Is factor analysis useful for revising diagnostic criteria for PTSD? A systematic review of five issues ten years after DSM-5.

BACKGROUND: Based on factor analysis research, DSM-5 revised the diagnostic criteria for posttraumatic stress disorder (PTSD) by increasing symptom clusters from three to four. AIMS: To question whether that is an appropriate use of factor analysis. METHODS: Reviewed the literature on five issues of factor analysis relevant to diagnostic criteria: (1) discovery of factors identical to symptom clusters, (2) consensus about the number of factors in best-fitting models, (3) configural variance between subpopulations to explain inconsistent model results, (4) methods to externally validate factors after discovery, and (5) treatment response of symptom clusters to externally validate factors. Two hundred four articles using DSM-IV or DSM-5 symptoms were included. RESULTS: Two of four DSM-5 clusters were discovered with exploratory factor analysis. Support for a best-fitting model was inconsistent. Models with the highest number of factors were the best mathematical fit 87% of the time. Subpopulations did not reveal a pattern of configural variance to explain inconsistent findings. External validation of factors relied entirely on questionnaires. A review of 143 randomized controlled trials did not reveal differential treatment response of any symptom cluster. CONCLUSION: Findings did not support the usefulness of factor analysis because the findings are too disparate to be helpful.

Post-Traumatic Stress and Autobiographical Memory Accuracy in Young Children: Traumatic Events Versus Stressful and Pleasant Events.

This study examined the influence of trauma exposure and posttraumatic stress (PTS) severity on accuracy of recall of autobiographical memory of traumatic events and pleasant events in very young children. Two hundred sixteen 3-6 year-old children with trauma exposure were interviewed with standardized interviews. Forty-one non-trauma-exposed controls were interviewed about stressful events for comparison. Accuracy of recall for both traumatic and pleasant events was not associated with severity of PTS. Trauma-exposed children showed significantly less accurate recall of trauma events compared to pleasant events. This difference was limited to children who experienced repeated trauma or Hurricane Katrina-related trauma experiences as opposed to single-blow types of trauma experiences. There was no difference in accuracy of recall of trauma events in the trauma-exposed group versus stressful events in the control group. There was also no difference in accuracy of recall of pleasant events between the trauma-exposed and the control groups. These findings do not support traditional theories that autobiographical recall is impaired in those with posttraumatic stress disorder or with trauma exposure. These findings demonstrate that very young children have access to and can verbalize accurate autobiographical recall of trauma events, which is important for clinical assessment and treatment.

Links between Oppositional Defiant Disorder Dimensions, Psychophysiology, and Interpersonal versus Non-interpersonal Trauma.

The etiology of oppositional defiant disorder (ODD) is not well understood but appears to have both biologically-based roots and can develop following adverse experiences. The current study is the first to examine the interaction between biologically-based factors and type of trauma experience (i.e., interpersonal and non-interpersonal) and associations with ODD. The psychophysiological factors included baseline resting heart rate, respiratory sinus arrhythmia (RSA), and cortisol. ODD was measured as two dimensions of irritable and defiant/vindictive. The sample included 330 children, 3-7 years-old, oversampled for a history of trauma. Results showed the interactions between baseline physiological arousal variables and trauma type in predicting ODD dimensions were not supported. However, the baseline RSA by trauma interaction was a significant predictor of defiance/vindictiveness among boys, but not girls, when interpersonal trauma was compared to controls. Several other gender differences emerged. Among boys, both interpersonal and non-interpersonal trauma were predictive of ODD dimensions; however, among girls, non-interpersonal trauma was not. Among girls, there was a significant negative bivariate relationship between baseline cortisol and irritability. Also, when the sample was restricted to those with interpersonal trauma only and controls, baseline RSA was negatively associated with irritability in girls only (controlling for trauma). Finally, retrospective reports revealed that children who met criteria for ODD diagnosis and experienced interpersonal trauma were more likely to exhibit ODD symptoms prior to their trauma compared to those who experienced non-interpersonal trauma. Results are discussed in the context of previous mixed findings, and avenues for future research are highlighted.

Child and parent secondary outcomes in stepped care versus standard care treatment for childhood trauma.

