The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

Contextual Triggers and Tic Severity Across Life Periods: A Retrospective Analysis in Adults with Tic Disorders.

In tic disorders (TD), tic expression varies across the lifespan and as a function of contextual factors. This study explored connections between tic expression and contextual triggers across life periods in 74 adults (Mage = 23.2) with TDs. The Tic History and Coping Strategies form assessed retrospective self-reports of contextual antecedents, consequences, and tic severity during four life periods (middle school; 9th/10th grade; 11th/12th grade; college/work) and past month. Tics reportedly worsened during and after school in school-aged years and worsened in the evening during college/work years. Stress and anxiety were reported to consistently trigger tics across time. The impact of activities, places, and emotions did not differ across life periods. Attention-based consequences, most prevalent during middle school, were more common than escape- or avoidance-related consequences across all periods. Findings illuminate how contextual factors may influence tics across life periods and underscore the consistent impact of tic-triggering emotions and attention-related consequences.

Anxiety symptom trajectories from treatment to 5- to 12-year follow-up across childhood and adolescence.

OBJECTIVE: The current study examined trajectories of anxiety during (a) acute treatment and (b) extended follow-up to better characterize the long-term symptom trajectories of youth who received evidence-based intervention for anxiety disorders using a person-centered approach. METHOD: Participants were 319 youth (age 7-17 years at enrollment), who participated in a multicenter randomized controlled trial for the treatment of pediatric anxiety disorders, Child/Adolescent Anxiety Multimodal Study, and a 4-year naturalistic follow-up, Child/Adolescent Anxiety Multimodal Extended Long-term Study, an average of 6.5 years later. Using growth mixture modeling, the study identified distinct trajectories of anxiety across acute treatment (Weeks 0-12), posttreatment (Weeks 12-36), and the 4-year-long follow-up, and identified baseline predictors of these trajectories. RESULTS: Three nonlinear anxiety trajectories emerged: "short-term responders" who showed rapid treatment response but had higher levels of anxiety during the extended follow-up; "durable responders" who sustained treatment gains; and "delayed remitters" who did not show an initial response to treatment, but showed low levels of anxiety during the maintenance and extended follow-up periods. Worse anxiety severity and better family functioning at baseline predicted membership in the delayed remitters group. Caregiver strain differentiated short-term responders from durable responders. CONCLUSIONS: Findings suggest that initial response to treatment does not guarantee sustained treatment gains over time for some youth. Future follow-up studies that track treated youth across key developmental transitions and in the context of changing social environments are needed to inform best practices for the long-term management of anxiety.

Asthma and anxiety in children and adolescents: characteristics and treatment outcomes.

OBJECTIVE: This study (a) examined anxious youth with and without asthma on measures of negative self-talk, parental psychopathology, worry content, physical symptoms, panic symptoms, generalized symptoms, and separation anxiety symptoms, and (b) tested if outpatient CBT or medication were differentially effective in reducing anxiety for youth with asthma and anxiety. METHODS: This secondary analysis separated youth with an anxiety disorder into asthma and non-asthma groups. Youth were also compared on response to treatments (i.e. CBT, sertraline, combined, and placebo). RESULTS: A total of 488 participants participated in the original study, with an average age of 10 years (SD 2.87). Youth with comorbid asthma and anxiety demonstrated higher rates of negative self-talk. Youth with comorbid asthma and anxiety did not differ from the non-asthma group on measures of physical symptoms, anxiety disorder specific symptoms, parental psychopathology, or worry content. Youth with asthma and anxiety responded similarly to the non-asthma group to treatment across treatment conditions. CONCLUSIONS: Treatment was comparably effective for youth with comorbid asthma and anxiety and youth with anxiety. Future research could examine the effects of psychopharmaceuticals on asthma and anxiety comorbidity.

Neurobiology of subtypes of trichotillomania and skin picking disorder.

