Changes in Brain Volume Associated with Trauma-Focused Cognitive Behavioral Therapy Among Youth with Posttraumatic Stress Disorder.

This study investigated group differences and longitudinal changes in brain volume before and after trauma-focused cognitive behavioral therapy (TF-CBT) in 20 unmedicated youth with maltreatment-related posttraumatic stress disorder (PTSD) and 20 non-trauma-exposed healthy control (HC) participants. We collected MRI scans of brain anatomy before and after 5 months of TF-CBT or the same time interval for the HC group. FreeSurfer software was used to segment brain images into 95 cortical and subcortical volumes, which were submitted to optimal scaling regression with lasso variable selection. The resulting model of group differences at baseline included larger right medial orbital frontal and left posterior cingulate corticies and smaller right midcingulate and right precuneus corticies in the PTSD relative to the HC group, R2 = .67. The model of group differences in pre- to posttreatment change included greater longitudinal changes in right rostral middle frontal, left pars triangularis, right entorhinal, and left cuneus corticies in the PTSD relative to the HC group, R2 = .69. Within the PTSD group, pre- to posttreatment symptom improvement was modeled by longitudinal decreases in the left posterior cingulate cortex, R2 = .45, and predicted by baseline measures of a smaller right isthmus (retrosplenial) cingulate and larger left caudate, R2 = .77. In sum, treatment was associated with longitudinal changes in brain regions that support executive functioning but not those that discriminated PTSD from HC participants at baseline. Additionally, results confirm a role for the posterior/retrosplenial cingulate as a correlate of PTSD symptom improvement and predictor of treatment outcome.

Practitioner Review: Emotional dysregulation in attention-deficit/hyperactivity disorder - implications for clinical recognition and intervention.

BACKGROUND: Because emotional symptoms are common in attention-deficit/hyperactivity disorder (ADHD) patients and associate with much morbidity, some consider it to be a core feature rather than an associated trait. Others argue that emotional symptoms are too nonspecific for use as diagnostic criteria. This debate has been difficult to resolve due, in part, to the many terms used to describe emotional symptoms in ADHD and to concerns about overlap with mood disorders. METHODS: We sought to clarify the nature of emotional symptoms in ADHD by reviewing conceptual and measurement issues and by examining the evidence base regarding specificity of such symptoms for ADHD. We reviewed the various terms used to define emotional symptoms in ADHD, clarify how these symptoms are demarcated from mood disorders, and assess the possibility that symptoms of emotional impulsivity and deficient emotional self-regulation should be considered as core symptoms. We addressed psychiatric comorbidities, the effects of ADHD treatments on associated emotional dysregulation, and the utility of current rating scales to assess emotional symptoms associated with ADHD. RESULTS: Emotional symptoms are common and persistent in youth and adults with ADHD. Although emotional symptoms are common in other psychiatric disorders, emotional impulsivity (EI), and deficient emotional self-regulation (DESR) may be sufficiently specific for ADHD to function as diagnostic criteria. CONCLUSIONS: Emotional symptoms in ADHD cause clinically significant impairments. Although there is a solid theoretical rationale for considering EI and DESR to be core symptoms of ADHD, there is no consensus about how to define these constructs sin a manner that would be specific to the disorder. An instrument to measure EI and DESR which demarcates them from irritability and other emotional symptoms could improve the accuracy of diagnostic criteria for ADHD.

Linking trauma to mental health in the statewide Texas Youth Depression and Suicide Research Network (TX-YDSRN).

Rates of youth depression and suicide are rising worldwide and represent public health crises. The present study examined the relationship between trauma history and symptoms of depression, suicidal ideation, and anxiety among suicidal and depressed youth. A diverse group of 1000 8-20-year-olds enrolled in the statewide Texas Youth Depression and Suicide Research Network (TX-YDSRN) reported their trauma history (Traumatic Events Screening Inventory for Children) and symptoms of depression (Patient Health Questionnaire for adolescents; PHQ-A), anxiety (Generalized Anxiety Disorder scale; GAD-7), and suicidality (Concise Health Risk Tracking scale; CHRT-SR). Nearly half of the sample reported exposure to multiple categories of traumatic experiences. Number of trauma exposure categories significantly predicted PHQ-A and GAD-7 scores. Exposure to interpersonal trauma and to sexual trauma were significantly associated with PHQ-A, GAD-7, and CHRT-SR scores. The number of trauma exposure categories was associated with increased levels of anxiety and depression; however, only exposure to interpersonal or sexual trauma was associated with more suicidality. Clinicians should assess trauma exposure in patients seeking psychiatric care, especially for interpersonal and sexual trauma, which may be predictive of increased risk for suicidality in depressed youth. Future work should disentangle the effects of specific trauma types from multiple trauma exposure.

