The impact of early factors on persistent negative symptoms in youth at clinical high risk for psychosis.

Introduction: Persistent negative symptoms (PNS) are described as continuing moderate negative symptoms. More severe negative symptoms have been associated with poor premorbid functioning in both chronic schizophrenia and first episode psychosis patients. Furthermore, youth at clinical high risk (CHR) for developing psychosis may also present with negative symptoms and poor premorbid functioning. The aim of this current study was to: (1) define the relationship between PNS and premorbid functioning, life events, trauma and bullying, previous cannabis use, and resource utilization, and (2) to examine what explanatory variables best predicted PNS. Method: CHR participants (N = 709) were recruited from the North American Prodrome Longitudinal Study (NAPLS 2). Participants were divided into two groups: those with PNS (n = 67) versus those without PNS (n = 673). A K-means cluster analysis was conducted to distinguish patterns of premorbid functioning across the different developmental stages. The relationships between premorbid adjustment and other variables were examined using independent samples t-tests or chi square for categorical variables. Results: There was significantly more males in the PNS group. Participants with PNS had significantly lower levels of premorbid adjustment in childhood, early adolescence, and late adolescence, compared to CHR participants without PNS. There were no differences between the groups in terms of trauma, bullying, and resource utilization. The non-PNS group had more cannabis use and more desirable and non-desirable life events. Conclusion: In terms of better understanding relationships between early factors and PNS, a prominent factor associated with PNS was premorbid functioning, in particular poor premorbid functioning in later adolescence.

Feasibility and acceptability of a brief, online transdiagnostic psychotherapy for young adults.

Background: The Unified Protocol (UP) for Transdiagnostic Treatment of Emotional Disorders is a flexible form of cognitive behavioural therapy targeting diverse mental health disorders in children and adults. Objective: The goal was to develop a brief version of UP tailored to the unique needs of young adults that could be administered in an online therapist-directed, group format. Method: Nineteen young adults (age 18-23) receiving mental health services from a community agency or a specialty clinic were enrolled in a feasibility test of the novel transdiagnostic, online intervention (five sessions, 90 minutes each). Qualitative interviews were conducted with participants after each session they attended and upon study completion (n = 80 interviews with n = 17 participants). Standardized quantitative mental health measures were collected at baseline (n = 19), end of treatment (5 weeks; n = 15) and at follow-up (12 weeks; n = 14). Results: Thirteen of the 18 participants (72%) who began treatment attended at least four of the five sessions. During the qualitative interviews, participants noted that core UP concepts such as understanding of emotions, mindfulness, cognitive flexibility, and behavioural activation are applicable in their day-to-day lives. Quantitative data showed a significant reduction in anxiety-related life impairment at follow-up compared to baseline, but not end of treatment compared to baseline. Reductions in global anxiety and depression symptoms were not statistically significant. Conclusions: This novel, brief version of the UP may be a feasible online intervention for young adults seen at mental health clinics for diverse mental health issues and warrants further study to demonstrate effectiveness.

Contexte: Le protocole unifié (PU) pour le traitement transdiagnostique des troubles émotionnels est une forme flexible de thérapie cognitivo-comportementale ciblant divers troubles de santé mentale flexible chez les enfants et les adultes. Objectif: Le but était d'élaborer une version abrégée du PU adaptée aux besoins uniques des jeunes adultes qui pourrait être administrée à un format de groupe en ligne dirigé par un thérapeute. Méthode: Dix-neuf jeunes adultes (18­23 ans) recevant des services de santé mentale d'un organisme communautaire ou d'une clinique spécialisée ont été inscrits à un test de faisabilité de la nouvelle intervention transdiagnostique en ligne (cinq séances, 90 minutes chacune). Des entrevues qualitatives ont été menées auprès des participants après chaque séance à laquelle ils ont assisté et à la fin de l'étude (n = 80 entrevues avec n = 17 participants). Les mesures de santé mentale standardisée quantitative ont été recueillies à la base (n = 19), à la fin du traitement (5 semaines; n = 15) et au suivi (12 semaines; n = 14). Résultats: Treize des 18 participants (72 %) qui ont commencé le traitement ont assisté à au moins quatre des cinq séances. Durant les entrevues qualitatives, les participants ont noté que les principaux concepts du PU comme la compréhension des émotions, la pleine conscience, la flexibilité cognitive et l'activation comportementale sont applicables dans leur vie quotidienne. Les données quantitatives indiquaient une réduction significative dans les troubles de la vie liés à l'anxiété au suivi comparé à la base, mais pas à la fin du traitement comparé à la base. Les réductions de l'anxiété générale et des symptômes de dépression n'étaient pas statistiquement significatives. Conclusions: Cette nouvelle version abrégée du PU peut être une intervention faisable en ligne pour les jeunes adultes vus dans des cliniques de santé mentale pour divers problèmes de santé mentale et demande plus d'étude pour en démontrer l'efficacité.

