Individualized prediction models in ADHD: a systematic review and meta-regression.

There have been increasing efforts to develop prediction models supporting personalised detection, prediction, or treatment of ADHD. We overviewed the current status of prediction science in ADHD by: (1) systematically reviewing and appraising available prediction models; (2) quantitatively assessing factors impacting the performance of published models. We did a PRISMA/CHARMS/TRIPOD-compliant systematic review (PROSPERO: CRD42023387502), searching, until 20/12/2023, studies reporting internally and/or externally validated diagnostic/prognostic/treatment-response prediction models in ADHD. Using meta-regressions, we explored the impact of factors affecting the area under the curve (AUC) of the models. We assessed the study risk of bias with the Prediction Model Risk of Bias Assessment Tool (PROBAST). From 7764 identified records, 100 prediction models were included (88% diagnostic, 5% prognostic, and 7% treatment-response). Of these, 96% and 7% were internally and externally validated, respectively. None was implemented in clinical practice. Only 8% of the models were deemed at low risk of bias; 67% were considered at high risk of bias. Clinical, neuroimaging, and cognitive predictors were used in 35%, 31%, and 27% of the studies, respectively. The performance of ADHD prediction models was increased in those models including, compared to those models not including, clinical predictors (ß = 6.54, p = 0.007). Type of validation, age range, type of model, number of predictors, study quality, and other type of predictors did not alter the AUC. Several prediction models have been developed to support the diagnosis of ADHD. However, efforts to predict outcomes or treatment response have been limited, and none of the available models is ready for implementation into clinical practice. The use of clinical predictors, which may be combined with other type of predictors, seems to improve the performance of the models. A new generation of research should address these gaps by conducting high quality, replicable, and externally validated models, followed by implementation research.

What is the duration of untreated psychosis worldwide? - A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies.

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6-44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6-88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8-53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0-54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0-41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0-46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9-35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0-48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0-43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (ß = 0.836, p < 0.001), older publication year (ß = 0.404, p = 0.038) and higher proportion of non-White FEP patients (ß = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8-28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries.

Meta-analytic prevalence of comorbid mental disorders in individuals at clinical high risk of psychosis: the case for transdiagnostic assessment.

Comorbid mental disorders in subjects at clinical high risk for psychosis (CHR-P) may impact preventive care. We conducted a PRISMA/MOOSE-compliant systematic meta-analysis, searching PubMed/PsycInfo up to June 21st, 2021 for observational studies/randomized controlled trials reporting on comorbid DSM/ICD-mental disorders in CHR-P subjects ( protocol ). The primary and secondary outcomes were baseline and follow-up prevalence of comorbid mental disorders. We also explored the association of comorbid mental disorders compared with CHR-P versus psychotic/non-psychotic control groups, their impact on baseline functioning and transition to psychosis. We conducted random-effects meta-analyses, meta-regression, and assessed heterogeneity/publication bias/quality (Newcastle Ottawa Scale, NOS). We included 312 studies (largest meta-analyzed sample = 7834, any anxiety disorder, mean age = 19.98 (3.40), females = 43.88%, overall NOS > 6 in 77.6% of studies). The prevalence was 0.78 (95% CI = 0.73-0.82, k = 29) for any comorbid non-psychotic mental disorder, 0.60 (95% CI = 0.36-0.84, k = 3) for anxiety/mood disorders, 0.44 (95% CI = 0.39-0.49, k = 48) for any mood disorders, 0.38 (95% CI = 0.33-0.42, k = 50) for any depressive disorder/episode, 0.34 (95% CI = 0.30-0.38, k = 69) for any anxiety disorder, 0.30 (95% CI 0.25-0.35, k = 35) for major depressive disorders, 0.29 (95% CI, 0.08-0.51, k = 3) for any trauma-related disorder, 0.23 (95% CI = 0.17-0.28, k = 24) for any personality disorder, and <0.23 in other mental disorders (I2 > 50% in 71.01% estimates). The prevalence of any comorbid mental disorder decreased over time (0.51, 95% CI = 0.25-0.77 over 96 months), except any substance use which increased (0.19, 95% CI = 0.00-0.39, k = 2, >96 months). Compared with controls, the CHR-P status was associated with a higher prevalence of anxiety, schizotypal personality, panic, and alcohol use disorders (OR from 2.90 to 1.54 versus without psychosis), a higher prevalence of anxiety/mood disorders (OR = 9.30 to 2.02) and lower prevalence of any substance use disorder (OR = 0.41, versus psychosis). Higher baseline prevalence of alcohol use disorder/schizotypal personality disorder was negatively associated with baseline functioning (beta from -0.40 to -0.15), while dysthymic disorder/generalized anxiety disorder with higher functioning (beta 0.59 to 1.49). Higher baseline prevalence of any mood disorder/generalized anxiety disorder/agoraphobia (beta from -2.39 to -0.27) was negatively associated with transition to psychosis. In conclusion, over three-quarters of CHR-P subjects have comorbid mental disorders, which modulate baseline functionig and transition to psychosis. Transdiagnostic mental health assessment should be warranted in subjects at CHR-P.

