significant unique positive association between CD symptoms and GMC in the amygdala, and unique negative associations between CU traits and GMC in the amygdala and insula. These findings are in line with accumulating evidence of distinct associations of CD symptoms and CU traits with amygdala and insula GMC in juvenile antisocial populations.

Fear extinction, persistent disruptive behavior and psychopathic traits: fMRI in late adolescence.

Children diagnosed with a Disruptive Behavior Disorder (DBD, i.e. Oppositional Defiant Disorder or Conduct Disorder), especially those with psychopathic traits, are at risk of developing persistent and severe antisocial behavior. Reduced fear conditioning has been proposed to underlie persistent antisocial development. However, we have recently shown that both DBD persisters and desisters are characterized by increased fear conditioning compared with healthy controls (HCs). In this study, we investigated whether brain function during fear extinction is associated with DBD subgroup-membership and psychopathic traits. Adolescents from a childhood arrestee cohort (mean age 17.6 years, s.d. 1.4) who met criteria for a DBD diagnosis during previous assessments were re-assessed and categorized as persistent DBD (n = 25) or desistent DBD (n = 25). Functional MRI during the extinction phase of a classical fear-conditioning task was used to compare regional brain function between these subgroups and 25 matched controls. Both DBD persisters and desisters showed hyperreactivity during fear extinction, when compared with HCs. Impulsive-irresponsible psychopathic traits were positively associated with responses in the fear neurocircuitry and mediated the association between neural activation and group membership. These results suggest that fear acquisition and fear extinction deficits may provide an endophenotype for an emotionally hyperreactive subtype of antisocial development.

Psychopathic traits in adolescents are associated with higher structural connectivity.

Altered structural connectivity has been reported in antisocial juveniles, but findings have been inconsistent. Given the phenotypical heterogeneity among individuals showing antisocial behavior, specification of the association between structural connectivity and the dimensions of psychopathic traits (i.e., callous-unemotional, grandiose-manipulative, and impulsive-irresponsible traits) may aid in more reliably elucidating the neural mechanisms underlying antisocial behavior during adolescence. In this study, a sample of 145 adolescents (mean age 17.6, SD 1.6) from a childhood arrestee cohort participated in a neuroimaging protocol including diffusion tensor imaging (DTI). Fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD), as obtained by tract-based spatial statistics, were associated with juveniles' scores on the Youth Psychopathic Traits Inventory. Grandiose-manipulative traits were positively associated with FA and negatively with RD in a wide range of white matter tracts, suggesting abnormal myelination related to these traits. Callous-unemotional traits were positively associated with FA and AD in specific white matter tracts, including the corpus callosum and corticospinal tract. The differential associations between dimensions of psychopathic traits and measures of structural connectivity support the notion that multiple distinct neural mechanisms underlie antisocial and psychopathic development.

Differential relations between juvenile psychopathic traits and resting state network connectivity.

Traditionally, neurobiological research on psychopathy has focused on categorical differences in adults. However, there is evidence that psychopathy is best described by a set of relatively independent personality dimensions, that is, callous-unemotional, grandiose-manipulative, and impulsive-irresponsible traits, which can be reliably detected in juveniles, allowing investigation of the neural mechanisms leading to psychopathy. Furthermore, complex psychiatric disorders like psychopathy are increasingly being conceptualized as disorders of brain networks. The intrinsic organization of the brain in such networks is reflected by coherent fluctuations in resting state networks (RSNs), but these have not been studied in sufficient detail in relation to juvenile psychopathic traits yet. The current study investigated the distinct associations of juvenile psychopathic traits dimensions with RSN connectivity. Resting-state functional MRI and independent component analysis were used to assess RSN connectivity in a large sample of adolescents (n = 130, mean age 17.8 years) from a childhood arrestee cohort. Associations between scores on each of the three psychopathic traits dimensions and connectivity within and between relevant RSNs were investigated. Callous-unemotional traits were related to aberrant connectivity patterns of the default mode network, which has been implicated in self-referential and moral processes. Impulsive-irresponsible traits were associated with altered connectivity patterns in the frontoparietal cognitive control networks. Grandiose-manipulative traits were not associated with altered connectivity patterns. These findings confirm the association between psychopathic traits and brain network connectivity, and considerably add to emerging evidence supporting neurobiological heterogeneity in the processes leading to psychopathy.

Incentive Processing in Persistent Disruptive Behavior and Psychopathic Traits: A Functional Magnetic Resonance Imaging Study in Adolescents.

BACKGROUND: Children with early-onset disruptive behavior disorder (DBD), especially those with callous-unemotional traits, are at risk of developing persistent and severe adult antisocial behavior. One possible underlying mechanism for persistence is deficient reward and loss sensitivity, i.e., deficient incentive processing. However, little is known about the relation between deficient incentive processing and persistence of antisocial behavior into adulthood or its relation with callous-unemotional and other psychopathic traits. In this study, we investigate the relationship between the neural correlates of incentive processing and both DBD persistence and psychopathic traits. METHODS: In a sample of 128 adolescents (mean age 17.7) with a history of criminal offending before age 12, functional magnetic resonance imaging was performed during a monetary incentive delay task designed to assess neural responses during incentive processing. Neural activation during incentive processing was then associated with DBD persistence and psychopathic traits, measured with the Youth Psychopathic Traits Inventory. RESULTS: Compared with both healthy control subjects and youths who had desisted from DBD, persistent DBD subjects showed lower neural responses in the ventral striatum during reward outcomes and higher neural responses in the amygdala during loss outcomes. Callous-unemotional traits were related to lower neural responses in the amygdala during reward outcomes, while other psychopathic traits were not related to incentive processing. CONCLUSIONS: In the current study, aberrant incentive processing is related to persistence of childhood antisocial behavior into late adolescence and to callous-unemotional traits. This mechanism may underlie treatment resistance in a subgroup of antisocial youth and provide a target for intervention.

Externalizing psychopathology and persistence of offending in childhood first-time arrestees.

This study aims to investigate the predictive validity of externalizing psychopathology for persistence in delinquent behavior when controlling for socio-demographic and first arrest characteristics in childhood first-time arrestees. A sample of first-time arrestees aged under 12 (n = 192) was assessed using the Diagnostic Interview Schedule for Children (DISC-IV) parent-version on attention deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). Based on child and parent reports of offending as obtained at arrest and at 2-year follow-up, three groups of offenders were differentiated: (1) persistent high (n = 48), (2) occasional (n = 62), and (3) persistent low offenders (n = 82). Over one-third of the sample (33.9%) was diagnosed with an externalizing disorder, and 13.5% with both ADHD and ODD or CD. Higher levels of externalizing psychopathology distinguished persistent high offenders from occasional (comorbid ADHD and ODD/CD: OR 8.2, CI 2.6-25.5) and persistent low offenders (comorbid ADHD and ODD/CD: OR 18.2, CI 4.6-72.3; ADHD: OR 4.1, CI 1.3-13.0), over and above socio-demographic and first offense characteristics. Living with both biological parents distinguished the persistent low offenders from the occasional offenders (OR 2.5, CI 1.2-5.0). Since the prevalence of externalizing disorders was high and predicted re-offending, mental health screening and intervention initiatives, aiming at these conditions, should be investigated for this high-risk sample.