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Epidemiological studies have provided varying prevalence estimates of trichotillomania (TTM) and other hair-pulling behaviors. We performed a systematic review and meta-analysis to provide data-driven prevalence estimates of TTM and hair-pulling. PubMed, PsycInfo and Embase were searched on June 2020 (updated in November 2021). Studies reporting the frequency of TTM defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria or hair-pulling behaviors were included. Prevalence data was extracted for both genders, and female-to-male odds ratios (OR) were computed for TTM and any hair-pulling behaviors. Data were pooled through random-effects meta-analyses. Of the 713 records identified through database searches, 30 studies involving 38,526 participants were included. Meta-analyses indicated TTM had a prevalence of 1.14% (95% CI 0.66%, 1.96%), while any hair-pulling behavior had a prevalence of 8.84% (95% CI 6.33%, 12.20%). Meta-analyses demonstrated females were at an increased risk of any hair-pulling when noticeable hair loss was required (OR = 2.23, 95% CI 1.60, 3.10, p 0.0001), but not of any hair-pulling when noticeable hair loss was not required (OR = 0.90, 95% CI 0.72, 1.64, p = 0.33). Meta-analyses did not indicate female preponderance in TTM (k = 10; N = 22,775; OR = 1.29; 95% CI 0.91, 1.83; I

Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing neurodevelopmental disorder in which genetic factors play an important role. DNA sequencing of parent-child trios provides a powerful approach for identifyingde novo(spontaneous) variants, which has led to the discovery of hundreds of clinically informative risk genes for other neurodevelopmental disorders but has yet to be extensively leveraged in studying ADHD. Here, we conducted whole-exome DNA sequencing in 152 parent-child trios with ADHD and demonstrate for the first time a significant enrichment of rare and ultra-rarede novoprotein-truncating variants and missense variants predicted to be damaging in ADHD cases compared to unaffected controls. Combining these results with a large independent case-control DNA sequencing cohort (3,206 ADHD cases and 5,002 controls), we identifylysine demethylase 5B(KDM5B)as a high-confidence risk gene for ADHD as well as two likely risk genes. We estimate that 862 genes contribute to ADHD risk. Finally, using our list of genes harboring ultra-rarede novodamaging variants, we show that these genes overlap with previously reported risk genes for other neuropsychiatric conditions in both DNA sequencing and genome-wide association studies. We also show that these genes are enriched for several canonical biological pathways, suggesting early neurodevelopmental underpinnings of ADHD. Overall, this work provides critical new insight into the biology of ADHD and demonstrates the discovery potential of DNA sequencing in larger parent-child trio cohorts.Significance statementGiven the important role of genetic factors in the development of attention-deficit/hyperactivity disorder (ADHD), research aimed at identifying risk genes can provide critical insight into underlying biological processes. We conducted whole-exome DNA sequencing in parent-child trios with ADHD, showing that these children have a significantly greater rate of rare and ultra-rarede novogene-damaging mutations compared to unaffected controls, expanding our understanding of the genetic landscape of ADHD. We then use this information to identifyKDM5Bas a high-confidence risk gene for ADHD and highlight several enriched biological pathways. This work advances our etiologic understanding of ADHD and illustrates a previously unexplored path for risk gene discovery in this common neurodevelopmental disorder.

Vesicular monoamine transporter type 2 (VMAT2) inhibitors may be an effective therapy for chronic tic disorders (CTD), including Tourette syndrome (TS), but there has not been a meta-analysis compiling available evidence from randomized controlled trials (RCTs). We performed a systematic review and meta-analysis to evaluate the efficacy, acceptability, and tolerability of VMAT2 inhibitors for CTD/TS. PubMed, CENTRAL, and Embase were searched for double-blinded RCTs of VMAT2 inhibitors versus placebo for the treatment of CTD/TS. Change in tic severity measured by the Yale Global Tic Severity Scale (efficacy) and rates of discontinuation attributed to adverse effects (tolerability) or all causes (acceptability) were extracted closest to 12 weeks. Mean difference (MD) and odds ratio (OR) were the effect size indexes for efficacy and acceptability/tolerability, respectively. Data were pooled through random-effects meta-analysis weighted by inverse variance. Five RCTs involving eight comparisons were included. Meta-analysis found a nonsignificant effect on efficacy (k = 8; N = 583; MD = -0.71; 95% confidence interval [CI], -1.93 to 0.50; P = 0.24), and there was certainty that the true effect is nonclinically meaningful (high quality of evidence). Meta-analysis found decreased tolerability (k = 7; N = 626; OR = 2.67; 95% CI, 1.21-5.92; P = 0.01) and decreased acceptability (k = 8; N = 626; OR = 1.90; 95% CI, 1.14-3.18; P = 0.01), although those comparisons were limited because of the relatively small number of events across trials. Meta-analyses did not support the efficacy of VMAT2 inhibitors in the short-term treatment of tic disorders and suggested no clinically meaningful effect of these agents on tic symptoms. © 2022 International Parkinson and Movement Disorder Society.

