L'espace vécu and Its Perturbations in Schizophrenia: Systematic Review and Meta-analysis of Altered Body-Centric Metrics-Personal and Peripersonal Space.

Subtle distortions of the experience of lived space have long been associated with schizophrenia. Although a body-centric transformation of space is considered an essential component of anomalous subjective experience in schizophrenia, its impact on the 2 major body-centric spatial constructs, that is, personal space (PS) and peripersonal space (PPS), is still not clear. This systematic review and meta-analysis have been set up to: (1) summarize the evidence on putative extensional differences of PS and PPS in schizophrenia as compared with controls, and (2) evaluate the quality and the limitations of available studies on the topic. Four electronic literature databases (MEDLINE, EMBASE, PsychINFO, and CINAHL) were searched with the keywords "Personal space OR Interpersonal distance AND Schizophrenia," "Peripersonal space AND Schizophrenia" from inception until December 31, 2023, resulting in 15 studies on PS and 5 studies on PPS included in this systematic review. The 12 studies on PS included in the meta-analysis revealed that individuals with a diagnosis of schizophrenia place a larger interpersonal distance from the stimuli than controls, with a moderate effect size in both the fixed-effect model (Hedges' g = 0.558 [95% confidence interval, CI: 0.445-0.671]; z = 9.67; P < 0.0001) and the random effects model (0.547 [0.294-0.799]; z = 4.77; P = 0.0006). The 5 studies included in the meta-analysis on PPS showed that individuals with a diagnosis of schizophrenia exhibit a narrower PPS than the controls at the fixed-effect (Hedges' g = 1.043 [95%CI: .739-1.348]; z = 6.72; P < .0001), but not at the random effects model (1.318 [-0.721 to 3.359]; z = 1.79; P = .147). Heterogeneity was substantial in both meta-analyses. Overall, the findings indicate that both body-centered space constructs (PS and PPS) are affected in schizophrenia, with an enlargement PS and a reduction PPS, thereby supporting the distinction of these constructs. These modifications cohere with the subjective transformation of the lived space (aka espace vécu) reported in classical psychopathology and may be promising, neurodevelopmentally grounded, biomarkers of vulnerability to schizophrenia and its spectrum conditions.

Early detection and intervention through the lens of the neurodevelopmental framework: the salience of developmental years and related services.

Broadening prediction efforts from imminent psychotic symptoms to neurodevelopmental vulnerabilities can enhance the accuracy of diagnosing severe mental disorders. Early interventions, especially during adolescence, are vital as these disorders often follow a long prodromal phase of neurodevelopmental disturbances. Child and adolescent mental health services should lead a developmentally-sensitive model for timely, effective detection and intervention.

Schizophrenia spectrum disorders in children and adolescents: Clinical, phenomenological, diagnostic, and prognostic features across subtypes.

Schizophrenia spectrum disorders (SSD) typically have a diagnostically recognizable onset in young adulthood, yet it is not unusual that help-seeking due to initial SSD-related clinical manifestations emerge in earlier developmental phases, such as childhood and adolescence. Varieties of SSD manifestations in children and adolescents can be distinguished according to variations in clinical expressivity, severity and timing (i.e. developmental stage). Some individuals may reach the full clinical threshold for a diagnosis of schizophrenia according to the same descriptive diagnostic criteria used for adults, and in this case, it's possible to distinguish a pre-pubertal onset in childhood (aka Very Early Onset Schizophrenia, VEOS) and a post-pubertal onset in adolescence (aka Early Onset Schizophrenia, EOS). Other individuals may not reach such clinically overt diagnostic threshold but nonetheless present Childhood Schizotypal Disorder (CSD) or a Clinical High-Risk for Psychosis (CHRP). While EOS is clinically more similar to the canonical adult-onset presentation, the other 3 subgroups (i.e. VEOS, CSD, CHRP) present more nuances and specific clinical characteristics, which require ad-hoc developmental and phenomenological considerations for appropriate differential diagnosis and prognosis. Therefore, current scoping review intends to saturate such knowledge gap with respect to early SSD-phenotypes.

Multiple complex developmental disorder (MCDD): Did we throw the baby out with the bathwater too fast? A systematic review.