Non-suicidal self-injury, suicidal thoughts and behaviors in individuals with an eating disorder relative to healthy and psychiatric controls: A systematic review and meta-analysis.

OBJECTIVE: Eating disorders (ED) may be associated with an increased prevalence of non-suicidal self-injury (NSSI) and suicidal thoughts and behaviors (STBs) relative to healthy (HC) and psychiatric (PC) controls. However, precise estimates of differences in prevalence between individuals with EDs and controls are unclear. We compared the prevalence of NSSI, suicidal ideation (SI), suicide attempts (SA), and deaths by suicide in controls and individuals with EDs. METHOD: We searched MEDLINE, PsycINFO, EMBASE, and CINAHL for peer-reviewed publications reporting the prevalence of NSSI and/or STBs in EDs and HC or PC group (PROSPERO: CRD42021286754). A series of random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for NSSI, SI, SA, and death by suicide in EDs. RESULTS: Across 32 studies, individuals with an ED had a significantly increased prevalence of NSSI (HC: OR = 6.85 [95% CI: 3.60, 13.04]; PC: OR = 2.74 [95% CI: 1.49, 5.06]), SI (HC: OR = 3.63 [95% CI: 2.43, 5.41]; PC: OR = 3.10 [95% CI: 2.01, 4.78]), and SA (HC: OR = 5.16 [95% CI: 4.27, 6.24]; PC: OR = 1.37 [95% CI: 0.37, 4.99]) relative to HC and PC groups. A 2.93-times increased odd of death by suicide did not achieve statistical significance. There was a high-level of heterogeneity between studies. DISCUSSION: Our findings indicate that ED populations have an increased prevalence of NSSI, SI, and SA but not death by suicide compared to controls and emphasize the need for effective clinical strategies to address these behaviors in ED populations. PUBLIC SIGNIFICANCE: This review provides evidence for an increased prevalence of non-suicidal self-injury, suicidal ideation, and suicide attempts in populations with eating disorders compared to controls. Our findings emphasize the need for effective clinical strategies to address these behaviors in patients with eating disorders.

The COVID-19 Pandemic and Canadian Pediatric Tertiary Care Hospitalizations for Anorexia Nervosa.

PURPOSE: Global studies show an increase in hospitalizations for pediatric eating disorders (EDs). No published Canadian studies have confirmed these findings in pediatric ED programs for one-year post onset of the COVID-19 pandemic. The primary objective was to examine health administrative data from two pediatric tertiary care ED programs: Alberta Children's Hospital (ACH) and Hospital for Sick Children (SickKids) to determine the number of pediatric hospitalizations with the most responsible discharge diagnosis of anorexia nervosa (AN). METHODS: This hospital-based design explored monthly pediatric hospitalizations in seven-year-olds to 18-year-olds between March 11, 2014 and March 11, 2021 using the Discharge Abstract databases. The analysis used negative binomial regression with robust standard errors to compare hospitalization counts in the months preceding and following the World Health Organization pandemic declaration (March 11, 2020). RESULTS: Hospitalizations due to pediatric AN increased by 63% and 132% at SickKids (p < .001) and ACH (p < .001), respectively, in the first year of the pandemic compared to the previous six years. The total number of non-ED hospitalizations decreased by 29.3% and 2.4% at SickKids and ACH, respectively. DISCUSSION: This is the first Canadian study to show a rise in pediatric hospitalizations over one year due to AN in two tertiary care hospitals following the onset of the pandemic, confirming the impact that the pandemic has had on children and adolescents with AN in Canada.

