PTSD, depression, and treatment outcomes: A latent profile analysis among active duty personnel in a residential PTSD program.

Depression frequently co-occurs with posttraumatic stress disorder (PTSD), including among active duty service members. However, symptom heterogeneity of this comorbidity is complex and its association with treatment outcomes is poorly understood, particularly among active duty service members in residential treatment. This study used latent profile analysis (LPA) to identify symptom-based subgroups of PTSD and depression among 282 male service members in a 10-week, residential PTSD treatment program with evidence-based PTSD psychotherapies and adjunctive interventions. The PTSD Checklist-Military Version and Patient Health Questionnaire-8 were completed by service members at pre- and posttreatment and weekly during treatment. Multilevel models compared subgroups on PTSD and depression symptom change across treatment. LPA indicated four subgroups provided optimal fit: Depressive (high depression severity, low PTSD avoidance; n = 33, 11.7%), Avoidant (high PTSD avoidance, moderate depression severity; n = 89, 31.6%), Moderate (moderate PTSD and depression severity; n = 27, 9.6%), and Distressed (high PTSD and depression severity; n = 133, 47.2%). Treatment response differed across classes for both PTSD and depression outcomes (time × LPA class interaction ps < 0.001). In PTSD models, post-hoc comparisons indicated the Moderate class was associated with less PTSD symptom improvement relative to the other classes (ps < 0.006). In depression models, symptom reduction was greatest for the Distressed and Depressive subgroups relative to the other two classes (ps < 0.009). Study results provide an initial model for two prevalent, impairing disorders among service members and show how these symptom-based subgroups may differentially respond to residential PTSD treatment.

Changes in guilt cognitions mediate the effect of trauma-informed guilt reduction therapy on PTSD and depression outcomes.

OBJECTIVE: Trauma-informed guilt reduction therapy (TrIGR), a six-session cognitive behavioral therapy targeting trauma-related guilt and distress, reduces guilt and symptoms of posttraumatic stress disorder (PTSD) and depression, yet little is known regarding how and why TrIGR may be effective. METHOD: This study examined treatment-related changes in avoidant coping and trauma-related guilt cognitions as possible mediators of treatment effects on PTSD and depression outcomes at 3- and 6-month follow-up. Data were from a randomized controlled trial for treatment of trauma-related guilt comparing TrIGR and supportive care therapy among 145 post-9/11 US veterans (Mage = 39.2 [8.1], 93.8% male). RESULTS: At pretreatment, most (86%) met PTSD criteria. Intent to treat analyses using parallel mediation models indicated changes in guilt cognitions, but not avoidant coping, mediated the effect of TrIGR on reducing PTSD severity at 3-month (a × b = -0.15, p < 0.01, 95% CI: [-0.24 to -0.06], p = 0.001) and 6-month (a × b = -0.17, 95% CI: [-0.26 to -0.07], p = 0.001) follow-up. Similarly, changes in guilt cognitions, but not avoidant coping, mediated the effect of TrIGR on reducing depression severity at 3-month (a × b = -0.10, 95% CI: [-0.18 to -0.02], p = 0.02) and 6-month (a × b = -0.11, 95% CI: [-0.20 to -0.03], p = 0.01) follow-up. CONCLUSIONS: Compared to guilt cognitions, changes in avoidant coping were less integral to downstream PTSD and depression symptom reduction. Guilt cognition change may be a salient active ingredient of PTSD and depression treatment for those with trauma-related guilt and a key therapy element to which providers should be attuned.

Firearm storage practices among military veterans in the United States: Findings from a nationally representative survey.