BACKGROUND: Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown. METHODS: Two hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume. RESULTS: When the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital-parietal lobe compared with controls. CONCLUSIONS: These data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.

Do youth anxiety measures assess the same construct consistently throughout treatment? Results are...complicated.

Interventionists interpret changes in symptoms as reflecting response to treatment. However, changes in symptom functioning and the measurement of the underlying constructs may be reflected in reported change. Longitudinal measurement invariance (LMI) is a statistical approach that assesses the degree to which measures consistently capture the same construct over time. We examined LMI in measures of anxiety severity/symptoms [i.e., Pediatric Anxiety Rating Scale (PARS), Multidimensional Anxiety Scale for Children (MASC), Screen for Child Anxiety and Related Disorders (SCARED)] in anxious youth at baseline and posttreatment. Initial fit was inadequate for 27 of 38 baseline and posttreatment models, but model modifications resulted in acceptable fit. Tests of LMI supported scalar invariance for the PARS and many, but not all, MASC and SCARED subscales. Findings suggest that the PARS, and many MASC and SCARED subscales can accurately be used to measure change over time, however, others may reflect changes in measurement properties.

Cognitive control processes in behavior therapy for youth with Tourette's disorder.

BACKGROUND: Cognitive control processes are implicated in the behavioral treatment of Tourette's disorder (TD). However, the influence of these processes on treatment outcomes has received minimal attention. This study examined whether cognitive control processes and/or tic suppression predicted reductions in tic severity and treatment response to behavior therapy. METHOD: Fifty-three youth with TD or a pervasive tic disorder participated in a randomized wait list-controlled trial of behavior therapy. Following a baseline assessment to evaluate psychiatric diagnoses, tic severity, and cognitive control processes (e.g., response selection, inhibition, and suppression), youth were randomly assigned to receive eight sessions of behavior therapy (n = 23) or a wait list of equal duration (n = 28). Youth receiving immediate treatment completed a post-treatment assessment to determine improvement in tic severity. Meanwhile, youth in the wait list condition completed another assessment to re-evaluate tic severity and cognitive control processes, and subsequently received 8 sessions of behavior therapy followed by a post-treatment assessment to determine improvement. RESULTS: A multiple linear regression model found that pretreatment inhibition/switching on the Delis-Kaplan Executive Function System Color-Word Interference Test predicted reductions in tic severity after behavior therapy (ß = -.36, t = -2.35, p = .025, ƞ2 = .15). However, other cognitive control processes and tic suppression did not predict treatment response and/or reductions in tic severity. Small nonsignificant effects were observed in cognitive control processes after behavior therapy. CONCLUSION: Cognitive control processes may influence tic severity reductions in behavior therapy. Notably, even when other cognitive control processes are impaired and youth are initially unable to voluntarily suppress their tics, youth with TD can still benefit from behavior therapy. Findings offer implications for clinical practice and research for TD.

Pain perception and physiological correlates in body-focused repetitive behavior disorders.

BACKGROUND: Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking. METHODS: A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups. RESULTS: There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4). CONCLUSION: The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.

Academic, Interpersonal, Recreational, and Family Impairment in Children with Tourette Syndrome and Attention-Deficit/Hyperactivity Disorder.

This study describes impairment in academic, interpersonal, recreational, and family financial or occupational domains across children in three mutually exclusive diagnostic groups: ever diagnosed with Tourette syndrome (TS), attention-deficit/hyperactivity disorder (ADHD), and both disorders. In 2014, parents reported on impairment and diagnostic status of children aged 4-17 years (n = 3014). Weighted analysis and pairwise t-tests showed more children with ADHD (with or without TS) experienced impairment in overall school performance, writing, and mathematics, relative to children with TS but not ADHD. More children with TS and ADHD had problematic handwriting relative to children with ADHD but not TS. More children with TS and ADHD had problematic interpersonal relationships relative to those with ADHD but not TS. Children with TS and ADHD had higher mean impairment across domains than children with either TS or ADHD. Findings suggest assessing disorder-specific contributions to impairment could inform targeted interventions for TS and ADHD.

