National Institute of Mental Health Support for Cognitive Treatment Development in Schizophrenia: A Narrative Review.

For several decades the National Institute of Mental Health (NIMH) has supported basic and translational research into cognitive impairment in schizophrenia. This article describes the Institute's ongoing commitment to cognitive assessment and intervention research, as reflected by three signature initiatives-Measurement and Treatment Research to Improve Cognition in Schizophrenia; Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia; and Research Domain Criteria-and related funding announcements that span basic experimental studies, efficacy and comparative effectiveness trials, and implementation research designed to promote cognitive healthcare in real-world treatment settings. We discuss how trends in science and public health policy since the early 2000s have influenced NIMH treatment development activities, resulting in greater attention to (1) inclusive teams that reflect end-user perspectives on the utility of proposed studies; (2) measurement of discrete neurocognitive processes to inform targeted interventions; (3) clinical trials that produce useful information about putative illness mechanisms, promising treatment targets, and downstream clinical effects; and (4) "productive urgency" in pursuing feasible and effective cognitive interventions for psychosis. Programs employing these principles have catalyzed cognitive measurement, drug development, and behavioral intervention approaches that aim to improve neurocognition and community functioning among persons with schizophrenia. NIMH will maintain support for innovative and impactful investigator-initiated research that advances patient-centered, clinically effective, and continuously improving cognitive health care for persons with psychotic disorders.

Trends in Children's Mental Health Services Research Funding: Response to Hoagwood and Colleagues' Commentary.

In their recent JAACAP Commentary, Hoagwood et al.1 examined data extracted from the National Institutes of Health Research Portfolio Online Reporting Tools (RePORT) and concluded there has been a decrease in National Institute of Mental Health (NIMH) funding for child and adolescent services and intervention research during the 10-year period from 2005 to 2015. They eloquently argued for the importance of research that can guide practice and inform the organization and delivery of children's mental health services in the current context of unmet need and the state of mental health service delivery.

Secondary Outcomes From the Child/Adolescent Anxiety Multimodal Study: Implications for Clinical Practice.

BACKGROUND: Controlled evaluations comparing medication, cognitive-behavioral therapy (CBT), and their combination in the treatment of youth anxiety have predominantly focused on global ratings by independent evaluators. Such ratings are resource-intensive, may be of limited generalizability, and do not directly inform our understanding of treatment responses from the perspective of treated families. We examined outcomes from the perspective of treated youth and parents in the Child/Adolescent Anxiety Multimodal Study (CAMS). METHODS: Participants (N=488; ages 7-17 years) who had a primary diagnosis of separation, social, and/or generalized anxiety disorder were randomly assigned to a treatment condition in the CAMS trial. Linear mixed-effects and ANCOVA models examined parent- and youth-reported anxiety symptoms, impact of anxiety, broader internalizing and externalizing psychopathology, depressive symptoms, and family burden throughout the 12-week acute treatment phase and 6-month follow-up. RESULTS: At week 12, combination treatment showed superiority over placebo, sertraline, and CBT with regard to parent-reported youth anxiety symptoms, and sertraline and CBT as monotherapies showed superiority over placebo with regard to parent-reported youth anxiety. Combination therapy and sertraline also showed week 12 superiority over placebo with regard to parent-reported internalizing psychopathology, and superiority over placebo and CBT with regard to parent-reported impact of anxiety, family burden, and youth depressive symptoms. By week 36, parent reports of many youth outcomes were comparable across active conditions. Youth measures tracked parent measures on many outcomes. CONCLUSIONS: Findings were drawn on brief, readily available questionnaires that in conjunction with clinician measures can inform patient-centered care and collaborative decision-making.Trial Registry Name: Child and Adolescent Anxiety Disorders (CAMS)Registry identification number: NCT00052078Registry URL: https://www.clinicaltrials.gov/ct2/show/NCT00052078.

Sleep-Related Problems and the Effects of Anxiety Treatment in Children and Adolescents.

This study examined (a) demographic and clinical characteristics associated with sleep-related problems (SRPs) among youth with anxiety disorders, and (b) the impact of anxiety treatment: cognitive-behavioral therapy (CBT; Coping Cat), medication (sertraline), their combination, and pill placebo on SRPs. Youth (N = 488, ages 7-17, 50% female, 79% White) with a principal diagnosis of generalized anxiety disorder, separation anxiety disorder, or social phobia participated. SRPs were reported by parents and youth. Findings differed by informant and by type of SRP, with evidence that SRPs are associated with age, anxiety severity, externalizing problems, functional impairment, and family burden at pretreatment. Anxiety treatment reduced SRPs; effect sizes were small to medium. Reductions in parent-reported separation-related sleep difficulties were significantly greater in active treatment than in the placebo condition, with the greatest reductions reported by parents of youth whose active treatment was multimodal or included sertraline. Youth whose anxiety treatment involved CBT reported significantly greater decreases in dysregulated sleep (e.g., sleeplessness). Both CBT for anxiety and sertraline appear to be somewhat effective in reducing SRPs, and multimodal treatment may be preferable depending on the symptom presentation. To inform practice, future research should examine a broad range of SRPs, incorporate objective measures of sleep, and evaluate the impact of behavioral strategies that directly target SRPs in youth with anxiety disorders.

