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.

Autism spectrum disorder and obstetric optimality: a twin study and meta-analysis of sibling studies.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a strong genetic basis. Recent studies have suggested that its aetiology is also influenced by environmental factors. Some of the most examined environmental factors are obstetric complications. However, the results are inconsistent. METHODS: We aimed to explore the association between obstetric complications and autism in a population-based twin sample using the Obstetric Enquiry Scale (OES), a scale that measures the presence or absence of pre-, peri- and neonatal factors. Additionally, we report the meta-analytic results for obstetrical factors reported in previously published sibling studies. RESULTS: Our study included 115 cases pairs and 62 controls pairs and showed that children with autism and their unaffected co-twins present significantly more obstetric complications than controls (ASD vs. controls ß 1.26, CI 95% 1.11-1.40 p < .001; unaffected co-twin vs. controls ß 1.20, 95% CI 1.07-1.36 p < .003). However, we did not find statistically significant differences between children with ASD and their unaffected co-twins (ß .96, 95% CI 0.85-1.09, p 0.55). Meta-analysis demonstrated that maternal hypertension (RR 1.35, CI 95% 1.23-1.48), uterine bleeding (RR 1.20 CI 95% 1.01-1.42) and exposure to antibiotic during pregnancy (1.11 CI 95% 1.00-1.22) increase risk of ASD. CONCLUSIONS: This study confirms that children with ASD and their unaffected twins show more obstetric complications than controls. However, these complications do not distinguish between ASD twins and their unaffected co-twins. In addition, the meta-analysis showed little influence of birth factors on ASD which suggests a shared familial liability for both obstetric complications and autism, rather than a causal association.

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.

Developmental Differences Between Schizophrenia and Bipolar Disorder.

Ample evidence supports a neurodevelopmental origin in some cases of schizophrenia (SZ). More inconsistent information is available for bipolar disorder (BD). We herein review studies with a focus on premorbid (adjustment and functionality) and early developmental milestones that include both SZ and BD patients. A search was performed in the PubMed electronic database, retrieving 619 abstracts; 30 were ultimately included in this systematic review. Eight prospective cohorts, 15 retrospective studies, and 7 studies based on national registries. Psychomotor developmental deviations and general adjustment problems characterize the childhood of subjects later diagnosed with SZ or BD; they are more marked in those later diagnosed with SZ vs BD, earlier onset vs later onset, and psychotic vs nonpsychotic disorders. Cognitive impairment follows a linear risk trend for SZ and a U-shaped trend for BD. Social isolation and visuoperceptual/reading anomalies more frequently antecede SZ. Pervasive developmental disorders increase the risk for both SZ and BD, more so in cases with normal intelligence. The predictive risk of each isolated developmental marker is low, but a significant percentage of subjects with SZ and a minority of adults with BD showed signs of premorbid abnormalities in childhood. The great limitation is still the lack of studies comparing SZ and BD that include psychotic and nonpsychotic bipolar cases separately. There are many cases, even in childhood/adolescent SZ, where no premorbid anomalies are found, and immunological disorders or other etiologies should be searched for. At least in cases with clear neurodevelopmental markers, rare genetic variants should be investigated.