INTRODUCTION: Stepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT) is comparable in efficacy to standard TF-CBT for child posttraumatic stress symptoms (PTSS), but less is known about the effectiveness of SC-TF-CBT on child and parent secondary outcomes. The aim of this community-based randomized clinical trial was to compare child- and caregiver-secondary outcomes among SC-TF-CBT versus TF-CBT participants. METHODS: Children (ages 4 to 12) with PTSS and their caregivers were randomly assigned to either SC-TF-CBT (n = 91) or TF-CBT (n = 92). Secondary child (internalizing and externalizing behavior problems, anger outburst and sleep disturbances) and parent outcomes (PTSS, depression symptoms, and parenting stress) were measured at baseline, post-treatment and 6- and 12-month follow-up. RESULTS: There were comparable changes at all-time points in child and caregiver secondary outcomes. Non-inferiority tests indicated that for completers and intent-to-treat samples, SC-TF-CBT was non-inferior to TF-CBT for all outcomes except parenting stress at 6-months. The analysis with completers did not support non-inferiority at post-treatment for internalizing and externalizing problems and at 6- and 12-month follow-up assessments for externalizing problems, but the intent-to-treat analysis did support non-inferiority. LIMITATIONS: Limitations included modest rates of attrition, excluding in vivo component for standard TF-CBT, parent-only assessments, and no control condition. CONCLUSIONS: SC-TF-CBT is an effective alternative treatment method although parents with high stress may need more support and children with externalizing problems may need more standard TF-CBT sessions.

Stepped Care Versus Standard Care for Children After Trauma: A Randomized Non-Inferiority Clinical Trial.

OBJECTIVE: Trauma-focused cognitive-behavioral therapy (TF-CBT) is an evidence-based therapist-led treatment for children after trauma. Parents often experience barriers to treatment engagement, including cost. Stepped care TF-CBT (SC-TF-CBT) was developed as an alternative delivery system. Step One is a parent-led therapist-assisted treatment. Step Two provides therapist-led TF-CBT for children who did not benefit from Step One and require more intensive treatment. This study compared SC-TF-CBT to standard TF-CBT in a community-based non-inferiority trial. METHOD: A total of 183 children (aged 4-12 years) experiencing posttraumatic stress symptoms (PTSS) and their caregivers were randomly assigned to SC-TF-CBT or standard TF-CBT within 6 community clinics. Assessments occurred at baseline, mid- and posttreatment, and 6 and 12 months. Primary outcomes included PTSS and impairment. Secondary outcomes included severity, diagnostic status, remission, and response. Treatment cost, acceptability, and satisfaction were measured. Difference and non-inferiority tests were applied. RESULTS: SC-TF-CBT participants changed at rates comparable to participants in TF-CBT for primary and secondary measures. SC-TF-CBT was non-inferior to TF-CBT for PTSS, impairment, and severity at all time points except for impairment at the 6-month assessment. Attrition did not differ between treatment arms (132 participants were completers). Baseline treatment acceptability was lower for SC-TF-CBT parents, although there was no difference in expected treatment improvements or treatment satisfaction at posttreatment. Based on regression estimates, total costs were 38.4% lower for SC-TF-CBT compared to TF-CBT, whereas recurring costs were 53.7% lower. CONCLUSION: Stepped Care TF-CBT provides an alternative way to deliver treatment for some children and parents, with reduced cost for providers and parents. CLINICAL TRIAL REGISTRATION INFORMATION: Stepped Care for Children after Trauma: Optimizing Treatment; https://clinicaltrials.gov; NCT02537678.

Reexamination of diathesis stress and neurotoxic stress theories: A qualitative review of pre-trauma neurobiology in relation to posttraumatic stress symptoms.

