Dysfunction in differential reward-punishment responsiveness in conduct disorder relates to severity of callous-unemotional traits but not irritability.

BACKGROUND: Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD. METHODS: The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment. RESULTS: Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices. CONCLUSIONS: The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.

Different forms of childhood maltreatment have different impacts on the neural systems involved in the representation of reinforcement value.

BACKGROUND: The current study aimed to address two gaps in the literature on child maltreatment, reinforcement processing and psychopathology. First, the extent to which compromised reinforcement processing might be particularly associated with either neglect or abuse. Second, the extent to which maltreatment-related compromised reinforcement processing might be associated with particular symptom sets (depression, conduct problems, anxiety) or symptomatology more generally. METHODS: A sample of adolescents (N = 142) aged between 14 and 18 years with varying levels of prior maltreatment participated in this fMRI study. They were scanned while performing a passive avoidance learning task, where the participant learns to respond to stimuli that engender reward and avoid responding to stimuli that engender punishment. Maltreatment (abuse and neglect) levels were assessed with the Childhood Trauma Questionnaire (CTQ). RESULTS: We found that: (i) level of neglect, but not abuse, was negatively associated with differential BOLD responses to reward-punishment within the striatum and medial frontal cortex; and (ii) differential reward-punishment responses within these neglect-associated regions were particularly negatively associated with level of conduct problems. CONCLUSION: Our findings demonstrate the adverse neurodevelopmental impact of childhood maltreatment, particularly neglect, on reinforcement processing. Moreover, they suggest a neurodevelopmental route by which neglect might increase the risk for conduct problems.

Reduced top-down attentional control in adolescents with generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) can significantly impair quality of life and is associated with a relatively poor long-term prognosis. Anxiety disorders are often associated with hyper-responsiveness to threat, perhaps coupled with impaired executive functioning. However, GAD, particularly adolescent GAD, has been the focus of little functional neuroimaging work compared to other anxiety disorders. Here, we examine the neural association of adolescent GAD with responsiveness to threat and response control. METHODS: The study involved 35 adolescents with GAD and 34 healthy comparison individuals (N = 69) matched on age, gender, and IQ. Participants were scanned during an affective number Stroop task. RESULTS: We found significant Group-by-Task Condition interactions in regions involved in response control/motor responding (bilateral precentral gyri and cerebellum) and/or cognitive control/attention (dorsomedial and lateral frontal cortex, posterior cingulate cortex, cuneus, and precuneus). In line with predictions, the youth with GAD showed significantly less recruitment during task trials than the healthy comparison individuals. However, no indications of specific heightened responses to threat were seen. CONCLUSIONS: GAD involves reduced capacity for engaging regions involved in response control/motor responding and/or cognitive control/attention. This might reflect either a secondary consequence of the patient's worry or an early risk factor for the development of worry.

Callous-Unemotional Traits Moderate the Relationship Between Irritability and Threatening Responding.

Background: Irritability and callous-unemotional (CU; reduced guilt/empathy) traits vary dimensionally in the typically developing population but may be particularly marked in youth with conduct disorder (CD). While these dimensional traits are positively correlated, they have been associated with divergent forms of dysfunction, particularly with respect to threat processing (i.e., irritability with increased, and CU traits with decreased, threat responsiveness). This suggests that interactions between these two dimensions may be complex at the neurobiological level. However, this issue has received minimal empirical attention. Methods: The study included 105 adolescents (typically developing and cases with CD; N = 59). They were scanned with fMRI during a looming threat task that involved images of threatening and neutral human faces or animals that appeared to be either looming or receding. Results: Significant irritability-by-CU traits-by-Direction-by-Emotion interactions were seen within right thalamus/PAG, left lingual gyrus and right fusiform gyrus; irritability was positively associated with the BOLD response for Looming Threatening vs. Receding Threatening trials, particularly for youth with low CU traits. In contrast, CU traits were negatively associated with the same differential BOLD response but particularly for youth showing higher levels of irritability. Similar findings were seen within left ventral anterior and posterior cingulate cortices, though the addition of the interaction with CU traits was only seen at slightly more lenient thresholds. Conclusions: The results support previous work linking irritability to increased, and CU traits to reduced, threat responsiveness. However, for adolescents with high irritability, if CU traits are also high, the underlying neuropathology appears to relate to reduced, rather than increased, threat responsiveness.

Alcohol Use Disorder and Cannabis Use Disorder Symptomatology in Adolescents and Aggression: Associations With Recruitment of Neural Regions Implicated in Retaliation.

