Anxiety symptoms and disorders during the COVID-19 pandemic in children and adolescents: Systematic review and meta-analysis

Background and Objectives The COVID-19 pandemic and its associated factors have been shown to affect anxiety levels of young people. We meta-analytically assessed the prevalence of anxiety symptoms and anxiety disorders in children and adolescents during the pandemic, and the predictors and moderating factors influencing anxiety. Methods Multiple databases and registers were searched in this PRISMA and MOOSE-compliant systematic review and meta-analysis (PROSPERO:CRD42021266695) until 27/06/2021. We included individual studies evaluating the prevalence and characteristics of anxiety symptoms or anxiety disorders in children and adolescents (mean age ≤18 years), during the COVID-19 pandemic. Data extraction and quality assessment were carried out by independent authors. Random-effects meta-analyses of the prevalence of anxiety symptoms and anxiety disorders were conducted using Comprehensive Meta-Analysis (CMA) V3. Results 74 articles (total participant sample=478,882) were included (mean age=13.4 years, 52.3% female). The pooled rate of children and adolescents fulfilling diagnostic criteria for anxiety disorders was 13.0% (95%CI=4.9–30.1); the pooled prevalence of anxiety symptoms was 26.5% (95%CI=20.3–33.9). Anxiety symptoms were significantly more prevalent in females than males (B = 0.103, p<.001), significantly higher during the second wave of COVID-19, following July 2020, than during the first wave, prior to June 2020, (Q= 8.136, p=.017), and during school closure (Q= 8.100, p=.014). Quality of included studies was overall moderate. Conclusions There is a high prevalence of anxiety symptoms in children and adolescents during the COVID-19 pandemic, especially amongst females. This study identifies vulnerable groups, risk, and protective factors, which is crucial to developing clinical practice to prevent further mental health deterioration in young people. (AU)

Negative symptoms in children and adolescents with early-onset psychosis and at clinical high-risk for psychosis: systematic review and meta-analysis.

BACKGROUND: Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research focusing on children and adolescents is limited. AIMS: To provide meta-analytical evidence and a comprehensive review of the status and advances in the diagnosis, prognosis and treatment of negative symptoms in children and adolescents with EOP and at CHR-P. METHOD: PRISMA/MOOSE-compliant systematic review (PROSPERO: CRD42022360925) from inception to 18 August 2022, in any language, to identify individual studies conducted in EOP/CHR-P children and adolescents (mean age <18 years) providing findings on negative symptoms. Findings were systematically appraised. Random-effects meta-analyses were performed on the prevalence of negative symptoms, carrying out sensitivity analyses, heterogeneity analyses, publication bias assessment and quality assessment using the Newcastle-Ottawa Scale. RESULTS: Of 3289 articles, 133 were included (n = 6776 EOP, mean age 15.3 years (s.d. = 1.6), males = 56.1%; n = 2138 CHR-P, mean age 16.1 years (s.d. = 1.0), males = 48.6%). There were negative symptoms in 60.8% (95% CI 46.4%-75.2%) of the children and adolescents with EOP and 79.6% (95% CI 66.3-92.9%) of those at CHR-P. Prevalence and severity of negative symptoms were associated with poor clinical, functional and intervention outcomes in both groups. Different interventions were piloted, with variable results requiring further replication. CONCLUSIONS: Negative symptoms are common in children and adolescents at early stages of psychosis, particularly in those at CHR-P, and are associated with poor outcomes. Future intervention research is required so that evidence-based treatments will become available.

Systematic Review and Meta-analysis: Efficacy of Pharmacological Interventions for Irritability and Emotional Dysregulation in Autism Spectrum Disorder and Predictors of Response.

