Mapping the structural organization of the brain in conduct disorder: replication of findings in two independent samples.

BACKGROUND: Neuroimaging methods that allow researchers to investigate structural covariance between brain regions are increasingly being used to study psychiatric disorders. Structural covariance analyses are particularly well suited for studying disorders with putative neurodevelopmental origins as they appear sensitive to changes in the synchronized maturation of different brain regions. We assessed interregional correlations in cortical thickness as a measure of structural covariance, and applied this method to investigate the coordinated development of different brain regions in conduct disorder (CD). We also assessed whether structural covariance measures could differentiate between the childhood-onset (CO-CD) and adolescence-onset (AO-CD) subtypes of CD, which may differ in terms of etiology and adult outcomes. METHODS: We examined interregional correlations in cortical thickness in male youths with CO-CD or AO-CD relative to healthy controls (HCs) in two independent datasets. The age range in the Cambridge sample was 16-21 years (mean: 18.0), whereas the age range of the Southampton sample was 13-18 years (mean: 16.7). We used FreeSurfer to perform segmentations and applied structural covariance methods to the resulting parcellations. RESULTS: In both samples, CO-CD participants displayed a strikingly higher number of significant cross-cortical correlations compared to HC or AO-CD participants, whereas AO-CD participants presented fewer significant correlations than HCs. Group differences in the strength of the interregional correlations were observed in both samples, and each set of results remained significant when controlling for IQ and comorbid attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: This study provides new evidence for quantitative differences in structural brain organization between the CO-CD and AO-CD subtypes, and supports the hypothesis that both subtypes of CD have neurodevelopmental origins.

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.

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance-Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT).

BACKGROUND: Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. METHODS/DESIGN: Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). DISCUSSION: MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response. TRIAL REGISTRATION: Adjunctive study to IMPACT trial (Current Controlled Trials: ISRCTN83033550).

Computationally-defined markers of uncertainty aversion predict emotional responses during a global pandemic.

Exposure to stressful life events involving threat and uncertainty often results in the development of anxiety. However, the factors that confer risk and resilience for anxiety following real world stress at a computational level remain unclear. We identified core components of uncertainty aversion moderating response to stress posed by the COVID-19 pandemic derived from computational modeling of decision making. Using both cross-sectional and longitudinal analyses, we investigated both immediate effects at the onset of the stressor, as well as medium-term changes in response to persistent stress. 479 subjects based in the United States completed a decision-making task measuring risk aversion, loss aversion, and ambiguity aversion in the early stages of the pandemic (March 2020). Self-report measures targeting threat perception, anxiety, and avoidant behavior in response to the pandemic were collected at the same time point and 8 weeks later (May 2020). Cross-sectional analyses indicated that higher risk aversion predicted higher perceived threat from the pandemic, and ambiguity aversion for guaranteed gains predicted perceived threat and pandemic-related anxiety. In longitudinal analyses, ambiguity aversion for guaranteed gains predicted greater increases in perceived infection likelihood. Together, these results suggest that individuals who have a low-level aversion toward uncertainty show stronger negative emotional reactions to both the onset and persistence of real-life stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

MEG demonstrates a supra-additive response to facial and vocal emotion in the right superior temporal sulcus.

An influential neural model of face perception suggests that the posterior superior temporal sulcus (STS) is sensitive to those aspects of faces that produce transient visual changes, including facial expression. Other researchers note that recognition of expression involves multiple sensory modalities and suggest that the STS also may respond to crossmodal facial signals that change transiently. Indeed, many studies of audiovisual (AV) speech perception show STS involvement in AV speech integration. Here we examine whether these findings extend to AV emotion. We used magnetoencephalography to measure the neural responses of participants as they viewed and heard emotionally congruent fear and minimally congruent neutral face and voice stimuli. We demonstrate significant supra-additive responses (i.e., where AV > [unimodal auditory + unimodal visual]) in the posterior STS within the first 250 ms for emotionally congruent AV stimuli. These findings show a role for the STS in processing crossmodal emotive signals.