Suicidal thoughts and behaviors in youth seeking mental health treatment in Texas: Youth Depression and Suicide Network research registry.

INTRODUCTION: Suicidality in youth is a serious public health problem. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) was initiated in 2020 to create a research registry for youth with depression and/or suicidality in Texas. This report presents baseline clinical/demographic characteristics of the first 1000 participants, focusing on suicidal thoughts and behaviors. METHODS: The registry includes 8-20-year-old youth receiving treatment for depression, or who screen positive for depression and/or suicidal ideation/behavior. Baseline data include diagnosis, depression/anxiety severity, suicidal ideation/behavior, trauma history, and measures of resilience. RESULTS: We present baseline data on the first 1000 participants. Most (79.6%) of the sample had a primary depressive disorder. The sample had moderate to severe depression (Patient Health Questionnaire for Adolescents, PHQ-A; 12.9 ± 6.4) and anxiety (Generalized Anxiety Disorder, GAD-7; 11.3 ± 5.9). Nearly half reported ≥1 lifetime suicide attempts and 90% reported lifetime or current suicidal ideation. Participants with past/current suicidality (attempts and/or ideation) had greater illness severity (depression, anxiety, and suicidal thoughts/behaviors), lower resilience, and higher rates of trauma exposure than those without suicidality. CONCLUSIONS: Baseline data indicate moderate levels of depression, anxiety, and suicidality and their correlates in this cohort. Future reports will determine trajectories of outcomes and predictors, moderators, and social determinants related to these outcomes.

Psychometric properties of Concise Associated Symptom Tracking (CAST) scale in youths and young adults: Findings from the Texas youth depression and suicide research network (TX-YDSRN).

Symptoms of irritability, anxiety, panic, and insomnia are common in patients with depression, and their worsening after antidepressant treatment initiation is associated with poorer long-term outcomes. The Concise Associated Symptom Tracking (CAST) scale was developed to measure these symptoms in adults with major depressive disorder (MDD). Here, we evaluate the psychometric properties of CAST in an ongoing community-based observational study involving children, adolescents, and young adults. Individuals from the ongoing Texas Youth Depression and Suicide Research Network (TX-YDSRN; N = 952) with CAST data available were included. Fit statistics [Goodness of Fit Index (GFI), Comparative Fit Index (CFI), and Root Mean Square Error of Approximation (RMSEA)] from confirmatory factor analyses were used to evaluate the five- and four-domain structure of CAST. Item response theory (IRT) analyses were also used. Individuals were grouped based on age (in years) as youths (8-17) and young adults (18-20). Correlations with other clinical measures were used to inform construct validity. Four-domain (irritability, anxiety, panic, and insomnia) 12-item structure of CAST (CAST-12) was optimal for youths (N = 709, GFI = 0.906, CFI = 0.919, RMSEA = 0.095) and young adults (N = 243, GFI = 0.921, CFI = 0.938, RMSEA = 0.0797) with Cronbach's alpha of 0.87 and 0.88, respectively. Slope of each item exceeded 1.0 on IRT analyses suggesting adequate discrimination for each item. Scores on irritability, anxiety, panic, and insomnia were significantly correlated with similar items on other scales. Together these findings suggest that CAST-12 is a valid self-report measure of irritability, anxiety, insomnia, and panic in youths and young adults.

Psychometric evaluation of the 9-item Concise Health Risk Tracking - Self-Report (CHRT-SR9) (a measure of suicidal risk) in adolescent psychiatric outpatients in the Texas Youth Depression and Suicide Research Network (TX-YDSRN).