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders.

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.

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.

Psychosis and substance abuse increase the COVID-19 mortality risk.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has been a global challenge. High mortality rates have been reported in some risk groups, including patients with pre-existing mental disorders. METHODS: We used electronic health records to retrospectively identify people infected due to COVID-19 (between March 2020 and March 2021) in the three territories of the Basque Country. COVID-19 cases were defined as individuals who had tested positive on a reverse transcription-polymerase chain reaction (PCR) test. Univariate and multivariate logistic regression models and multilevel analyses with generalized estimated equations were used to determine factors associated with COVID-19-related mortality and hospital admission. RESULTS: The COVID-19 mortality rate was increased for patients with psychotic disorders [odds ratio (OR) adjusted: 1.45, 95% confidence interval (CI) (1.09-1.94), p = 0.0114] and patients with substance abuse [OR adjusted: 1.88, 95% CI (1.13-3.14, p < 0.0152)]. The mortality rate was lower for patients with affective disorders [OR adjusted: 0.80, 95% CI (0.61-0.99), p = 0.0407]. Hospital admission rates due to COVID-19 were higher in psychosis [OR adjusted: 2.90, 95% CI (2.36-3.56), p < 0.0001] and anxiety disorder groups [OR adjusted: 1.54, 95% CI (1.37-1.72), p < 0.0001]. Among admitted patients, COVID-19 mortality rate was decreased for those with affective disorders rate [OR adjusted: 0.72, 95% CI (0.55-0.95), p = 0.0194]. CONCLUSIONS: COVID-19-related mortality and hospitalizations rates were higher for patients with a pre-existing psychotic disorder.

Prognostic accuracy and clinical utility of psychometric instruments for individuals at clinical high-risk of psychosis: a systematic review and meta-analysis.

Accurate prognostication of individuals at clinical high-risk for psychosis (CHR-P) is an essential initial step for effective primary indicated prevention. We aimed to summarise the prognostic accuracy and clinical utility of CHR-P assessments for primary indicated psychosis prevention. Web of Knowledge databases were searched until 1st January 2022 for longitudinal studies following-up individuals undergoing a psychometric or diagnostic CHR-P assessment, reporting transition to psychotic disorders in both those who meet CHR-P criteria (CHR-P + ) or not (CHR-P-). Prognostic accuracy meta-analysis was conducted following relevant guidelines. Primary outcome was prognostic accuracy, indexed by area-under-the-curve (AUC), sensitivity and specificity, estimated by the number of true positives, false positives, false negatives and true negatives at the longest available follow-up time. Clinical utility analyses included: likelihood ratios, Fagan's nomogram, and population-level preventive capacity (Population Attributable Fraction, PAF). A total of 22 studies (n = 4 966, 47.5% female, age range 12-40) were included. There were not enough meta-analysable studies on CHR-P diagnostic criteria (DSM-5 Attenuated Psychosis Syndrome) or non-clinical samples. Prognostic accuracy of CHR-P psychometric instruments in clinical samples (individuals referred to CHR-P services or diagnosed with 22q.11.2 deletion syndrome) was excellent: AUC = 0.85 (95% CI: 0.81-0.88) at a mean follow-up time of 34 months. This result was driven by outstanding sensitivity (0.93, 95% CI: 0.87-0.96) and poor specificity (0.58, 95% CI: 0.50-0.66). Being CHR-P + was associated with a small likelihood ratio LR + (2.17, 95% CI: 1.81-2.60) for developing psychosis. Being CHR-P- was associated with a large LR- (0.11, 95%CI: 0.06-0.21) for developing psychosis. Fagan's nomogram indicated a low positive (0.0017%) and negative (0.0001%) post-test risk in non-clinical general population samples. The PAF of the CHR-P state is 10.9% (95% CI: 4.1-25.5%). These findings consolidate the use of psychometric instruments for CHR-P in clinical samples for primary indicated prevention of psychosis. Future research should improve the ability to rule in psychosis risk.

Differential expression of MicroRNAs in Alzheimer's disease: a systematic review and meta-analysis.

Alzheimer's disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs' expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

The impact of COVID-19 lockdown on child and adolescent mental health: systematic review.