Seven computations of the social brain.

The social environment presents the human brain with the most complex information processing demands. The computations that the brain must perform occur in parallel, combine social and nonsocial cues, produce verbal and nonverbal signals and involve multiple cognitive systems, including memory, attention, emotion and learning. This occurs dynamically and at timescales ranging from milliseconds to years. Here, we propose that during social interactions, seven core operations interact to underwrite coherent social functioning; these operations accumulate evidence efficiently-from multiple modalities-when inferring what to do next. We deconstruct the social brain and outline the key components entailed for successful human-social interaction. These include (i) social perception; (ii) social inferences, such as mentalizing; (iii) social learning; (iv) social signaling through verbal and nonverbal cues; (v) social drives (e.g. how to increase one's status); (vi) determining the social identity of agents, including oneself and (vii) minimizing uncertainty within the current social context by integrating sensory signals and inferences. We argue that while it is important to examine these distinct aspects of social inference, to understand the true nature of the human social brain, we must also explain how the brain integrates information from the social world.

Mentalizing during social InterAction: A four component model.

Mentalizing, conventionally defined as the process in which we infer the inner thoughts and intentions of others, is a fundamental component of human social cognition. Yet its role, and the nuanced layers involved, in real world social interaction are rarely discussed. To account for this lack of theory, we propose the interactive mentalizing theory (IMT) -to emphasize the role of metacognition in different mentalizing components. We discuss the connection between mentalizing, metacognition, and social interaction in the context of four elements of mentalizing: (i) Metacognition-inference of our own thought processes and social cognitions and which is central to all other components of mentalizing including: (ii) first-order mentalizing-inferring the thoughts and intentions of an agent's mind; (iii) personal second-order mentalizing-inference of other's mentalizing of one's own mind; (iv) Collective mentalizing: which takes at least two forms (a) vicarious mentalizing: adopting another's mentalizing of an agent (i.e., what we think others think of an agent) and (b) co-mentalizing: mentalizing about an agent in conjunction with others' mentalizing of that agent (i.e., conforming to others beliefs about another agent's internal states). The weights of these four elements is determined by metacognitive insight and confidence in one's own or another's mentalizing ability, yielding a dynamic interaction between these circuits. To advance our knowledge on mentalizing during live social interaction, we identify how these subprocesses can be organized by different target agents and facilitated by combining computational modeling and interactive brain approaches.

Changes in risk perception and self-reported protective behaviour during the first week of the COVID-19 pandemic in the United States.

Efforts to change behaviour are critical in minimizing the spread of highly transmissible pandemics such as COVID-19. However, it is unclear whether individuals are aware of disease risk and alter their behaviour early in the pandemic. We investigated risk perception and self-reported engagement in protective behaviours in 1591 United States-based individuals cross-sectionally and longitudinally over the first week of the pandemic. Subjects demonstrated growing awareness of risk and reported engaging in protective behaviours with increasing frequency but underestimated their risk of infection relative to the average person in the country. Social distancing and hand washing were most strongly predicted by the perceived probability of personally being infected. However, a subgroup of individuals perceived low risk and did not engage in these behaviours. Our results highlight the importance of risk perception in early interventions during large-scale pandemics.

Psychopathic traits influence amygdala-anterior cingulate cortex connectivity during facial emotion processing.