OBJECTIVE: Associations of neurobiological differences with posttraumatic stress disorder (PTSD) have generated interest in their temporal relation. Support has been voiced for the neurotoxic stress theory (NST) in which neurobiological differences develop following exposure and PTSD development. In contrast, the diathesis stress theory (DST) posits that neurobiological differences existed prior to exposure and may be vulnerability factors for PTSD. Studies in the first wave of neurobiological PTSD research were all cross sectional, but a second wave of research followed which used prospective repeated-measures designs that measured neurobiology prior to trauma exposure experiences, allowing greater causal inference. METHODS: This study reviewed the second-wave studies in hopes of developing a preliminary consensus to support either the NST or the DST based on this more powerful prospective, repeated-measures study design. RESULTS: Twenty-five second-wave studies were located that measured neurobiology prior to traumatic experiences. Nineteen studies supported the DST. Of 10 studies that were capable of testing the NST, only 3 were supportive. CONCLUSION: The implications of the NST versus the DST have profound implications for understanding the fragility of the human brain and possible paths forward for future research on assessment, treatment, and social policy.

A Different Way to Mind the Gap: Mandated Versus Voluntary Collection of Measures.

Measurement-based care (MBC) has been called the bridge for the gap between outcomes achieved in randomized clinical trials and routine clinical care.1 Trials of MBC have improved outcomes, helped identify patients with residual symptoms, prompted clinicians to know when to intensify treatment, created more informed patients, and improved the patient-provider relationship.1 These previous studies were grant-funded projects, however, which were implemented on project deadlines with research staff committed to the success of the project. In a recent Letter to the Editor in the Journal, Liu et al.2 reported on their efforts to implement a digital measurement feedback system in a pediatric clinic. This Letter to the Editor, to my knowledge, was the first report about how a clinic implements MBC without grant funding on a project deadline, which is likely to be more generalizable to community practice. The purpose of this report is to add our clinic experience.

The Diagnostic Infant Preschool Assessment-Likert Version: Preparation, Concurrent Construct Validation, and Test-Retest Reliability.

Objective: The Diagnostic Infant and Preschool Assessment was revised to include Likert ratings (DIPA-L) to give a broader range of severity ratings that may have greater utility for clinical and research purposes. In addition, the instrument was updated for Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), and two types of Likert ratings-frequency versus problem intensity-were explored for posttraumatic stress disorder (PTSD) symptoms. Concurrent construct validation and test-retest reliability were examined for the five most common disorders seen in very young children in outpatient clinics: PTSD, attention-deficit/hyperactivity disorder, oppositional defiant disorder, separation anxiety disorder, and generalized anxiety disorder (GAD). A sixth disorder, disruptive mood dysregulation disorder (DMDD), which was created in DSM-5, was tested for the first time. Functional impairment was also examined. Methods: The caregivers of 58 two- through six-year-old children (57 mothers and 1 father) were recruited from an outpatient clinic. They were interviewed at Time 1, and 52 were reinterviewed at Time 2 by research assistants (children's age M 4.7 years, standard deviation 1.2). Results: Few differences were found between the ratings of frequency versus problem intensity for PTSD symptoms. Tests of concurrent criterion validation were acceptable for all disorders when compared against disorder-specific questionnaires; the range of Pearson correlation coefficients was 0.56-0.94. A trend for attenuation of diagnoses from Time 1 to Time 2 was evident, but not statistically significant. Test-retest reliabilities were strong when examined with continuous Likert scores, except for GAD (the range of intraclass correlation coefficients values was 0.29-0.91, but were less consistent for categorical disorder-level status [the range of Cohen's κs was 0.35-0.79]). The range of internal consistencies was 0.78-0.95, excluding DMDD, which could not be calculated. Conclusions: The updated and revised DIPA-L demonstrated many acceptable features of a valid and reliable instrument for the assessment of very young children. While the findings are tentative given the small sample size, the DIPA-L is the only diagnostic instrument for young children with a replication, tested in clinic populations, updated for DSM-5, with psychometrics for functional impairment, and has Likert ratings.

The Dimensionality of Proposed DSM-5 PTSD Symptoms in Trauma-Exposed Young Children.

