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.

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

Importance Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding. Observations The first theme considered is the role of early-life environmental and genetic risk factors in altering neurodevelopmental trajectories to predispose an individual to the disorder and leading to the development of prodromal symptoms. The second theme is the role of cortical excitatory-inhibitory imbalance in the development of the cognitive and negative symptoms of the disorder. The third theme considers the role of psychosocial stressors, psychological factors, and subcortical dopamine dysfunction in the onset of the positive symptoms of the disorder. The final theme considers the mechanisms underlying treatment for schizophrenia and common adverse effects of treatment. Conclusions and Relevance Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D2receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2753514/jamapsychiatry_mccutcheon_2019_rv_190002.pdf

Schizophrenia-An Overview

Objective Evidence syntheses such as systematic reviews and meta-analyses provide a rigorous and transparent knowledge base for translating clinical research into decisions, and thus they represent the basic unit of knowledge in medicine. Umbrella reviews are reviews of previously published systematic reviews or meta-analyses. Therefore, they represent one of the highest levels of evidence synthesis currently available, and are becoming increasingly influential in biomedical literature. However, practical guidance on how to conduct umbrella reviews is relatively limited. Methods We present a critical educational review of published umbrella reviews, focusing on the essential practical steps required to produce robust umbrella reviews in the medical field. Results The current manuscript discusses 10 key points to consider for conducting robust umbrella reviews. The points are: ensure that the umbrella review is really needed, prespecify the protocol, clearly define the variables of interest, estimate a common effect size, report the heterogeneity and potential biases, perform a stratification of the evidence, conduct sensitivity analyses, report transparent results, use appropriate software and acknowledge the limitations. We illustrate these points through recent examples from umbrella reviews and suggest specific practical recommendations. Conclusions The current manuscript provides a practical guidance for conducting umbrella reviews in medical areas. Researchers, clinicians and policy makers might use the key points illustrated here to inform the planning, conduction and reporting of umbrella reviews in medicine.

https://ebmh.bmj.com/content/ebmental/21/3/95.full.pdf

Ten simple rules for conducting umbrella reviews

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20693

Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

Importance Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohend = 0.57) or educational functioning (Cohend = 0.21), social functioning (Cohend = 1.25), and quality of life (Cohend = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohend = 0.35) and negative symptoms (Cohend = 0.39) as well as low functioning (Cohend = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2762529/jamapsychiatry_fusarpoli_2020_rv_190007.pdf

Prevention of Psychosis: Advances in Detection, Prognosis, and Intervention

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20490

Hyi Yenn Thoo

Papers

What Causes Psychosis? An Umbrella Review of Risk and Protective Factors