OBJECTIVE: Knowledge of outcome in psychotic illness is limited by the paucity of very long-term epidemiologically representative studies of incidence first episode psychosis (FEP) cohorts that measur

The gap

Consensus across the literature

Supporting evidence — 3 representative gaps

• Medium-term Prediction of Clinically-relevant Outcomes in First-episode Schizophrenia Patients (2026) · doi

  The study on patients with first-episode schizophrenia had several limitations that may affect the interpretation of results. Using a sample size of only 68 patients could limit the generalizability of the findings. Additionally, excluding patients with an organic mental disorder, intellectual disability, substance addiction, and onset at age >40 may have further restricted generalizability. The modest sample size was also the reason for using linear models rather than incorporating more complex relationships. However, the highly nonlinear dependencies were addressed by transforming the input variables after exploratory data analysis, as in the case of DUP, which was logarithmically transformed. The study focused on predicting three outcome measures, potentially overlooking other important outcome indicators. Moreover, retrospective data collection may have introduced errors or bias. Finally, selection bias may have occurred because only patients who completed all three visits were included. These limitations should be taken into account when interpreting the study's results.

  Keywords: patients limitations using sample size generalizability three outcome bias first episode schizophrenia several affect interpretation
• The iHOPE-20 study: Relationships between and prospective predictors of remission, clinical recovery, personal recovery and resilience 20 years on from a first episode psychosis (2019) · doi

  OBJECTIVE: Knowledge of outcome in psychotic illness is limited by the paucity of very long-term epidemiologically representative studies of incidence first episode psychosis (FEP) cohorts that measure and compare outcomes reflecting modern clinical practice, mental health policy and research agendas.

  Keywords: objective knowledge outcome psychotic illness limited paucity long term epidemiologically representative incidence first episode psychosis
• Early deviations from normative brain morphology and cortical microstructure in schizophrenia spectrum disorders (2026) · doi

  Several limitations must be acknowledged. First, the primary inclusion criterion was the diagnosis of SSD, which predominantly included schizophrenia but also other psychotic disorders so we cannot specify the results for each disorder. Second, given the limited effect sizes reported here, larger cohorts may be needed to validate subtler associations or subgroup effects. Third, the cross- sectional design limits our ability to draw conclusions about developmental trajectories. Longitudinal studies are required to characterize the progression of microstructural changes over time and evaluate their potential utility as prognostic markers. Fourth, given the low SANS scores observed in our patient sample, the statistical power to detect associations with negative symptoms was lower than for the other symptom dimensions explored in this study. Fifth, although hospitalization and its duration may reasonably correlate with first- episode severity, they are also influenced by patient-specific factors, clinical features, and institutional practices. Consequently, hospitalization should not be interpreted as a direct measure of severity. CONCLUSIONS In summary, our findings provide converging evidence that early-stage psychosis is characterized by a distinct pattern of structural alterations involving cortical, subcortical, and WM alterations. Raw cMD showed the highest sensitivity to positive symptoms and was associated with key clinical features at the first episode, including hospitalization and overall illness severity. While reductions in CT, ventricular enlargement, and increased cortical diffusivity were prominent, weaker effect sizes were found in DWM. The differential correlations between symptom dimensions and structural features support the presence of medRxiv preprint doi: https://doi.org/10.64898/2026.01.09.26343760 ; this version posted June 26, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . distinct neurobiological mechanisms underlying positive, negative, and global psychopathology. These results emphasize the need for multidimensional clinical assessment and suggest that early deviations from normative brain structure, together with alterations in raw cMD measures, may reflect microstructural and macrostructural abnormalities associated with SSD.

  Keywords: first hospitalization severity clinical features alterations preprint given effect sizes associations conclusions microstructural patient negative