A subtype of the posttraumatic stress disorder diagnosis for children 6 years and younger (PTSD-6Y) was introduced in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5). This study utilized confirmatory factor analytic techniques to evaluate the proposed DSM-5 PTSD-6Y factor structure and criterion and convergent validity against competing models. Data for N = 284 (3-6 years) trauma-exposed young children living in New Orleans were recruited following a range of traumas, including medical emergencies, exposure to Hurricane Katrina and repeated exposure to domestic violence. The model was compared to DSM-IV, a 4-factor 'dysphoria' model that groups symptoms also associated with anxiety and depression, and alternate 1- and 2- factor models. Convergent validity was established against the Child Behavior Checklist (CBCL). Criterion related validity was established by comparing each model to a categorical rating of impairment. The Dysphoria and PTSD-6Y models offered the better accounts of symptom structure, although neither satisfied minimum requirements for a good fitting model. These two models also only showed small levels of convergence with CBCL dimensions. The 1-factor model offered the most compelling balance of sensitivity and specificity, with the 2-factor model and the Dysphoria model following closely behind. These CFA results do not support the symptom clusters proposed within the DSM-5 for PTSD-6Y. Although a 4-factor Dysphoria model offers a better overall account of clustering patterns (relative to alternate models), alongside acceptable sensitivity and specificity for detecting clinical impairment, it also falls short of being an adequate model in this younger age group.

Development of a Brief Screen for Symptoms of Posttraumatic Stress Disorder in Young Children: The Young Child PTSD Screen.

OBJECTIVE: The ability to reliably detect posttraumatic stress disorder (PTSD) symptoms that require treatment in young children through screening efforts is a critical step toward providing appropriate treatment. The developmental differences in this age group compared to older youths pose challenges for accurate detection. A brief age-appropriate screen has not yet been quantitatively validated. This study aimed to address that gap by creating a rapid and brief screen based on empirical data that focused on sensitivity and face validity for children aged 3 to 6 years. METHODS: A trauma-exposed group (N = 284) and a non-trauma-exposed group (N = 46), aged 3 to 6 years, were assessed using a semistructured diagnostic interview with their primary caregivers. RESULTS: One hundred twenty combinations of items were evaluated for sensitivity, specificity, positive predictive value, negative predictive value, associations with functional impairment, and frequency of false positives. Many combinations of items performed well on these psychometrics, and the final selection of a 6-item screener was influenced by considerations of face validity so that the screen would best reflect the unique symptoms of PTSD. CONCLUSION: The screener proposed is a promising tool that will benefit from additional research to examine its psychometric properties as a stand-alone PTSD screen. Future research ought to include test-retest reliability and replication of these findings in other samples and settings. Eventual uses of a brief screen for PTSD in young children include screening during primary care visits and large-scale screening efforts following disasters, for which cost and time need to be considered.

A statewide training of community clinicians to treat traumatized youths involved with child welfare.

Despite considerable investment in efforts to disseminate evidence-based treatments (EBTs), few data are available on how frequently clinicians achieve competence in delivering the treatments or on whether clinical outcomes actually improve. The Louisiana Child Welfare Trauma Project (LCTP) was a 5-year demonstration project funded by the Children's Bureau. One of the aims of the LCTP was to train community clinicians statewide in an EBT for posttraumatic stress disorder (PTSD). A training model was designed to reach any willing community practitioner, with minimal travel, cost, and time involved for trainees and trainer. Of the 335 clinicians who attended a 1-day training in youth PTSD treatment (YPT; Scheeringa & Weems, 2014), a manualized treatment for youths with PTSD, 117 began consultation calls. Forty-five (38%) clinicians who began calls achieved "Advanced" training, completing at least 1 case using YPT and attending weekly calls. Of the 102 clients discussed during calls, 64 (63%) completed YPT. Pre- and posttreatment measures were available for 17 (27%) of the completers. All 17 clients showed decreases in their PTSD symptoms by youth or caregiver report, with 12 (71%) showing a decrease in symptom count by at least half of the pretreatment score. This is the first known report of the proportion of community clinicians who voluntarily completed consultation calls to achieve competence following initial training in an EBT. The results suggest that effectiveness of an EBT is possible in community settings but is likely constrained by clinicians' being willing and/or able to complete training requirements geared toward achieving competency in and fidelity to the protocol. Because the majority of clinicians did not complete training requirements, this suggests major limitations in the current models of dissemination. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Generalized Anxiety Disorder in Very Young Children: First Case Reports on Stability and Developmental Considerations.

