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.

Early life adversity is associated with greater similarity in neural representations of ambiguous and threatening stimuli.

Exposure to early life adversity (ELA) is hypothesized to sensitize threat-responsive neural circuitry. This may lead individuals to overestimate threat in the face of ambiguity, a cognitive-behavioral phenotype linked to poor mental health. The tendency to process ambiguity as threatening may stem from difficulty distinguishing between ambiguous and threatening stimuli. However, it is unknown how exposure to ELA relates to neural representations of ambiguous and threatening stimuli, or how processing of ambiguity following ELA relates to psychosocial functioning. The current fMRI study examined multivariate representations of threatening and ambiguous social cues in 41 emerging adults (aged 18 to 19 years). Using representational similarity analysis, we assessed neural representations of ambiguous and threatening images within affective neural circuitry and tested whether similarity in these representations varied by ELA exposure. Greater exposure to ELA was associated with greater similarity in neural representations of ambiguous and threatening images. Moreover, individual differences in processing ambiguity related to global functioning, an association that varied as a function of ELA. By evidencing reduced neural differentiation between ambiguous and threatening cues in ELA-exposed emerging adults and linking behavioral responses to ambiguity to psychosocial wellbeing, these findings have important implications for future intervention work in at-risk, ELA-exposed populations.

Research Review: The neuroscience of emerging adulthood - reward, ambiguity, and social support as building blocks of mental health.

BACKGROUND: The interval between adolescence and adulthood, 'emerging adulthood' (EA), lays the foundation for lifelong health and well-being. To date, there exist little empirical data - particularly in the neurobiological domain - to establish markers of risk and resilience during the transition to adulthood. This gap in the literature is concerning given the numerous forms of psychiatric illness that emerge or worsen during this period. METHODS: In this review, we focus on two strands of research with distinct importance for EA: reward sensitivity, and tolerance of ambiguity. We begin by placing these domains in a framework that considers the unique developmental goals of EA and then synthesize emerging neurobiological research on how these domains develop during EA. We then consider their role in common mental health problems that occur during this interval as well as how social support may moderate outcomes. Finally, we offer recommendations for advancing research to understand developmental process and outcomes in EA. FINDINGS AND CONCLUSIONS: Few longitudinal studies specifically address emerging adult development and the milestones that characterize this interval. Data on neurobiological development are similarly sparse. Understanding neurobiological development during this window and its links to key adjustment outcomes is crucial for optimizing outcomes.

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.

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.

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.

Resting State Psychophysiology in Youth with OCD and Their Caregivers: Preliminary Evidence for Trend Synchrony and Links to Family Functioning.

The burden of OCD in children and adolescents extends to their caregivers. Prior work in other disorders and unaffected youth has found synchrony in psychophysiological arousal for youth-caregiver dyads. This preliminary study explored whether psychophysiological trend synchrony in youth-caregiver dyads (N = 48) occurred and was moderated by youth OCD diagnosis. We also explored whether psychophysiological indices (i.e., electrodermal activity, heart rate, respiratory sinus arrhythmia) were correlated with reported family functioning in the OCD subsample (n = 25). Youth with OCD had higher resting heart rate than unaffected peers; this was not replicated in caregivers. Trend synchrony was found across the full sample of dyads for electrodermal activity and heart rate, with no moderation by diagnostic group. In the OCD group, youth heart rate was correlated with family conflict and caregiver heart rate with expressiveness. Findings provide preliminary support for further examination of heart rate and family factors in OCD-affected youth and their caregivers.

Parent and Friend Relationship Quality and Links to Trajectories of Loneliness During the First Year of College.

Beginning college involves changes that can increase one's vulnerability to loneliness and associated negative outcomes. Parent and friend relationships are potential protective factors against loneliness given their positive association with adjustment. The present longitudinal study, with data collection at baseline, 1 month, and 2 months later, assessed the comparative effects of self-reported parent and friend relationship quality on loneliness in first-year college students (N = 101; 80 female, Mage = 18.36). At baseline, parent and friend relationship quality were negatively associated with loneliness. Longitudinal data revealed that friend relationship quality interacted with time, such that its effects on loneliness attenuated over the course of 2 months. By contrast, parent relationship quality continued to predict lower loneliness 2 months post-baseline. These results highlight the importance of close relationships and suggest that targeting relationship quality could be effective in helping youth transition to college.

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.

Research Review: Pediatric anxiety disorders - what have we learnt in the last 10 years?