BACKGROUND: Unsafe storage of firearms is associated with increased risk of suicide.. However, contemporary population-based data on the prevalence and correlates of firearm storage practices among veterans are limited. METHODS: Data were from the 2022 National Health and Resilience in Veterans Study, a nationally representative sample of 2441 veterans. Analyses examined: (1) the prevalence of firearm storage practices; (2) sociodemographic, psychiatric, and clinical characteristics associated with storing firearms loaded and/or in non-secure location; and (3) associations between types of potentially traumatic events and storage practices. RESULTS: More than half of veterans reported owning one or more personal firearms (50.9%). Among firearm owners, 52.9% reported some form of unsafe firearm storage practice (i.e., loaded and/or non-secure location), with 39.9% reporting that they stored one or more firearms loaded. After adjusting for sociodemographic characteristics, major depressive, alcohol and drug use disorders, direct trauma exposures, future suicidal intent, and traumatic brain injury were associated with storing firearms loaded and/or in a non-secure location (ORs = 1.09-7.16). Veterans with a history of specific forms of direct trauma exposure (e.g., physical assault) were more likely to store firearms unsafely. LIMITATIONS: Cross-sectional design precludes causal inference. CONCLUSIONS: Half of U.S. veterans who own firearms store at least one personal firearm loaded and/or in a non-secure location, with approximately four-in-ten keeping a loaded firearm in the home. These high rates underscore the importance of nationwide training initiatives to promote safe firearm storage for all service members and veterans, regardless of risk status, as well as for healthcare professionals working with veterans.

Firearm Ownership Among a Nationally Representative Sample of U.S. Veterans.

INTRODUCTION: This study aimed to identify the prevalence and correlates of firearm ownership in a large, contemporary, nationally representative sample of U.S. military veterans. METHODS: Data were analyzed from the 2022 National Health and Resilience in Veterans Study (N=2,326; mean age=60.2 years). Weighted independent-sample t-tests and chi-square analyses were conducted to compare veterans who did with those who did not report firearm ownership on sociodemographic, military, and psychiatric variables. A multivariable logistic regression analysis using backward elimination was conducted to identify the characteristics independently associated with firearm ownership, and a relative importance analysis was conducted to quantify the relative variance in firearm ownership that was explained by each of the statistically significant main effects. RESULTS: Of the total 2,326 veterans, 1,217 (weighted 50.9%, 95% CI=48.0%, 53.9%) reported owning any firearms. Male sex, conservative political ideology, living in rural area, home ownership, cumulative trauma burden, and lifetime history of alcohol use disorder were most strongly associated with firearm ownership. CONCLUSIONS: This study provides an updated characterization of the prevalence and correlates of firearm ownership among the U.S. veterans. Results of this nationally representative study suggest that firearm ownership in this group may be higher than previously reported and underscore the importance of targeted suicide prevention efforts promoting firearm safety among vulnerable segments of this population.

Epidemiology of DSM-5 alcohol use disorder in U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

BACKGROUND: Alcohol use disorder (AUD) is a prevalent public health concern in the U.S. that disproportionately affects veterans relative to civilians. Given changes to the demographic composition of the veteran population and AUD diagnostic criteria in the DSM-5, updated knowledge regarding the epidemiology of DSM-5 AUD in a national sample of veterans is critical to informing the population-based burden of this disorder. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 4069 U.S. veterans. Lifetime DSM-5 AUD (mild, moderate, severe) and past-year DSM-5 AUD were assessed using validated self-report measures, and sociodemographic, military, and psychiatric characteristics associated with lifetime and past-year AUD were evaluated. RESULTS: Prevalences of lifetime and past-year DSM-5 AUD were 40.8% (95% confidence interval [CI]=39.2-42.3%) and 10.5% (95%CI=9.6-11.5%), respectively. Lifetime prevalences of mild, moderate, and severe AUD were 20.5%, 8.3%, and 12.0%, respectively. Veterans with lifetime AUD had elevated rates of psychiatric disorders and suicidal behavior, which generally increased as a function of AUD severity. Lifetime AUD was also associated with being younger, male, white, unmarried, retired and experiencing more adverse childhood experiences and traumas. For past-year AUD, being younger, male, white, having more adverse childhood experiences, and experiencing lifetime PTSD were significant correlates. CONCLUSIONS: AUD is highly prevalent among U.S. veterans and associated with substantial psychopathology, including elevated odds of suicidal behaviors. Results underscore the importance of comprehensive screening and preventive efforts for AUD, and interventions that concurrently target overlapping alcohol use and psychiatric difficulties.