Pharmacotherapies for Adults With Alcohol Use Disorders: A Systematic Review and Network Meta-analysis.

BACKGROUND: We aimed to determine medications' comparative efficacy and safety for adults with alcohol use disorders. METHODS: We searched eleven electronic data sources for randomized clinical trials with at least 4 weeks of treatment reporting on alcohol consumption (total abstinence and reduced heavy drinking), dropouts, and dropouts due to adverse events. We conducted network meta-analyses using random-effects, frequentist models, and calculated summary rate ratios (RRs) with 95% confidence intervals (CIs). RESULTS: We included 156 trials (N = 27,334). Nefazodone (RR = 2.11; 95% CI, 1.42-3.13), aripiprazole (RR = 1.97; 95% CI, 1.36-2.88), carbamazepine (RR = 1.85; 95% CI, 1.03-3.32), and nalmefene (RR = 1.17; 95% CI, 1.01-1.35) were associated with the most dropouts. Baclofen (RR = 0.83; 95% CI, 0.70-0.97) and pregabalin (RR = 0.63; 95% CI, 0.43-0.94) caused fewer dropouts than placebo. Nalmefene (RR = 3.26; 95% CI, 2.34-4.55), fluvoxamine (RR = 3.08; 95% CI, 1.59-5.94), and topiramate (RR=2.18; 95% CI, 1.36-3.51) caused more dropouts from adverse events over placebo. Gamma-hydroxy-butyrate (RR = 1.90; 95% CI, 1.03-3.53), baclofen (RR = 1.80; 95% CI, 1.39-2.34), disulfiram (RR = 1.71; 95% CI, 1.39-2.10), gabapentin (RR = 1.66; 95% CI, 1.04-2.67), acamprosate (RR = 1.33; 95% CI, 1.15-1.54), and oral naltrexone (RR = 1.15; 95% CI, 1.01-1.32) improved total abstinence over placebo (Fig. 3C). For reduced heavy drinking, disulfiram (RR = 0.19; 95% CI, 0.10-0.35), baclofen (RR = 0.72; 95% CI, 0.57-0.91), acamprosate (RR = 0.78; 95% CI, 0.70-0.86), and oral naltrexone (RR = 0.81; 95% CI, 0.73-0.90) were efficacious against placebo. CONCLUSIONS: The current meta-analyses provide evidence that several medications for AUDs are effective and safe and encourage the expanded use of these medications in the clinical setting. Our review found that acamprosate (2-3 g/d), disulfiram (250-500 mg/d), baclofen (30 mg/d), and oral naltrexone (50 mg/d) had the best evidence for improving abstinence and heavy drinking for patients with AUD. PROSPERO: CRD42020208946.

Supporting the Transition to Postsecondary Institutions for Students with Mental Health Conditions: A Scoping Review.

Objective: To conduct a scoping review to identify programs and interventions to support youth with mental health conditions (MHCs) with their transition to postsecondary institution (PSI). Method: A database search of MEDLINE, PsycINFO, Embase, SocINDEX, ERIC, CINHAL, and Education Research Complete was undertaken. In this review, MHC was defined as a mental, behavioural, or emotional condition, or problematic substance use, and excluded neurodevelopmental or physical disorders. Two reviewers independently screened studies and extracted the data. Included studies are described and a risk-of-bias assessment was conducted on included studies. Results: Nine studies were included in this review, describing eight unique interventions. Sixty-two percent of interventions were nonspecific in the MHCs that they were addressing in postsecondary students. These interventions were designed to support students upon arrival to their PSIs. Peer mentorship, student engagement, goal setting, and interagency collaboration were some of the strategies employed. However, the overall quality and level of evidence in these studies was low and the effectiveness of these programs was not established. Conclusion: The volume of research identified was limited, no reliable nor policy informing conclusions can yet be made about the impact of these interventions as the evaluation methods, quality of the research methodologies, and the levels of evidence available were of low-quality. Future randomized control trials are required that are designed to target and improve transitions from secondary education to PSIs for those with MHCs.