BACKGROUND: Anxiety disorders first emerge during the critical developmental periods of childhood and adolescence. This review synthesizes recent findings on the prevalence, risk factors, and course of the anxiety disorders; and their neurobiology and treatment. METHODS: For this review, searches were conducted using PubMed, PsycINFO, and clinicaltrials.gov. Findings related to the epidemiology, neurobiology, risk factors, and treatment of pediatric anxiety disorders were then summarized. FINDINGS: Anxiety disorders are high prevalence, and early-onset conditions associated with multiple risk factors including early inhibited temperament, environment stress, and structural and functional abnormalities in the prefrontal-amygdala circuitry as well as the default mode and salience networks. The anxiety disorders are effectively treated with cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). CONCLUSIONS: Anxiety disorders are high prevalence, early-onset conditions associated with a distinct neurobiological fingerprint, and are consistently responsive to treatment. Questions remain regarding who is at risk of developing anxiety disorders as well as the way in which neurobiology predicts treatment response.

Neural correlates of emotional reactivity and regulation in youth with and without anxiety.

BACKGROUND: Youth with anxiety disorders struggle with managing emotions relative to peers, but the neural basis of this difference has not been examined. METHODS: Youth (Mage = 13.6; range = 8-17) with (n = 37) and without (n = 24) anxiety disorders completed a cognitive reappraisal task while undergoing functional magnetic resonance imaging. Emotional reactivity and regulation, functional activation, and beta-series connectivity were compared across groups. RESULTS: Groups did not differ on emotional reactivity or regulation. However, fronto-limbic activation after viewing aversive imagery with and without regulation, as well as affect ratings without regulation, were higher for anxious youth. Neither group demonstrated age-related changes in regulation, though anxious youth became less reactive with age. Stronger amygdala-ventromedial prefrontal cortex connectivity related to greater anxiety in control youth, but less anxiety in anxious youth. CONCLUSION: Anxious youth regulated when instructed, but regulation ability did not relate to age. Viewing aversive imagery related to heightened fronto-limbic activation even after reappraisal. Emotion dysregulation in youth anxiety disorders may stem from heightened emotionality and potent bottom-up neurobiological responses to aversive stimuli. Findings suggest the importance of treatments focused on both reducing initial emotional reactivity and bolstering regulatory capacity.

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.

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.

Child and Adolescent Adherence With Cognitive Behavioral Therapy for Anxiety: Predictors and Associations With Outcomes.

Cognitive behavioral therapy (CBT) for anxiety disorders is effective, but nonadherence with treatment may reduce the benefits of CBT. This study examined (a) four baseline domains (i.e., demographic, youth clinical characteristics, therapy related, family/parent factors) as predictors of youth adherence with treatment and (b) the associations between youth adherence and treatment outcomes. Data were from 279 youth (7-17 years of age, 51.6% female; 79.6% White, 9% African American), with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) diagnoses of separation anxiety disorder, generalized anxiety disorder, and/or social phobia, who participated in CBT in the Child/Adolescent Anxiety Multimodal Study. Adherence was defined in three ways (session attendance, therapist-rated compliance, and homework completion). Multiple regressions revealed several significant predictors of youth adherence with CBT, but predictors varied according to the definition of adherence. The most robust predictors of greater adherence were living with both parents and fewer youth comorbid externalizing disorders. With respect to outcomes, therapist ratings of higher youth compliance with CBT predicted several indices of favorable outcome: lower anxiety severity, higher global functioning, and treatment responder status after 12 weeks of CBT. Number of sessions attended and homework completion did not predict treatment outcomes. Findings provide information about risks for youth nonadherence, which can inform treatment and highlight the importance of youth compliance with participating in therapy activities, rather than just attending sessions or completing homework assignments.

Comparing OCD-affected youth with and without religious symptoms: Clinical profiles and treatment response.

BACKGROUND: Childhood obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric condition, with varied symptom presentations that have been differentially associated with clinical characteristics and treatment response. One OCD symptom cluster of particular interest is religious symptoms, including fears of offending religious figures/objects; patients affected by these symptoms have been characterized as having greater overall OCD severity and poorer treatment response. However, the extant literature primarily examines this symptom subtype within adults, leaving a gap in our understanding of this subtype in youth. METHOD: Consequently, this study examined whether presence of religious symptoms in OCD-affected children and adolescents (N = 215) was associated with greater clinical impairments across OCD symptoms and severity, insight, other psychiatric comorbidity, family variables, or worse treatment response. RESULTS: Results found that youth with religious OCD symptoms presented with higher OCD symptom severity and exhibited more symptoms in the aggressive, sexual, somatic, and checking symptom cluster, as well as the symmetry, ordering, counting, and repeating cluster. Religious OCD symptoms were also significantly associated with poorer insight and higher family expressiveness. No differences in treatment response were observed in youths with versus without religious OCD symptoms. CONCLUSION: Ultimately, youths with religious OCD symptoms only differed from their OCD-affected counterparts without religious symptoms on a minority of clinical variables; this suggests they may be more comparable to youths without religious OCD symptoms than would be expected based on the adult OCD literature and highlights the importance of examining these symptoms within a pediatric OCD sample.

