How can research benefit children of parents with severe mental illness? The FAMILY consortium, an EU-funded study, aims to understand the intergenerational transmission of mental illness risk by examining the interactions between genetics and the environment, and therefore, improve early intervention and mental health care. Severe mental illnesses (SMI), such as schizophrenia, bipolar disorder, and major depressive disorder, are among the most disabling health conditions worldwide. (1) Despite decades of research, their causes remain complex and only partially understood. One of the most informative approaches to uncovering the etiology, i.e., the origination, of these disorders has been the study of children born to parents with severe mental illness. Studies of ‘familial high-risk offspring’ offer a unique window into how genetics, the environment, and development interact over time, increasing the risk of developing a mental illness or, importantly, strengthening resilience. The FAMILY consortium, an interdisciplinary, multisite study funded by the European Union, builds on this approach. It focuses on understanding and predicting the so-called ‘intergenerational transmission’ of risk for mental illness. (3)

Preventive interventions for young help-seekers at clinical high risk for psychosis (CHR-P) critically depend on the progressive improvement of risk stratification. However, there is evidence that the transparent reporting of relevant variables plausibly affecting longitudinal outcomes (e.g. pre-assessment pharmacological exposure) remains suboptimal. In this study we focused on familial high-risk (FHR) for severe mental illness in CHR-P studies, as regards reporting habits, prevalence and possible role in the transition to psychosis. We performed a systematic review and meta-analysis on studies published on Medline and the Cochrane Library on CHR-P individuals with possible transition as outcome, and published from inception to March 31, 2024. The literature review identified 93 independent samples. Up to 26

Comments on the article by Caspi et al. (see record 2026-80066-001). The general psychopathology factor, or p-factor, has emerged as a latent structure capturing shared liability across mental disorders. However, it may reflect more than statistical covariance and instead index a developmental vulnerability architecture, an emergent feature shaped by genetic, social, and environmental interactions over time. Viewed in this way, the p-factor represents the trace of a deeper risk process unfolding across generations. This perspective supports integrative models of psychopathology and motivates transdiagnostic, network-based approaches to prediction and prevention. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Converging evidence indicates that schizophrenia reshapes the embodied structure of subjectivity, profoundly altering how individuals experience their bodies and surrounding space. This Perspective proposes a neurodevelopmental framework linking measurable distortions of personal space (PS) and peripersonal space (PPS) to deeper phenomenological disruptions of lived spatiality. Experimental findings consistently show an enlarged PS and a contracted PPS, maybe reflecting an excessive feeling of overexposure as well as a diminished sense of possible spatial enactment of bodily capacities. These anomalies likely stem from early neurodevelopmental disturbances in multisensory integration and sensorimotor learning. Phenomenological psychopathology further reveals how such spatial disorganization manifests as instability in self-world boundaries and a pervasive sense of altered atmosphere. Integrating neurodevelopmental, cognitive, and experiential dimensions provides a unified account of how schizotaxic vulnerability unfolds into spatial and Self-disturbances. This approach reframes embodiment and spatiality as developmental interfaces between neural processes and subjective transformation in schizophrenia.

BACKGROUND:Anomalous experiences at the mirror have been classically described in patients with schizophrenia and conceptualized as "mirror sign". Mirror and self-face-based paradigms offer a unique window into the experiential and cognitive architecture of self-disturbances in schizophrenia, yet empirical findings in this area remain scattered and heterogeneous. METHODS:This systematic review synthesizes experimental studies investigating mirror, self-face recognition, and enfacement-illusion tasks in individuals with schizophrenia or at clinical high-risk for psychosis. Four electronic databases (MEDLINE, Embase, PsycInfo, and CINAHL) were searched with the keywords "Schizophrenia" OR "Psychosis" AND "Enfacement illusion" OR "Mirror gazing" OR "Double mirror" OR "Self face recognition" from inception until 31 December 2024. RESULTS:The search identified 16 experimental studies. Patients consistently exhibited impairments in self-face recognition, altered self-other boundary processing, and increased anomalous experiences during mirror exposure. Illusion-based paradigms revealed attenuated typical enfacement effects alongside heightened misattribution tendencies, suggesting instability in multisensory integration. Mirror-gazing tasks elicited frequent perceptual distortions and self-estrangement phenomena, in line with phenomenological accounts of diminished self-presence. Clinical correlates were generally weak and inconsistent, although some studies indicated associations with positive symptoms and anomalous self-experiences. Methodological quality was overall low, with common limitations including small sample sizes, insufficient blinding, and heterogeneous outcome measures. CONCLUSIONS:Evidence may preliminary support the view that schizophrenia involves fundamental alterations in the dynamic integration between embodied and reflective self-representations. Mirror tasks could provide a promising experimental platform to probe these vulnerabilities, but more rigorous, standardized, and longitudinal research is needed to clarify their diagnostic and mechanistic relevance.