OBJECTIVE: Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response. METHOD: Following a preregistered protocol (PROSPERO: CRD42021235779), we systematically searched multiple databases until January 1, 2021. We included placebo-controlled randomized controlled trials (RCTs) and evaluated the efficacy of pharmacological interventions and predictors of response for emotional dysregulation and irritability. We assessed heterogeneity using Q statistics and publication bias. We conducted subanalyses and meta-regressions to identify predictors of response. The primary effect size was the standardized mean difference. Quality of studies was assessed using the Cochrane Risk of Bias Tool (RoB2). RESULTS: A total of 2,856 individuals with ASD in 45 studies were included, among which 26.7% of RCTs had a high risk of bias. Compared to placebo, antipsychotics (standardized mean difference = 1.028, 95% CI = 0.824-1.232) and medications used to treat attention-deficit/hyperactivity disorder (ADHD) (0.471, 0.061-0.881) were significantly better than placebo in improving emotional dysregulation and irritability, whereas evidence of efficacy was not found for other drug classes (p > .05). Within individual medications, evidence of efficacy was found for aripiprazole (1.179, 0.838-1.520) and risperidone (1.074, 0.818-1.331). Increased rates of comorbid epilepsy (ß = -0.049, p = .026) were associated with a lower efficacy. CONCLUSION: Some pharmacological interventions (particularly risperidone and aripiprazole) have proved efficacy for short-term treatment of emotional dysregulation and irritability in ASD and should be considered within a multimodal treatment plan, taking into account also the tolerability profile and families' preferences.

A systematic review and meta-analysis investigating the impact of childhood adversities on the mental health of LGBT+ youth.

Background: The presence of trauma as a backdrop to the lives of LGBT+ youth has been recognised in recent literature. LGBT+ youth report a higher frequency, severity and pervasiveness of adverse childhood experiences when compared to their heterosexual and cisgender counterparts. This exposure has been directly related to an increased risk of mental health problems. Method: A systematic literature search of Medline, Embase, PsycINFO, PubMed and Web of Science was conducted from the date of their inception until the 1st September 2021. The study protocol was registered in PROSPERO (CRD42021240472). Results: A total of 27 studies satisfied the inclusion criteria and were used in the systematic review, representing 199,285 participants, 26,505 of whom identified as LGBT+ (mean age 16.54). Female participants (ranging from 11% to 74%) and white participants (7.7%-96%) made up the largest percentage of most samples. Depressive symptoms were the most commonly described psychiatric outcome (n = 17, 63%), followed by anxiety symptoms (n = 6, 31.5%). 18 studies provided meta-analysable data, compromising 21,781 LGBT+ young people. LGBT+ youth reported a higher prevalence of adverse experiences in comparison to their heterosexual or cisgender counterparts (p < .001), with sexual abuse representing the most commonly reported experience (29.7%), followed by verbal abuse (28.7%), physical abuse (26.5%) and cyberbullying (19.1%). LGBT+ youth were also at a heightened risk of mental health disorders (p < .001), with 36.9% and 31.5% of sample meeting the clinical criteria for depression and anxiety, respectively. Conclusions: Continued advocacy is needed from communities and Allies to support and empower LGBT+ youth in the face of adversity. Longitudinal and longer-term studies are required to further understand the relationship between adverse experiences in LGBT+ youth and the impact on mental health.

Autism Spectrum Disorder and Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis.

Psychotic experiences can occur in autism spectrum disorders (ASD). Some of the ASD individuals with these experiences may fulfil Clinical High-Risk for Psychosis (CHR-P) criteria. A systematic literature search was performed to review the information on ASD and CHR-P. A meta-analysis of the proportion of CHR-P in ASD was conducted. The systematic review included 13 studies. The mean age of ASD individuals across the included studies was 11.09 years. The Attenuated Psychosis Syndrome subgroup was the most frequently reported. Four studies were meta-analysed, showing that 11.6% of CHR-P individuals have an ASD diagnosis. Symptoms of prodromal psychosis may be present in individuals with ASD. The transition from CHR-P to psychosis is not affected by ASD.

Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis.

BACKGROUND: To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). METHODS: A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. RESULTS: One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. CONCLUSIONS: Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.

Primary prevention of depression: An umbrella review of controlled interventions.