There is accumulating evidence that youths with antisocial behavior or psychopathic traits show deficits in facial emotion recognition, but little is known about the neural mechanisms underlying these impairments. A number of neuroimaging studies have investigated brain activity during facial emotion processing in youths with Conduct Disorder (CD) and adults with psychopathy, but few of these studies tested for group differences in effective connectivity-i.e. changes in connectivity during emotion processing. Using functional magnetic resonance imaging and psycho-physiological interaction methods, we investigated the impact of CD and psychopathic traits on amygdala activity and effective connectivity in 46 male youths with CD and 25 typically-developing controls when processing emotional faces. All participants were aged 16-21 years. Relative to controls, youths with CD showed reduced amygdala activity when processing angry or sad faces relative to neutral faces, but the groups did not significantly differ in amygdala-related effective connectivity. In contrast, psychopathic traits were negatively correlated with amygdala-ventral anterior cingulate cortex connectivity for angry vs neutral faces, but were unrelated to amygdala responses to angry or sad faces. These findings suggest that CD and psychopathic traits have differential effects on amygdala activation and functional interactions between limbic regions during facial emotion processing.

Cognitive Behavioral Therapy Lowers Elevated Functional Connectivity in Depressed Adolescents.

Imaging studies have implicated altered functional connectivity in adults with major depressive disorder (MDD). Whether similar dysfunction is present in adolescent patients is unclear. The degree of resting-state functional connectivity (rsFC) may reflect abnormalities within emotional ('hot') and cognitive control ('cold') neural systems. Here, we investigate rsFC of these systems in adolescent patients and changes following cognitive behavioral therapy (CBT). Functional Magnetic Resonance Imaging (fMRI) was acquired from adolescent patients before CBT, and 24-weeks later following completed therapy. Similar data were obtained from control participants. Cross-sectional Cohort: From 82 patients and 34 controls at baseline, rsFC of the amygdala, anterior cingulate cortex (ACC), and pre-frontal cortex (PFC) was calculated for comparison. Longitudinal Cohort: From 17 patients and 30 controls with longitudinal data, treatment effects were tested on rsFC. Patients demonstrated significantly greater rsFC to left amygdala, bilateral supragenual ACC, but not with PFC. Treatment effects were observed in right insula connected to left supragenual ACC, with baseline case-control differences reduced. rsFC changes were significantly correlated with changes in depression severity. Depressed adolescents exhibited heightened connectivity in regions of 'hot' emotional processing, known to be associated with depression, where treatment exposure exerted positive effects, without concomitant differences in areas of 'cold' cognition.

Adolescent Major Depressive Disorder: Neuroimaging Evidence of Sex Difference during an Affective Go/No-Go Task.

Compared to female major depressive disorder (MDD), male MDD often receives less attention. However, research is warranted since there are significant sex differences in the clinical presentation of MDD and a higher rate of suicide in depressed men. To the best of our knowledge, this is the first functional magnetic resonance imaging (fMRI) study with a large sample addressing putative sex differences in MDD during adolescence, a period when one of the most robust findings in psychiatric epidemiology emerges; that females are twice as likely to suffer from MDD than males. Twenty-four depressed and 10 healthy male adolescents, together with 82 depressed and 24 healthy female adolescents, aged 11-18 years, undertook an affective go/no-go task during fMRI acquisition. In response to sad relative to neutral distractors, significant sex differences (in the supramarginal gyrus) and group-by-sex interactions (in the supramarginal gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to the healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with a significant group-by-age interaction in connectivity. Future research may consider altered developmental trajectories and the possible implications of sex-specific treatment and prevention strategies for MDD.

Functional MRI of emotional memory in adolescent depression.

INTRODUCTION: Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. Mood-congruent biases in memory tasks are frequently reported in MDD patients, with facilitated memory for negative stimuli. Most functional MRI studies to date have examined the neural correlates of these biases in depressed adults, with fewer studies in adolescents with MDD. Investigation of MDD in adolescence may aid greater understanding of the aetiology and development of the disorder. METHODS: Cognitive biases were investigated in 56 MDD patients aged 11-17 years and a matched group of 30 healthy control participants with a self-referential memory task. Behavioural performance and BOLD fMRI data were collected during both encoding and retrieval stages. RESULTS: The neural response to encoding in adolescents with MDD was found to differ significantly from controls. Additionally, neural responses during encoding and retrieval showed differential relationships with age between patient and control groups, specifically in medial, temporal, and prefrontal regions. CONCLUSIONS: These findings suggest that during adolescence neurophysiological activity associated with emotional memory differs in those with depression compared to controls and may be age sensitive.

Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents.

BACKGROUND: Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. METHODS: Eighty-two Depressed and 24 healthy female adolescents, aged 12-17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. RESULTS: At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalised after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35-13.27) were related at trend-level to activation changes in orbitofrontal cortex. LIMITATIONS: In the follow-up section, a limited number of post-CBT patients were recruited. CONCLUSIONS: To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.

The ecology of human fear: survival optimization and the nervous system.

We propose a Survival Optimization System (SOS) to account for the strategies that humans and other animals use to defend against recurring and novel threats. The SOS attempts to merge ecological models that define a repertoire of contextually relevant threat induced survival behaviors with contemporary approaches to human affective science. We first propose that the goal of the nervous system is to reduce surprise and optimize actions by (i) predicting the sensory landscape by simulating possible encounters with threat and selecting the appropriate pre-encounter action and (ii) prevention strategies in which the organism manufactures safe environments. When a potential threat is encountered the (iii) threat orienting system is engaged to determine whether the organism ignores the stimulus or switches into a process of (iv) threat assessment, where the organism monitors the stimulus, weighs the threat value, predicts the actions of the threat, searches for safety, and guides behavioral actions crucial to directed escape. When under imminent attack, (v) defensive systems evoke fast reflexive indirect escape behaviors (i.e., fight or flight). This cascade of responses to threat of increasing magnitude are underwritten by an interconnected neural architecture that extends from cortical and hippocampal circuits, to attention, action and threat systems including the amygdala, striatum, and hard-wired defensive systems in the midbrain. The SOS also includes a modulatory feature consisting of cognitive appraisal systems that flexibly guide perception, risk and action. Moreover, personal and vicarious threat encounters fine-tune avoidance behaviors via model-based learning, with higher organisms bridging data to reduce face-to-face encounters with predators. Our model attempts to unify the divergent field of human affective science, proposing a highly integrated nervous system that has evolved to increase the organism's chances of survival.

Cortical thickness, surface area, and folding alterations in male youths with conduct disorder and varying levels of callous-unemotional traits.

PURPOSE: Previous studies have reported changes in gray matter volume in youths with conduct disorder (CD), although these differences are difficult to interpret as they may have been driven by alterations in cortical thickness, surface area (SA), or folding. The objective of this study was to use surface-based morphometry (SBM) methods to compare male youths with CD and age and sex-matched healthy controls (HCs) in cortical thickness, SA, and folding. We also tested for structural differences between the childhood-onset and adolescence-onset subtypes of CD and performed regression analyses to assess for relationships between CD symptoms and callous-unemotional (CU) traits and SBM-derived measures. METHODS: We acquired structural neuroimaging data from 20 HCs and 36 CD participants (18 with childhood-onset CD and 18 with adolescence-onset CD) and analyzed the data using FreeSurfer. RESULTS: Relative to HCs, youths with CD showed reduced cortical thickness in the superior temporal gyrus, reduced SA in the orbitofrontal cortex (OFC), and increased cortical folding in the insula. There were no significant differences between the childhood-onset and adolescence-onset CD subgroups in cortical thickness or SA, but several frontal and temporal regions showed increased cortical folding in childhood-onset relative to adolescence-onset CD participants. Both CD subgroups also showed increased cortical folding relative to HCs. CD symptoms were negatively correlated with OFC SA whereas CU traits were positively correlated with insula folding. CONCLUSIONS: Cortical thinning in the superior temporal gyrus may contribute to the social cognitive impairments displayed by youths with CD, whereas reduced OFC SA may lead to impairments in emotion regulation and reward processing in youths with CD. The increased cortical folding observed in the insula may reflect a maturational delay in this region and could mediate the link between CU traits and empathy deficits. Altered cortical folding was observed in childhood-onset and adolescence-onset forms of CD.