OBJECTIVE: There is limited evidence about the cross-cultural validity of autistic symptoms in school-aged children in Brazil. We used data from a large school survey to evaluate the factor structure of autism symptoms in community-dwelling children and adolescents. METHODS: We translated the Childhood Autism Spectrum Test to Brazilian Portuguese and performed factor analyses to investigate the factor structure of parent-reported autistic symptoms in a large sample (n=8,571) of children/adolescents from a school survey in the metropolitan area of São Paulo. RESULTS: Autistic symptoms were best conceptualized under a correlated-factors model with two factors: one predominantly characterized by social-communication symptoms and the other by symptoms of inflexible/restricted language, behaviors, and interests. CONCLUSIONS: These findings provide evidence that the structure of autistic symptoms in Brazil is similar to that described in other countries, indicating the cross-cultural validity of autism in Brazil.

Item does not contain fulltext Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice. 01 februari 2023

Recreational and problem gambling have been linked with adverse health and functioning outcomes among adolescents. Youth may gamble and engage in other risk-taking behaviors in casinos. There are limited data available regarding casino gambling in high-school students, and factors linked to adolescent gambling in casinos have yet to be systematically investigated. To address this gap, we analyzed cross-sectional data from 2010 Connecticut high-school students with chi-square tests and logistic regression models to examine casino gambling in relation to at-risk/problem gambling (ARPG) with respect to sociodemographic characteristics, gambling perceptions & attitudes, health/functioning measures and gambling behaviors. Approximately 11 % of adolescents acknowledged gambling in casinos. ARPG was more frequent and gambling perceptions were more permissive among adolescents endorsing casino gambling. Stronger relationships between ARPG and heavy alcohol and drug use and weaker relationships between ARPG and engagement in extracurricular activities, gambling with friends, gambling with strangers and gambling for financial reasons were observed among adolescents endorsing casino gambling. In conclusion, gambling in casinos was endorsed by a sizable minority of adolescents who gamble, and prevention efforts should consider targeting permissive attitudes towards gambling, adolescent drinking and participation in extracurricular activities when addressing underage casino gambling.

Introduction: pharmacotherapy is an important component of the multimodal treatment of attention-deficit/hyperactivity disorder (ADHD). Cardiovascular safety of medications for ADHD is of concern from a clinical and public health standpoint. We aim to conduct a network meta-analysis (NMA) comparing the effects of available medications for ADHD on blood pressure (diastolic and systolic), heart rate and ECG parameters over the short-term and long-term treatment.Methods and analysis: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for protocols and NMAs will be followed. We will include parallel group or cross-over randomised controlled trials (RCTs) conducted in patients with a primary diagnosis of ADHD (no age limits). We will search an extensive number of electronic databases (including MEDLINE, CINAHL, CENTRAL, EMBASE, ERIC, PsycINFO, OpenGrey, Web of Science) from their inception and contact study authors/drug manufacturers to gather relevant unpublished information. No language restrictions will be applied. The main outcomes (assessed at 12 weeks, 26 weeks and 52 weeks) will be: (1) change in diastolic and systolic blood pressure (mm Hg); (2) change in heart rate, measured in beats/min; (3) change in any available ECG parameters. We will conduct random effects of NMA using standardised mean differences with 95% CIs for continuous outcomes and ORs with 95% CIs for dichotomous outcomes. We will use the Cochrane risk of bias tool-version 2 to assess the risk of bias of included RCTs and the Confidence In Network Meta-Analysis tool to evaluate the confidence of evidence contributing to each network estimate. Sensitivity analyses will investigate effects at different dose regimens.Ethics and dissemination: no institutional review board approval will be necessary. The results of this systematic review and meta-analysis will be presented at national and international conferences and published in peer-reviewed journals.PROSPERO registration number: CRD42021295352.

Objective A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children’s Yale−Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. Method A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. Results The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7−84.1; specificity = 81.7, 95% CI = 81.5−81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8−82.2; specificity = 84.6, 95% CI = 84.4−84.8). Conclusion Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.