BACKGROUND: This study evaluated the psychometric properties of the 9-item Concise Health Risk Tracking Self-Report (CHRT-SR9), a measure of suicidality, in adolescent psychiatric outpatients. METHODS: Altogether, 933 depressed or suicidal adolescents (12-20 years of age), receiving treatment at psychiatric outpatient clinics in Texas, completed the 16-item CHRT-SR at baseline and one month later. CHRT-SR9 was extracted from CHRT-SR16 using multigroup confirmatory factor analysis. Sex and age measurement invariance, classical test theory, item response theory (IRT), and concurrent validity analyses (against the suicidal ideation Item 9 of Patient Health Questionnaire-Adolescent (PHQ-A)) were conducted. RESULTS: The CHRT-SR9 demonstrated excellent model fit with four factors (pessimism, helplessness, despair, and suicidal thoughts). Measurement invariance was upheld. Acceptable item-total correlations (0.56-0.80) and internal consistency (Spearman-Brown 0.78-0.89) were revealed. IRT analyses showed a unidimensional instrument with excellent item performance. Using the CHRT-SR9 total score as a measure of overall suicidality and comparing it against levels of PHQ-A Item 9, the mean (standard deviation) of CHRT-SR9 total score was 8.64 (SD = 5.97) for no-risk (0 on Item 9), 17.05 (SD = 5.00) for mild, 23.16 (SD = 5.05) for moderate, and 26.96 (SD = 5.24) for severe-risk (3 on Item 9). Significant differences (p-value<0.0001) indicated that CHRT-SR9 total score distinguished between levels of suicidal risk. Furthermore, CHRT-SR9 was sensitive to change over a one-month period. LIMITATIONS: Whether CHRT-SR9 predicts actual suicidal attempts in adolescents is not well defined. CONCLUSION: The CHRT-SR9 is an easy-to-administer, user-friendly self-report with good psychometric qualities which makes it an excellent screening measure of suicidal risk in adolescent psychiatric outpatients.

Texas Youth Depression and Suicide Research Network (TX-YDSRN) research registry and learning healthcare network: Rationale, design, and baseline characteristics.

BACKGROUND: American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was initiated in 2020 to develop predictive models for treatment outcomes in youth with depression and/or suicidality. This report presents the study rationale, design and baseline characteristics of the first 1000 participants. METHODS: TX-YDSRN consists of the Network Hub (coordinating center), 12 medical school "Nodes" (manage/implement study), each with 1-5 primary care, inpatient, and/or outpatient Sub-Sites (recruitment, data collection). Participants are 8-20-year-olds who receive treatment or screen positive for depression and/or suicidality. Baseline data include mood and suicidality symptoms, associated comorbidities, treatment history, services used, and social determinants of health. Subsequent assessments occur every two months for 24 months. RESULTS: Among 1000 participants, 68.7 % were 12-17 years, 24.6 % were ≥ 18 years, and 6.7 % were < 12. Overall, 36.8 % were non-Hispanic Caucasian, 73.4 % were female, and 79.9 % had a primary depressive disorder. Nearly half of the sample reported ≥1 suicide attempt, with rates similar in youth 12-17 years old (49.9 %) and those 18 years and older (45.5 %); 29.9 % of children <12 reported at least one suicide attempt. Depression and anxiety scores were in the moderate-severe range for all age groups (Patient Health Questionnaire for Adolescents [PHQ-A]: 12.9 ± 6.4; Generalized Anxiety Disorder [GAD-7]: 11.3 ± 5.9). LIMITATIONS: The sample includes youth who are receiving depression care at enrollment and may not be representative of non-diagnosed, non-treatment seeking youth. CONCLUSIONS: The TX-YDSRN is one of the largest prospective longitudinal cohort registries designed to develop predictive models for outcome trajectories based on disorder heterogeneity, social determinants of health, and treatment availability.

Obsessive-compulsive disorder in youth and young adults with depression: Clinical characteristics of comorbid presentations.

