Graeme Fairchild

The evidence for a neurobiological model of childhood antisocial behavior.

Children with persistent antisocial and aggressive behavior are diagnosed as having disruptive behavior disorder. The authors review evidence that antisocial children, and especially those who persist with this behavior as they grow older, have a range of neurobiological characteristics. It is argued that serotonergic functioning and stress-regulating mechanisms are important in explaining individual differences in antisocial behavior. Moreover, low fear of punishment and physiological underactivity may predispose antisocial individuals to seek out stimulation or take risks and may help to explain poor conditioning and socialization. The authors propose a theoretical model highlighting the interplay between neurobiological deficits and cognitive and emotional functioning as mediators of the link between early adversity and antisocial behavior problems in childhood. Implications for intervention programs are discussed.

Brain structure abnormalities in early-onset and adolescent-onset conduct disorder

OBJECTIVE The developmental taxonomic theory proposes that neurodevelopmental factors play a critical role in the etiology of early-onset conduct disorder, whereas adolescent-onset conduct disorder arises as a result of social mimicry of deviant peers. Recent studies have challenged this theory by demonstrating that adolescents with both early- and adolescent-onset forms of conduct disorder show impaired emotional learning and abnormal neural activation during facial expression processing. The present study extends this work by investigating brain structure in both subtypes of conduct disorder. METHOD Voxel-based morphometry was used to compare gray matter volumes in four regions of interest (amygdala, insula, anterior cingulate, and orbitofrontal cortex) in male adolescents with early-onset (N=36) or adolescent-onset (N=27) conduct disorder and in healthy comparison subjects (N=27). Whole-brain structural analyses were also performed. RESULTS The combined conduct disorder group displayed gray matter volume reductions in the bilateral amygdala, extending into the insula, relative to healthy comparison subjects. Separate comparisons between healthy subjects and each conduct disorder subgroup revealed lower amygdala volume in both subgroups and reduced right insula volume in the adolescent-onset subgroup. Regression analyses within the conduct disorder subjects alone demonstrated a negative correlation between conduct disorder symptoms and right insula volume. CONCLUSIONS The results demonstrate that gray matter volume reductions in brain regions involved in processing socioemotional stimuli are associated with conduct disorder, regardless of age of onset. Brain structural abnormalities may contribute to the emergence of adolescent-onset as well as early-onset conduct disorder.

Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder.

Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that early-onset and adolescence-limited forms of CD are subject to different aetiological processes. Method: Male adolescents with either early-onset CD (n =42) or adolescence-onset CD (n =39), and controls with no history of serious antisocial behaviour and no current psychiatric disorder (n =40) completed tests of facial expression and facial identity recognition. Dependent measures were: (a) correct recognition of facial expressions of anger, disgust, fear, happiness, sadness, and surprise, and (b) the number of correct matches of unfamiliar faces. Results: Relative to controls, recognition of anger, disgust, and happiness in facial expressions was disproportionately impaired in participants with early-onset CD, whereas recognition of fear was impaired in participants with adolescence-onset CD. Participants with CD who were high in psychopathic traits showed impaired fear, sadness, and surprise recognition relative to those low in psychopathic traits. There were no group differences in facial identity recognition. Conclusions: Both CD subtypes were associated with impairments in facial recognition, although these were more marked in the early-onset subgroup. Variation in psychopathic traits appeared to exert an additional influence on the recognition of fear, sadness and surprise. Implications of these data for the developmental taxonomic theory of antisocial behaviour are discussed.

Cortisol Diurnal Rhythm and Stress Reactivity in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

Background Previous studies have reported lower basal cortisol levels and reduced cortisol responses to stress in children and adolescents with conduct disorder (CD). It is not known whether these findings are specific to early-onset CD. This study investigated basal and stress-induced cortisol secretion in male participants with early-onset and adolescence-onset forms of CD. Methods Forty-two participants with early-onset CD, 28 with adolescence-onset CD, and 95 control subjects participated in the study. They collected saliva across the day to assess their cortisol awakening response and diurnal rhythm. Subsequently, salivary cortisol was measured before, during, and after a psychosocial stress procedure designed to elicit frustration. Cardiovascular activity and subjective mood states were also assessed during stress exposure. Results There were no group differences in morning cortisol levels or the size of the cortisol awakening response. Basal cortisol levels in the evening and at 11 am during the laboratory visit were higher in both CD subgroups relative to control subjects. In contrast, cortisol and cardiovascular responses to psychosocial stress were reduced in both CD subgroups compared with control subjects. All groups reported similar increases in negative mood states during stress. Conclusions Our findings suggest that group differences in cortisol secretion are most pronounced during stress exposure, when participants with CD show cortisol hyporeactivity compared with control subjects. There was no evidence for reduced basal cortisol secretion in participants with CD, but rather increased secretion at specific time points. The results do not support developmentally sensitive differences in cortisol secretion between CD subtypes.