Developmental Differences in Functioning in Youth With Social Phobia.

Social phobia (SoP) in youth may manifest differently across development as parent involvement in their social lives changes and social and academic expectations increase. This cross-sectional study investigated whether self-reported and parent-reported functioning in youth with SoP changes with age in social, academic, and home/family domains. Baseline anxiety impairment data from 488 treatment-seeking anxiety-disordered youth (ages 7-17, N = 400 with a SoP diagnosis) and their parents were gathered using the Child Anxiety Impact Scale and were analyzed using generalized estimating equations. According to youth with SoP and their parents, overall difficulties, social difficulties, and academic difficulties increased with age, even when controlling for SoP severity. These effects significantly differed for youth with anxiety disorders other than SoP. Adolescents may avoid social situations as parental involvement in their social lives decreases, and their withdrawn behavior may result in increasing difficulty in the social domain. Their avoidance of class participation and oral presentations may increasingly impact their academic performance as school becomes more demanding. Implications are discussed for the early detection and intervention of SoP to prevent increased impairment over the course of development.

Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions.

This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing.

Mediators of change in the Child/Adolescent Anxiety Multimodal Treatment Study.

OBJECTIVE: Test changes in (a) coping efficacy and (b) anxious self-talk as potential mediators of treatment gains at 3-month follow-up in the Child/Adolescent Anxiety Multimodal Treatment Study (CAMS). METHOD: Participants were 488 youth (ages 7-17; 50.4% male) randomized to cognitive-behavioral therapy (CBT; Coping cat program), pharmacotherapy (sertraline), their combination, or pill placebo. Participants met Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV) criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. Coping efficacy (reported ability to manage anxiety provoking situations) was measured by youth and parent reports on the Coping Questionnaire, and anxious self-talk was measured by youth report on the Negative Affectivity Self-Statement Questionnaire. Outcome was measured using the Pediatric Anxiety Rating Scale (completed by Independent Evaluators blind to condition). For temporal precedence, residualized treatment gains were assessed at 3-month follow-up. RESULTS: Residualized gains in coping efficacy mediated gains in the CBT, sertraline, and combination conditions. In the combination condition, some unique effect of treatment remained. Treatment assignment was not associated with a reduction in anxious self-talk, nor did anxious self-talk predict changes in anxiety symptoms. CONCLUSIONS: The findings suggest that improvements in coping efficacy are a mediator of treatment gains. Anxious self-talk did not emerge as a mediator.

Predicting Anxiety Diagnoses and Severity with the CBCL-A: Improvement Relative to Other CBCL Scales?

The Child Behavior Checklist (CBCL) is a widely used parent-report of child and adolescent behavior. We examined the ability of the CBCL-A scale, a previously published subset of CBCL items, to predict the presence of generalized anxiety disorder (GAD), separation anxiety disorder (SAD), and social phobia (SoP), as well as anxiety severity, among 488 youth randomized in the Child Anxiety Multimodal Study (CAMS). We predicted that the CBCL-A's unique inclusion of items related to somatic symptoms would better identify anxiety disorder and severity than other CBCL scales, given that somatic complaints are often key features of anxiety among youth. Results support the use of the anxiety-based CBCL subscales as first-line screeners for generally elevated symptoms of anxiety, rather than tools to identify specific anxiety disorders. Although somatic symptoms are often reported and included in diagnostic criteria for certain anxiety disorders (e.g., SAD, GAD), the unique combination of somatic and non-somatic symptoms for the CBCL-A subscale did not increase its ability to consistently predict the presence of specific anxiety disorders.

Child/Adolescent anxiety multimodal study: evaluating safety.