The desire to escape from pressures/anxiety represents an important motivation for problematic engagement with short-term rewarding behaviors that could contribute to the development of recognized and candidate behavioral addictions, including problematic shopping, a prevalent condition among youth in the U.S.A. characterized by excessive shopping cognitions/behaviors that lead to distress/impairment. However, to date, the specific correlates of shopping to relieve anxiety or tension have yet to be evaluated. We aimed at addressing this gap by analyzing data (N = 2556) from a high-school survey from Connecticut in an exploratory fashion. Adolescents who acknowledged experiencing a growing tension or anxiety that could only be relieved by shopping were classified as having negative-reinforcement shopping and compared to the remaining students. Data were analyzed in chi-square and logistic regression models to examine negative-reinforcement shopping in relation to socio-demographics, health correlates, gambling-related perceptions/attitudes, and problem-gambling severity/gambling behaviors. Negative-reinforcement shopping was more frequent in female and Hispanic students, was linked to more permissive gambling attitudes and at-risk/problematic gambling, and was associated with the use of alcohol, tobacco, marijuana, and other drugs, dysphoria/depression, and weapon-carrying and physical fighting. Taken together, these findings highlight adverse measures of health and functioning linked to negative-reinforcement shopping that may be particularly relevant to girls and Hispanic youth. Additional efforts to prevent negative outcomes are warranted.

Clinical guidelines currently recommend practitioners titrate stimulant medications, i.e., methylphenidate (MPH) and amphetamines (AMP), to the dose that maximizes symptom control without eliciting intolerable adverse events (AEs) when treating attention-deficit/hyperactivity disorder (ADHD) in school-aged children/adolescents. However, robust evidence-base regarding the effects of doses and dosing strategies of stimulants on clinical outcomes in the treatment of children/adolescents with ADHD is currently lacking and stimulants are often underdosed in clinical practice. To address this gap and provide rigorous evidence-base in relation to the dose and dosing strategy of stimulants, we conducted the largest systematic review and dose–response meta-analysis examining change in ADHD symptoms (efficacy), and treatment discontinuations due to AEs (tolerability) and any reason (acceptability). We conducted one-stage random-effects dose–response meta-analyses examining MPH and AMP separately, stratifying trials based on fixed-dose and flexible-dose design. Daily doses of stimulants were converted to MPH- and AMP-equivalent doses by adjusting for different pharmacokinetics across formulations. We also conducted pairwise meta-analyses to provide indirect comparisons between flexible-dose versus fixed-dose trials. Our study included 65 RCTs involving 7 877 children/adolescents. Meta-analyses of fixed-dose trials for both MPH and AMP demonstrated increased efficacy and increased likelihood of discontinuation due to AEs with increasing doses of stimulants. The incremental benefits of stimulants in terms of efficacy decreased beyond 30 mg of MPH or 20 mg of AMP in fixed-dosed trials. In contrast, meta-analyses of flexible-dose trials for both MPH and AMP demonstrated increased efficacy and reduced likelihood of discontinuations for any reason with increasing stimulant doses. The incremental benefits of stimulants in terms of efficacy remained constant across the FDA-licensed dose range for MPH and AMP in flexible-dose trials. Our results suggest that flexible titration as needed, i.e., considering the presence of ADHD symptoms, and tolerated, i.e., considering the presence of dose-limiting AEs, to higher doses of stimulants is associated with both improved efficacy and acceptability because practitioners can increase/reduce doses based on control of ADHD symptoms/dose-limiting AEs. Although fixed-dose trials that are required by the FDA are valuable to characterize dose-dependency, they may underestimate the true potential benefit of trialing dose-increases of stimulants in clinical practice by not allowing dose adjustment based on response and tolerability. Additional research is required to investigate potential long-term effects of using high doses of stimulants in clinical practice.

Whether parental age, i.e., paternal or maternal, at childbirth is associated with the risk of bipolar disorder (BD) in offspring remains unclear. We conducted a meta-analysis of observational studies to address this gap.PubMed, PsycINFO, Embase, and Web of Science were searched up to June 2021. Studies investigating the associations between parental age at childbirth (exposure) and the risk of BD in offspring (outcome) were eligible for inclusion in our study. Paternal and maternal age were examined separately. Odds ratio (OR) was used as the effect size index. Data were pooled through random-effects meta-analyses.Seven studies involving 3,183,539 participants and 23,253 individuals with BD were included in our meta-analyses. Meta-analyses indicated an increased risk of BD in the offspring of the older paternal age groups (35-44 years old [k = 5; OR = 1.09; 95% CI 1.05, 1.14; p 0.0001] and ≥45 years old [k = 5; OR = 1.44; 95% CI 1.19, 1.14; p = 0.0001]) in comparison with the reference category (25-34 years old). Meta-analysis also indicated an increased risk of BD in the offspring of the older maternal age group (≥40 years old [k = 3; OR = 1.20; 95% CI 1.10, 1.31; p 0.0001]) in comparison with the reference category (20-29 years old).Advanced paternal and maternal age were both associated with an increased risk of BD in offspring. Further studies are needed to investigate the mechanisms behind this association.