Generalized anxiety disorder (GAD) is purported to start in early childhood but concerns about attenuation of anxiety symptoms over time and the development of emerging cognitive and emotional processing capabilities pose multiple challenges for accurate detection. This paper presents the first known case reports of very young children with GAD to examine these developmental challenges at the item level. Three children, five-to-six years of age, were assessed with the Diagnostic Infant and Preschool Assessment twice in a test-retest reliability study. One case appeared to show attenuation of the worries during the test-retest period based on caregiver report but not when followed over two years. The other two cases showed stability of the full complement of diagnostic criteria. The cases were useful for demonstrating that the current diagnostic criteria appear adequate for this developmental period. The challenges of accurate assessment of young children that might cause missed diagnoses are discussed. Future research on the underlying dysregulation of negative emotionality and long-term follow-ups are needed to better understand the etiology, treatment, and course of GAD in this age group.

Examining the Prospective Relationship between Pre-Disaster Respiratory Sinus Arrhythmia and Post-Disaster Posttraumatic Stress Disorder Symptoms in Children.

Previous studies have examined the concurrent relationship between posttraumatic stress disorder (PTSD) and a range of psychophysiological variables, including respiratory sinus arrhythmia (RSA). However, there is a lack of research examining the prospective development of trauma symptomatology, and the directionality of the association between RSA level and PTSD has yet to be determined. The current study is the first prospective study to examine whether RSA level and RSA reactivity are risk factors for PTSD symptoms in children. Assessments were conducted both prior to (Time 1) and following (Time 2) a natural disaster (i.e., Hurricane Katrina). Participants were 36 children who were 3-6 years-old during the Time 1 assessment. Structured diagnostic interviews were used to assess PTSD symptoms at both Time 1 and Time 2. RSA level during a neutral stimulus, RSA reactivity to emotional video stimuli (distress, joy, and trauma videos) and RSA reactivity to memory stimuli (remote happy memory, trauma memory, mother's recall of the trauma memory) were also collected at both time points. Time 1 RSA level during a neutral stimulus was a significant predictor of Time 2 PTSD symptoms (controlling for age, Time 1 PTSD symptoms, Time 2 neutral RSA level), such that lower RSA during a neutral condition was related to higher PTSD symptoms. Also, Time 1 RSA reactivity in response to memory (but not video) stimuli, in the form of relatively less vagal withdrawal, was a significant predictor of more Time 2 PTSD symptoms (controlling for age, Time 1 PTSD symptoms, Time 2 RSA reactivity). This unique prospective study provides evidence for level of RSA and RSA reactivity as pre-existing clinical markers of stress sensitivity that predict psychopathology following a trauma.

CBT for Child PTSD is Associated with Reductions in Maternal Depression: Evidence for Bidirectional Effects.

Cognitive behavioral therapy techniques are empirically supported for posttraumatic stress disorder (PTSD) in youth, but the role of parents in such treatments is less clear. Theoretically there may be a reciprocal relationship such that as children improve, their parents may feel better, and conversely as parents feel better, psychologically the child may improve or improve at a greater rate. This study tested if there were indirect effects of change in child PTSD symptoms on change in parent depression symptoms, and vice versa, across treatment sessions. The data came from a randomized trial of treatment for PTSD and included youth (N = 47) 7-18 years old (51.1% female; ethnicity was reported as 40.4% White and 40.4% Black, with the remainder reporting Mixed [17%] or other ethnicity [2.1%]) who had been exposed to trauma and experienced significant PTSD symptoms. Maternal depression and child PTSD symptoms were assessed at each session. Maternal perceptions of who changed first were also assessed at posttreatment. Maternal depression significantly decreased over the course of treatment, and maternal depression had an indirect effect on child PTSD symptom change. Evidence for the reciprocal relationship, child symptom change having an indirect effect on parent symptom change, was also found. Age, gender, and treatment condition did not moderate these indirect effects. Findings highlight the potential benefits of child therapy on parents and the reciprocal benefits of improved parent symptoms on the child.

Respiratory Sinus Arrhythmia in Cognitive Behavioral Therapy for Posttraumatic Stress Symptoms in Children: Preliminary Treatment and Gender Effects.