BACKGROUND: Multiple complex developmental disorder (MCDD) manifests as early-onset impairment across different domains. Although it could appear as a transitional condition between autism and childhood-onset schizophrenia, interest in MCDD has progressively waned. This study attempts to discern MCDD current relevance to avoid "throwing the baby out with the bathwater" too fast. METHODS: All available studies published up to January 2024 were retrieved and evaluated following on the PRISMA guidelines for systematic reviews using the term "multiple complex developmental disorder" or "MCDD", without any filter for study design nor year of publication. RESULTS: Only 16 studies were included and analyzed. Overall, a variable heterogeneity was observed in terms of country of investigation, study design, and clinical groups. Most of the included studies explored the construct of MCDD in developmental age, comparing MCDD mostly with autistic patients, and observing how the former group had higher levels of paranoia, illusions, and psychotic thoughts, whereas the latter showed more frequently difficulties in social interactions and stereotypical behaviors. CONCLUSION: Overall, these results showed how progressive changes in diagnostic criteria over time led MCDD to be abandoned as nosographic construct, leaving perhaps a diagnostic void between autism and psychotic disorders that needs to be further studied. A systematic review on the Multiple Complex Developmental Disorder (MCDD): a forgotten diagnosis between autism and schizophrenia.

Multiple complex developmental disorder (MCDD) seems to have covered in the past years a grey area between autism and schizophrenia with onset in childhood, as it includes some symptoms usually observed in the former condition (dysregulation of affectivity, impairment in social interactions) and some in the latter (behavioral disorganization and thought problems, such as bizarre ideas, paranoid concerns, or magical thinking). This systematic review aims at summarizing the published scientific literature about the MCDD, wondering whether it is worth reconsidering its current relevance. In over 20 years (from 1993 to 2015) only 16 studies dealt with the topic, with a great heterogeneity in terms of country of investigation, study design, and clinical groups. Most of the studies compared MCDD with autism, trying to outline clinical differences between the two conditions. This information may help child psychiatrists and other mental health professionals reflect about those "weird" young patients they usually visit in their practice, and whose diagnosis appears not centered because they do not completely fulfill the diagnostic criteria of autism or schizophrenia.

Ontogenesis of self-disorders in the schizophrenia spectrum: A phenomenological neuro-developmental model.

The concept of basic Self-disorders (SD) captures the experiential aspects associated with vulnerability to schizophrenia spectrum disorders (SSD). SD emerge prior to, and constitute the underlying structure for, the emergence of major diagnostic symptoms, including positive psychotic ones. SD are also detectable in populations with familial risk for SSD. This paper proposes a two-stage phenomenological-developmental model, exploring the early deficit in multisensory integration and their impact on the ontogeny of the Minimal Self in the first years of life. It also examines subsequent emergence of schizotaxic vulnerability, which later manifests as typical anomalies of subjectivity, such as basic symptoms and self-disorders.

Clinical High-Risk for Psychosis (CHR-P) circa 2024: Synoptic analysis and synthesis of contemporary treatment guidelines.

The construct of Clinical-High Risk for Psychosis (CHR-P) identifies young help-seeking subjects in putative prodromal stages of psychosis and is a central component of the Early Intervention (EI) paradigm in Mental Health, aimed at facilitating rapid entry into appropriate care pathways to prevent the onset of psychosis or mitigate is biopsychosocial consequences. This approach, which promotes an innovative culture of care for early, at risk situations, is inspired by a clinical staging concept as a guide to optimal treatment. The objective of this article is to map the existing guidelines in the field of CHR-P treatment recommendations, examine overlaps and differences, and critically evaluate blind spots to be addressed in future guideline updated. The search identified 9 guidelines focused on CHR-P or schizophrenia and other psychotic conditions but containing a specific section on CHR-P or prodromal psychosis. All guidelines acknowledge that psychosis is preceded by more or less pronounced prodromal stages, and most detail CHR-P criteria. Among guidelines, 8 out of 9 indicate cognitive-behavioural therapy as the best psychotherapeutic option and 7 out of 9 suggest that antipsychotics can be prescribed as second option in case psychosocial and/or other pharmacological interventions prove insufficient or inadequate in reducing clinical severity and subjective suffering. Antidepressants, mood stabilizers, and benzodiazepines were considered for the treatment of comorbid disorders. Only the European Psychiatric Association Guidance paper distinguished treatment recommendations for adults and minors. Agreements in treatment guidelines were discussed in light of recent meta-analytical evidences on pharmacological and non-pharmacological treatments for CHR-P, suggesting the need to provide an updated, age-sensitive consensus on how to manage CHR-P individuals.