BACKGROUND: Primary prevention has the potential to modify the course of depression, but the consistency and magnitude of this effect are currently undetermined. METHODS: PRISMA and RIGHT compliant (PROSPERO:CRD42020179659) systematic meta-review, PubMed/Web of Science, up to June 2020. Meta-analyses of controlled interventions for the primary prevention of depressive symptoms [effect measures: standardized mean difference (SMD)] or depressive disorders [effect measure: relative risk (RR)] were carried out. Results were stratified by: (i) age range; (ii) target population (general and/or at-risk); (iii) intervention type. Quality (assessed with AMSTAR/AMSTAR-PLUS content) and credibility (graded as high/moderate/low) were assessed. USPSTF grading system was used for recommendations. RESULTS: Forty-six meta-analyses (k=928 individual studies, n=286,429 individuals, mean age=22.4 years, 81.1% female) were included. Effect sizes were: SMD=0.08-0.53; for depressive symptoms; RR=0.90-0.28 for depressive disorders. Sensitivity analyses including only RCTs did not impact the findings. AMSTAR median=9 (IQR=8-9); AMSTAR-PLUS content median=4.25 (IQR=4-5). Credibility of the evidence was insufficient/low in 43 (93.5%) meta-analyses, moderate in two (4.3%), and high in one (2.2%): reduction of depressive symptoms using psychosocial interventions for young adults only, and a combination of psychological and educational interventions in primary care had moderate credibility; preventive administration of selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in individuals with a stroke had high credibility. LIMITATIONS: Intervention heterogeneity and lack of long-term efficacy evaluation. CONCLUSIONS: Primary preventive interventions for depression might be effective. Among them, clinicians may offer SSRIs post-stroke to prevent depressive disorders, and psychosocial interventions for children/adolescents/young adults with risk factors or during the prenatal/perinatal period.

Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis.

Importance: Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research. Objective: To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P. Data Sources: PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles. Study Selection: Longitudinal studies reporting transition risks in individuals at CHR-P. Data Extraction and Synthesis: Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves. Main Outcome and Measures: Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted. Results: A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (ß = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (ß = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%). Conclusions and Relevance: In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.

Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis.

BACKGROUND: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals. METHODS: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant meta-analysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were two-tailed with α=0.05. FINDINGS: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges' g=0.753, 95%CI=0.495-1.012) and 24 (Hedges' g=0.836, 95%CI=0.463-1.209), but not ≥36 months (Hedges' g=0.315. 95%CI=-0.176-0.806). Negative symptoms improved at 12 (Hedges' g=0.496, 95%CI=0.315-0.678), but not 24 (Hedges' g=0.499, 95%CI=-0.137-1.134) or ≥36 months (Hedges' g=0.033, 95%CI=-0.439-0.505). Depressive symptoms improved at 12 (Hedges' g=0.611, 95%CI=0.441-0.782) and 24 (Hedges' g=0.583, 95%CI=0.364-0.803), but not ≥36 months (Hedges' g=0.512 95%CI=-0.337-1.361). Functioning improved at 12 (Hedges' g=0.711, 95%CI=0.488-0.934), 24 (Hedges' g=0.930, 95%CI=0.553-1.306) and ≥36 months (Hedges' g=0.392, 95%CI=0.117-0.667). Remission from CHR-P status occurred in 33.4% (95%CI=22.6-44.1%) at 12 months, 41.4% (95%CI=32.3-50.5%) at 24 months and 42.4% (95%CI=23.4-61.3%) at ≥36 months. Heterogeneity across the included studies was significant and ranged from I2=53.6% to I2=96.9%. The quality of the included studies (mean±SD) was 4.6±1.1 (range=2-8). INTERPRETATION: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes. FUNDING: None.

Implementing Precision Psychiatry: A Systematic Review of Individualized Prediction Models for Clinical Practice.