Objectif: Mener une étude de la portée afin d'identifier les programmes et interventions qui soutiennent les jeunes souffrant de troubles de santé mentale (TSM) dans leur transition à une institution post-secondaire (IPS). Méthode: Une recherche des bases de données MEDLINE, PsycINFO, Embase, SocINDEX, ERIC, CINHAL, et Education Research Complete a été entreprise. Dans cette revue, les TSM étaient définis comme un trouble mental, comportemental ou émotionnel, ou une utilisation de substances problématique et excluaient les troubles neurodéveloppementaux ou physiques. Deux réviseurs ont examiné indépendamment les études et extrait les données. Les études incluses sont décrites et une évaluation du risque de biais a été menée sur les études incluses. Résultats: Neuf études ont été incluses dans cette revue, qui décrivaient huit interventions uniques. Soixante-deux pour cent des interventions étaient non spécifiques dans les TSM qu'ils abordaient chez les élèves du post-secondaire. Ces interventions étaient conçues pour soutenir les élèves à leur arrivée à leur IPS. Le mentorat par les pairs, l'engagement des élèves, l'établissement de buts, et la collaboration inter-agence étaient certaines des stratégies employées. Toutefois, la qualité globale et le niveau des données probantes de ces études étaient faibles et l'efficacité de ces programmes n'a pas été établie. Conclusion: Le volume de recherche identifié était limité, rien de fiable ni aucune politique éclairant les conclusions ne peut encore révéler l'impact de ces interventions comme méthodes d'évaluation, la qualité des méthodologies de recherche, et les niveaux des données probantes disponibles étaient de faible qualité. Il faut de futurs essais randomisés contrôlés qui sont conçus pour cibler et améliorer les transitions de l'éducation secondaire aux IPS pour ceux qui souffrent de TSM.

Comparative efficacy and safety of pharmacotherapies for alcohol withdrawal: a systematic review and network meta-analysis.

BACKGROUND AND AIMS: There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW. METHODS: Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs). RESULTS: Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision. CONCLUSIONS: Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.

Experiences of Canadian mental health providers in identifying and responding to online and in-person sexual abuse and exploitation of their child and adolescent clients.

BACKGROUND: Sex offenders often use the internet to communicate with children to facilitate in-person sexual abuse or to create and distribute sexual images of children. Mental healthcare providers are a major source of referrals to child welfare authorities and are well-positioned to identify sexual exploitation. OBJECTIVE: This study investigated the perceived ability of mental healthcare workers to recognize and respond to concerns about online and in-person sexual exploitation of their pediatric clients. PARTICIPANTS AND SETTING: The authors administered a cross-sectional survey to 209 mental healthcare providers within the public health system of Alberta, Canada. METHODS: The survey contained four sections related to sexual exploitation: two of which can take place online or in-person (grooming and sexual abuse) and two of which require the internet or a digital device (luring and sexual image distribution). Each section asked whether the mental healthcare provider had experience working with clients affected by these concerns, what barriers they encounter, how confident they are in their abilities and whether they have formal training in a topic. RESULTS: The vast majority of participants (83%) worked with a client impacted by grooming, luring, sexual abuse or sexual image distribution in the last year. Participants reported more training, more confidence and fewer barriers when identifying and responding to sexual abuse as compared to grooming, luring or sexual image distribution. CONCLUSIONS: There is a need to improve mental health providers understanding of how technology is being utilized to exploit children, so that they can respond effectively to protect their clients.

The prevalence of substance use disorders and substance use in anorexia nervosa: a systematic review and meta-analysis.