Clinical Characteristics of Youth with Trichotillomania (Hair-Pulling Disorder) and Excoriation (Skin-Picking) Disorder.

Body-focused repetitive disorders (BFRBDs) are understudied in youth and understanding of their underlying mechanisms is limited. This study evaluated BFRBD clinical characteristics, and two factors commonly implicated in their maintenance - emotion regulation and impulsivity - in 53 youth aged 11 to 17 years: 33 with BFRBDs and 20 controls. Evaluators administered psychiatric diagnostic interviews. Participants rated BFRBD severity, negative affect, quality of life, family functioning, emotion regulation, distress tolerance, and impulsivity. Youth with BFRBDs showed poorer distress tolerance and quality of life, and higher impulsivity and negative affect than controls, with no differences in family impairment. BFRBD distress/impairment, but not BFRBD severity, correlated with anxiety and depression, and poorer distress tolerance. Findings suggest youth with BFRBDs show clinical patterns aligning with prior research; highlight the role of distress tolerance in child BFRBDs; and suggest the utility of acceptance and mindfulness-based therapies for unpleasant emotions in BFRBDs. Continued research should evaluate factors underlying BFRBDs in youth.

Client-rated facilitators and barriers to long-term youth anxiety disorder recovery.

OBJECTIVE: This study examined client ratings of 26 facilitators and barriers to anxiety improvement approximately 6 years after randomization to treatment for anxiety. METHOD: 319 youth (average 17.12 years old; 82.1% Caucasian; 58.6% female) participated in the longitudinal follow-up study to child and adolescent anxiety multimodal study (CAMS), a randomized controlled trial of medication, cognitive-behavioral therapy (CBT), combination, and placebo. RESULTS: Correcting for multiple comparisons, CBT components (i.e., problem solving, changing unhelpful thoughts, relaxation skills) were rated significantly more helpful among youth without, versus with, an anxiety disorder at follow-up. Barriers that differentiated youth with and without an anxiety disorder included being bullied and difficulty applying therapy content to new situations. Comparisons between youth with different anxiety disorder trajectories (e.g., stable remission, relapsed, or chronically ill) also revealed several differences. CONCLUSION: Findings suggest that client-rated facilitators and barriers covary with anxiety disorder recovery and may serve as useful tools when evaluating long-term treatment efficacy.

Sleep and chronotype in adults with persistent tic disorders.

OBJECTIVE: This study examined sleep disorders and sleep medication use rates, nighttime tics, and sleep and chronotype in relation to tic and co-occurring symptoms in adults with persistent tic disorders (PTDs), including Tourette's disorder (TD). METHODS: One hundred twenty-five adult internet survey respondents rated sleep history, sleep, chronotype, tic severity, impairment, attention deficit hyperactivity disorder, obsessive-compulsive symptoms, anxiety, depression, and emotional and behavioral dyscontrol. RESULTS: Bruxism, insomnia, tic-related difficulty falling asleep, and melatonin use were commonly endorsed. Sleep disturbance correlated with impairment, obsessive-compulsive symptoms, and emotional and behavioral dyscontrol. Eveningness correlated with vocal and total tic severity only in TD. Controlling for age and sex, age, impairment, and obsessive-compulsive symptoms predicted sleep disturbance, and age and tic severity predicted chronotype. CONCLUSIONS: Impairment and obsessive-compulsive symptoms play a role in sleep disturbance in adults with PTDs, and may be intervention targets. Eveningness relates to tic severity, which may suggest the utility of interventions to advance chronotype.

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

Antidepressant Use in a 3- to 12-Year Follow-up of Anxious Youth: Results from the CAMELS Trial.