Baseline Antipsychotic Dose and Transition to Psychosis in Individuals at Clinical High Risk: A Systematic Review and Meta-Analysis.

Importance: Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics is associated with an increased risk of transitioning to psychosis in individuals at clinical high-risk for psychosis (CHR-P) and that such effect is not a result of pretest risk enrichment. However, to maximize its translational utility for prognostic stratification in clinical practice, testing for the potential presence of a dose-response association is crucial. Objective: To test whether the negative prognostic effect of baseline antipsychotic exposure in individuals at CHR-P follows a dose-effect pattern, as indicated by mean chlorpromazine equivalent doses (CPZ-ED). Data Sources: MEDLINE and Cochrane Library, performed up to August 31, 2023, searching for English-language studies on individuals at CHR-P reporting data on exposure to antipsychotics at baseline and detailed information on dosage by transition status. Study Selection: Studies that provided information on antipsychotic exposure at baseline and included detailed dosage data categorized by transition status. Data Extraction and Synthesis: Eligible studies were identified following PRISMA guidelines and evaluated independently by 2 reviewers with the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses. Main Outcomes and Measures: The primary outcome was transition to psychosis in individuals at CHR-P who were receiving antipsychotic treatment at baseline, measured by baseline mean CPZ-ED in individuals at CHR-P who transitioned to psychosis compared to those who did not. Results: Eight studies were included in the systematic review and meta-analysis. Among 290 individuals at CHR-P (mean [SD] age, 19.4 [2.6] years) who were exposed to antipsychotics at baseline and remained in contact up to the completion of the study, 66 converted to psychosis and 224 did not. The mean CPZ-ED ranged 60 to 395 mg/d in those who converted and 13 to 224 mg/d in those who did not. Those who converted to psychosis had higher CPZ-ED than those who did not in both the common-effects model (Hedges g, 0.41; 95% CI, 0.12-0.70; z, 2.78; P = .005) and in the random-effects model (Hedges g, 0.41; 95% CI, 0.15-0.67; z, 3.69; P = .008; τ2, 0.0). There was no relevant heterogeneity (Cochran Q, 3.99; df, 7; P = .78; I2, 0.0%; 95% CI, 0.0-68.0). The radial plot indicated a good fit of the model. Conclusions and Relevance: In individuals at CHR-P who were exposed to antipsychotics at baseline, those receiving higher antipsychotic doses demonstrated an increased likelihood of transitioning to psychosis. This meta-analytic evidence of putative dose-effect association confirms that baseline antipsychotic exposure and the corresponding dosage carry salient prognostic information that could improve current CHR-P criteria-based risk stratification at inception.

Debate: The prevention of psychosis in child and adolescent mental health services.

Psychopathological conditions in adolescence and young adulthood often result from an altered neurodevelopment already phenotypically expressed in childhood. Child and adolescent mental health services are ideally placed to intercept in the developmental trajectories of younger adolescents and contribute to the early detection of a risk for psychosis, as proposed by Salazar de Pablo and Arango (2023, Child and Adolescent Mental Health), opening a debate to which we contribute. The early detection of a specific risk for psychosis and of a broader risk for severe mental illness requires an understanding of the clinical staging of psychosis, neurodevelopmental antecedents of severe mental illness and of heterotypic trajectories between childhood phenotypes and adult disorders.

Baseline antipsychotic prescription and short-term outcome indicators in individuals at clinical high-risk for psychosis: Findings from the Parma At-Risk Mental States (PARMS) program.