AIM: Individuals with anorexia nervosa (AN) often present with substance use and substance use disorders (SUDs). However, the prevalence of substance use and SUDs in AN has not been studied in-depth, especially the differences in the prevalence of SUDs between AN types [e.g., AN-R (restrictive type) and AN-BP (binge-eating/purge type]. Therefore, this systematic review and meta-analysis aimed to assess the prevalence of SUDs and substance use in AN samples. METHOD: Systematic database searches of the peer-reviewed literature were conducted in the following online databases: MEDLINE, PsycINFO, Embase, and CINAHL from inception to January 2021. We restricted review eligibility to peer-reviewed research studies reporting the prevalence for either SUDs or substance use in individuals with AN. Random-effects meta-analyses using Freeman-Tukey double arcsine transformations were performed on eligible studies to estimate pooled proportions and 95% confidence intervals (CIs). RESULTS: Fifty-two studies met the inclusion criteria, including 14,695 individuals identified as having AN (mean age: 22.82 years). Random pooled estimates showed that substance use disorders had a 16% prevalence in those with AN (AN-BP = 18% vs. AN-R = 7%). Drug abuse/dependence disorders had a prevalence of 7% in AN (AN-BP = 9% vs. AN-R = 5%). In studies that looked at specific abuse/dependence disorders, there was a 10% prevalence of alcohol abuse/dependence in AN (AN-BP = 15% vs. AN-R = 3%) and a 6% prevalence of cannabis abuse/dependence (AN-BP = 4% vs. AN-R = 0%). In addition, in terms of substance use, there was a 37% prevalence for caffeine use, 29% prevalence for alcohol use, 25% for tobacco use, and 14% for cannabis use in individuals with AN. CONCLUSION: This is the most comprehensive meta-analysis on the comorbid prevalence of SUDs and substance use in persons with AN, with an overall pooled prevalence of 16%. Comorbid SUDs, including drugs, alcohol, and cannabis, were all more common in AN-BP compared to AN-R throughout. Therefore, clinicians should be aware of the high prevalence of SUD comorbidity and substance use in individuals with AN. Finally, clinicians should consider screening for SUDs and integrating treatments that target SUDs in individuals with AN. Individuals with anorexia nervosa (AN) may also present with substance use or have a substance use disorder (SUDs). Thus, we conducted a systematic review and meta-analysis to determine the prevalence of substance use and substance use disorders in individuals with AN. We examined published studies that reported the prevalence of either substance use or SUDs in individuals with AN. We found that substance use disorders had a 16% prevalence and that drug abuse/dependence disorders had a prevalence of 7% in those with AN. These rates were much higher in individuals with binge-eating/purging type compared to the restrictive AN. However, many specific substance use disorders and substance use types were low in individuals with AN. Nonetheless, clinicians should be aware of the high prevalence of SUD comorbidity and substance use in individuals with AN.

Negative symptoms: associations with defeatist beliefs, self-efficacy, and maladaptive schemas in youth and young adults at-risk for psychosis.

BACKGROUND: Investigations into possible mechanisms that may contribute to the development, maintenance, and exacerbation of negative symptoms are needed. Defeatist beliefs, self-efficacy, and early maladaptive schemas have been shown to contribute to negative symptoms in schizophrenia. Likewise, negative symptoms occur in those at clinical high-risk (CHR) for psychosis. AIMS: The aim of this study was to determine if negative symptoms were associated with defeatist beliefs, self-efficacy, and early maladaptive schemas in CHR participants of a group therapy intervention study. METHOD: All CHR participants (n = 203; 99 males, 104 females) were recruited as part of a three-site randomized control trial: Recovery through Group Study (ReGroup). Negative symptoms, defeatist beliefs, self-efficacy and early maladaptive schemas were assessed by trained clinical raters. Mediation analyses were conducted to examine the relationship between defeatist beliefs, self-efficacy, functioning, and negative symptoms. RESULTS: The majority of CHR youth (72.9%) had at least one negative symptom of moderate to above moderate severity at baseline. In multiple mediation analyses, both asocial beliefs and social self-efficacy mediated the effects of social functioning on negative symptoms. Finally, defeatist performance attitudes significantly mediated the effects of role functioning on negative symptoms. CONCLUSIONS: These results highlight the importance of considering beliefs and attitudes in relation to functioning and severity of negative symptoms. Psychosocial interventions may wish to target beliefs and attitudes in effort to reduce negative symptoms and improve functioning in CHR youth.

The Prevalence of Impulse Control Disorders and Behavioral Addictions in Eating Disorders: A Systematic Review and Meta-Analysis.

