Association of anxiety phenotypes with risk of depression and suicidal ideation in community youth.

BACKGROUND: Anxiety symptoms are common in adolescence and are often considered developmentally benign. Yet for some, anxiety presents with serious comorbid nonanxiety psychopathology. Early identification of such "malignant" anxiety presentations is a major challenge. We aimed to characterize anxiety symptoms suggestive of risk for depression and suicidal ideation (SI) in community youths. METHODS: Cross-sectional associations were evaluated in community youths (n = 7,054, mean age: 15.8) who were assessed for anxiety, depression, and SI. We employed factor and latent class analyses to identify anxiety clusters and subtypes. Longitudinal risk of anxiety was evaluated in a subset of 330 youths with longitudinal data on depression and SI (with baseline mean age of 12.3 years and follow-up mean age of 16.98 years). OUTCOMES: Almost all (92%) adolescents reported anxiety symptoms. Data-driven approaches revealed anxiety factors and subtypes that were differentially associated with depression and SI. Cross-sectional analyses revealed that panic and generalized anxiety symptoms show the most robust associations with depression and SI. Longitudinal, multivariate analyses revealed that panic symptoms during early adolescence, not generalized anxiety symptoms, predict depression and SI for later adolescent years, particularly in males. INTERPRETATION: Anxiety is common in youths, with certain symptom clusters/subtypes predicting risk for depression and SI. Panic symptoms in early adolescence, even below disorder threshold, predict high risk for late adolescent depression and SI.

Differences in Parent and Child Report on the Screen for Child Anxiety-Related Emotional Disorders (SCARED): Implications for Investigations of Social Anxiety in Adolescents.

Social anxiety typically emerges by adolescence and is one of the most common anxiety disorders. Many clinicians and researchers utilize the Screen for Child Anxiety Related Disorders (SCARED) to quantify anxiety symptoms, including social anxiety, throughout childhood and adolescence. The SCARED can be administered to both children and their parents, though reports from each informant tend to only moderately correlate. Here, we investigated parent-child concordance on the SCARED in a sample of adolescents (N = 360, Mage = 13.2) using a multi-trait multi-method (MTMM) model. Next, in a selected sample of the adolescents, we explored relations among child report, parent report, and latent social anxiety scores with two laboratory tasks known to elicit signs of social anxiety in the presence of unfamiliar peers: a speech task and a "Get to Know You" task. Findings reveal differences in variance of the SCARED accounted for by parent and child report. Parent report of social anxiety is a better predictor of anxiety signs elicited by a structured speech task, whereas child report of social anxiety is a better predictor of anxiety signs during the naturalistic conversation with unfamiliar peers. Moreover, while latent social anxiety scores predict both observed anxiety measures, parent report more closely resembles latent scores in relation to the speech task, whereas child report functions more similarly to latent scores in relation to the peer conversation. Thus, while latent scores relate to either observed anxiety measure, parent and child report on the SCARED each provide valuable information that differentially relate to naturalistic social anxiety-related behaviors.

A neuromarker of clinical outcome in attention bias modification therapy for social anxiety disorder.

BACKGROUND: Attention bias modification (ABM) therapy aims to modify threat-related attention patterns via computerized tasks. Despite showing medium clinical effect sizes for anxiety disorders, underlying neural-cognitive mechanisms of change remain unclear. We used visual mismatch negativity (vMMN), an event-related potential sensitive to violations of learned statistical contingencies, to assess therapy-related contingency extraction processes in healthy participants and in patients with social anxiety disorder (SAD). We then assessed whether vMMN amplitude predicts ABM treatment outcome. METHODS: A modified version of the dot-probe task was used to elicit vMMN, in which 80% of trials were standard and 20% were deviant. In study 1, 30 healthy adults were randomly assigned to one of two ABM conditions: one in which threat-congruent targets were deviant trials and threat-incongruent targets were standard trials, and another in which the contingency was reversed. Electroencephalography (EEG) was continuously measured and vMMN analyzed. In study 2, 38 patients with SAD underwent six sessions of ABM therapy. We tested whether rule extraction in the ABM task, indicated by vMMN amplitude, predicts treatment outcome. RESULTS: vMMN clearly emerged over prespecified scalp locations indicating contingency extraction during ABM (study 1). vMMN amplitude predicted clinical improvement after ABM therapy, uniquely accounting for 7% and 14.4% of the variance in clinician-rated and self-reported posttreatment SAD symptoms, respectively. CONCLUSIONS: vMMN emerges as a neural marker for contingency learning in ABM, suggesting a significant role for contingency extraction processes in the clinical efficacy of this therapy.