Motivational characteristics such as excitement-seeking are key components of models of addiction, including problem gambling. Previous studies have established associations between excitement-seeking and problem gambling in youth. However, these studies have employed dimensional psychological assessments which are unlikely to be routinely administered. Other approaches to conceptualize excitement-seeking could be of value. In the present study, we employed a single question (What are the reasons that you gamble?) to identify adolescents who reported excitement-seeking motivation for gambling. Cross-sectional data from 2030 adolescent gamblers who participated in a Connecticut high-school survey were examined. Gambling perceptions and correlates of problem-gambling severity were examined relative to excitement-seeking and non-excitement-seeking gambling. Gambling perceptions were more permissive and at-risk/problem gambling was more frequent among adolescents with excitement-seeking gambling versus non-excitement-seeking gambling. A weaker relationship between problem-gambling severity and moderate and heavy alcohol use was observed for excitement-seeking versus non-excitement-seeking gambling. Excitement-seeking gambling is associated with more permissive gambling-related attitudes and riskier gambling behaviors and may account for some variance in adolescent risk of heavy alcohol use. A single question may provide important information for identifying adolescents who are at elevated risk of problem gambling and associated negative outcomes, although the utility of the question in specific settings warrants direct examination, especially given the observed high prevalence of excitement-seeking motivations for gambling.

BACKGROUND Trichotillomania (TTM) is a difficult-to-treat psychiatric condition with no first-line medications approved by the Food and Drug Administration. Individuals with TTM often feel that clinicians know little about this disorder. Here, we present an updated meta-analysis of randomized controlled trials (RCTs) examining treatments for TTM. METHODS Pubmed, PsychINFO, Embase, and CENTRAL were searched with the terms "Trichotillomania OR Hair Pulling Disorder" to identify randomized controlled clinical trials evaluating treatments for TTM. RESULTS Twenty-four trials involving 26 comparisons and 857 participants were included in this meta-analysis. Behavioral therapy with habit-reversal training components (BT-HRT) demonstrated a large benefit compared to control conditions (standardized mean difference [SMD] [95% CI] = -1.22 [-1.71, -0.73], p

Studies have suggested Brain-Derived Neurotrophic Factors (BDNF) increase after electroconvulsive therapy (ECT) although they were methodologically limited and enrolled small sample sizes. We aimed at updating a systematic review and meta-analysis to explore BDNF changes after ECT for the treatment of depression. PubMed, PsycInfo, Embase and Global health were searched (March, 2021). Clinical trials that measured BDNF in the blood before and after ECT in adults (≥ 18 years old) with depression (major depressive disorder or bipolar disorder) were eligible. Data were pooled through random-effects meta-analyses. Twenty-eight studies involving 778 participants were included. Meta-analysis showed a significant increase in BDNF levels after ECT (Hedges’ g = 0.28; 95% CI: 0.10, 0.46) while there was evidence of significant heterogeneity (I2 = 67.64%) but not publication bias/small-study effect. Subgroup analyses and meta-regressions were underpowered to detect significant differences. Meta-analysis of depression severity scores demonstrated a considerable larger treatment effect in reducing depressive symptoms after ECT (Hedge’s g = −3.72 95% CI: −4.23, −3.21). This updated review showed that BDNF blood levels increased after ECT treatment. However, there was still evidence of substantial heterogeneity and there were limited sample sizes to investigate factors driving the variability of effects across studies. Importantly, the increase in BDNF levels was substantially smaller than the observed in depressive symptomatology, which could be indicative that the former was independent than the latter. Additional studies with larger sample sizes are currently required.

In this issue, Rodrigues et al. (2020) present a systematic review with meta-analyses that reports the efficacy of five treatments for children with attention-deficit hyperactivity disorder symptoms in the context of autism spectrum disorder - (a) methylphenidate; (b) atomoxetine; (c) guanfacine; (d) aripiprazole; and (e) risperidone. In this commentary, we highlight the contrast between the scarce evidence base of treatment for ADHD in the context of autism and other subpopulations, such as tic disorders and intellectual disability, and the extensive evidence base of treatment for ADHD in general. The commentary weighs about the conundrum clinicians face of whether to rely on the limited evidence base of treatment for ADHD in subpopulation, or to derive conclusions from the larger body of evidence of treatment for ADHD in general. The commentary also discusses potential avenues for future research to address this clinical problem.

