Atypical Dorsolateral Prefrontal Activity in Female Adolescents With Conduct Disorder During Effortful Emotion Regulation.

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD.

Neurodevelopmental correlates of behavioural and emotional problems in a neuropaediatric sample.

Most research does not address the overlap between neurodevelopmental disorders when investigating concomitant mental health problems. The purpose of the present study was to examine the association of intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) with the presence of behavioural and emotional problems after controlling for other well-known correlates and risk factors. The sample included 4- to 18-year-old children who attended neuropaediatric clinics (N = 331). After controlling for adversity, age, gender, other developmental/neurological disorders, parental emotional problems, and parenting strategies, the presence of ADHD but not ASD or ID was uniquely associated with behaviour problems. Neither ADHD nor ASD nor ID was significantly associated with emotional problems after controlling for other risk factors. However, ADHD, ASD and behavioural/emotional disorders but not ID were significantly associated with functional impairment in everyday activities after controlling for other risk factors. Because children with neurodevelopmental disorders have complex needs, a holistic approach to diagnosis and interventions is highly warranted, including the assessment and treatment of behavioural and emotional disorders.

The better of two evils? Evidence that children exhibiting continuous conduct problems high or low on callous-unemotional traits score on opposite directions on physiological and behavioral measures of fear.

The present study examines whether heterogeneous groups of children identified based on their longitudinal scores on conduct problems (CP) and callous-unemotional (CU) traits differ on physiological and behavioral measures of fear. Specifically, it aims to test the hypothesis that children with high/stable CP differentiated on CU traits score on opposite directions on a fear-fearless continuum. Seventy-three participants (M age = 11.21; 45.2% female) were selected from a sample of 1,200 children. Children and their parents completed a battery of questionnaires assessing fearfulness, sensitivity to punishment, and behavioral inhibition. Children also participated in an experiment assessing their startle reactivity to fearful mental imagery, a well-established index of defensive motivation. The pattern of results verifies the hypothesis that fearlessness, assessed with physiological and behavioral measures, is a core characteristic of children high on both CP and CU traits (i.e., receiving the DSM-5 specifier of limited prosocial emotions). To the contrary, children with high/stable CP and low CU traits demonstrated high responsiveness to fear, high behavioral inhibition, and high sensitivity to punishment. The study is in accord with the principle of equifinality, in that different developmental mechanisms (i.e., extremes of high and low fear) may have the same behavioral outcome manifested as phenotypic antisocial behavior.

A general population twin study of conduct problems and the auditory P300 waveform.

Reduced amplitude of the P300 event-related potential has been consistently associated with a variety of externalising problems, including conduct disorder. The few available genetically-informative studies of these relationships, however, were conducted among adolescents/adults (i.e., at an age when conduct disorder has typically already become manifest). Among 200 general population twins with a mean age of 9 years (range 6-14 years), we studied the relationship between the P300 waveform elicited by an auditory oddball task and the DSM-oriented conduct problems scale of the Child Behavior Checklist 6-18. Conduct problems scores were negatively and significantly correlated (r = -0.19, p = 0.01) with P300 amplitude; correlations between P300 amplitude and the other DSM-oriented Child Behavior Checklist scales were non-significant, except for oppositional defiant problems (p = 0.01). We found moderate heritability estimates for both P300 amplitude (0.58, CI:0.37;0.73) and conduct problems (0.52, CI:0.25;0.70). Bivariate twin analyses indicated that the covariation between these two phenotypes can be explained by additive genetic factors only, with a genetic correlation of -0.33. An association between reduced P300 amplitude and conduct problems can be substantiated already in childhood, at an age that precedes the most typical onset of conduct disorder. This relationship appears to be genetic in nature. Reduced P300 amplitude can represent a valuable marker for conduct problems, and can contribute to the early identification of children at high-risk for conduct disorder.

Structural brain alterations associated with schizophrenia preceded by conduct disorder: a common and distinct subtype of schizophrenia?