The current study explored whether patient characteristics predicted patterns of antidepressant use (i.e., never used, single episode of use, or two or more episodes) in a naturalistic follow-up. Participants in the child/adolescent multimodal (CAMS) extended long-term study. (n = 318) indicated medication use over the course of eight follow-up visits, 3-12 years after receiving treatment in CAMS. 40.6% of participants reported never using an antidepressant during follow-up, 41.4% reported a single episode of antidepressant use, and 18.0% reported multiple episodes of antidepressant use. Greater baseline anxiety severity marginally predicted a single episode of antidepressant use; baseline depression severity predicted multiple episodes of use. Reasons for discontinuing antidepressants included perceived ineffectiveness (31.8%), side effects (25.5%), and improvement in symptoms (18.5%). Exploratory analyses examined predictors of medication use. Findings suggest that antidepressant use is common among anxious youth, as is discontinuation of antidepressant use. Clinical implications and future directions are discussed.

Effect of behavior therapy for Tourette's disorder on psychiatric symptoms and functioning in adults.

BACKGROUND: Although behavior therapy reduces tic severity, it is unknown whether it improves co-occurring psychiatric symptoms and functional outcomes for adults with Tourette's disorder (TD). This information is essential for effective treatment planning. This study examined the effects of behavior therapy on psychiatric symptoms and functional outcomes in older adolescents and adults with TD. METHOD: A total of 122 individuals with TD or a chronic tic disorder participated in a clinical trial comparing behavior therapy to psychoeducation and supportive therapy. At baseline, posttreatment, and follow-up visits, participants completed assessments of tic severity, co-occurring symptoms (inattention, impulsiveness, hyperactivity, anger, anxiety, depression, obsessions, and compulsions), and psychosocial functioning. We compared changes in tic severity, psychiatric symptoms, and functional outcomes using repeated measure and one-way analysis of variance. RESULTS: At posttreatment, participants receiving behavior therapy reported greater reductions in obsessions compared to participants in supportive therapy ($\eta _p^2 $ = 0.04, p = 0.04). Across treatments, a positive treatment response on the Clinical Global Impression of Improvement scale was associated with a reduced disruption in family life ($\eta _p^2 $ = 0.05, p = 0.02) and improved functioning in a parental role ($\eta _p^2 $ = 0.37, p = 0.02). Participants who responded positively to eight sessions of behavior therapy had an improvement in tic severity ($\eta _p^2 $ = 0.75, p < 0.001), inattention ($\eta _p^2 $ = 0.48, p < 0.02), and functioning ($\eta _p^2 $ = 0.39-0.42, p < 0.03-0.04) at the 6-month follow-up. CONCLUSION: Behavior therapy has a therapeutic benefit for co-occurring obsessive symptoms in the short-term, and reduces tic severity and disability in adults with TD over time. Additional treatments may be necessary to address co-occurring symptoms and improve functional outcomes.

Symptom-specific effects of cognitive-behavioral therapy, sertraline, and their combination in a large randomized controlled trial of pediatric anxiety disorders.

BACKGROUND: Pediatric anxiety disorders are highly prevalent and associated with significant functional disabilities and lifelong morbidity. Cognitive-behavioral therapy (CBT), sertraline, and their combination are effective treatments, but little is known about how these treatments exert their effects. METHODS: Using network intervention analysis (NIA), we analyzed data from the largest randomized controlled treatment trial of pediatric anxiety disorders (Child/Adolescent Anxiety Multimodal Study, NCT00052078, clinicaltrials.gov/ct2/show/NCT00052078) and outlined the causal symptom domain-specific effects of CBT, sertraline, and their combination over the course of the 12-week treatment while taking into account both specificity and overlap between symptom domains. RESULTS: All active treatments produced positive effects with the most pronounced and consistent effects emerging in relation to psychological distress, family interference, and avoidance. Psychological distress was consistently the most and physical symptoms the least central symptom domain in the disorder network. CONCLUSIONS: All active treatments showed beneficial effects when compared to placebo, and NIA identified that these effects were exerted similarly across treatments and primarily through a reduction of psychological distress, family interference, and avoidance. CBT and sertraline may have differential mechanisms of action in relation to psychological distress. Given the lack of causal effects on interference outside family and physical symptoms, interventions tailored to target these domains may aid in the building of more effective treatments. Psychological distress and avoidance should remain key treatment focuses because of their central roles in the disorder network. The findings inform and promote developing more effective interventions.