Recreational and problem gambling have been linked with adverse health and functioning outcomes among adolescents. Youth may gamble and engage in other risk-taking behaviors in casinos. There are limited data available regarding casino gambling in high-school students, and factors linked to adolescent gambling in casinos have yet to be systematically investigated. To address this gap, we analyzed cross-sectional data from 2010 Connecticut high-school students with chi-square tests and logistic regression models to examine casino gambling in relation to at-risk/problem gambling (ARPG) with respect to sociodemographic characteristics, gambling perceptionsattitudes, health/functioning measures and gambling behaviors. Approximately 11 % of adolescents acknowledged gambling in casinos. ARPG was more frequent and gambling perceptions were more permissive among adolescents endorsing casino gambling. Stronger relationships between ARPG and heavy alcohol and drug use and weaker relationships between ARPG and engagement in extracurricular activities, gambling with friends, gambling with strangers and gambling for financial reasons were observed among adolescents endorsing casino gambling. In conclusion, gambling in casinos was endorsed by a sizable minority of adolescents who gamble, and prevention efforts should consider targeting permissive attitudes towards gambling, adolescent drinking and participation in extracurricular activities when addressing underage casino gambling.

Clinical guidelines currently recommend practitioners titrate stimulant medications, i.e., methylphenidate (MPH) and amphetamines (AMP), to the dose that maximizes symptom control without eliciting intolerable adverse events (AEs) when treating attention-deficit/hyperactivity disorder (ADHD) in school-aged children/adolescents. However, robust evidence-base regarding the effects of doses and dosing strategies of stimulants on clinical outcomes in the treatment of children/adolescents with ADHD is currently lacking and stimulants are often underdosed in clinical practice. To address this gap and provide rigorous evidence-base in relation to the dose and dosing strategy of stimulants, we conducted the largest systematic review and dose-response meta-analysis examining change in ADHD symptoms (efficacy), and treatment discontinuations due to AEs (tolerability) and any reason (acceptability). We conducted one-stage random-effects dose-response meta-analyses examining MPH and AMP separately, stratifying trials based on fixed-dose and flexible-dose design. Daily doses of stimulants were converted to MPH- and AMP-equivalent doses by adjusting for different pharmacokinetics across formulations. We also conducted pairwise meta-analyses to provide indirect comparisons between flexible-dose versus fixed-dose trials. Our study included 65 RCTs involving 7 877 children/adolescents. Meta-analyses of fixed-dose trials for both MPH and AMP demonstrated increased efficacy and increased likelihood of discontinuation due to AEs with increasing doses of stimulants. The incremental benefits of stimulants in terms of efficacy decreased beyond 30 mg of MPH or 20 mg of AMP in fixed-dosed trials. In contrast, meta-analyses of flexible-dose trials for both MPH and AMP demonstrated increased efficacy and reduced likelihood of discontinuations for any reason with increasing stimulant doses. The incremental benefits of stimulants in terms of efficacy remained constant across the FDA-licensed dose range for MPH and AMP in flexible-dose trials. Our results suggest that flexible titration as needed, i.e., considering the presence of ADHD symptoms, and tolerated, i.e., considering the presence of dose-limiting AEs, to higher doses of stimulants is associated with both improved efficacy and acceptability because practitioners can increase/reduce doses based on control of ADHD symptoms/dose-limiting AEs. Although fixed-dose trials that are required by the FDA are valuable to characterize dose-dependency, they may underestimate the true potential benefit of trialing dose-increases of stimulants in clinical practice by not allowing dose adjustment based on response and tolerability. Additional research is required to investigate potential long-term effects of using high doses of stimulants in clinical practice.

Although the term has been relatively ill defined in psychiatric research, "biomarker" is typically considered a measurable objective characteristic that can predict clinical outcomes such as risk, diagnosis, subgroups, severity, prognosis, and response to treatment.1 Among several fields of medicine, such as cardiology and oncology, biomarkers have been used to aid clinicians during the various stages of decision-making processes, advancing toward precision medicine and health in which care is tailored based on specific characteristics of individuals. However, that has not been the case for psychiatry until now. Despite the remarkable advancements in our understanding of the etiology and pathophysiology of mental disorders over the past decades, there is no well-validated biomarker incorporated into our clinical practice. We as psychiatrists still find ourselves establishing diagnoses, allocating individuals to treatment, and predicting response without inputs from the accumulated knowledge from neuroscience.