Reflected glory and failure: the role of the medial prefrontal cortex and ventral striatum in self vs other relevance during advice-giving outcomes.

Despite the risks, people enjoy giving advice. One explanation is that giving beneficial advice can result in reflected glory, ego boosts or reputation enhancement. However, giving poor advice can be socially harmful (being perceived as incompetent or untrustworthy). In both circumstances, we have a vested interest in the advice follower's success or failure, especially when it reflects specifically on us compared with when it is diffused between multiple advisors. We examined these dynamics using an Advisor-Advisee Game, where subjects acted as an Advisor to a confederate Advisee who selected one of the three options when trying to win money: accept the subject's advice, accept the advice of a second confederate Advisor or accept both Advisors' advice. Results showed that having one's advice accepted, compared with being rejected, resulted in activity in the ventral striatum--a core reward area. Furthermore, the ventral striatum was only active when the subject's advice led to the advisee winning, and not when the advisee won based on the confederate's advice. Finally, the medial prefrontal cortex (MPFC) was more active when the Advisee won or lost money based solely on the subject's advice compared with when the second Advisor's advice was accepted. One explanation for these findings is that the MPFC monitors self-relevant social information, while the ventral striatum is active when others accept advice and when their success leads to reflected glory.

Neurodevelopment and ages of onset in depressive disorders.

How and why do clinical depressive disorders emerge in adolescence? In this Personal View, we present a neurodevelopmental theory to address causes for adolescent onsets of clinical depressive disorders. We argue that theories should account for three perplexing aspects of depressive disorders in adolescence: the episodic nature of depression; differences between sexes in rates of depression across development; and age-differentiated onsets. We consider how theories such as psychosocial acceleration, heterochronic brain development, dual-process models, glucocorticoid vulnerability hypothesis linked to early life stress, and epigenetic and genetic susceptibility might explain some aspects of adolescent depressive disorders. We argue that some synthesis between existing theories might be needed to establish a sufficient neurodevelopmental theoretical framework to explain onsets of depressive disorders in adolescence.

Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder.

INTRODUCTION: The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD) time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric), such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric), where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC) and major depressive disorder (MDD). RESULTS: Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome. CONCLUSION: These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders.

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

OBJECTIVE: There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. METHOD: Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. RESULTS: Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. CONCLUSIONS: The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.

Atypical neural responses during face processing in female adolescents with conduct disorder.

OBJECTIVE: Conduct disorder (CD) in females is associated with negative adult outcomes including mental health problems and personality disorders. Although recent neuroimaging studies have reported changes in neural activity during facial emotion processing in males with CD or callous-unemotional (CU) traits, there have been no neuroimaging studies specifically assessing females with CD. We addressed this gap by investigating whether female adolescents with CD show atypical neural activation when processing emotional or neutral faces. METHOD: We acquired functional magnetic resonance imaging (fMRI) data from 20 female adolescents with CD and 20 female control participants while they viewed angry, sad, and neutral faces. RESULTS: An omnibus group (CD, control) by facial emotion (angry, sad, neutral) analysis of variance (ANOVA) revealed main effects of facial emotion in superior temporal cortex, fusiform gyrus, ventrolateral prefrontal cortex and insula, and main effects of group in medial orbitofrontal cortex (OFC) and right anterior insula. Female participants with CD showed reduced medial OFC and increased anterior insula responses relative to healthy controls. There were no significant group × facial emotion interactions. Lifetime CD symptoms were negatively correlated with amygdala, superior temporal cortex, fusiform gyrus, and dorsolateral prefrontal cortex activity for the contrast "all-faces versus fixation." CU traits were negatively correlated with fusiform gyrus activity for the contrast sad versus neutral faces. CONCLUSION: Females with CD showed atypical neural activation during the processing of all facial expressions, irrespective of valence. Our results demonstrate that severity of CD symptoms and CU traits is important in explaining abnormal patterns of neural activity.