AIM: The prognostic prediction of outcomes in individuals at clinical high-risk for psychosis (CHR-P) is still a significant clinical challenge. Among multiple baseline variables of risk calculator models, the role of ongoing pharmacological medications has been partially neglected, despite meta-analytical evidence of higher risk of psychosis transition associated with baseline prescription exposure to antipsychotics (AP) in CHR-P individuals. The main aim of the current study was to test the hypothesis that ongoing AP need at baseline indexes a subgroup of CHR-P individuals with more severe psychopathology and worse prognostic trajectories along a 1-year follow-up period. METHODS: This research was settled within the 'Parma At-Risk Mental States' program. Baseline and 1-year follow-up assessment included the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). CHR-P individuals who were taking AP medications at entry were included in the CHR-P-AP+ subgroup. The remaining participants were grouped as CHR-P-AP-. RESULTS: Hundred and seventy-eight CHR-P individuals (aged 12-25 years) were enrolled (91 CHR-P-AP+, 87 CHR-P-AP-). Compared to CHR-P AP-, CHR-P AP+ individuals had older age, greater baseline PANSS 'Positive Symptoms' and 'Negative Symptoms' factor subscores and a lower GAF score. At the end of our follow-up, CHR-P-AP+ subjects showed higher rates of psychosis transition, new hospitalizations and urgent/non-planned visits compared to CHRP- AP- individuals. CONCLUSIONS: In agreement with increasing empirical evidence, also the results of the current study suggest that AP need is a significant prognostic variable in cohorts of CHR-P individuals and should be included in risk calculators.

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis.

BACKGROUND: Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap. METHODS: Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome. RESULTS: Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7-39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38-4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I2 = 0.0% (95% CI 0.0-79%). Quality was good in four studies. CONCLUSIONS: Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria.

The temporal dynamics of transition to psychosis in individuals at clinical high-risk (CHR-P) shows negative prognostic effects of baseline antipsychotic exposure: a meta-analysis.

Meta-analytic evidence indicates that baseline exposure to antipsychotics (AP) in individuals at clinical high-risk for psychosis (CHR-P) is associated with an even higher risk of transition to psychosis. However, the temporal dynamics of such prognostic effect have not been clarified yet. This study was therefore designed to address this knowledge gap. We performed a systematic review and meta-analysis of all longitudinal studies published up to 31 December 2021 on CHR-P individuals identified according to a validated diagnostic procedure and reporting numeric data of transition to psychosis according to baseline antipsychotic exposure. 28 studies covering a total of 2405 CHR-P were included. 554 (23.0%) were exposed to AP at baseline, whereas 1851 (77.0%) were not. At follow-up (12 to 72 months), 182 individuals among AP-exposed (32.9%; 95% CI: 29.4% to 37.8%) and 382 among AP-naive CHR-P (20.6%; 18.8% to 22.8%) developed psychosis. Transition rates increased over time, with the best-fit for an ascending curve peaking at 24 months and reaching then a plateau, with a further increase at 48 months. Baseline AP-exposed CHR-P had higher transition risk at 12 months and then again at 36 and 48 months, with an overall higher risk of transition (fixed-effect model: risk ratio = 1.56 [95% CI: 1.32-1.85]; z = 5.32; p < 0.0001; Random-effect model: risk ratio = 1.56 [95% CI: 1.07-2.26]; z = 2.54; p = 0.0196). In conclusion, the temporal dynamics of transition to psychosis differ in AP-exposed vs. AP-naive CHR-P. Baseline AP exposure in CHR-P is associated with a persistently higher risk of transition at follow up, supporting the rationale for more stringent clinical monitoring in AP-exposed CHR-P. The insufficiency of more granular information in available primary literature (e.g., temporal and quantitative details of AP exposure as well as psychopathological dimensions in CHR-P) did not allow the testing of causal hypotheses on this negative prognostic association.

Anhedonia and suicidal ideation in young people with early psychosis: Further findings from the 2-year follow-up of the ReARMS program.

Hedonic deficits have been extensively studied in schizophrenia, but little is known about their association with suicidal ideation in early psychosis. The aim of this research was to examine the relationship between anhedonia and suicidal thoughts across a 2-year follow-up period in people with First Episode Psychosis (FEP) and at Ultra High Risk (UHR) of psychosis. Ninty-six UHR and 146 FEP, aged 13-35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Beck Depression Inventory-II (BDI-II). The BDI-II "Anhedonia" subscale score to assess anhedonia and the CAARMS "Depression" item 7.2 subscore to measure depression were used across the 2 years of follow-up. Hierarchical regression analyses were performed. No difference in anhedonia scores between FEP and UHR individuals was found. In the FEP group, a significant enduring association between anhedonia and suicidal ideation was found at baseline and across the follow-up, independent of clinical depression. In the UHR subgroup, the enduring relationship between anhedonia and suicidal thoughts were not completely independent from depression severity. Anhedonia is relevant in predicting suicidal ideation in early psychosis. Specific pharmacological and/or psychosocial interventions on anhedonia within specialized EIP program could reduce suicide risk overtime.