OBJECTIVE: To evaluate the frequency of adverse events (AEs) across 4 treatment conditions in the Child/Adolescent Anxiety Multimodal Study (CAMS), and to compare the frequency of AEs between children and adolescents. METHOD: Participants ages 7 to 17 years (mean = 10.7 years) meeting the DSM-IV criteria for 1 or more of the following disorders: separation anxiety disorder, generalized anxiety disorder, or social phobia were randomized (2:2:2:1) to cognitive-behavioral therapy (CBT, n = 139), sertraline (SRT, n = 133), a combination of both (COMB, n = 140), or pill placebo (PBO, n = 76). Data on AEs were collected via a standardized inquiry method plus a self-report Physical Symptom Checklist (PSC). RESULTS: There were no differences between the double-blinded conditions (SRT versus PBO) for total physical and psychiatric AEs or any individual physical or psychiatric AEs. The rates of total physical AEs were greater in the SRT-alone treatment condition when compared to CBT (p < .01) and COMB (p < .01). Moreover, those who received SRT alone reported higher rates of several physical AEs when compared to COMB and CBT. The rate of total psychiatric AEs was higher in children (≤12 years) across all arms (31.7% versus 23.1%, p < .05). Total PSC scores decreased over time, with no significant differences between treatment groups. CONCLUSION: The results support the tolerability/safety of selective serotonin reuptake inhibitor (SSRI) treatment for anxiety disorders even after adjusting for the number of reporting opportunities, leading to no differences in overall rates of AEs. Few differences occurred on specific items. Additional monitoring of psychiatric AEs is recommended in children (≤12 years). Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); http://clinicaltrials.gov; NCT00052078.

Parental psychopathology and treatment outcome for anxious youth: roles of family functioning and caregiver strain.

OBJECTIVE: Research has examined the effects of parental psychopathology, family functioning, and caregiver strain on treatment response in anxious youths. Although these variables have shown individual links to youth treatment response, theoretical models for their combined effects remain unexplored. This study tested the hypothesis that improvements in family functioning and reductions in caregiver strain explained the effects of parental psychopathology on youth treatment outcome in an anxiety treatment trial. METHOD: A multiple mediation technique was used to test the proposed model across independent evaluator (IE), parent, and youth informants in 488 youths, aged 7-17 years (50% female; mean age = 10.7) meeting Diagnostic and Statistical Manual of Mental Disorders criteria for social phobia, separation anxiety, and/or generalized anxiety disorder. Youths were randomized to receive 12 weeks of cognitive-behavioral treatment (Coping Cat), medication (sertraline), their combination, or a pill placebo. At pre- and posttreatment, parents completed self-report measures of global psychopathology symptoms, family functioning, and caregiver strain; parents, youths, and IEs rated youths' anxiety symptom severity. RESULTS: Changes in family functioning and caregiver strain jointly explained relations between parental psychopathology and reductions in youth anxiety. Specifically, across IE and parent informants, families with higher pretreatment parental psychopathology showed more improvement in family functioning and caregiver strain, which in turn predicted greater youth anxiety reductions. Further, higher pretreatment parental psychopathology predicted greater caregiver strain reductions and, in turn, greater youth anxiety reductions, based on youths' reports of their own anxiety. CONCLUSIONS: Findings suggest that improvements in family functioning and reductions in caregiver strain can influence treatment outcomes for anxious youths, especially among youths with more distressed parents.

Trajectories of change in youth anxiety during cognitive-behavior therapy.

OBJECTIVE: To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive-behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. METHOD: Four hundred eighty-eight youths ages 7-17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children's Global Assessment Scale (CGAS; Shaffer et al., 1983) and every 4 weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; RUPP Anxiety Study Group, 2002). Youths in SRT and PBO were included as controls. RESULTS: Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior). CONCLUSIONS: Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety. Implications for future research are discussed. (PsycINFO Database Record

Treatment Outcomes in Anxious Youth with and without Comorbid ADHD in the CAMS.

The purpose of this study is to examine the influence of Attention-Deficit/Hyperactivity Disorder (ADHD), independent of Oppositional Defiant Disorder (ODD), on acute treatment response, remission rates and maintenance of gains at 6-month follow-up in anxious youth (ages 7-17, 76% Caucasian, 52% female) who received cognitive-behavioral therapy (CBT) alone, pharmacotherapy alone, the combination of CBT and pharmacotherapy or placebo pill in the Child/Adolescent Multimodal Study. Treatment response was defined as independent evaluator rated meaningful improvement in anxiety. Remission was operationalized as the absence of targeted anxiety disorders. ADHD and ODD were examined as moderators of outcomes at a diagnostic level. In the CBT group only, an ADHD diagnosis predicted poorer immediate treatment response and remission rates. However, these associations were not obtained for the pharmacotherapy groups. Participants with comorbid ODD were not less likely to achieve acute treatment response and remission rates than their counterparts across treatment conditions. Due to small sample size of the comorbid subgroups, our analyses must be considered preliminary. Nevertheless, our initial findings suggest further exploration of the separate roles of ADHD and ODD are worth pursuing, as they may be differentially associated with treatment outcomes in anxious youth treated with CBT but not youth treated with pharmacotherapy. If confirmed, findings may indicate that anxious youth with comorbid ADHD are less likely to benefit from CBT strategies alone and raise the possibility that these youth need adjunctive pharmacotherapy or psychosocial interventions.

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.