Cognitive behavioral therapy (CBT) is an efficacious treatment for posttraumatic stress disorder (PTSD) symptoms, but the effect of CBT on physiological indicators is largely unknown. Respiratory sinus arrhythmia (RSA) is an established parasympathetic marker of self-regulatory capacity and stress responsivity. The present study tested if and how resting RSA and RSA reactivity changed following treatment among a sample of children (n = 48) who experienced at least one traumatic event and presented with PTSD symptoms. RSA reactivity was measured in response to personalized trauma-related scripts. Results indicated that changes in RSA after treatment were dependent on pretreatment resting levels of RSA, with individuals with high and low pretreatment resting RSA levels appearing to converge over time in both resting RSA and RSA reactivity by the 3-month follow up. Specific to RSA reactivity, a sex difference was evident, as following treatment, females showed less RSA withdrawal whereas males showed more RSA withdrawal. PTSD symptoms were significantly reduced after CBT but symptom change was not associated with pretreatment resting RSA levels. Overall, these results suggest that there may be multiple physiological patterns within children with PTSD and the direction of the physiological changes after CBT may depend on initial differences in resting RSA levels.

Do Children and Adolescents Have Different Types of Trauma Narratives and Does It Matter? Reliability and Face Validation for a Narrative Taxonomy.

The construction of trauma narratives is a major component of several psychotherapy approaches for trauma-related problems, but questions remain as to whether fully expressive narratives are necessary and whether it is detrimental to ask avoidant youths to tell their narratives repeatedly. Characteristics of trauma narratives during psychotherapy have not been examined in youths and this represents a salient gap in knowledge. This study aimed to begin filling this gap by identifying categories of trauma narratives and empirically validating them. Youths (N = 47) aged 7 to 18 years, who were involved in a randomized controlled trial, received cognitive behavioral therapy. Transcripts of all narrative exposure therapy sessions for each youth were rated. Four categories were identified and were named expressive, avoidant, fabricated, and undemonstrative. Interrater reliability for identifying these categories was good, and face validation of the categories was supported by statistically significant differences between categories on the number of data elements of the trauma events, negative emotion words, and positive emotion words. These promising findings indicate that different types of narrative styles can be reliably identified. There was strong evidence for reduction of posttraumatic stress symptoms in each of the categories (Cohen's d = 0.9 to 2.5). Favorable treatment outcomes for all categories suggest that more remembering is not always better and clients appeared to effectively deal with memories in different ways.

Evaluating Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Posttraumatic Stress Disorder Diagnostic Criteria in Older Children and Adolescents.

OBJECTIVES: Few studies have assessed how the diagnostic criteria for posttraumatic stress disorder (PTSD) apply to older children and adolescents. With the introduction of a new, developmentally sensitive set of criteria for very young children (age 6 years and younger) in Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), this raises new questions about the validity of the criteria for older children and adolescents. The current study investigated how diagnostic changes in DSM-5 impact diagnosis rates in 7-18-year olds. METHODS: PTSD, impairment, and comorbid psychopathology were assessed in 135 trauma-exposed, treatment-seeking participants. Children (ages 7-12) were examined separately from adolescents (ages 13-18) to assess for potential developmental differences. RESULTS: A significantly higher proportion of 7-12-year-old children met criteria for DSM-5 diagnosis (53%) compared to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (37%). However, among 13-18-year-old adolescents, the proportions diagnosed with DSM-5 (73%) and DSM-IV (74%) did not differ. Participants who met criteria for DSM-5 only (17%) did not differ from those diagnosed with DSM-IV in terms impairment or comorbidity. Using the newly accepted age 6 years and younger criteria resulted in a significantly higher proportion of 7-12-year-old (but not 13-18-year olds) children meeting criteria compared to DSM-IV or DSM-5. However, these children showed less impairment and comorbidity than those diagnosed with DSM-IV. CONCLUSION: These findings suggest that DSM-5 criteria may be more developmentally sensitive than DSM-IV criteria, and may lead to higher prevalence rates of PTSD for 7-12-year-old children, but not for adolescents. Using the very young children criteria for 7-12-year-old children may further increase prevalence, but capture children with less severe psychopathology.

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data.

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.