BACKGROUND: The impact of precision psychiatry for clinical practice has not been systematically appraised. This study aims to provide a comprehensive review of validated prediction models to estimate the individual risk of being affected with a condition (diagnostic), developing outcomes (prognostic), or responding to treatments (predictive) in mental disorders. METHODS: PRISMA/RIGHT/CHARMS-compliant systematic review of the Web of Science, Cochrane Central Register of Reviews, and Ovid/PsycINFO databases from inception until July 21, 2019 (PROSPERO CRD42019155713) to identify diagnostic/prognostic/predictive prediction studies that reported individualized estimates in psychiatry and that were internally or externally validated or implemented. Random effect meta-regression analyses addressed the impact of several factors on the accuracy of prediction models. FINDINGS: Literature search identified 584 prediction modeling studies, of which 89 were included. 10.4% of the total studies included prediction models internally validated (n = 61), 4.6% models externally validated (n = 27), and 0.2% (n = 1) models considered for implementation. Across validated prediction modeling studies (n = 88), 18.2% were diagnostic, 68.2% prognostic, and 13.6% predictive. The most frequently investigated condition was psychosis (36.4%), and the most frequently employed predictors clinical (69.5%). Unimodal compared to multimodal models (ß = .29, P = .03) and diagnostic compared to prognostic (ß = .84, p < .0001) and predictive (ß = .87, P = .002) models were associated with increased accuracy. INTERPRETATION: To date, several validated prediction models are available to support the diagnosis and prognosis of psychiatric conditions, in particular, psychosis, or to predict treatment response. Advancements of knowledge are limited by the lack of implementation research in real-world clinical practice. A new generation of implementation research is required to address this translational gap.

Annual Research Review: Prevention of psychosis in adolescents - systematic review and meta-analysis of advances in detection, prognosis and intervention.

BACKGROUND: The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established. METHODS: We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age <18 years). Findings were systematically appraised around core themes: detection, prognosis and intervention. We performed meta-analyses (employing Q statistics and I 2 test) regarding the proportion of CHR-P subgroups, the prevalence of baseline comorbid mental disorders, the risk of psychosis onset and the type of interventions received at baseline. Quality assessment and publication bias were also analysed. RESULTS: Eighty-seven articles were included (n = 4,667 CHR-P individuals). Quality of studies ranged from 3.5 to 8 (median 5.5) on a modified Newcastle-Ottawa scale. Detection: Individuals were aged 15.6 ± 1.2 years (51.5% males), mostly (83%) presenting with attenuated positive psychotic symptoms. CHR-P psychometric accuracy improved when caregivers served as additional informants. Comorbid mood (46.4%) and anxiety (31.4%) disorders were highly prevalent. Functioning and cognition were impaired. Neurobiological studies were inconclusive. PROGNOSIS: Risk for psychosis was 10.4% (95%CI: 5.8%-18.1%) at 6 months, 20% (95%CI: 15%-26%) at 12 months, 23% (95%CI: 18%-29%) at 24 months and 23.3% (95%CI: 17.3%-30.7%) at ≥36 months. INTERVENTIONS: There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy. CONCLUSIONS: It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required.

Universal and selective interventions to promote good mental health in young people: Systematic review and meta-analysis.

Promotion of good mental health in young people is important. Our aim was to evaluate the consistency and magnitude of the efficacy of universal/selective interventions to promote good mental health. A systematic PRISMA/RIGHT-compliant meta-analysis (PROSPERO: CRD42018088708) search of Web of Science until 04/31/2019 identified original studies comparing the efficacy of universal/selective interventions for good mental health vs a control group, in samples with a mean age <35 years. Meta-analytical random-effects model, heterogeneity statistics, assessment of publication bias, study quality and sensitivity analyses investigated the efficacy (Hedges' g=effect size, ES) of universal/selective interventions to promote 14 good mental health outcomes defined a-priori. 276 studies were included (total participants: 159,508, 79,142 interventions and 80,366 controls), mean age=15.0 (SD=7.4); female=56.0%. There was a significant overall improvement in 10/13 good mental health outcome categories that could be meta-analysed: compared to controls, interventions significantly improved (in descending order of magnitude) mental health literacy (ES=0.685, p<0.001), emotions (ES=0.541, p<0.001), self-perceptions and values (ES=0.49, p<0.001), quality of life (ES=0.457, p=0.001), cognitive skills (ES=0.428, p<0.001), social skills (ES=0.371, p<0.001), physical health (ES=0.285, p<0.001), sexual health (ES=0.257, p=0.017), academic/occupational performance (ES=0.211, p<0.001) and attitude towards mental disorders (ES=0.177, p=0.006). Psychoeducation was the most effective intervention for promoting mental health literacy (ES=0.774, p<0.001) and cognitive skills (ES=1.153, p=0.03). Physical therapy, exercise and relaxation were more effective than psychoeducation and psychotherapy for promoting physical health (ES=0.498, p<0.001). In conclusion, several universal/selective interventions can be effective to promote good mental health in young people. Future research should consolidate and extend these findings.