Reducing the burden of suicide in the U.S.: the aspirational research goals of the National Action Alliance for Suicide Prevention Research Prioritization Task Force.

BACKGROUND: The National Action Alliance for Suicide Prevention Research Prioritization Task Force (RPTF) has created a prioritized national research agenda with the potential to rapidly and substantially reduce the suicide burden in the U.S. if fully funded and implemented. PURPOSE: Viable, sustainable scientific research agendas addressing challenging public health issues such as suicide often need to incorporate perspectives from multiple stakeholder groups (e.g., researchers, policymakers, and other end-users of new knowledge) during an agenda-setting process. The Stakeholder Survey was a web-based survey conducted and analyzed in 2011-2012 to inform the goal-setting step in the RPTF agenda development process. The survey process, and the final list of "aspirational" research goals it produced, are presented here. METHODS: Using a modified Delphi process, diverse constituent groups generated and evaluated candidate research goals addressing pressing suicide prevention research needs. RESULTS: A total of 716 respondents representing 49 U.S. states and 18 foreign countries provided input that ultimately produced 12 overarching, research-informed aspirational goals aimed at reducing the U.S. suicide burden. Highest-rated goals addressed prevention of subsequent suicidal behavior after an initial attempt, strategies to retain patients in care, improved healthcare provider training, and generating care models that would ensure accessible treatment. CONCLUSIONS: The Stakeholder Survey yielded widely valued research targets. Findings were diverse in focus, type, and current phase of research development but tended to prioritize practical solutions over theoretical advancement. Other complex public health problems requiring input from a broad-based constituency might benefit from web-based tools that facilitate such community input.

Cognitive training in mental disorders: update and future directions.

OBJECTIVE: This article reviews the conceptual basis, definitions, and evolution of cognitive training approaches for the treatment of mental disorders. METHOD: The authors review the current state of the knowledge on cognitive training in psychiatric illnesses, and its neural and behavioral targets, and summarize the factors that appear to relate to a successful response, including learner characteristics that influence clinical outcome. They also discuss methodological issues relevant to the development and testing of cognitive training approaches, with the goal of creating maximally efficient and effective approaches to training. Finally, they identify gaps in existing knowledge and outline key research directions for the future. RESULTS: While much of the early research has been conducted in schizophrenia, cognitive training has more recently been applied to a widening range of neuropsychiatric illnesses, including attention deficit hyperactivity disorder, mood disorders, and substance use disorders. Cognitive training harnesses the inherent neuroplastic capacities of the brain, targeting neural system function across psychiatric disorders, thus improving the cognitive processes that play a role in emotion regulation, clinical symptoms, and adaptive community functioning. CONCLUSIONS: Cognitive training offers considerable promise, especially given the limited efficacy of pharmacological interventions in ameliorating cognitive deficits. However, more research is needed to understand the mechanisms underlying cognitive training, predictors of response, generalization and real-world applicability, and approaches to dissemination in practice settings.

24- and 36-week outcomes for the Child/Adolescent Anxiety Multimodal Study (CAMS).

OBJECTIVE: We report active treatment group differences on response and remission rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent Anxiety Multimodal Study (CAMS). METHOD: CAMS youth (N = 488; 74% ≤ 12 years of age) with DSM-IV separation, generalized, or social anxiety disorder were randomized to 12 weeks of cognitive-behavioral therapy (CBT), sertraline (SRT), CBT+SRT (COMB), or medication management/pill placebo (PBO). Responders attended 6 monthly booster sessions in their assigned treatment arm; youth in COMB and SRT continued on their medication throughout this period. Efficacy of COMB, SRT, and CBT (n = 412) was assessed at 24 and 36 weeks postrandomization. Youth randomized to PBO (n = 76) were offered active CAMS treatment if nonresponsive at week 12 or over follow-up and were not included here. Independent evaluators blind to study condition assessed anxiety severity, functioning, and treatment response. Concomitant treatments were allowed but monitored over follow-up. RESULTS: The majority (>80%) of acute responders maintained positive response at both weeks 24 and 36. Consistent with acute outcomes, COMB maintained advantage over CBT and SRT, which did not differ, on dimensional outcomes; the 3 treatments did not differ on most categorical outcomes over follow-up. Compared to COMB and CBT, youth in SRT obtained more concomitant psychosocial treatments, whereas those in SRT and CBT obtained more concomitant combined (medication plus psychosocial) treatment. CONCLUSIONS: COMB maintained advantage over CBT and SRT on some measures over follow-up, whereas the 2 monotherapies remained indistinguishable. The observed convergence of COMB and monotherapy may be related to greater use of concomitant treatment during follow-up among youth receiving the monotherapies, although other explanations are possible. Although outcomes were variable, most CAMS-treated youth experienced sustained treatment benefit. Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); URL: http://clinicaltrials.gov. Unique identifier: NCT00052078.