A clinical trial comparing trauma-informed guilt reduction therapy (TrIGR), a brief intervention for trauma-related guilt, to supportive care therapy.

INTRODUCTION: Trauma-related guilt is common, associated with posttraumatic mental health problems, and can persist after posttraumatic stress disorder (PTSD) treatment. We compared the efficacy of two six-session psychotherapies, Trauma-Informed Guilt Reduction (TrIGR) and Supportive Care Therapy (SCT), for reducing trauma-related guilt. TrIGR helps patients accurately appraise their role in the trauma and re-engage in values. In SCT, patients guide session content. METHODS: A total of 184 veterans seeking VA mental health services were enrolled across two sites; 145 veterans (mean age: 39.2 [8.1]; 92.4% male; 84.8% with PTSD) who endorsed guilt related to a traumatic event that occurred during a post 9/11 Iraq or Afghanistan deployment were randomized and assessed at baseline, posttreatment, 3- and 6-month follow-up. RESULTS: Linear mixed models using intent-to-treat analyses showed guilt decreased in both conditions with a greater decrease for TrIGR (treatment × time, -0.22; F 1, 455.2 = 18.49, p = .001; d = 0.92) than supportive therapy. PTSD and depressive symptoms showed the same pattern. TrIGR had significantly higher likelihood of PTSD treatment response (67% vs. 40%), loss of PTSD diagnosis (50% vs. 14%), and meaningful change in depression (54% vs. 27%) than supportive therapy. Psychological distress and trait shame improved in both conditions. Quality of life did not change. CONCLUSIONS: Targeting guilt appears to be an effective means for reducing posttraumatic symptoms and distress.

PTSD symptom heterogeneity and alcohol-related outcomes in U.S. military veterans: Indirect associations with coping strategies.

INTRODUCTION: This study investigated the role of coping strategies in mediating the relationship between the 7-factor model of posttraumatic stress disorder (PTSD) symptoms and alcohol misuse in veterans. METHODS: Data were analyzed from 615 veterans from a nationally representative study of U.S. veterans who met criteria for probable full or subthreshold PTSD. Path analyses examined the role of self-sufficient, socially-supported, and avoidant coping strategies in mediating associations between PTSD symptom clusters and alcohol use disorder (AUD), alcohol consumption, and alcohol-related consequences. RESULTS: Negative affect PTSD symptoms were associated with AUD through increased use of avoidant coping. Additionally, dysphoric arousal PTSD symptoms were associated with AUD; avoidant coping was associated with AUD and increased alcohol consumption; self-sufficient coping was associated with reduced AUD likelihood anhedonia symptoms with decreased use of self-sufficient coping; and negative affect with decreased use of socially-supported coping and increased use of avoidant coping. CONCLUSIONS: Results underscore the importance of avoidant coping strategies as potential mediators of the relation between PTSD symptoms and AUD. Interventions designed to mitigate engagement in avoidant coping strategies, and to bolster engagement in self-sufficient and socially-supported strategies may help reduce alcohol misuse in veterans with full or subthreshold PTSD.

Mental Health Care Use Among U.S. Military Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study.