Specific and social fears in children and adolescents: separating normative fears from problem indicators and phobias

Objective: To distinguish normative fears from problematic fears and phobias. Methods: We investigated 2,512 children and adolescents from a large community school-based study, the High Risk Study for Psychiatric Disorders. Parent reports of 18 fears and psychiatric diagnosis were investigated. We used two analytical approaches: confirmatory factor analysis (CFA)/item response theory (IRT) and nonparametric receiver operating characteristic (ROC) curve. Results: According to IRT and ROC analyses, social fears are more likely to indicate problems and phobias than specific fears. Most specific fears were normative when mild; all specific fears indicate problems when pervasive. In addition, the situational fear of toilets and people who look unusual were highly indicative of specific phobia. Among social fears, those not restricted to performance and fear of writing in front of others indicate problems when mild. All social fears indicate problems and are highly indicative of social phobia when pervasive. Conclusion: These preliminary findings provide guidance for clinicians and researchers to determine the boundaries that separate normative fears from problem indicators in children and adolescents, and indicate a differential severity threshold for specific and social fears.

Does MAOA increase susceptibility to prenatal stress in young children?

BACKGROUND: We previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure. METHODS: Participants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences. RESULTS: Concurrent stress exposure predicted DB in children (ß=0.310, p=0.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOA×PSE×sex on DB (ß=0.813, p=0.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (ß=0.774, p=0.015), and as a function of PTE, controlling for PSE (ß=0.362, p=0.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (ß=-0.133, p=0.561) nor PTE (ß=-0.144; p=0.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters' concurrent stress exposure (r=-0.240, p=0.013). DISCUSSION: Findings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression.

Attention bias modification for youth with social anxiety disorder.

BACKGROUND: Attention bias modification treatment (ABMT) targets threat-related attention biases in anxiety disorders. Most clinical trials of ABMT have focused on adults or small samples of youth. The current randomized controlled trial (RCT) examines ABMT efficacy in youth with social anxiety disorder (SAD) and tests possible moderators of treatment outcomes. METHOD: Sixty-seven youth with SAD were randomly assigned to ABMT or attention control training (ACT) conditions. Anxiety severity was measured at baseline, posttreatment, and 3-month follow-up. ClinicalTrials.gov name and identifier: Attention bias modification treatment for children with social anxiety, NCT01397032; http://www.clinicaltrials.gov. RESULTS: Both ABMT and ACT induced significant reductions in clinician and self-rated social anxiety (ps < .001). An additional reduction was observed at the 3-month follow-up in clinician-rated anxiety symptoms (p = .03). Moderation effects were nonsignificant for the clinician-rated anxiety outcome, but age moderated self-reported anxiety. Older but not younger children, showed significant reduction in anxiety following ABMT relative to ACT (p < .001). Individual differences in attention control also moderated ABMT's effect on self-reported anxiety (p = .05). Children rated by their parents as lower on attention control benefited more from ABMT than those rated higher on attention control. Baseline attention bias did not moderate anxiety (p = .17). CONCLUSIONS: Despite significant reductions in social anxiety, no specific evidence for ABMT was found relative to a control condition. Age and attention control moderated ABMT effects on self-reported SAD symptoms, with clinical effects for older relative to younger children and for those with lower attention control. These results highlight the need to consider developmental influences in the implementation of ABMT protocols.

Preliminary evidence for the interaction of the oxytocin receptor gene (oxtr) and face processing in differentiating prenatal smoking patterns.

Prenatal smoking cessation has been described as an empathic action "for the baby," but this has not been empirically demonstrated. We capitalized on a genetically-characterized extant dataset with outstanding measurement of prenatal smoking patterns and maternal face processing data (as an indicator of empathy) to test this hypothesis, and explore how empathy and smoking patterns may be moderated by a genetic substrate of empathy, the oxytocin receptor gene (OXTR). Participants were 143 Caucasian women from the East Boston family study with repeated prospective reports of smoking level, adjusted based on repeated cotinine bioassays. Salivary DNA and face processing (Diagnostic Analysis of Nonverbal Accuracy-2) were assessed 14 years later at an adolescent follow-up of offspring. Two-thirds of participants reported smoking prior to pregnancy recognition. Of these, 21% quit during pregnancy; 56% reduced smoking, and 22% smoked persistently at the same level. A significant interaction between face processing and OXTR variants previously associated with increased sensitivity to social context, rs53576GG and rs2254298A, was found (ß = -.181; p = .015); greater ability to identify distress in others was associated with lower levels of smoking during pregnancy for rs53576(GG)/rs2254298(A) individuals (p = .013), but not for other genotypes (p = .892). Testing this "empathy hypothesis of prenatal smoking cessation" in larger studies designed to examine this question can elucidate whether interventions to enhance empathy can improve prenatal smoking cessation rates.