Aim: Individuals with eating disorders (EDs) may present with impulse control disorders (ICDs) and behavioral addictions (BAs), which may result in additional suffering and treatment resistance. However, the prevalence of ICDs and BAs in EDs has not been systematically examined. Therefore, this systematic review and meta-analysis aimed to assess the prevalence of ICDs and BAs in ED samples. Methods: A comprehensive electronic database search of the peer-reviewed literature was conducted in the following online databases: MEDLINE, PsycINFO, Embase, and CINAHL from their inception to May 2021. We restricted review eligibility to research studies reporting prevalence for ICDs or BAs in individuals with diagnosed EDs. The outcome for this review was the prevalence of ICDs or BAs in individuals with EDs. A series of random-effects meta-analyses were performed on eligible studies to estimate the pooled proportions and 95% confidence intervals (CIs). Results: Thirty-five studies met the inclusion criteria, including a total of 9,646 individuals identified as having an ED, 18 of these studies specifically examined ICDs/BAs in AN, BN, and BED. Random-effects pooled estimates demonstrated that the comorbid prevalence of any ICD was 22%. The prevalence of comorbid pathological/compulsive buying was highest (19%), followed by kleptomania (18%), pathological internet use (12%), intermittent explosive disorder (4%), trichotillomania (3%), and gambling disorder (2%). In addition, the prevalence of stealing/shoplifting behaviors was 30% in those with EDs. Conclusion: This is the first meta-analysis on the comorbid prevalence of EDs and ICDs/BAs. We found a moderate prevalence for these comorbid conditions, with approximately one out of five individuals with an ED also displaying a comorbid ICD/BA. Although causal inferences cannot be drawn, the numbers strongly suggest that clinical screening/monitoring of ICDs/BAs should be part of the clinical routine in cohorts with EDs. ED settings need either the capacity to manage these disorders or adequate access to relevant services. Further investigations are needed to reveal common underlying pathomechanisms. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020202044.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Post-traumatic Stress Disorder: A Systematic Review and Network Meta-analysis: La Stimulation Magnétique Transcrânienne Répétitive Pour le Traitement du Trouble de Stress Post-Traumatique : Une Revue Systématique et une Méta-Analyse en Réseau.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment modality for Post-traumatic stress disorder (PTSD). Several targets and stimulation parameters have been investigated, and while previous meta-analyses have suggested that rTMS is efficacious, these have pooled different stimulation parameters and targets, and the relative efficacy of each is unknown. METHODS: We therefore performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) by searching MEDLINE, EMBASE, CENTRAL, and PsycINFO and retaining RCTs with at least 5 individuals per arm and clinician-rated PTSD symptoms (PROSPERO CRD42019134984). We adhered to PRISMA guidelines, and 2 independent reviewers screened studies for eligibility and extracted the primary outcome of clinician-rated PTSD symptoms. Dropouts were extracted as a proxy for acceptability. Random effects pairwise meta-analyses and a network meta-analysis were performed. RESULTS: We synthesize data from 10 RCTs with a total of 421 participants. Two rTMS interventions targeting the right dorsolateral prefrontal cortex (DLPFC) improved PTSD symptoms relative to sham: low-frequency stimulation (SMD = 0.70; 95% CI, 0.22 to 1.18) and high-frequency stimulation (SMD = 0.71; 95% CI, 0.11 to 1.31). Medial PFC dTMS, right DLPFC intermittent theta-burst stimulation, and left DLPFC high-frequency stimulation did not separate from sham. Dropouts as a proxy for acceptability revealed no differences between any of the active conditions or sham nor did any of the active conditions differ from each other. CONCLUSION: The current literature does not support efficacy differences between interventions; however, protocols stimulating the right DLPFC appear superior to sham. It is unclear whether this reflects heterogeneity in pathology requiring a personalized medicine approach or nonspecific mechanisms of rTMS.

Negative Symptoms and Functioning in Youth at Risk of Psychosis: A Systematic Review and Meta-analysis.