Impact of coronavirus syndromes on physical and mental health of health care workers: Systematic review and meta-analysis.

BACKGROUND: Health care workers (HCW) are at high risk of developing physical/mental health outcomes related to coronavirus syndromes. Nature and frequency of these outcomes are undetermined. METHODS: PRISMA/MOOSE-compliant (PROSPERO-CRD42020180205) systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-. Proportion random effect meta-analyses, I2 statistic, quality assessment and sensitivity analysis. RESULTS: 115 articles were included (n=60,458 HCW, age 36.1±7.1, 77.1% female). Physical health outcomes: 75.9% HCW infected by SARS/MERS/COVID-19 reported fever (95%CI=65.9-83.7%, k=12, n=949), 47.9% cough (95%CI=39.2-56.8%, k=14, n=970), 43.6% myalgias (95%CI=31.9-56.0%, k=13, n=898), 42.3% chills (95%CI=20.2-67.9%, k=7, n=716), 41.2% fatigue (95%CI=18.2-68.8%, k=6, n=386), 34.6% headaches (95%CI=23.1-48.2%, k=11, n=893), 31.2% dyspnoea (95%CI=23.2-40.5%, k=12, n=1003), 25.3% sore throat (95%CI=18.8-33.2%, k=8, n=747), 22.2% nausea/vomiting (95%CI=14.9-31.8%, k=6, n=662), 18.8% diarrhoea (95%CI=11.9-28.4%, k=9, n=824). Mental health outcomes: 62.5% HCW exposed to SARS/MERS/COVID-19 reported general health concerns (95%CI=57.0-67,8%, k=2, n=2254), 43.7% fear (95%CI=33.9-54.0%, k=4, n=584), 37.9% insomnia (95%CI=30.9-45.5%, k=6, n=5067), 37.8% psychological distress (95%CI=28.4-48.2%, k=15, n=24,346), 34.4% burnout (95%CI=19.3-53.5%, k=3, n=1337), 29.0% anxiety features (95%CI=14.2-50.3%, k=6, n=9191), 26.3% depressive symptoms (95%CI=12.5-47.1%, k=8, n=9893), 20.7% post-traumatic stress disorder features (95%CI=13.2-31%, k=11, n=3826), 16.1% somatisation (95%CI=0.2-96.0%, k=2, n=2184), 14.0% stigmatisation feelings (95%CI=6.4-28.1%, k=2, n=411). LIMITATIONS: Limited amount of evidence for some outcomes and suboptimal design in several studies included. CONCLUSIONS: SARS/MERS/COVID-19 have a substantial impact on the physical and mental health of HCW, which should become a priority for public health strategies.

Applications of Developmental Psychopathology.

Developmental psychopathology studies the basic mechanisms, including not only biological factors but also environmental and social factors that may interact with them, by means of which developmental pathways deviate toward pathological or typical outcomes. Family studies conducted during the last century show substantial evidence of heritability among psychiatric disorders. Besides, a large number of genes implicated in shaping the development of the central nervous system have been related to psychiatric conditions. In addition, there is a wide range of stressors and harmful agents that, when acting on sensitive developmental periods, might damage brain function and generate or precipitate psychopathology over time. All these factors have the potential to change the way disorders with a neurodevelopmental origin are expressed, including their age of appearance and clinical manifestations. Both symptoms and social impairment need to be considered in clinical evaluations, as treatment is unlikely to be effective if the problem has not been characterized correctly or if the patients' particular characteristics, which change throughout development, are not taken into consideration.