Obsessive-compulsive disorder (OCD), anxiety disorders, and depressive disorders are highly comorbid, and each contribute to significant functional impairment for affected youth. Comorbid anxiety disorders in depressed youth have been associated with greater depressive symptom severity and impairment, but the impact of comorbid OCD in this population remains unclear. Accordingly, the present study examined the differential clinical characteristics of youth with depression and comorbid OCD relative to age/gender matched depressed youth with no such comorbidity and to those with depression and a comorbid (non-OCD) anxiety disorder. A sample of 797 youth and young adults ages 8-20 years who met diagnostic criteria for depression alone, depression with co-occurring OCD or any anxiety disorder were included in the present study. Rates of comorbid anxiety and OCD were very high (60.5% and 15.5%, respectively). Relative to youth with only depression, depressed youth with comorbid OCD or anxiety had greater severity of depression, suicidality, and overall impairment in social, physical, and emotional functioning. These results highlight the contribution of OCD or anxiety comorbidity in more complex clinical presentations for depressed youth.

Attention-Deficit Hyperactivity Disorder and the Dysregulation of Emotion Generation and Emotional Expression.

Individuals with attention-deficit/hyperactivity disorder (ADHD) frequently experience strong reactions to emotionally evocative situations. Difficulties modulating anger and other upsets have clinically significant behavioral consequences. Those with ADHD may have anomalies in emotion generation, emotion expression, or both that predispose to these problems. The association between ADHD and emotion dysregulation raises Important clinical and research issues, including possible heterogeneity in the mechanisms by which they are related. Although first-line treatments for ADHD often help to resolve emotional dysregulation symptoms as well, the evidence base for widespread practice of combination pharmacotherapy remains sparse. Psychosocial treatments that engage processes underlying emotional dysregulation are in development.

Stepped Treatment for Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior: A Randomized, Controlled Trial of Adjunctive Risperidone, Divalproex Sodium, or Placebo After Stimulant Medication Optimization.

OBJECTIVE: Stimulant medications are the most prevalent first-line pharmacotherapy for attention-deficit/hyperactivity disorder, but children with aggressive behavior often receive multiagent treatment. There is sparse evidence for the benefits of adjunctive medications when stimulant monotherapy provides inadequate benefit for aggressive behavior, yet the adverse effects of common adjuncts are well established. This study compared the efficacy in reducing aggressive behavior of risperidone (RISP), divalproex sodium (DVPX), and placebo (PBO) added to stimulant medication among childrenwhose symptoms persisted after individually optimized stimulant treatment. METHOD: This trial enrolled 6- to 12-year-old with attention-deficit/hyperactivity disorder, a disruptive disorder, significant aggressive behavior, and prior stimulant treatment. Open, systematically titrated stimulant treatment identified patients with inadequate reductions in aggressive behavior, who were then randomly assigned to receive adjunctive RISP, DVPX, or PBO under double-blinded conditions for 8 weeks. Family-based behavioral treatment was offered throughout the trial. The primary outcome was the parent-completed Retrospective Modified Overt Aggression Scale. RESULTS: Participants included 175 children (mean [SD] age 9.48 [2.04] years, 19% female). Of participants, 151 completed the stimulant optimization phase, with aggression remitting among 96 (63%), and 45 were randomly assigned to adjunctive treatment groups. The adjunctive RISP group showed greater reductions in aggression ratings than the PBO group (least squares means difference [ΔLSM], -2.33; 95% CI, -3.83 to -0.82; effect size [ES], -1.32), as did the DVPX group (ΔLSM, -1.60; 95% CI, -3.18 to -0.03; ES, -0.91). Mean standardized body mass index scores increased more among RISP-treated participants than participants receiving PBO (ΔLSM, 1.54; 95% CI, 0.68 to 2.40; ES, 0.58). CONCLUSION: High response rate during the trial's open stimulant optimization phase suggests that rigorous titration of stimulant medication and concurrent behavioral therapy may avert the need for additional medications. Among nonremitters, RISP and DVPX were efficacious adjunctive treatments, although RISP was associated with weight gain. CLINICAL TRIAL REGISTRATION INFORMATION: Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study); https://www.clinicaltrials.gov; NCT00794625.