BACKGROUND: Alcohol and cannabis are commonly used by adolescents in the United States. Both alcohol use disorder (AUD) and cannabis use disorder (CUD) have been associated with an increased risk of aggression. One form of aggression seen during retaliation is reactive aggression to social provocation. This study investigated the association between AUD and CUD symptom severity and recruitment of neural regions implicated in retaliation. METHODS: In this study, 102 youths aged 13-18 years (67 male; 84 in residential care) completed self-report measures of aggression-related constructs and participated in a retaliation task during functional magnetic resonance imaging to investigate the association between relative severity of AUD/CUD and atypical recruitment of regions implicated in retaliation. RESULTS: AUD Identification Test scores were positively associated with irritability and reactive aggression scores. CUD Identification Test scores were positively associated with callous-unemotional traits and both proactive and reactive aggression scores. In functional magnetic resonance imaging analyses, only AUD Identification Test (not CUD Identification Test) scores were associated with an exaggerated recruitment of regions implicated in retaliation (dorsomedial frontal, anterior insula cortices, caudate, and, to a lesser extent, periaqueductal gray). CONCLUSIONS: These data suggest that relative severity of AUD is associated with a disinhibited, exaggerated retaliation response that relates to an increased risk for reactive aggression. Similar findings were not related to severity of CUD.

Temporal Discounting Impulsivity and Its Association with Conduct Disorder and Irritability.

Objectives: Temporal reward discounting impulsivity (TDI) reflects a propensity to choose smaller immediate rather than larger delayed rewards relative to age/IQ-matched peers. Previous work with adults has linked TDI to an increased risk for antisocial behavior but also psychopathology in general. However, little work has examined TDI in adolescents with conduct disorder (CD), or considered whether TDI might be associated dimensionally with traits associated with antisocial behavior, that is, impulsivity, irritability, and/or callous-unemotional traits. In this study TDI was investigated in a large adolescent group with varying levels of antisocial behavior. Methods: Participants consisted of 195 adolescents (67 with CD, 77 in a psychiatric comparison group and 51 typically developing adolescents). Participants performed a temporal discounting task and individual differences were measured through the Connors rating scale for attention-deficit/hyperactivity disorder (impulsivity), Affective Reactivity Index (irritability), and Inventory of Callous-Unemotional traits. Results: The adolescents with CD and those in the psychiatric comparison group showed significantly greater TDI than typically developing adolescents. However, these group differences were abolished when dimensional covariates were included. Irritability was significantly associated with TDI. Conclusions: We conclude that TDI reflects a transdiagnostic form of dysfunction that particularly manifests in adolescents with increased irritability.

Alcohol Use Disorder, But Not Cannabis Use Disorder, Symptomatology in Adolescents Is Associated With Reduced Differential Responsiveness to Reward Versus Punishment Feedback During Instrumental Learning.

BACKGROUND: The two most commonly used illegal substances by adolescents in the United States are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) have been associated with dysfunction in decision-making processes in adolescents. One potential mechanism for these impairments is thought to be related to abnormalities in reward and punishment processing. However, very little work has directly examined potential differential relationships between AUD and CUD symptom severity and neural dysfunction during decision making in adolescents. METHODS: In the current study, 154 youths participated in a passive avoidance learning task during functional magnetic resonance imaging to investigate the relationship between relative severity of AUD/CUD and dysfunction in processing reward and punishment feedback. RESULTS: Increasing Alcohol Use Disorder Identification Test scores were associated with reduced neural differentiation between reward and punishment feedback within regions of striatum, posterior cingulate cortex, and parietal cortex. However, increasing Cannabis Use Disorder Identification Test scores were not associated with any neural dysfunction during the passive avoidance task. CONCLUSIONS: These data expand on emerging literature that relative severity of AUD is associated with reduced responsivity to rewards in adolescents and that there are differential associations between AUD and CUD symptoms and neurocircuitry dysfunction in the developing adolescent brain.

Sexual Abuse in Adolescents Is Associated With Atypically Increased Responsiveness Within Regions Implicated in Self-Referential and Emotional Processing to Approaching Animate Threats.

Childhood sexual abuse is associated with significant subsequent pathology and neurodevelopmental disruption. In particular, childhood sexual abuse has been associated with heightened threat sensitivity. However, little work has directly investigated this issue. In this study, we examine the association of childhood sexual abuse to neural and behavioral responses to looming, threatening face stimuli. The study involved 23 adolescents with significant past sexual abuse and 24 comparison individuals matched on IQ, age, and sex. Participants were scanned during a looming threat task that involved negative and neutral, human faces and animals that appeared to either loom toward or recede from the participant. We found that adolescents who had been previously subjected to sexual abuse, relative to comparison adolescents, showed increased neural responses to threatening looming stimuli in regions including rostral and superior frontal gyrus as well as posterior cingulate gyrus. In addition, they were significantly more slowed by looming stimuli, particularly if these were human faces, than adolescents who had not been exposed. These data demonstrate that prior sexual abuse was associated with heightened neural responsiveness to looming threats in a series of regions beyond the amygdala. These data are interpreted within models of rostromedial frontal and posterior cingulate cortices that stress their role in self-referential emotional processing and emotional maintenance.

Threat Responsiveness as a Function of Cannabis and Alcohol Use Disorder Severity.

