Association of Irritability and Anxiety With the Neural Mechanisms of Implicit Face Emotion Processing in Youths With Psychopathology

Importance: Psychiatric comorbidity complicates clinical care and confounds efforts to elucidate the pathophysiology of commonly occurring symptoms in youths. To our knowledge, few studies have simultaneously assessed the effect of 2 continuously distributed traits on brain-behavior relationships in children with psychopathology. Objective: To determine shared and unique effects of 2 major dimensions of child psychopathology, irritability and anxiety, on neural responses to facial emotions during functional magnetic resonance imaging. Design, Setting, and Participants: Cross-sectional functional magnetic resonance imaging study in a large, well-characterized clinical sample at a research clinic at the National Institute of Mental Health. The referred sample included youths ages 8 to 17 years, 93 youths with anxiety, disruptive mood dysregulation, and/or attention-deficit/hyperactivity disorders and 22 healthy youths. Main Outcomes and Measures: The child's irritability and anxiety were rated by both parent and child on the Affective Reactivity Index and Screen for Child Anxiety Related Disorders, respectively. Using functional magnetic resonance imaging, neural response was measured across the brain during gender labeling of varying intensities of angry, happy, or fearful face emotions. In mixed-effects analyses, the shared and unique effects of irritability and anxiety were tested on amygdala functional connectivity and activation to face emotions. Results: The mean (SD) age of participants was 13.2 (2.6) years; of the 115 included, 64 were male. Irritability and/or anxiety influenced amygdala connectivity to the prefrontal and temporal cortex. Specifically, irritability and anxiety jointly influenced left amygdala to left medial prefrontal cortex connectivity during face emotion viewing (F4,888 = 9.20; P < .001 for mixed model term). During viewing of intensely angry faces, decreased connectivity was associated with high levels of both anxiety and irritability, whereas increased connectivity was associated with high levels of anxiety but low levels of irritability (Wald χ21 = 21.3; P < .001 for contrast). Irritability was associated with differences in neural response to face emotions in several areas (F2, 888 ≥ 13.45; all P < .001). This primarily occurred in the ventral visual areas, with a positive association to angry and happy faces relative to fearful faces. Conclusions and Relevance: These data extend prior work conducted in youths with irritability or anxiety alone and suggest that research may miss important findings if the pathophysiology of irritability and anxiety are studied in isolation. Decreased amygdala-medial prefrontal cortex connectivity may mediate emotion dysregulation when very anxious and irritable youth process threat-related faces. Activation in the ventral visual circuitry suggests a mechanism through which signals of social approach (ie, happy and angry expressions) may capture attention in irritable youth

Pediatric Bipolar Disorder Versus Severe Mood Dysregulation: Risk for Manic Episodes on Follow-Up

OBJECTIVE: An important question in pediatric bipolar research is whether marked nonepisodic irritability is a manifestation of bipolar disorder in youth. This study tests the hypothesis that youth with severe mood dysregulation (SMD), a category created for the purpose of studying children presenting with severe nonepisodic irritability, will be significantly less likely to develop (hypo-)manic or mixed episodes over time than will youth with bipolar disorder (BD). METHOD: Patients with SMD (N = 84) and narrowly defined BD (N = 93) at baseline were followed up in 6-monthly intervals using the relevant K-SADS modules to ascertain (hypo-)manic or mixed episodes. RESULTS: Only one of 84 SMD subjects (1/84 [1.2%]; 95% confidence interval CI = 0.0003 to 0.064) experienced a (hypo-)manic or mixed episode during the study (median follow-up = 28.7 months). The frequency of such episodes was more than 50 times higher in those with narrowly defined BD (58/93 [62.4%]; 95% CI 0.52 to 0.72). CONCLUSIONS: These data suggest that, over an approximately 2-year follow-up period, youth with SMD are unlikely to develop (hypo-)manic or mixed episodes

Empirically Derived Patterns of Psychiatric Symptoms in Youth: A Latent Profile Analysis

BACKGROUND: By conceptualizing domains of behavior transdiagnostically, the National Institute of Mental Health Research Domain Criteria (NIMH RDoC) initiative facilitates new ways of studying psychiatric symptoms. In this study, latent profile analysis (LPA) was used to empirically derive classes or patterns of psychiatric symptoms in youth that transect traditional nosologic boundaries. METHODS: Data were drawn from 509 children and adolescents (ages 7 to 18 years; mean age = 12.9 years; 54% male) who were evaluated in the NIMH Emotion and Development Branch and were heterogeneous with respect to presenting diagnoses and symptoms. Youth and/or their parents completed measures of several core symptom dimensions: irritability, anxiety, depression, and attention deficit hyperactivity disorder (ADHD). LPA was used to parse response patterns into distinct classes, based on the levels of, and interrelations among, scores on the different measures. RESULTS: Five classes emerged: low levels of symptomatology (52% of sample); anxiety and mild depressive symptoms (17%); parent-reported irritability and ADHD (16%); irritability and mixed comorbid symptoms (10%); and high levels of irritability, anxiety, depression, and ADHD (5%). Importantly, these latent classes cut across informants and the clinical conditions for which youth were initially evaluated. Further, the classes characterized by irritability exhibited the poorest overall functioning. LIMITATIONS: These data were cross-sectional. Examination of external validators, including neurobiological correlates and symptom course, is warranted. CONCLUSIONS: Results inform our understanding of the structure of psychiatric symptoms in youth and suggest new ways to operationalize psychopathology and examine it in relation to neurobiology