LEARNING OBJECTIVE: After participating in this activity, learners should be better able to:• Evaluate the relationship between negative symptoms and functioning in youth at clinical high risk for psychosis. AIM: Youth at CHR for psychosis often demonstrate significant negative symptoms and poor functioning, though the magnitude and direction of the relationship between the two remains unknown. The objective of this systematic review is to summarize the relationship between negative symptoms and functioning in CHR samples. METHOD: Electronic databases CINAHL, EBM, Embase, MEDLINE, and PsycINFO were searched from inception. Studies were selected if they included any study that reported a relationship between negative symptoms and functioning in youth at clinical high risk (CHR). The correlation coefficient r was converted to Cohen's d, and all random-effects meta-analyses were performed using the transformed values. RESULTS: Forty-one studies met the inclusion criteria, including a total of 4574 individuals at CHR for psychosis. Negative symptom total scores were significantly associated with poorer global functioning (d, -1.40; 95% CI, -1.82 to -0.98; I = 79.4%; p < .001 [9 studies, n = 782]), social functioning (d, -1.10; 95% CI, -1.27 to -0.93; I = 10.40%; p < .001 [12 studies, n = 811]), and role functioning (d, -0.96; 95% CI, -1.17 to -0.76; I = 41.1%; p < .001 [9 studies, n = 881]). In addition, negative symptoms were consistently associated with poor premorbid functioning. When examining negative symptom domains, avolition, anhedonia, and blunted affect were each significantly and independently associated with poorer social functioning and role functioning. In terms of prediction models, negative symptoms contributed to the prediction of lower functioning across multiple studies. CONCLUSION: This meta-analysis demonstrates a strong relationship between negative symptoms and functioning in youth at clinical high risk for psychosis.

Brain changes associated with negative symptoms in clinical high risk for psychosis: A systematic review.

The negative symptoms of schizophrenia are linked to poorer functional outcomes and decreases in quality of life, and are often the first to develop in individuals who are at clinical high risk (CHR) for psychosis. However, the accompanying neurobiological changes are poorly understood. Therefore, we conducted a systematic review of the studies that have examined the brain metrics associated with negative symptoms in those at CHR. Electronic databases were searched from inception to August 2019. Studies were selected if they mentioned negative symptoms in youth at CHR for psychosis, and brain imaging. Of 261 citations, 43 studies with 2144 CHR participants met inclusion criteria. Too few studies were focused on the same brain regions using similar neuroimaging methods to perform a meta-analysis, however, the results of this systematic review suggest a relationship between negative symptom increases and decreases in grey matter. The paucity of studies linking changes in brain structure and function with negative symptoms in those at CHR suggests that future work should focus on examining these relationships.

Interventions and Transition in Youth at Risk of Psychosis: A Systematic Review and Meta-Analyses.

OBJECTIVE: The primary objective of this systematic review and meta-analyses was to summarize the impact of all reported treatments on transition to psychosis in high-risk samples. DATA SOURCES: PsycINFO, Embase, CINAHL, EBM, and MEDLINE online databases were searched from inception to May 2017 using the keywords psychosis, risk, and treatment with no geographical, date, or language restrictions. STUDY SELECTION: A total of 38 independent studies met the inclusion criteria: conducted a treatment study in a sample at high risk for psychosis and reported on transition to psychosis as an outcome. DATA EXTRACTION: The following data were extracted: study characteristics (eg, sample size), participant characteristics (eg, mean age), and clinical outcome data (eg, number and percentage of patients transited for each intervention group at each time-point and transition assessment employed). Data were analyzed using random-effects pairwise meta-analysis (to explore differences between treatment and controls) and multivariate network meta-analyses (NMAs; to explore differences between treatment types on transition) and were reported as risk ratios (RR). RESULTS: In pairwise meta-analyses, cognitive-behavioral therapy (CBT) studies were associated with a significant reduction in transition compared with controls at 12-month and 18-month follow-up (RR = 0.57; 95% CI, 0.35-0.93; I² = 7%; P = .02 vs RR = 0.54; 95% CI, 0.32-0.92; I² = 0%; P = .02). In the NMAs, integrated psychological therapy, CBT, supportive therapy, family therapy, needs-based interventions, omega-3, risperidone plus CBT, ziprasidone, and olanzapine were not significantly more effective at reducing transition at 6 and 12 months relative to each other. CONCLUSIONS: This systematic review and pairwise meta-analyses demonstrated a reduced risk for transition favoring CBT at 12 and 18 months. No interventions were significantly more effective at reducing transition compared with all other interventions in the NMAs. NMA results should be interpreted with caution due to the small sample size.

Attrition rates in trials for adolescents and young adults at clinical high-risk for psychosis: A systematic review and meta-analysis.