Obsessive-Compulsive disorder (OCD) is a common psychiatric condition that leads to significant impairment in everyday life. Advancements in neurobiological investigations contributed to a better understanding of pathophysiological mechanisms behind OCD, leading to the understanding that current models employed to conceptualize OCD are not adequate and might be a significant factor in precluding further advancements in how OCD is treated. In this paper, we will use OCD as a model to discuss the limitations of the current diagnostic systems in Psychiatry and to present the novel perspectives based on neurobiological findings that might lead to considerable advancements in treatments for OCD.

Objectives: In clinical trials of pediatric trichotillomania (TTM), three instruments are typically employed to rate TTM severity: (1) the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS), (2) the National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS), and (3) the Trichotillomania Scale for Children (TSC). These instruments lack standardized definitions of treatment response, which lead researchers to determine their own definitions of response post hoc and potentially inflate results. We performed a meta-analysis to provide empirically determined accuracy measures for percentage reduction cut points in these three instruments. Methods: MEDLINE was searched for TTM clinical trials. A total of 67 studies were initially identified, but only 5 were clinical trials focused on TTM in pediatric populations and therefore were included in this meta-analysis (n = 180). A Clinical Global Impressions Improvement score ≤2 was used to define clinical response. Receiver operating characteristic principles were employed to determine accuracy measures for percentage reduction cut points on each one of the instruments. Meta-DiSc software was employed to provide pooled accuracy measures for each cut point for each instrument. The Youden Index and the distance to corner methods were used to determine the optimal cut point. Results: The optimal cut points to determine treatment response were a 45% reduction on the MGH-HPS (Youden Index 0.40, distance to corner 0.20), a 35% reduction on the NIMH-TSS (Youden Index 0.42, distance to corner 0.17), a 25% reduction on the TSC child version (TSC-C; Youden Index 0.40, distance to corner 0.18), and a 45% (distance to corner 0.30) or 50% reduction (Youden Index 0.33) on the TSC parent version (TSC-P). The TSC-C had less discriminative ability at determining response in younger children in comparison to older children; no age-related differences were observed on the TSC-P. Conclusions: This study provides empirically determined cut points of treatment response on three instruments that rate TTM severity. These data-driven cut points will benefit future research on pediatric TTM.

Gambling is prevalent among adolescents and adolescents are vulnerable to experiencing gambling-related problems. Although problem gambling and suicidal behavior have been linked in adults and self-injurious behaviors may predict future suicidality, prior studies have not investigated relationships between problem-gambling severity and self-injurious behavior in adolescents. Data from 2234 Connecticut high-school students were analyzed in chi-square tests and logistic regression models to examine self-injurious behaviors in relation to at-risk/problem gambling with respect to sociodemographic characteristics, gambling attitudes and perceptions, and extracurricular and health measures. Individuals who engaged in self-injurious behavior (versus those who did not) reported more permissive views towards gambling and were more likely to exhibit at-risk/problem gambling. Stronger relationships between problem-gambling severity and gambling in casinos (OR 4.85, 95%CI 1.94, 12.12) and non-strategic gambling (1.92, 95%CI 1.01, 3.66) were observed in adolescents who acknowledged engagement in self-injurious behavior versus those who did not. Links between self-injurious behaviors and more permissive gambling attitudes and perceptions and at-risk/problem gambling suggest the need for improved interventions targeting co-occurring self-injurious behaviors and gambling. Stronger relationships between problem-gambling severity and casino and non-strategic gambling among adolescents with self-injurious behaviors suggest adolescents with self-injurious behavior may engage in specific forms of gambling as maladaptive coping strategies to alleviate suffering. Prevention and treatment approaches targeting distress management and improving adaptive coping skills may be important for targeting self-injurious behaviors in adolescents with at-risk/problem gambling.