Measurement-Based Care in the Treatment of Attention-Deficit/Hyperactivity Disorder and Disruptive Behavior Disorders.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric diagnoses. The core symptoms of ADHD include inattention, impulsivity, and hyperactivity. ADHD entails impairments that have extensive and profound detrimental effects on many critical developmental areas. As a valid neurobiologic condition that causes significant impairments in those affected, it is one of the best-researched disorders in medicine. Measurement-based care in treatment of ADHD is critical in establishing a diagnosis, determining a treatment target, and assessing treatment response. This article highlights the rationale for measurement-based care in ADHD, how to implement measurement-based care in clinical practice, and common challenges encountered.

Longitudinal changes in brain function associated with symptom improvement in youth with PTSD.

BACKGROUND: Previous studies indicate that youth with posttraumatic stress disorder (PTSD) have abnormal activation in brain regions important for emotion processing. It is unknown whether symptom improvement is accompanied by normative changes in these regions. This study identified neural changes associated with symptom improvement with the long-term goal of identifying malleable targets for interventions. METHODS: A total of 80 functional magnetic resonance imaging (fMRI) scans were collected, including 20 adolescents with PTSD (ages 9-17) and 20 age- and sex-matched healthy control subjects, each scanned before and after a 5-month period. Trauma-focused cognitive behavioral therapy was provided to the PTSD group to ensure improvement in symptoms. Whole brain voxel-wise activation and region of interest analyses of facial expression task data were conducted to identify abnormalities in the PTSD group versus HC at baseline (BL), and neural changes correlated with symptom improvement from BL to EOS of study (EOS). RESULTS: At BL, the PTSD group had abnormally elevated activation in the cingulate cortex, hippocampus, amygdala, and medial frontal cortex compared to HC. From BL to EOS, PTSD symptoms improved an average of 39%. Longitudinal improvement in symptoms of PTSD was associated with decreasing activation in posterior cingulate, mid-cingulate, and hippocampus, while improvement in dissociative symptoms was correlated with decreasing activation in the amygdala. CONCLUSIONS: Abnormalities in emotion-processing brain networks in youth with PTSD normalize when symptoms improve, demonstrating neural plasticity of these regions in young patients and the importance of early intervention.

Increased rates of bipolar disorder diagnoses among U.S. child, adolescent, and adult inpatients, 1996-2004.

BACKGROUND: Volatile, aggressive behavior is the chief complaint that brings children to inpatient psychiatric care. These difficulties are increasingly conceptualized as bipolar disorder (BD). The impact of doing so on clinical diagnoses in clinical care is uncertain. METHODS: We extracted records from the annual National Hospital Discharge Survey (NHDS) for which a psychiatric diagnosis was primary and examined trends in the rates of hospitalization for BD. RESULTS: Population-adjusted rates of hospital discharges of children with a primary diagnosis of BD increased linearly over survey years. The rate in 1996 was 1.3 per 10,000 U.S. children and climbed to 7.3 per 10,000 U.S. children in 2004. Bipolar disorder related discharges also increased fourfold among adolescents. Adults showed a more modest, though still marked, rise of 56%. Bipolar disorder related hospitalization was more prevalent among female adolescents and adults, while male children had larger risk than female children. Children's BD diagnoses tended not to specify a prevailing mood state, while depression and psychotic features were the most common codes for adults. Black individuals, especially men, had lower rates of BD diagnoses in early survey years, but more recently their rate of BD related hospitalizations has exceeded other NHDS race groups. CONCLUSIONS: Higher rates of inpatient admissions among youth associated with BD may reflect greater appreciation of the importance of affective dysregulation in this patient group or "upcoding" to putatively more severe conditions for reimbursement or administrative reasons. Further study is warranted to examine this shift's causes and implications for treatments and outcomes.

Double-disease management or one care manager for two chronic conditions: pilot feasibility study of nurse telephonic disease management for depression and congestive heart failure.