Conduct disorder (CD) prior to age 15 is a precursor of schizophrenia in a minority of cases and is associated with violent behavior through adulthood, after taking account of substance misuse. The present study used structural magnetic imaging to examine gray matter (GM) volumes among 27 men with schizophrenia preceded by CD (SZ+CD), 23 men with schizophrenia but without CD (SZ-CD), 27 men with CD only (CD), and 25 healthy (H) men. The groups with schizophrenia were similar in terms of age of onset and duration of illness, levels of psychotic symptoms, and medication. The 2 groups with CD were similar as to number of CD symptoms, lifelong aggressive behavior, and number of criminal convictions. Men with SZ+CD, relative to those with SZ-CD, displayed (1) increased GM volumes in the hypothalamus, the left putamen, the right cuneus/precuneus, and the right inferior parietal cortex after controlling for age, alcohol, and drug misuse and (2) decreased GM volumes in the inferior frontal region. Men with SZ+CD (relative to the SZ-CD group) and CD (relative to the H group) displayed increased GM volumes of the hypothalamus and the inferior and superior parietal lobes, which were not associated with substance misuse. Aggressive behavior, both prior to age 15 and lifetime tendency, was positively correlated with the GM volume of the hypothalamus. Thus, among males, SZ+CD represents a distinct subtype of schizophrenia. Although differences in behavior emerge in childhood and remain stable through adulthood, further research is needed to determine whether the differences in GM volumes result from abnormal neural development distinct from that of other males developing schizophrenia.

Disorder-specific dissociation of orbitofrontal dysfunction in boys with pure conduct disorder during reward and ventrolateral prefrontal dysfunction in boys with pure ADHD during sustained attention.

OBJECTIVE: Among children, attention deficit hyperactivity disorder (ADHD) and conduct disorder are often comorbid and overlap clinically. Neuropsychological evidence suggests that children with conduct disorder demonstrate more prominent motivational problems and children with ADHD demonstrate more prominent attention deficits relative to healthy comparison subjects. The purpose of the present study was to investigate disorder-specific abnormalities in the neurobiological correlates of motivation and sustained attention in children and adolescents with pure conduct disorder and children and adolescents with pure ADHD. METHOD: Participants were male pediatric patients, ages 9-16 years, with noncomorbid conduct disorder (N=14) and noncomorbid ADHD, combined hyperactive-inattentive subtype (N=18), as well as age- and IQ-matched healthy comparison subjects (N=16). Both patient groups were medication naive. Event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation during a rewarded continuous performance task that measured sustained attention as well as the effects of reward on performance. RESULTS: During the sustained attention condition, patients with noncomorbid ADHD showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex and increased activation in the cerebellum relative to patients with noncomorbid conduct disorder and healthy comparison subjects. Patients with noncomorbid conduct disorder showed decreased activation in paralimbic regions of the insula, hippocampus, and anterior cingulate as well as the cerebellum relative to patients with noncomorbid ADHD and healthy comparison subjects. However, during the reward condition, patients with noncomorbid conduct disorder showed disorder-specific underactivation in the right orbitofrontal cortex, while patients with noncomorbid ADHD showed disorder-specific dysfunction in the posterior cingulate gyrus. CONCLUSIONS: The findings revealed a process-related dissociation of prefrontal dysfunction in ADHD and conduct disorder patients. Attention-related dysfunction in the ventrolateral prefrontal cortex was seen in ADHD patients, and reward-related dysfunction in the orbitofrontal cortex was seen in conduct disorder patients. These findings, together with the pattern of paralimbic dysfunction demonstrated among children with conduct disorder during sustained attention, support theories of abnormalities in orbitofrontal-paralimbic motivation networks in individuals with conduct disorder and, in contrast, ventrolateral fronto-cerebellar attention network dysfunction in individuals with ADHD.

Fear conditioning and affective modulation of the startle reflex in male adolescents with early-onset or adolescence-onset conduct disorder and healthy control subjects.

BACKGROUND: Impairments in emotional processing may play an etiological role in the development of aggressive or antisocial behavior such as is seen in conduct disorder (CD). These findings may be developmentally sensitive, with neuropsychological impairments confined to those with the early-onset form of CD, which emerges in childhood. We investigated whether adolescents with early- or adolescence-onset CD would acquire fear conditioned responses to a visual conditioned stimulus and show a normal pattern of affective modulation of the startle reflex. METHODS: Electrodermal activity was measured during the fear conditioning process, and electromyographic recording methods were used to assess blink magnitudes elicited by acoustic startle probes during the viewing of emotionally valenced pictures. Forty-one early-onset CD, 28 adolescence-onset CD, and 54 healthy control adolescents participated in the study. RESULTS: Both CD groups showed impaired differential fear conditioning relative to control subjects, while retaining the ability to generate normal skin conductance responses to the aversive unconditioned stimulus. There was a similar relationship between emotional valence of the slides and startle magnitude in CD and control adolescents, but startle-elicited blinks were lower across all emotion categories in both CD subtypes. CONCLUSIONS: Fear conditioning deficits and reduced startle amplitudes were observed in participants with early- and adolescence-onset forms of CD. These findings are consistent with impairments in neural systems subserving emotion and involving the amygdala in CD, regardless of age of onset.