OBJECTIVE: Psychiatric and substance use disorders are prevalent among U.S. military veterans, yet many veterans do not engage in treatment. The authors examined characteristics associated with use of mental health care in a nationally representative veteran sample. METHODS: Using 2019-2020 data from the National Health and Resilience in Veterans Study (N=4,069), the authors examined predisposing, enabling, and need factors and perceived barriers to care as correlates of mental health care utilization (psychotherapy, counseling, or pharmacotherapy). Hierarchical logistic regression and relative importance analyses were used. RESULTS: Among all veterans, 433 (weighted prevalence, 12%) reported current use of mental health care. Among 924 (26%) veterans with a probable mental or substance use disorder, less than a third (weighted prevalence, 27%) reported care utilization. Mental dysfunction (24%), posttraumatic stress disorder symptom severity (18%), using the U.S. Department of Veterans Affairs as primary health care provider (14%), sleep disorder (12%), and grit (i.e., trait perseverance including decision and commitment to address one's needs on one's own; 7%) explained most of the variance in mental health care utilization in this subsample. Grit moderated the relationship between mental dysfunction and use of care; among veterans with high mental dysfunction, those with high grit (23%) were less likely to use services than were those with low grit (53%). CONCLUSIONS: A minority of U.S. veterans engaged in mental health care. Less stigmatized need factors (e.g., functioning and sleep difficulties) may facilitate engagement. The relationship between protective and need factors may help inform understanding of veterans' decision making regarding treatment seeking and outreach efforts.

Psychosocial functioning in integrated treatment of co-occurring posttraumatic stress disorder and alcohol use disorder.

Co-occurring posttraumatic stress disorder and alcohol use disorder (PTSD/AUD) is associated with poorer psychosocial functioning than either disorder alone; however, it is unclear if psychosocial functioning improves in treatment for PTSD/AUD. This study examined if psychosocial functioning improved in integrated treatments for PTSD/AUD, and if changes in PTSD severity and percentage heavy drinking days (PHDD) during treatment were associated with functioning outcomes. 119 veterans with PTSD/AUD randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure or Seeking Safety completed measures of functioning (Medical Outcomes Survey SF-36), PTSD (Clinician Administered PTSD Scale for DSM-5), and alcohol use (Timeline Follow-Back) at baseline, posttreatment, 3- and 6-month follow-ups. Our findings suggest that psychosocial functioning improved to a statistically significant degree with no significant differences between conditions. Reductions in PTSD severity during treatment were associated with psychosocial functioning improvements, whereas reductions in PHDD were associated with improvement in role impairment at posttreatment. Although psychosocial functioning improves to a statistically significant degree in interventions designed to treat PTSD/AUD, these improvements do not represent clinically meaningful improvements in patients' abilities to navigate important roles. Findings underscore the need to study how to best treat psychosocial functioning impairment in PTSD/AUD.

Subgroups of comorbid PTSD and AUD in U.S. military veterans predict differential responsiveness to two integrated treatments: A latent class analysis.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur. Integrated treatments are effective, but not all patients respond and predicting outcome remains difficult. In this study, latent class analysis (LCA) identified symptom-based subgroups of comorbid PTSD/AUD among 119 veterans with PTSD/AUD from a randomized controlled trial of integrated exposure therapy (I-PE) versus integrated coping skills therapy (I-CS). Multilevel models compared subgroups on PTSD severity and percentage of heavy drinking days at post-treatment and 3- and 6-month follow-up. LCA revealed three subgroups best fit the data: Moderate PTSD/Low AUD Impairment (21%), High PTSD/High AUD Impairment (48%), and Low PTSD/High AUD Impairment (31%). There was a three-way interaction between time, treatment condition, and subgroup in predicting PTSD outcomes (p < .05). For the Moderate PTSD/Low AUD Impairment class, outcomes at post-treatment and 3-months were similar (ds = 0.17, 0.55), however I-PE showed greater reductions at 6-months (d = 1.36). For the High PTSD/High AUD Impairment class, I-PE demonstrated better post-treatment (d = 0.83) but comparable follow-up (ds = -0.18, 0.49) outcomes. For the Low PTSD/High AUD Impairment class, I-PE demonstrated stronger outcomes at every timepoint (ds = 0.82-1.15). Heavy drinking days declined significantly through follow-up, with an effect of subgroup, but not treatment, on timing of response. This was the first study modeling how PTSD and AUD symptoms might cluster together in a treatment sample of veterans with PTSD/AUD. Symptom-based subgroups show promise in helping understand variability in treatment response among patients with PTSD/AUD and deserve further study.