Incidence of social anxiety disorder and the consistent risk for secondary depression in the first three decades of life.

CONTEXT: Epidemiological findings demonstrating an increased risk for individuals with social anxiety disorder (SAD) to develop depression have been challenged by discrepant findings from prospective longitudinal examinations in childhood and early adolescence. OBJECTIVES: To examine patterns of SAD incidence, the consistency of associations of SAD with subsequent depression, and distal and proximal predictors for subsequent depression. DESIGN: Face-to-face, 10-year prospective longitudinal and family study of up to 4 waves. The DSM-IV Munich-Composite International Diagnostic Interview was administered by clinically trained interviewers. SETTING: Community sample in Munich. PARTICIPANTS: Three thousand twenty-one individuals aged 14 to 24 years at baseline and 21 to 34 years at follow-up. MAIN OUTCOME MEASURES: Cumulative incidence of SAD and depression (major depressive episode or dysthymia). RESULTS: Cumulative incidence for SAD was 11.0%; for depression, 27.0%. Standardized person-years of incidence for SAD were highest for those aged 10 to 19 years (0.72%) and were low before (0.20%) and after (0.19%) that age range. Depression incidence was different, characterized by delayed and continued high rates. Social anxiety disorder was consistently associated with subsequent depression, independent of age at onset for SAD (relative risk range, 1.49-1.85, controlling for age and sex). Crude Cox regressions showed significant distal (eg, parental anxiety or depression, behavioral inhibition) and proximal SAD characteristics (eg, severity measures, persistence) as predictors. Most associations were attenuated in multiple models, leaving behavioral inhibition (hazard ratio, 1.30 [95% confidence interval, 1.04-1.62; P = .02]) and, less consistently, panic (hazard ratio, 1.85 [95% confidence interval, 1.08-3.18; P = .03]) as the remaining significant predictors. CONCLUSIONS: Social anxiety disorder is an early, adolescent-onset disorder related to a substantially and consistently increased risk for subsequent depression. The demonstration of proximal and particularly distal predictors for increased depression risks requires further exploration to identify their moderator or mediator role. Along with previous evidence that comorbid SAD is associated with a more malignant course and character of depression, these results call for targeted prevention with the aim of reducing the burden of SAD and its consequences.

Elucidating early mechanisms of developmental psychopathology: the case of prenatal smoking and disruptive behavior.

There is a robust association between prenatal smoking and disruptive behavior disorders, but little is known about the emergence of such behaviors in early development. The association of prenatal smoking and hypothesized behavioral precursors to disruptive behavior in toddlers (N=93) was tested. Exposed toddlers demonstrated atypical behavioral patterns, including (1) escalating externalizing problems from 18 to 24 months and (2) observed difficulty modulating behavior in response to social cues. Specification of exposure-related behaviors is a first step toward generating testable hypotheses about putative mechanisms of effect. While it remains unclear whether prenatal exposure plays an etiologic role in the emergence of disruptive behavior, atypical exposure-related behavioral patterns are evident in the first years of life and demonstrate developmental coherence.

Consequences and correlates of adolescent depression.

OBJECTIVE: To examine the correlates and consequences of high levels of depressive symptoms among adolescents. DESIGN: Secondary analysis of the 1997 Commonwealth Fund Survey of the Health of Adolescent Girls, a survey of a nationally representative sample of 4648 adolescent boys and girls between the ages of 10 and 18 years, inclusive, conducted in school settings. The self-administered questionnaire contains a screening instrument for depression based on the Children's Depression Inventory. OUTCOME: Days of school missed, performance at grade level, alcohol use, drug use, smoking, and bingeing. RESULTS: After controlling for sociodemographics, life events, sexual abuse, physical abuse, and exposure to violence, relative to other children, children and adolescents with high degrees of depressive symptoms missed about 1 day more of school in the month preceding the survey (P<.05) and had higher odds of smoking (odds ratio, 1.84; P<.001), bingeing (odds ratio, 2.02; P<.001), and suicidal ideation (odds ratio, 16.59; P<.001). CONCLUSION: High levels of depressive symptoms are correlated with serious and significant consequences, even after controlling for life circumstances.