The Clinical High-Risk for Psychosis (CHR-P) paradigm underpins early detection strategies and informs the DSM-5 construct of Attenuated Psychosis Syndrome (APS), yet its discriminative predictive validity relative to CHR-P-negative help-seekers has not been systematically quantified. We conducted a systematic review and meta-analysis of longitudinal studies comparing transition to psychosis among help-seeking individuals according to CHR-P status. PubMed/MEDLINE and the Cochrane Library were searched from inception to June 22, 2026. Eligible studies included help-seeking samples assessed with validated CHR-P instruments and reporting psychosis transition outcomes separately for CHR-P-positive and CHR-P-negative participants. Random-effects meta-analyses estimated transition prevalence and relative risks (RRs), while heterogeneity, publication bias, and moderators were examined. 14 studies including 4477 participants (2220 CHR-P-positive and 2257 CHR-P-negative) met inclusion criteria. Estimated transition rates were 14.7% [95% CI, 9.7-21.7%) among CHR-P-positive individuals and 1.6% (95% CI, 0.8-3.2%) among CHR-P-negative individuals. CHR-P status was associated with an almost ten-fold increased risk of transition to psychosis (RR, 9.8; 95% CI, 4.5-21.82), with no significant moderation by follow-up duration or sample characteristics. These findings demonstrate strong discriminative and predictive validity of CHR-P criteria among help-seekers, supporting attenuated psychotic symptoms as a clinically meaningful pre-psychotic phenotype. Results support consideration of APS in DSM-6 within a prognostically grounded, stepped-care framework rather than as a categorical disorder.

OBJECTIVE:The clinical high-risk for psychosis (CHR-P) paradigm has been widely applied in child and adolescent mental health, yet its prognostic validity in adolescents remains debated. This study aimed to provide an updated meta-analysis of transition rates to psychosis in youth at CHR-P and to assess the influence of baseline antipsychotic (AP) exposure on transition outcomes. METHOD:A systematic review and meta-analysis was conducted following evidence-based guidelines (PROSPERO CRD420251064505). PubMed/MEDLINE and Cochrane Library were searched through August 30, 2025. Eligible studies included participants ≤18 years old or samples with mean age <18 years, defined CHR-P status with validated instruments, and reported longitudinal data on transition to psychosis. Transition prevalences were pooled using random-effects models. Subgroup analyses evaluated the impact of baseline AP exposure. RESULTS:The meta-analysis included twenty-eight independent cohorts comprising 2,951 CHR-P individuals, almost all in adolescence. Across studies restricted to minors, overall transition converged at ∼18%, while in past meta-analyses broader samples with mean age <18 years but including young adults reached ∼23%, approaching adult CHR-P estimates (∼25%). Baseline AP exposure was consistently associated with a higher risk of transition (risk ratio ≈1.5), supporting its role as a negative prognostic factor. CONCLUSION:CHR-P criteria demonstrate prognostic validity in developmental populations, with transition rates in adolescents comparable to young adult cohorts and significantly higher than in CHR-P-negative adolescents. In line with previous research in adult CHR-P, the need for AP treatment at baseline is substantially associated with an increased risk for transition. Future research should broaden prognostic focus beyond transition alone to capture remission, persistence, and functional outcomes in this vulnerable group. STUDY REGISTRATION INFORMATION:Transition rates to psychosis in children and adolescents at clinical high risk for psychosis: an updated meta-analysis; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251064505.

Baseline exposure to antipsychotics (AP) in individuals at clinical high risk for psychosis (CHR-P) has emerged as a robust prognostic marker for transition to psychosis. Recent meta-analyses show that CHR-P individuals receiving APs at study entry exhibit significantly higher transition rates, with a temporally discernible dose-effect pattern. To test the replicability of this prognostic signal, we conducted a secondary analysis of publicly available supplementary data from the PSYSCAN Consortium. Despite applying strict inclusion criteria that limited AP exposure to ≤30 days of low-dose treatment, transition rates in PSYSCAN remained higher in the AP-exposed group (28.0% vs. 12.2%; RR 2.29). Notably, this finding was not emphasized in the primary publication, thus representing inadvertent yet compelling support for the prognostic relevance of early AP need. These results reinforce the rationale for future CHR-P studies to adopt AP-naïve condition as a stratification criterion to avoid pharmacologically induced diagnostic obscuration and improve the precision of risk modelling. Furthermore, they corroborate the PSYSCAN-derived operational notion of transient pre-baseline AP exposure (TPAE) (i.e., ≤30 cumulative days in the 3 months preceding baseline, at subtherapeutic doses) as a pragmatic and testable prognostic specifier that supplements existing CHR-P criteria.