This study assessed the feasibility of a telephonic nurse double-disease management program (DDMP) for patients with depression and congestive heart failure. Thirty-five patients with depression and congestive heart failure were entered into a novel DDMP modeled after Wagner's chronic illness care model and implemented as part of a 13-month Breakthrough Series Collaborative administered by the Institute of Healthcare Improvement. Twenty-four patients remained in the program long enough to complete at least one follow-up assessment (ie, 6 weeks or longer). Patients were entered into the program based on depression severity scores from either the interactive voice response (IVR) version of the Hospital Anxiety and Depression Scale (HADS) or the self-administered (or telephonic) Patient Health Questionnaire (PHQ). Because use of the IVR version of the HADS was eliminated after several weeks into the program (because of poor patient acceptance), 19 patients had both entry and follow-up scores on the same instrument (PHQ). Depression "response" was defined as a 50% improvement in PHQ score. Mixed models regression was used to test the statistical significance of change in PHQ scores over time. Patient and clinician reports were obtained to evaluate program acceptability and satisfaction. Eighty-two percent of patients (n = 11) with Major Depressive Disorder (MDD) responded, and 75% of patients (n = 8) with "other depression" (PHQ score < 10) responded. Mean change in PHQ scores for the sample as a whole improved significantly over the 24 weeks of the program (p < 0.0003), as well as for those with major depression and other depression considered separately (p < 0.01 for both). In some patients who refused medication, depression seemed to respond to self-management support interventions of the care manager. Based on patient acceptance and clinicians' reports, the program appeared feasible and possibly effective. DDMP appears feasible and possibly effective. Future clinical trials are warranted.

Prevalence and Treatment Outcomes of Persistent Negative Mood Among Children with Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior.

OBJECTIVE: Diagnostic criteria for disruptive mood dysregulation disorder (DMDD) require 1) periodic rageful outbursts and 2) disturbed mood (anger or irritability) that persists most of the time in between outbursts. Stimulant monotherapy, methodically titrated, often culminates in remission of severe aggressive behavior, but it is unclear whether those with persistent mood symptoms benefit less.This study examined the association between the presence of persistent mood disturbances and treatment outcomes among children with attention-deficit/hyperactivity disorder (ADHD) and periodic aggressive, rageful outbursts. METHODS: Within a cohort of children with ADHD and aggressive behavior (n = 156), the prevalence of persistent mood symptoms was evaluated at baseline and after completion of a treatment protocol that provided stimulant monotherapy and family-based behavioral treatment (duration mean [SD] = 70.04 [37.83] days). The relationship of persistent mood symptoms on posttreatment aggressive behavior was assessed, as well as changes in mood symptoms. RESULTS: Aggressive behavior and periodic rageful outbursts remitted among 51% of the participants. Persistent mood symptoms at baseline did not affect the odds that aggressive behavior would remit during treatment. Reductions in symptoms of sustained mood disturbance accompanied reductions in periodic outbursts. Children who at baseline had high irritability but low depression ratings showed elevated aggression scores at baseline and after treatment; however, they still displayed large reductions in aggression. CONCLUSIONS: Among aggressive children with ADHD, aggressive behaviors are just as likely to decrease following stimulant monotherapy and behavioral treatment among those with sustained mood symptoms and those without. Improvements in mood problems are evident as well. Therefore, the abnormalities in persistent mood described by DMDD's criteria do not contraindicate stimulant therapy as initial treatment among those with comorbid ADHD. Rather, substantial improvements may be anticipated, and remission of both behavioral and mood symptoms seems achievable for a proportion of patients. TRIAL REGISTRATION: ClinicalTrials.gov (U.S.); IDs: NCT00228046 and NCT00794625; www.clinicaltrials.gov.

Can keeping clinical trial participants blind to their study treatment adversely affect subsequent care?