COVID-19 was declared a pandemic in March 2020, resulting in many countries worldwide calling for lockdowns. This study aimed to review the existing literature on the effects of the lockdown measures established as a response to the COVID-19 pandemic on the mental health of children and adolescents. Embase, Ovid, Global Health, PsycINFO, Web of Science, and pre-print databases were searched in this PRISMA-compliant systematic review (PROSPERO: CRD42021225604). We included individual studies reporting on a wide range of mental health outcomes, including risk and protective factors, conducted in children and adolescents (aged ≤ 19 years), exposed to COVID-19 lockdown. Data extraction and quality appraisal were conducted by independent researchers, and results were synthesised by core themes. 61 articles with 54,999 children and adolescents were included (mean age = 11.3 years, 49.7% female). Anxiety symptoms and depression symptoms were common in the included studies and ranged 1.8-49.5% and 2.2-63.8%, respectively. Irritability (range = 16.7-73.2%) and anger (range = 30.0-51.3%), were also frequently reported by children and adolescents. Special needs and the presence of mental disorders before the lockdown, alongside excessive media exposure, were significant risk factors for anxiety. Parent-child communication was protective for anxiety and depression. The COVID-19 lockdown has resulted in psychological distress and highlighted vulnerable groups such as those with previous or current mental health difficulties. Supporting the mental health needs of children and adolescents at risk is key. Clinical guidelines to alleviate the negative effects of COVID-19 lockdown and public health strategies to support this population need to be developed.

Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis.

BACKGROUND: Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes. METHODS: In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point. RESULTS: There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ. CONCLUSIONS: In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

Changes in telepsychiatry regulations during the COVID-19 pandemic: 17 countries and regions' approaches to an evolving healthcare landscape.

BACKGROUND: During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic. METHODS: We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020. RESULTS: Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic. CONCLUSIONS: Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.

Understanding source monitoring subtypes and their relation to psychosis: a systematic review and meta-analysis.

AIMS: Source monitoring (SM) is the metacognitive ability to determine the origin of one's experiences. SM is altered in primary psychiatric psychosis, although relationships between SM subtypes, other cognitive domains and symptoms are unclear. Our aims were to synthesize evidence comparing psychosis -with and without hallucinations- and healthy controls classifying SM subtypes by source discrimination (internal/external/reality monitoring) and stimulus modality (visual/auditory/imagined/performed). METHODS: This systematic review adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Meta-analyses Of Observational Studies in Epidemiology and Population, Intervention, Comparison and Outcomes guidelines. Core demographical and clinical parameters were extracted. Newcastle-Ottawa Scale was used as quality check. SM differences between (i) psychosis patients versus healthy controls and (ii) patients with versus without hallucinations were investigated via random-effect model meta-analysis. The primary effect size measure was standardized mean difference (SMD) in each SM subtype performance (error or accuracy). Heterogeneity, publication biases and meta-regressions were assessed. RESULTS: Five thousand two hundred and fifty-six records were screened to finally include 44 studies (1566 patients, 1175 controls). Mean Newcastle-Ottawa score was 7.41 out of 9. Few studies measured SM associations with cognition (n = 9) and symptoms (n = 19), with heterogeneous findings. SM performance across all measures was reduced in psychosis versus healthy controls (SMD = 0.458). Internal SM (SMD: errors = 0.513; accuracy = 0.733) and imagined stimuli (SMD: errors = 0.688; accuracy = 0.978) were specifically impaired. Patients with versus without hallucinations showed SM deficits only for externalizing (SMD = 0.410) and imagined/auditory (SMD = 0.498/0.277) errors. CONCLUSION: The proposed classifications highlight specific SM deficits for internal/imagined stimuli in psychosis, providing evidence-based indications to design and interpret future studies.

Affective symptom dimensions in early-onset psychosis over time: a principal component factor analysis of the Young Mania Rating Scale and the Hamilton Depression Rating Scale.

Early-onset psychosis (EOP) is a complex disorder characterized by a wide range of symptoms, including affective symptoms. Our aim was to (1) examine the dimensional structure of affective symptoms in EOP, (2) evaluate the predominance of the clinical dimensions and (3) assess the progression of the clinical dimensions over a 2-year period. STROBE-compliant prospective principal component factor analysis of Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale-21 (HDRS-21) at baseline, 6-months, 1-year and 2-year follow-up. We included 108 EOP individuals (mean age = 15.5 ± 1.8 years, 68.5% male). The factor analysis produced a four-factor model including the following dimensions: mania, depression/anxiety, sleep and psychosis. It explained 47.4% of the total variance at baseline, 60.6% of the total variance at 6-months follow-up, 54.5% of the total variance at 1-year follow-up and 49.5% of the total variance at 2-year follow-up. According to the variance explained, the mania factor was predominant at baseline (17.4%), 6-month follow-up (23.5%) and 2-year follow-up (26.1%), while the depression/anxiety factor was predominant at 1-year follow-up (23.1%). The mania factor was the most stable; 58.3% items that appeared in this factor (with a load > 0.4) at any time point appeared in the same factor at ≥ 3/4 time points. Affective symptoms are frequent and persistent in EOP. Mania seems to be the most predominant and stable affective dimension. However, depression and anxiety may gain predominance with time. A comprehensive evaluation of the dimensional structure and the progression of affective symptoms may offer clinical and therapeutic advantages.

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.

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.