BACKGROUND: Treatment of those at clinical high-risk (CHR) for developing psychosis may lead to preventive strategies. However, attrition in trials may hamper efforts to detect effective changes and lead to bias. Our objective was to synthesize the relative attrition rates in clinical trials conducted in CHR for psychosis samples. METHOD: We searched the following electronic databases: MEDLINE, Embase, PsycINFO, CINAHL and EBM with no restrictions. Inclusion criteria was any treatment-based randomized controlled trial (RCT) conducted in CHR samples that reported attrition. Relative attrition rates were calculated using random-effects meta-analysis, stratified by time, and reported as odds ratios (ORs), proportions, and 95% confidence intervals (CIs). RESULTS: Twenty-one RCTs met our inclusion criteria, including a total of 2260 CHR participants. Attrition rates between all treatment types identified were not statistically different from control treatments at any time-point. When accessing overall trial attrition, the pooled attrition rate was 29.57% (95% CI = 23.84-35.63%) with statistically significant heterogeneity (I2 = 88.70%; P < .001). Furthermore, 11 trials had a subsequent follow-up after the intervention was conducted and the pooled attrition was 33.96% (95% CI = 24.94-43.59%). When examining predictors of attrition, no statistically significant subgroup differences were observed in attrition rates. CONCLUSIONS: Almost one third of CHR participants will not complete participation in an RCT, however no predictors were found to be statistically significantly related to attrition. Methods to account for missing data and attrition are warranted in CHR trials to account for potential biases associated with high attrition rates.

Multidisciplinary Treatment for Individuals at Clinical High Risk of Developing Psychosis.

PURPOSE: One of the goals of identifying youth identified, based on clinical symptoms, as being at risk for developing psychosis, is to find ways to prevent or even delay the onset of the illness. Over the past 20 years, relatively few randomized control trials (RCTs), including both pharmacological and psychosocial interventions, have been conducted and often with inconsistent results. Several recent meta-analyses suggest that there are few treatments if any that might be effective and that no one treatment is seen as being more effective than any other treatment. This review aims to examine the existing RCTs and to critically review recent meta-analyses. RECENT FINDINGS: Individuals at clinical high risk for psychosis are a heterogenous group. Unfortunately, many interventions have not been specifically designed to address the outcome being assessed nor have participants been specifically selected for that treatment. SUMMARY: The trials completed to date and the recent systematic reviews should be seen positively and used to guide the design of future trials to ensure that the right interventions are offered to the right people at the right time.

Interventions and social functioning in youth at risk of psychosis: A systematic review and meta-analysis.

AIM: Youth at clinical high risk (CHR) for psychosis often exhibit difficulties in social functioning and poorer social functioning may be predictive of transition to a psychotic disorder. Therefore, the primary objective of this systematic review was to summarize the impact of all interventions on social functioning in CHR samples. METHOD: Electronic databases PsycINFO, CINAHL, Embase, EBM, and MEDLINE were searched from 1951 to June 2017. Studies were selected if they included any intervention that reported changes in social functioning in youth at CHR. Data were evaluated using random effects pairwise meta-analyses, stratified by time, and reported as the standardized mean difference (SMD). RESULTS: Nineteen studies met our inclusion criteria, including a total of 1513 CHR participants. The mean age was 20.5 years and 47% were male. Cognitive behavioural therapy (4 studies) did not significantly improve social functioning at 6 months (SMD = 0.06; 95% confidence interval [CI] = -0.35, 0.46), 12 months (SMD = -0.15; 95% CI = -0.38, 0.08) and 18 months (SMD = 0.20; 95% CI = -0.10, 0.50). Omega-3 (2 studies) did not significantly improve social functioning at 6 months (SMD = 0.01; 95% CI = -0.21, 0.24) and 12 months (SMD = -0.08; 95% CI = -0.33, 0.17). Lastly, cognitive remediation (3 studies) did not significantly improve social functioning at 2- to 3-month follow-up (SMD = 0.13, 95% CI = -0.18, 0.43). CONCLUSIONS: This systematic review and meta-analysis demonstrated that no treatment significantly improved social functioning in youth at CHR. Future randomized control trials are required that are designed to target and improve social functioning in youth at CHR for psychosis.