Within-treatment clinical markers of dropout risk in integrated treatments for comorbid PTSD and alcohol use disorder.

BACKGROUND: Integrated interventions for comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are effective, but many patients prematurely drop out from treatment. Little is known about within-treatment risk factors for dropout, limiting the ability during therapy to identify patients at risk for attrition. METHODS: We examined measures assessing PTSD (PTSD Checklist for DSM-5; PCL-5), alcohol use (Substance Use Inventory; SUI), and patient satisfaction (Client Satisfaction Questionnaire; CSQ-8) as potential within-treatment markers of dropout risk, administered to 110 veterans in a randomized clinical trial of integrated exposure therapy versus integrated coping skills therapy for comorbid PTSD + AUD. Hierarchical Cox proportional hazard models with dropout status as the endpoint assessed effects of PCL-5, SUI, and CSQ-8 on dropout risk, and whether effects differed by treatment modality. RESULTS: A significant interaction between treatment and changes in alcohol use was observed (HR = 2.86, p = .007), where between-session alcohol use was positively associated with dropout hazard rate for those receiving integrated exposure therapy (HR = 2.34, p = .004), but not coping skills therapy (HR = 0.73, p = .19). Specifically, an increase of one drink consumed per day in the interval since last assessment (typically 2-3 weeks) was associated with a 5-fold increase in dropout hazard rate. CONCLUSIONS: The findings provide preliminary evidence of detectable within-treatment markers of dropout during integrated treatment for PTSD + AUD. Study of within-treatment indicators proximal to dropout may help identify at-risk patients and inform timely strategies to boost retention.

N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial.

BACKGROUND: Current pharmacological treatments for Tourette Syndrome (TS), such as antipsychotic agents and α-2 agonists, are moderately effective in the treatment of tics, but have substantial side effects that limit their use. N-acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as an antioxidant agent with minimal side effects for decades. NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders. We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind, placebo-controlled, add-on study. METHODS: Thirty-one children and adolescents 8-17 years of age with TS were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total tic score. Secondary measures assessed comorbid obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD). Linear mixed models in SAS were used to examine differences between NAC and placebo. RESULTS: Of 31 randomized subjects, 14 were assigned to placebo (two females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years) treatment. No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes. CONCLUSIONS: We found no evidence for efficacy of NAC in treating tic symptoms. Our findings stand in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults, including OCD and trichotillomania, but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC.

Family accommodation in obsessive-compulsive and anxiety disorders: a five-year update.

Family accommodation describes changes that individuals make to their behavior, to help their relative who is dealing with a psychiatric and/or psychological disorder(s), avoid or alleviate distress related to the disorder. Research on family accommodation has advanced rapidly. In this update we aim to provide a synthesis of findings from the past five years. A search of available, peer-reviewed, English language papers was conducted through PubMed and PsycINFO, cross referencing psychiatric disorders with accommodation and other family-related terms. The resulting 121 papers were individually reviewed and evaluated and the main findings were discussed. Family accommodation is common in obsessive-compulsive disorder (OCD) and in anxiety disorders, and manifests similarly across these disorders. Family accommodation is associated with more severe psychopathology and poorer clinical outcomes. Treatments have begun to focus on the reduction of family accommodation as a primary therapeutic goal and finally, neurobiological underpinnings of family accommodation are beginning to be investigated.

LONG-TERM OUTCOME IN PEDIATRIC TRICHOTILLOMANIA.