Objective: Two of the most commonly abused substances by adolescents in the United States are alcohol and cannabis, both of which are associated with adverse medical and psychiatric outcomes throughout the lifespan. Both are assumed to impact the development of emotional processing although findings on the direction of this impact have been mixed. Preclinical animal work and some functional magnetic resonance imaging (fMRI) work with humans have suggested cannabis use disorder (CUD) and alcohol use disorder (AUD) are associated with increased threat responsiveness. However, other fMRI work has indicated CUD/AUD are associated with diminished threat responsiveness. In this study, we report on a study examining the relationship of severity of CUD/AUD and threat responsiveness in an adolescent population. Methods: The study involved 87 (43 male) adolescents with varying levels of CUD/AUD symptomatology (N = 45 above clinical cutoffs for CUD or AUD). They were scanned with fMRI during a looming threat task that involved images of threatening and neutral human faces or animals that appeared to be either looming or receding. Results: Increasing levels of CUD symptomatology were associated with decreased responding to looming stimuli within regions, including rostral frontal and fusiform gyrus as well as the amygdala. There were no relationships with AUD symptomatology. Conclusions: These data indicate that CUD in particular is associated with a decrease in responsiveness to the looming threat cue possibly relating to the putative neurotoxic impact of cannabis abuse.

Association of Different Types of Childhood Maltreatment With Emotional Responding and Response Control Among Youths.

Importance: Childhood maltreatment is associated with serious developmental consequences that may be different depending on the form of maltreatment. However, relatively little research has investigated this issue despite implications for understanding the development of psychiatric disorders after maltreatment. Objective: To determine the association of childhood maltreatment and potential differential associations of childhood abuse or neglect with neural responsiveness within regions of the brain implicated in emotional responding and response control. Design, Setting, and Participants: In this cross-sectional study, participants aged 10 to 18 years with varying levels of prior maltreatment as indexed by the Childhood Trauma Questionnaire (CTQ) were recruited from a residential care facility and the surrounding community. Blood oxygen level-dependent response data were analyzed via 2 analyses of covariance that examined 2 (sex) × 3 (task condition [view, congruent, incongruent]) × 3 (valence [negative, neutral, positive]) with Blom-transformed covariates: (1) total CTQ score; and (2) abuse and neglect subscores. Data were collected from April 1, 2016, to June 30, 2018. Data analyses occurred from June 10, 2018, to October 31, 2018. Main Outcomes and Measures: Blood oxygenation level-dependent signals in response to an Affective Stroop task were measured via functional magnetic resonance imaging. Results: The sample included 116 youths (mean [SD] age, 15.0 [2.2] years; 70 [60.3%] male). Fifteen participants reported no prior maltreatment. The remaining 101 participants (87.1%) reported at least some prior maltreatment, and 55 (54.5%) reported significant maltreatment, ie, total CTQ scores were greater than the validated CTQ score threshold of 40. There were significant total CTQ score × task condition associations within the bilateral postcentral gyrus, left precentral gyrus, midcingulate cortex, middle temporal gyrus, and superior temporal gyrus (left postcentral gyrus: F = 11.73; partial η2 = 0.14; right postcentral and precentral gyrus: F = 9.81; partial η2 = 0.10; midcingulate cortex: F = 12.76; partial η2 = 0.12; middle temporal gyrus: F = 13.24; partial η2 = 0.10; superior temporal gyrus: F = 10.33; partial η2 = 0.11). In all examined regions of the brain, increased maltreatment was associated with decreased differential responsiveness to incongruent task trials compared with view trials (left postcentral gyrus: r = -0.34; 95% CI, -0.17 to -0.51; right postcentral and precentral gyrus: r = -0.31; 95% CI, -0.14 to -0.49; midcingulate cortex: r = -0.36; 95% CI, -0.18 to -0.53; middle temporal gyrus: r = -0.35; 95% CI, -0.17 to -0.52; superior temporal gyrus: r = -0.37; 95% CI, -0.20 to -0.55). These interactions were particularly associated with level of abuse rather than neglect. A second analysis of covariance revealed significant abuse × task condition (but not neglect × task) interactions within the midcingulate cortex (F = 13.96; partial η2 = 0.11), right postcentral gyrus and inferior parietal lobule (F = 15.21; partial η2 = 0.12), left postcentral and precentral gyri (F = 11.16; partial η2 = 0.12), and rostromedial frontal cortex (F = 10.36; partial η2 = 0.08)). In all examined regions of the brain, increased abuse was associated with decreased differential responsiveness to incongruent task trials compared with view trials (midcingulate cortex: partial r = -0.33; P < .001; right postcentral gyrus and inferior parietal lobule: partial r = -0.41; P < .001; left postcentral and precentral gyri: partial r = -0.40; P < .001; and rostromedial frontal cortex: partial r = -0.40; P < .001). Conclusions and Relevance: These data document associations of different forms of childhood maltreatment with atypical neural response. This suggests that forms of maltreatment may differentially influence the development of psychiatric pathology.