Distinguishing Fear Versus Distress Symptomatology in Pediatric OCD.

Prior research has identified OCD subtypes or "clusters" of symptoms that differentially relate to clinical features of the disorder. Given the high comorbidity between OCD and anxiety, OCD symptom clusters may more broadly associate with fear and/or distress internalizing constructs. This study examines fear and distress dimensions, including physical concerns (fear), separation anxiety (fear), perfectionism (distress), and anxious coping (distress), as predictors of previously empirically-derived OCD symptom clusters in a sample of 215 youth diagnosed with primary OCD (ages 7-17, mean age = 12.25). Self-reported separation fears predicted membership in Cluster 1 (aggressive, sexual, religious, somatic obsessions, and checking compulsions) while somatic/autonomic fears predicted membership in Cluster 2 (symmetry obsessions and ordering, counting, repeating compulsions). Results highlight the diversity of pediatric OCD symptoms and their differential association with fear, suggesting the need to carefully assess both OCD and global fear constructs that might be directly targeted in treatment.

Clinical Characteristics of Pediatric Trichotillomania: Comparisons with Obsessive-Compulsive and Tic Disorders.

This study compared youth ages 5-17 years with a primary diagnosis of trichotillomania (TTM, n = 30) to those with primary OCD (n = 30) and tic disorder (n = 29) on demographic characteristics, internalizing, and externalizing symptoms. Findings suggest that youth with primary TTM score more comparably to youth with tics than those with OCD on internalizing and externalizing symptom measures. Compared to the OCD group, youth in the TTM group reported lower levels of anxiety and depression. Parents of youth in the TTM group also reported fewer internalizing, externalizing, attention, and thought problems than those in the OCD group. Youth with TTM did not significantly differ from those with primary Tic disorders on any measure. Findings suggest that pediatric TTM may be more similar to pediatric tic disorders than pediatric OCD on anxiety, depression, and global internalizing and externalizing problems.

Parental Expressed Emotion and Youth Psychopathology: New Directions for an Old Construct.

Levels of parental expressed emotion (EE) are prospectively associated with the symptomatic course of a range of childhood psychiatric disorders. This article reviews the literature linking parental EE to youth psychopathology and proposes a novel framework for understanding its mechanisms of action. We find that, despite noteworthy methodological limitations, parental EE is linked consistently to a more deleterious course of mood, anxiety, and psychotic disorders in youth. Its mechanism of action is unknown. Models of "toxic family stress" (referring to frequent, sustained, and uncontrollable stress without protective influences) provide one framework for understanding how high EE environments interact with individual biological vulnerabilities to promote illness onset and recurrence. Research aimed at understanding biological responses (e.g., stress reactivity, arousal) to familial EE is needed. Such work may inform efforts to understand how EE affects the course of psychiatric disorders and may guide the development of novel interventions emphasizing emotion regulation strategies.

Parental anxiety as a predictor of medication and CBT response for anxious youth.

The aim of this investigation was to evaluate how parental anxiety predicted change in pediatric anxiety symptoms across four different interventions: cognitive-behavioral therapy, medication (sertraline; SRT), their combination (COMB), and pill placebo. Participants were 488 youths (ages 7-17) with separation anxiety disorder, generalized anxiety disorder, and/or social phobia and their primary caregivers. Latent growth curve modeling assessed how pre-treatment parental trait anxiety symptoms predicted trajectories of youth anxiety symptom change across 12 weeks of treatment at four time points. Interactions between parental anxiety and treatment condition were tested. Parental anxiety was not associated with youth's pre-treatment anxiety symptom severity. Controlling for parental trait anxiety, youth depressive symptoms, and youth age, youths who received COMB benefitted most. Counter to expectations, parental anxiety influenced youth anxiety symptom trajectory only within the SRT condition, whereas parental anxiety was not significantly associated with youth anxiety trajectories in the other treatment conditions. Specifically, within the SRT condition, higher levels of parental anxiety predicted a faster and greater reduction in youth anxiety over the acute treatment period compared to youths in the SRT condition whose parents had lower anxiety levels. While all active treatments produced favorable outcomes, results provide insight regarding the treatment-specific influence of parental anxiety on the time course of symptom change.