Neural Abnormalities in Early-Onset and Adolescence-Onset Conduct Disorder

CONTEXT Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. OBJECTIVE To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. DESIGN Case-control study. SETTING Government research institute, university department. PARTICIPANTS Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. RESULTS Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

Decision Making and Executive Function in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder and Control Subjects

Background Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Methods Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Results Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Conclusions Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Brain structure abnormalities in adolescent girls with conduct disorder

Background Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD. Our primary objective was to investigate whether female adolescents with CD show changes in grey matter volume. Our secondary aim was to assess for sex differences in the relationship between CD and brain structure. Methods Female adolescents with CD (n = 22) and healthy control participants matched in age, performance IQ and handedness (n = 20) underwent structural magnetic resonance imaging. Group comparisons of grey matter volume were performed using voxel-based morphometry. We also tested for sex differences using archive data obtained from male CD and control participants. Results Female adolescents with CD showed reduced bilateral anterior insula and right striatal grey matter volumes compared with healthy controls. Aggressive CD symptoms were negatively correlated with right dorsolateral prefrontal cortex volume, whereas callous-unemotional traits were positively correlated with bilateral orbitofrontal cortex volume. The sex differences analyses revealed a main effect of diagnosis on right amygdala volume (reflecting reduced amygdala volume in the combined CD group relative to controls) and sex-by-diagnosis interactions in bilateral anterior insula. Conclusions We observed structural abnormalities in brain regions involved in emotion processing, reward and empathy in female adolescents with CD, which broadly overlap with those reported in previous studies of CD in male adolescents.

Research Review: Evaluating and reformulating the developmental taxonomic theory of antisocial behaviour

BackgroundThe developmental taxonomic theory proposes that there are two subtypes of antisocial behaviour. The first is a neurodevelopmental disorder which emerges in early childhood and follows a life-course persistent course, whereas the second emerges in adolescence, remits in early adulthood and reflects peer processes such as mimicry of antisocial peers. The aim of this review was to evaluate the developmental taxonomic theory in the light of recent empirical research. MethodsWe conducted a comprehensive literature review comparing these subtypes of antisocial behaviour based on searches on PubMed and other scientific databases covering the period from 1993 to 2013. We focused on research encompassing psychiatric epidemiology, personality assessment, neuropsychology, neuroendocrinology, genetics, and structural and functional neuroimaging. Sixty one empirical studies were identified that investigated one of these forms of antisocial behaviour separately or explicitly compared childhood-onset and adolescence-onset forms of antisocial behaviour. ResultsEmpirical research provides support for the hypothesis that life-course persistent antisocial behaviour is a neurodevelopmental disorder which emerges in the transactions between individual vulnerabilities and environmental adversity. In contrast to the developmental taxonomic theory, however, empirical findings suggest that severe antisocial behaviour that emerges in adolescence frequently has a negative prognosis and is rarely limited to the adolescent period. In addition, both forms of antisocial behaviour are associated with emotion processing deficits, changes in brain structure and function, alterations in cortisol secretion, and atypical personality traits (such as increased callous-unemotional traits). ConclusionsWe conclude that the developmental taxonomic theory is in need of revision, as differences between life-course persistent and adolescence-onset forms of antisocial behaviour appear to be quantitative, rather than qualitative, in nature. In addition, evidence is accumulating that adolescence-onset antisocial behaviour may also be a neurodevelopmental disorder. To account for the similarities between these groups, despite the differences in their age-of-onset, we propose that the quality of the childs early environment moderates the relationship between individual vulnerabilities and the age-of-onset of antisocial behaviour.

Facial Expression Recognition, Fear Conditioning, and Startle Modulation in Female Subjects with Conduct Disorder

Background Recent behavioral and psychophysiological studies have provided converging evidence for emotional dysfunction in conduct disorder (CD). Most of these studies focused on male subjects and little is known about emotional processing in female subjects with CD. Our primary aim was to characterize explicit and implicit aspects of emotion function to determine whether deficits in these processes are present in girls with CD. Methods Female adolescents with CD (n = 25) and control subjects with no history of severe antisocial behavior and no current psychiatric disorder (n = 30) completed tasks measuring facial expression and facial identity recognition, differential autonomic conditioning, and affective modulation of the startle reflex by picture valence. Results Compared with control subjects, participants with CD showed impaired recognition of anger and disgust but no differences in facial identity recognition. Impaired sadness recognition was observed in CD participants high in psychopathic traits relative to those lower in psychopathic traits. Participants with CD displayed reduced skin conductance responses to an aversive unconditioned stimulus and impaired autonomic discrimination between the conditioned stimuli, indicating impaired fear conditioning. Participants with CD also showed reduced startle magnitudes across picture valence types, but there were no significant group differences in the pattern of affective modulation. Conclusions Adolescent female subjects with CD exhibited deficits in explicit and implicit tests of emotion function and reduced autonomic responsiveness across different output systems. There were, however, no differences in emotional reactivity. These findings suggest that emotional recognition and learning are impaired in female subjects with CD, consistent with results previously obtained in male subjects with CD.

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.