Person-Centered Profiles Among Treatment-Seeking Children and Adolescents with Anxiety Disorders.

Latent profile analysis (LPA) was used to derive homogeneous subgroups within the Child/Adolescent Anxiety Multimodal Study sample (N = 488; 7-17 years, M = 10.69, SD = 2.80) and examine whether class membership predicted or moderated treatment response. Subgroups were identified on baseline multi-informant measures of variables most consistently associated with outcome (youth anxiety/diagnosis, impairment, family psychopathology/functioning). Subgroup membership was examined as a predictor/moderator of outcome across the four treatment conditions (CBT, Sertraline, CBT+Sertraline, pill placebo) at posttreatment (12 weeks) and open-extension follow-up (24 weeks). Four subgroups emerged: mild symptoms/impairment, moderate symptoms/impairment, moderate symptoms/impairment with family dysfunction/parental psychopathology, and severe symptoms/impairment. There were significant between-class differences on socioeconomic status (SES; lower reported SES in the moderate with family dysfunction/parental psychopathology class compared to the mild and moderate class) and age (older age in the severe symptoms class compared to the other three classes). Youth in the mild symptoms/impairment class showed lower posttreatment anxiety across conditions but reported significantly lower symptom severity at baseline. Controlling for demographic differences, response to treatment type did not differ across classes. Analyses indicate that elevated family dysfunction/parental psychopathology clusters primarily within one subgroup of anxious youth rather than mapping onto symptom severity, highlighting the utility of LPA for clarifying within-person combinations of predictor/moderator variables. Implications for development of interventions targeting class-relevant variables are discussed.

Mood and suicidality outcomes 3-11 years following pediatric anxiety disorder treatment.

BACKGROUND: Youth anxiety interventions have potential to reduce risk for depression and suicidality. METHODS: This naturalistic follow-up of the multi-site, comparative treatment trial, inking and behavior, and depressive symptoms 3-11 years (mean 6.25 years) following 12-week evidence-based youth anxiety treatment. Participants (N = 319; 10-26 years, mean 17 years) completed semiannual questionnaires and annual diagnostic interviews for 4 years. RESULTS: One-fifth (20.4%) of the sample met DSM-IV criteria for a mood disorder, 32.1% endorsed suicidal ideation, and 8.2% reported suicidal behavior. Latent class growth analysis yielded two linear trajectories of depressive symptoms, and 85% of the sample demonstrated a persistent low-symptom course over seven assessments. Child/Adolescent Anxiety Multimodal Study (CAMS) 12-week treatment outcome (positive response, remission) and treatment condition (cognitive behavior therapy [CBT], medication, CBT + medication, pill placebo) were not associated with subsequent mood disorder or suicidal thinking. CAMS remission predicted absence of suicidal behavior, and treatment response and remission predicted low depressive symptom trajectory. Greater baseline self-reported depressive symptoms predicted all long-term mood outcomes, and more negative life events predicted subsequent mood disorder, depressive symptom trajectory, and suicidal ideation. CONCLUSIONS: Effective early treatment of youth anxiety, including CBT, medication, or CBT + medication, reduces risk for subsequent chronic depressive symptoms and suicidal behavior. Attention to (sub)clinical depressive symptoms and management of negative life events may reduce odds of developing a mood disorder, chronic depressive symptoms, and suicidality. Findings contribute to evidence that early intervention for a primary disorder can serve as secondary prevention.