OBJECTIVE: To examine long-term outcome in children with trichotillomania. METHOD: We conducted follow-up clinical assessments an average of 2.8 ± 0.8 years after baseline evaluation in 30 of 39 children who previously participated in a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) for pediatric trichotillomania. Our primary outcome was change in hairpulling severity on the Massachusetts General Hospital Hairpulling Hospital Hairpulling Scale (MGH-HPS) between the end of the acute phase and follow-up evaluation. We also obtained secondary measures examining styles of hairpulling, comorbid anxiety and depressive symptoms, as well as continued treatment utilization. We examined both correlates and predictors of outcome (change in MGH-HPS score) using linear regression. RESULTS: None of the participants continued to take NAC at the time of follow-up assessment. No significant changes in hairpulling severity were reported over the follow-up period. Subjects reported significantly increased anxiety and depressive symptoms but improvement in automatic pulling symptoms. Increased hairpulling symptoms during the follow-up period were associated with increased depression and anxiety symptoms and increased focused pulling. Older age and greater focused pulling at baseline assessment were associated with poor long-term prognosis. CONCLUSIONS: Our findings suggest that few children with trichotillomania experience a significant improvement in trichotillomania symptoms if behavioral treatments are inaccessible or have failed to produce adequate symptom relief. Our findings also confirm results of previous cross-sectional studies that suggest an increased risk of depression and anxiety symptoms with age in pediatric trichotillomania. Increased focused pulling and older age among children with trichotillomania symptoms may be associated with poorer long-term prognosis.

A meta-analysis of computerized cognitive-behavioral therapy for the treatment of DSM-5 anxiety disorders.

OBJECTIVE: Access to qualified cognitive-behavioral therapy (CBT) remains a major barrier to improving clinical outcomes in anxiety disorders. The current meta-analysis examined the efficacy of computerized CBT (cCBT) for anxiety disorders and the durability of treatment gains during follow-up. DATA SOURCES: We searched PubMed and references from included trials and previous meta-analyses in the area. STUDY SELECTION: We included randomized controlled trials assessing the efficacy of cCBT for non-OCD and non-PTSD anxiety disorders. DATA EXTRACTION: Forty trials involving 2,648 participants were included in this meta-analysis. We used a fixed-effect model to examine standardized mean difference in posttreatment anxiety levels. cCBT was compared to wait-list, in-person CBT, and Internet control. We also examined moderators of cCBT treatment gains over follow-up. RESULTS: Meta-analysis indicated that cCBT was significantly more effective than wait-list control in the treatment of anxiety disorders (standardized mean difference [SMD] = 0.92 [95% CI, 0.83 to 1.02], k = 31, z = 18.8, P < .001). Moderator analyses also found that cCBT targeting specific anxiety disorders had greater efficacy than that targeting mixed anxiety symptoms. The efficacy of cCBT was equivalent to in-person CBT in studies that compared them head-to-head, for both children and adults (SMD = 0.05 [95% CI, -0.09 to 0.19], k = 15, z = 0.7, P = .46). Longitudinal studies indicate that individuals undergoing cCBT tended to continue to improve after completion of treatment, with longer follow-up periods associated with greater symptom reduction. CONCLUSIONS: cCBT represents an efficacious intervention for the treatment of anxiety disorders and may circumvent barriers to accessing traditional CBT treatments. Further research is needed to examine the effectiveness of cCBT in real-world settings, for individuals with clinical comorbidities, and in comparison with more ecologically valid comparison conditions.

Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice.

Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine (DA) D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal DA levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. DA D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm histidine decarboxylase deficiency as a rare cause of TS and identify HA-DA interactions in the basal ganglia as an important locus of pathology.

Cognitive-behavioral therapy for anxiety in children with high-functioning autism: a meta-analysis.

