Pathways from maternal depressive symptoms to adolescent depressive symptoms: the unique contribution of irritability symptoms

- Background: The authors tested three possible pathways linking prenatal maternal depressive symptoms to adolescent depressive symptoms. These pathways went through childhood Irritability Symptoms, Anxiety/Depressive Symptoms or Conduct Problems.\ud - Method: Data were collected from 3,963 mother–child pairs participating in the Avon Longitudinal Study of Parents and Children. Measures include maternal depressive symptoms (pre- and postnatal); toddler temperament (2 years); childhood (7–13 years) irritability symptoms, anxiety/depressive symptoms, conduct problems, and adolescent depressive symptoms (16 years).\ud - Results: Irritability Symptoms: This pathway linked sequentially – prenatal maternal depressive symptoms, toddler temperament (high perceived intensity and low perceived adaptability), childhood irritability symptoms, and adolescent depressive symptoms. Anxiety/Depressive symptoms: This pathway linked sequentially – prenatal maternal depressive symptoms, toddler temperament (negative perceived mood), childhood anxiety/depressive symptoms, and adolescent depressive symptoms. Childhood conduct problems were not associated with adolescent depressive symptoms, above and beyond irritability symptoms and anxiety/depressive symptoms.\ud - Conclusions: Results suggest evidence for two distinct developmental pathways to adolescent depressive symptoms that involve specific early and midchildhood features

Detecting the subtle shape differences in hemodynamic responses at the group level

The nature of the hemodynamic response (HDR) is still not fully understood due to the multifaceted processes involved. Aside from the overall amplitude, the response may vary across cognitive states, tasks, brain regions, and subjects with respect to characteristics such as rise and fall speed, peak duration, undershoot shape, and overall duration. Here we demonstrate that the fixed-shape or adjusted-shape methods may fail to detect some shape subtleties. In contrast, the estimated-shape method (ESM) through multiple basis functions can provide the opportunity to identify some subtle shape differences and achieve higher statistical power at both individual and group levels. Previously, some dimension reduction approaches focused on the peak magnitude, or made inferences based on the area under the curve or interaction, which can lead to potential misidentifications. By adopting a generic framework of multivariate modeling (MVM), we showcase a hybrid approach that is validated by simulations and real data. Unlike the few analyses that were limited to main effect, two- or three-way interactions, we extend the approach to an inclusive platform that is more adaptable than the conventional GLM, achieving a practical equipoise among representation, false positive control, statistical power, and modeling flexibility

fMRI predictors of treatment outcome in pediatric anxiety disorders

A growing number of studies have found evidence that anxiety and depressive disorders are associated with atypical amygdala hyperactivation, which decreases with effective treatment. Interest has emerged in this phenomenon as a possible biological marker for individuals who are likely to benefit from tailored treatment approaches. The present study was designed to examine relationships between pre-treatment amygdala activity and treatment response in a sample of anxious children and adolescents. Participants, who were diagnosed predominantly with Generalized Anxiety Disorder (GAD), underwent functional magnetic resonance imaging (fMRI) scanning prior to treatment with fluoxetine or cognitive behavioral therapy (CBT). Results indicated significant negative associations between degree of left amygdala activation and measures of post-treatment symptom improvement in the group as a whole. Taken together with research on associations between adult amygdala activation and treatment response, these findings suggest that patients whose pre-treatment amygdala activity is the strongest may be particularly likely to respond well to such widely used treatments as selective serotonin reuptake inhibitor (SSRI) medications and CBT

A Developmental Examination of Amygdala Response to Facial Expressions

Several lines of evidence implicate the amygdala in face-emotion processing, particularly for fearful facial expressions. Related findings suggest that face-emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala’s response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9–17 years old) and 30 adults (21–40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala–hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions

Specificity of facial expression labeling deficits in childhood psychopathology

Background: We examined whether face-emotion labeling deficits are illness-specific or an epiphenomenon of generalized impairment in pediatric psychiatric disorders involving mood and behavioral dysregulation. Method: Two hundred fifty-two youths (7-18 years old) completed child and adult facial expression recognition subtests from the Diagnostic Analysis of Nonverbal Accuracy (DANVA) instrument. Forty-two participants had bipolar disorder (BD), 39 had severe mood dysregulation (SMD; i.e., chronic irritability, hyperarousal without manic episodes), 44 had anxiety and/or major depressive disorders (ANX/MDD), 35 had attention-deficit/hyperactivity and/or conduct disorder (ADHD/CD), and 92 were controls. Dependent measures were number of errors labeling happy, angry, sad, or fearful emotions. Results: BD patients made more errors than ANX/MDD, ADHD/CD, or controls when labeling all emotional expressions, whether those expressions were on the faces of children or adults. SMD also showed emotion-labeling deficits, in particular as compared to ANX/MDD patients and controls. Conclusions: Face-emotion labeling deficits differentiate BD and SMD patients from those with ANX/MDD or ADHD/CD and controls. The extent to which such deficits cause vs. result from emotional dysregulation requires further study

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

Differential associations of conduct disorder, callous‑unemotional traits and irritability with outcome expectations and values regarding the consequences of aggression

Background: Previous work has examined the association of aggression levels and callous-unemotional traits with outcome expectations and values regarding the consequences of aggression. Less work has examined the outcome expectations and values regarding the consequences of aggression of adolescents with Conduct Disorder (CD). Also, no studies have examined links between irritability (a second socio-affective trait associated with CD) and these social cognitive processes despite the core function of anger in retaliatory aggression and establishing dominance. Method: The current study, investigating these issues, involved 193 adolescents (typically developing [TD; N = 106], 87 cases with CD [N = 87]). Participants completed an adaptation of the Outcomes Expectations and Values Questionnaire and were assessed for CU traits and irritability via the Inventory of Callous-Unemotional traits and the Affective Reactivity Index. Results: While CD was associated with atypical outcome expectations this was not seen within statistical models including CU traits and irritability. CU traits were associated with decreased expectation that aggression would result in feelings of remorse and victim suffering, as well as decreased concern that aggressive acts would result in punishment and victim suffering. Irritability was associated with increased expectations and concern that aggression would result in dominance and forced respect. Conclusions: The results suggest that CU traits and irritability, often present in youth with CD, are associated with different forms of maladaptive outcome expectations and values regarding the consequences of aggression. This suggests that the atypical social cognitive processes underlying aggressive behavior among youth exhibiting CU traits may differ from those exhibiting problems regulating anger

Common and specific amygdala-function perturbations in 2 depressed versus anxious adolescents

Context: Few studies directly compare amygdala function in depressive and anxiety disorders. 43 Data from longitudinal research emphasize the need for such studies in adolescents. 44 Objective: To compare amygdala response to varying attention and emotion conditions among 45 adolescents with Major Depressive Disorder (MDD) or anxiety disorders, relative to adolescents 46 with no psychopathology. 47 Design: Case-Control-Study. 48 Setting: Government Clinical Research Institute. 49 Participants: Eighty-seven adolescents matched on age, gender, intelligence, and social class: 26 50 with Major Depressive Disorder (MDD; 14 with and 12 without anxiety disorders), 16 with 51 anxiety disorders but no depression, and 45 with no psychopathology. 52 Main Outcome Measures: Blood oxygenated level dependent signal in the amygdala, measured 53 using event-related functional magnetic resonance imaging. During imaging, participants viewed 54 facial expressions (neutral, fearful, angry, happy) while attention was constrained (afraid, 55 hostility, nose width ratings) or unconstrained (passive-viewing). 56 Results: Left and right amygdala activation differed as a function of diagnosis, facial expression, 57 and attention-condition both when comorbid MDD/anxiety patients were included and excluded 58 (group-by-emotion-by-attention interactions: p-values≤.03). Focusing on fearful-face-viewing 59 events, anxiety and MDD patients both differed in amygdala responses from healthy participants 60 and from each other during passive-viewing. However, both MDD and anxiety patients, relative 61 to healthy participants, exhibited similar signs of amygdala hyper-activation to fearful faces when 62 rating subjectively experienced fear. 63 Conclusions: Adolescent MDD and anxiety disorders exhibit common and distinct functional 64 neural correlates during face processing. Attention modulates the degree to which common or 65 distinct amygdala perturbations manifest in these patient groups, relative to healthy peers