Exposure to fine particles may trigger pulmonary inflammation/systemic inflammation. The objective of this study was to investigate the association between daily individual exposure to air pollutants and airway inflammation and disease activity in childhood-onset systemic lupus erythematosus (cSLE) patients. A longitudinal panel study was carried out in 108 consecutive appointments with cSLE patients without respiratory diseases. Over four consecutive weeks, daily individual measures of nitrogen dioxide (NO2), fine particulate matter (PM2.5), ambient temperature, and humidity were obtained. This cycle was repeated every 2.5 months along 1 year, and cytokines of exhaled breath condensate-EBC [interleukins (IL) 6, 8, 17 and tumoral necrose factor-α (TNF-α)], fractional exhaled NO (FeNO), and disease activity parameters were collected weekly. Specific generalized estimation equation models were used to assess the impact of these pollutants on the risk of Systemic Lupus Erythematous Disease Activity Index 2000 (SLEDAI-2K) ≥ 8, EBC cytokines, and FeNO, considering the fixed effects for repetitive measurements. The models were adjusted for inflammatory indicators, body mass index, infections, medication, and weather variables. An IQR increase in PM2.5 4-day moving average (18.12 μg/m3) was associated with an increase of 0.05 pg/ml (95% CI 0.01; 0.09, p = 0.03) and 0.04 pg/ml (95% CI 0.02; 0.06, p = 0.01) in IL-17 and TNF-α EBC levels, respectively. Additionally, a short-term effect on FeNO was observed: the PM2.5 3-day moving average was associated with a 0.75 ppb increase (95% CI 0.38; 1.29, p = 0.03) in FeNO. Also, an increase of 1.47 (95% CI 1.10; 1.84) in the risk of SLEDAI-2K ≥ 8 was associated with PM2.5 7-day moving average. Exposure to inhalable fine particles increases airway inflammation/pulmonary and then systemic inflammation in cSLE patients.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which has been increasingly used as an investigational tool in neuroscience. In social and affective neuroscience research, the prefrontal cortex has been primarily targeted, since this brain region is critically involved in complex psychobiological processes subserving both Șhotș and Școldș domains. Although several studies have suggested that prefrontal tDCS can enhance neuropsychological outcomes, meta-analyses have reported conflicting results. Therefore, we aimed to assess the available evidence by performing an umbrella review of meta-analyses. We evaluated the effects of prefrontal active vs sham tDCS on different domains of cognition among healthy and neuropsychiatric individuals. A MeaSurement Tool to Assess Systematic Reviews 2 was employed to evaluate the quality of meta-analyses, and the GRADE system was employed to grade the quality of evidence of every comparison from each meta-analysis. PubMed/MEDLINE, PsycINFO and the Cochrane Database of Systematic Reviews were searched, and 11 meta-analyses were included resulting in 55 comparisons. Only 16 comparisons reported significant effects favoring tDCS, but 13 of them had either very low or low quality of evidence. Of the remaining 39 comparisons which reported non-significant effects, 38 had either very low or low quality of evidence. Meta-analyses were rated as having critically low and low quality. Among several reasons to explain these findings, the lack of consensus and reproducibility in tDCS research is discussed.

Objective To examine the efficacy of pharmacological treatments for restricted and repetitive behaviors (RRB) in autism spectrum disorders (ASD). Method We searched PubMed, Embase, and CENTRAL to identify all double-blind, randomized, placebo-controlled trials that examined the efficacy of pharmacological agents in the treatment of ASD and measured RRB as an outcome. Our primary outcome was the standardized mean difference in rating scales of RRB. Results We identified 64 randomized, placebo-controlled trials involving 3,499 participants with ASD. Antipsychotics significantly improved RRB outcomes compared to placebo (standardized mean difference [SMD] = 0.28, 95% CIs = 0.08−0.49), z = 2.77, p = .01) demonstrating a small effect size. Larger significant positive effects on RRB in ASD were seen in individual studies with fluvoxamine, buspirone, bumetanide, divalproex, guanfacine, and folinic acid that have not been replicated. Other frequently studied pharmacological treatments in ASD including oxytocin, omega-3 fatty acids, selective serotonin reuptake inhibitors (SSRI), and methylphenidate did not demonstrate significant benefit in reducing RRB compared to placebo (oxytocin: SMD = 0.23, 95% CI = −0.01 to 0.47, z = 1.85, p = .06; omega-3 fatty acids: SMD = 0.19, 95% CI = −0.05 to 0.43, z = 1.54, p = .12; SSRI: SMD = 0.09, 95% CI = −0.21 to 0.39, z = 0.60, p = .56; methylphenidate: SMD = 0.18, 95% CI = −0.11 to 0.46, z = 1.23, p = .22). Conclusion The results of the present meta-analysis suggest that currently available pharmacological agents have at best only a modest benefit for the treatment of RRB in ASD, with the most evidence supporting antipsychotic medications. Additional randomized controlled trials with standardized study designs and consistent and specific assessment tools for RRB are needed to further understand how we can best help ameliorate these behaviors in individuals with ASD.