BACKGROUND: Anxiety is a common and impairing problem in children and adolescents with autism spectrum disorder (ASD). There is emerging evidence that cognitive-behavioral therapy (CBT) could reduce anxiety in children with high-functioning ASD. OBJECTIVE: To systematically review the evidence of using CBT to treat anxiety in children and adolescents with ASD. Methods for this review were registered with PROSPERO (CRD42012002722). METHODS: We included randomized controlled trials published in English in peer-reviewed journals comparing CBT with another treatment, no treatment control, or waitlist control. Two authors independently screened 396 records obtained from database searches and hand searched relevant journals. Two authors independently extracted and reconciled all data used in analyses from study reports. RESULTS: Eight studies involving 469 participants (252 treatment, 217 comparison) met our inclusion criteria and were included in meta-analyses. Overall effect sizes for clinician- and parent-rated outcome measures of anxiety across all studies were d = 1.19 and d = 1.21, respectively. Five studies that included child self-report yielded an average d = 0.68 across self-reported anxiety. CONCLUSIONS: Parent ratings and clinician ratings of anxiety are sensitive to detecting treatment change with CBT for anxiety relative to waitlist and treatment-as-usual control conditions in children with high-functioning ASD. Clinical studies are needed to evaluate CBT for anxiety against attention control conditions in samples of children with ASD that are well characterized with regard to ASD diagnosis and co-occurring anxiety symptoms.

N-Acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trial.

OBJECTIVE: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. METHOD: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital-Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment×time interaction in an intention-to-treat population. RESULTS: No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group. CONCLUSIONS: We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania.

Age and gender correlates of pulling in pediatric trichotillomania.

OBJECTIVE: Our goals were to examine clinical characteristics and age and gender correlates in pediatric trichotillomania. METHOD: A total of 62 children (8-17 years of age) were recruited for a pediatric trichotillomania treatment trial and characterized using structured rating scales of symptoms of hairpulling and common comorbid conditions. We analyzed the association between qualitative and quantitative characteristics of pulling, comorbidities, and age and gender. We also examined the type of treatments these children previously received in the community. RESULTS: We found lower rates of comorbid depression and anxiety disorders than have been reported in adult trichotillomania samples. Focused hairpulling significantly increased with age, whereas automatic pulling remained constant. Older children with hairpulling experienced more frequent urges and a decreased ability to refrain from pulling. Female participants reported greater distress and impairment associated with hairpulling, even though the severity of pulling did not differ from that of male participants. CONCLUSION: These results confirm several findings from the Children and Adolescent Trichotillomania Impact Project (CA-TIP). Our cross-sectional findings suggest there may be a developmental progress of symptoms in trichotillomania. Children appeared to develop more focused pulling, to become more aware of their urges, and to experience more frequent urges to pull, as they get older. Although these are important findings, they need to be confirmed in prospective longitudinal studies.

Effects of ketamine in treatment-refractory obsessive-compulsive disorder.

BACKGROUND: Treatments for obsessive-compulsive disorder (OCD) usually lead to incomplete symptom relief and take a long-time to reach full effect. Convergent evidence suggests that glutamate abnormalities contribute to the pathogenesis of OCD. Ketamine is a potent noncompetitive antagonist of the N-methyl-D-aspartate glutamate receptor. Trials have reported rapid antidepressant effects after low-dose ketamine infusion. METHODS: We conducted an open-label trial of ketamine (.5 mg/kg IV over 40 min) in 10 subjects with treatment-refractory OCD. Response was defined as >35% improvement in OCD symptoms and >50% improvement in depression symptoms from baseline at any time between 1 and 3 days after infusion. RESULTS: None of 10 subjects experienced a response in OCD symptoms in the first 3 days after ketamine. Four of seven patients with comorbid depression experienced an antidepressant response to ketamine in the first 3 days after infusion. Both OCD and depression symptoms demonstrated a statistically significant improvement in the first 3 days after infusion compared with baseline, but the OCD response was <12%. The percentage reduction in depressive symptoms in the first 3 days after ketamine infusion was significantly greater than the reduction in OCD symptoms. CONCLUSIONS: Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.