Subjects in controlled clinical trials obtain experience with study-provided treatment that could inform their further therapy by awareness of the efficacy or inefficacy of the study treatment they received. However, patients in blinded trials typically do not learn right after their participation what treatment they actually received during the study, even though it is possible to do so while maintaining the necessary blinding of investigators. Keeping investigators and subjects blind to treatment assignment throughout a trial is a key element of clinical research methodology, but the value of keeping participants and their medical providers blinded after participation is less certain and may pose risks that include delay in the receipt of efficacious care, exacerbation of symptoms, or prolonged exposure to superfluous or toxic treatment. The significance of these risks is likely to vary with the specific disease and the time course of its response to available therapies. Currently, it seems appropriate for investigators a) to evaluate the risks of keeping subjects blind after participation, b) to justify doing so in relation to serious, identifiable risks to the study's validity and apprise prospective subjects clearly that information about their response to specific treatment during the trial will not be available to guide their post-study care, and c) to consider methods for debriefing subjects before their resumption of open treatment that preserve the integrity of investigator blinding. In the long-run, research on the impact that keeping subjects uninformed about study treatment has on post-study patient outcomes and on study integrity can foster the development of procedures that optimally balance both.

Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography.

Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry-a critical cortical pathway to subcortical limbic regions-and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10±2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.

Symptom, family, and service predictors of children's psychiatric rehospitalization within one year of discharge.

OBJECTIVE: To investigate predictors of readmission to inpatient psychiatric treatment for children aged 5 to 12 discharged from acute-care hospitalization. METHOD: One hundred nine children were followed for 1 year after discharge from inpatient care. Time to rehospitalization was the outcome of interest. Predictors of readmission, examined via the Cox proportional hazards model, were symptom and family factors assessed at admission, aspects of psychiatric treatment, and demographic variables. RESULTS: The Kaplan-Meier rehospitalization risk within 1 year of discharge, taking into account known readmissions and censored observations, was 0.37. Most readmissions (81%) occurred within 90 days of discharge. Four variables contributed simultaneously to predicting readmission risk. More severe conduct problems, harsh parental discipline, and disengaged parent-child relations conferred a higher risk for rehospitalization; these risks were attenuated when parents disclosed higher stress in their parenting roles. CONCLUSIONS: Findings showed that psychiatric rehospitalization of children is common, most likely in the trimester after discharge, and highly related to both child symptoms and family factors measurable at admission. Results suggest that efforts to improve postdischarge outcomes of children should target the initial period following inpatient care, address vigorously the complex treatment needs of those with severe conduct problems, and aim to improve parent-child relations.

Callous-unemotional traits, proactive aggression, and treatment outcomes of aggressive children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Stimulant treatment improves impulse control among children with attention-deficit/hyperactivity disorder (ADHD). Decreased aggression often accompanies stimulant pharmacotherapy, suggesting that impulsiveness is integral to aggressive behavior in these children. However, children with high callous-unemotional (CU) traits and proactive aggression may benefit less from ADHD pharmacotherapy, because their aggressive behavior seems more purposeful and deliberate. This study's objective was to determine whether pretreatment CU traits and proactive aggression affect treatment outcomes among aggressive children with ADHD receiving stimulant monotherapy. METHOD: We implemented a stimulant optimization protocol with 160 children 6 to 13 years of age (mean [SD] age of 9.31 [2.02] years; 78.75% male) with ADHD, oppositional defiant or conduct disorder, and significant aggressive behavior. Family-focused behavioral intervention was provided concurrently. The primary outcome was the Retrospective Modified Overt Aggression Scale. The Antisocial Process Screening Device and the Aggression Scale, also completed by parents, measured CU traits and proactive aggression, respectively. Analyses examined moderating effects of CU traits and proactive aggression on outcomes. RESULTS: In all, 82 children (51%) experienced remission of aggressive behavior. Neither CU traits nor proactive aggression predicted remission (CU traits: odds ratio [OR] = 0.94, 95% CI = 0.80-1.11; proactive aggression, OR = 1.05, 95% CI = 0.86-1.29). Children whose overall aggression remitted showed decreases in CU traits (effect size = -0.379, 95% CI = -0.60 to -0.16) and proactive aggression (effect size = -0.463, 95% CI = -0.69 to -0.23). CONCLUSIONS: Findings suggest that pretreatment CU traits and proactive aggression do not forecast worse outcomes for aggressive children with ADHD receiving optimized stimulant pharmacotherapy. With such treatment, CU traits and proactive aggression may decline alongside other behavioral improvements. Clinical trial registration information--Medication Strategies for Treating Aggressive Behavior in Youth With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00228046; and Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study); http://clinicaltrials.gov/; NCT00794625.