The field of Clinical High-Risk for Psychosis (CHR-P) is a dynamic area within contemporary psychiatry and serves as a crucial testing ground for precision prognostic models. Nonetheless, some foundational aspects remain inadequately conceptualized and consequently not transparently reported, such as baseline pharmacotherapy. A systematic review and meta-analysis were conducted by searching the MEDLINE and Cochrane Library databases for studies published up to August 31, 2024. Eligible studies included CHR-P samples, reported numeric data on outcomes at follow-up, and examined the transition to psychosis as an outcome. Data extraction adhered to PRISMA guidelines, focusing on baseline pharmacological exposure to antipsychotics, antidepressants, benzodiazepines, and mood stabilizers. A total of 95 studies were analyzed. The majority of studies (96.8 %) explicitly stated whether baseline exposure to antipsychotics was allowed as part of the inclusion criteria. However, actual baseline exposure to antipsychotics was quantified in only 60 % of these studies. Exposure to non-antipsychotic psychoactive therapies was reported in only a fraction of the studies (36.8 % for antidepressants, 16.8 % for benzodiazepines, and 14.7 % for mood stabilizers). In CHR-P longitudinal studies, the meta-analytic proportions of self-disclosed baseline pharmacological exposure ranged from 23.5 % to 24.5 % for antipsychotics, 28.5 % to 30.6 % for antidepressants, 11.2 % to 14.6 % for benzodiazepines, and 5.6 % to 5.9 % for mood stabilizers. Overall, a non negligible fraction of CHR-P participants is already under psychoactive pharmacological treatment at enrollment. The lack of consistent transparency in this respect may limit the effectiveness of prognostic models. Improved reporting practices are necessary to enhance precision in preventive psychiatry.

Background Diagnosis in psychiatry faces familiar challenges. Validity and utility remain elusive, and confusion regarding the fluid and arbitrary border between mental health and illness is increasing. The mainstream strategy has been conservative and iterative, retaining current nosology until something better emerges. However, this has led to stagnation. New conceptual frameworks are urgently required to catalyze a genuine paradigm shift.Methods We outline candidate strategies that could pave the way for such a paradigm shift. These include the Research Domain Criteria (RDoC), the Hierarchical Taxonomy of Psychopathology (HiTOP), and Clinical Staging, which all promote a blend of dimensional and categorical approaches.Results These alternative still heuristic transdiagnostic models provide varying levels of clinical and research utility. RDoC was intended to provide a framework to reorient research beyond the constraints of DSM. HiTOP began as a nosology derived from statistical methods and is now pursuing clinical utility. Clinical Staging aims to both expand the scope and refine the utility of diagnosis by the inclusion of the dimension of timing. None is yet fit for purpose. Yet they are relatively complementary, and it may be possible for them to operate as an ecosystem. Time will tell whether they have the capacity singly or jointly to deliver a paradigm shift.Conclusions Several heuristic models have been developed that separately or synergistically build infrastructure to enable new transdiagnostic research to define the structure, development, and mechanisms of mental disorders, to guide treatment and better meet the needs of patients, policymakers, and society.

Self-disorders (SD) designate a pattern of non-psychotic anomalous self-experiences, which specifically aggregate in clinical and subclinical forms of schizophrenia spectrum disorders (SSD), including familial high-risk configurations. SD have been corroborated as a valuable, quantitatively tractable, trait phenotype for indexing genetic liability to SSD, and, as a risk phenotype, they offer critical insights into the nature of these complex conditions which precede and shape the development of more overt clinical manifestations (including schizotypal features and positive, negative, and disorganized symptoms). In the last three decades, the concept of self-disorders has evolved from early clinical observations to a well-defined research domain, offering a nuanced understanding of schizophrenia spectrum vulnerabilities and holding promise for improving diagnostic accuracy, enhancing prognostic assessments, offering novel targets for intervention, and advancing our understanding of the schizophrenia spectrum.