Objectives Bipolar disorder is frequently associated with cognitive impairment even during euthymia. Previous studies have reported significant impairments in functional and quality of life outcomes and a possible relationship between these variables and cognitive performance. Cognitive rehabilitation interventions have been proposed to address these outcomes but positive results are still scarce. The objective of the present study is to evaluate the efficacy of a new intervention developed to address both cognitive and functional impairment. Methods Thirty-nine individuals were included in this randomized controlled trial. All participants were evaluated by the Cambridge Neuropsychological Test Automated Battery (CANTAB) and completed functional and quality of life (QOL) scales. Patients were randomized to either treatment as usual (TAU) or Cognitive Behavior Rehabilitation (CBR), an add-on treatment delivered in 12 weekly group sessions. All individuals were revaluated after 12 weeks. Results A total of 39 bipolar type I or II patients were included in the analysis, 19 in the TAU group and 20 in the CBR condition. At the entrance of the study, both groups were statistically similar regarding clinical, socio-demographics and cognitive variables. After the end of the intervention, CBR individuals had significantly improved reaction time, visual memory and emotion recognition. In contrast, individuals in the CBR did not present a statistically change in functional and QOL scores after the 12-week intervention. Conclusions CBR intervention showed promising results in improving some of the commonly impaired cognitive domains in BD. A longer follow-up period may be necessary to detect changes in functional and QOL domains.

Background Symptom severity in trichotillomania clinical trials is typically rated using the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS) and the National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS). There are no universal definitions of treatment response on these scales. The absence of empirically supported definitions of treatment response hampers advances in trichotillomania treatment. Methods PubMed and CENTRAL databases were searched for trichotillomania clinical trials. A total of 14 studies were identified and 7 provided adequate data to be included in the meta-analysis (n = 270). Meta-DiSc software was employed. The Youden index and distance to corner were used to determine the optimal cut-point. Response was defined by the Clinical Global Impressions Improvement scale score ≤ 2. Results The optimal cut-points for identifying response on the MGH-HPS was a 35% percent reduction [Youden Index 0.48; distance to corner 0.37] or a seven-point reduction [Youden Index 0.43; distance to corner 0.40]. The optimal cut-points for the NIMH-TSS was a 50% reduction [Youden Index 0.57; distance to corner 0.34] or a six-point reduction [Youden Index 0.53; distance to corner 0.36]. The optimal cut-points were similar when the analysis was confined to only trichotillomania trials involving adult subjects, but the scales appeared to have improved ability to define treatment response when pediatric subjects were excluded. Conclusion This study provides empirically determined cut-points of treatment response on the MGH-HPS and NIMH-TSS. These data-driven cut-points will benefit future research in trichotillomania by providing definitions of treatment response that can be defined a priori in clinical trials.

Psychiatry has always been considered a separate field of medicine among other medical specialties. Unlike Cardiology or Oncology, diagnoses of psychiatric disorders are made entirely based on patients’ presenting signs and symptoms. There are no sources of external validity (e.g. laboratory exam, imaging findings) that can be employed reliably to identify individuals with psychiatric disorders. [...]

The objective of this study is to evaluate the influence of exposure to air pollutants and inhalable environmental elements during pregnancy and after birth until childhood-onset systemic lupus erythematosus(cSLE) diagnosis.This case-control study comprised 30 cSLE patients and 86 healthy controls living in the Sao Paulo metropolitan area. A structured and reliable questionnaire (kappa index for test-retest was 0.78) assessed demographic data, gestational and perinatal-related-factors, and exposure to inhalable elements during pregnancy and after birth (occupational exposure to inhalable particles and/or volatile vapor, and/or tobacco, as well as, the presence of industrial activities or gas stations near the home/work/daycare/school). Tropospheric pollutants included: particulate matter (PMThe median current age was similar between cSLE patients and healthy controls [16.0 (5-21) versus 15.0 (4-21) years, p = .32], likewise the frequency of female gender (87% versus 78%, p = .43). The frequencies of prematurity (30% versus 6%, p = .001), maternal occupational exposure during pregnancy (59% versus 12%, p .001), exposure to volatile vapor (48% versus 8%, p .001) and fetal smoking (maternal and/or secondhand) (37% versus 19%, p = .008) were significantly higher in cSLE patients compared with controls. In a multivariate analysis regarding the gestation period, maternal occupational exposure (OR 13.5, 95% CI 2.5-72.4, p = .002), fetal smoking (OR 8.6, 95%CI 1.6-47, p = .013) and prematurity (OR 15.8, 95%CI 1.9-135.3, p = .012) remained risk factors for cSLE development. Furthermore, exposure to secondhand smoking during pregnancy and after birth (OR 9.1, 95%CI 1.8-42.1, p = .002) was also a risk factor for cSLE development.Prematurity and environmental factors were risk factors for developing cSLE.