Exploring parenthood in first episode of psychosis: the potential role of the offspring in the outcome of women.

PURPOSE: The study aimed to explore the role of parenthood at first episode of psychosis (FEP) on recovery, with a focus on potential sex differences. METHODS: Sociodemographic, clinical, and neurocognitive information was considered on 610 FEP patients form the PAFIP cohort (Spain). Baseline and three-year follow-up comparisons were carried out. Chi-square tests and ANCOVA analysis were performed controlling for the effect of age and years of education. RESULTS: Men comprised 57.54% of the sample, with only 5.41% having offspring when compared to 36.29% of women. Parenthood was related to shorter duration of untreated illness (DUI) in women with children (12.08 months mothers vs. 27.61 months no mothers), showing mothers better premorbid adjustment as well. Childless men presented the worst premorbid adjustment and the highest cannabis and tobacco consumption rates. Mothers presented better global cognitive function, particularly in attention, motor dexterity and executive function at three-year follow-up. CONCLUSIONS: Diminished parental rates among FEP men could be suggested as a consequence of a younger age of illness onset. Sex roles in caregiving may explain the potential role of parenthood on premorbid phase, with a better and heathier profile, and a more favorable long-term outcome in women. These characteristics may be relevant when adjusting treatment specific needs in men and women with and without offspring.

Education and long-term outcomes in first episode psychosis: 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Lower levels of education have been associated with the development of psychosis. Investigating educational achievement in the first episode of psychosis (FEP) patients may shed light on the origins of the alterations and on the variability of outcomes in psychotic disorders. METHODS: Education achievement was explored in a large sample (n = 659) of FEP patients enrolled in programa de atención a fases iniciales de psicosis (PAFIP), a research and assistance program conducted in Spain. Patients were stratified according to the Spanish educational system according to their attendance in primary (low), secondary (medium) or university studies (high). The three groups were compared on available premorbid, clinical and neuropsychological variables. A subgroup of patients (n = 209), comprising the 10-year follow-up PAFIP cohort, were again compared. RESULTS: Overall, 49% and 37% of FEP patients had low and medium levels of education, respectively. In total, 13% of the patients with a higher level of education were more frequently women (64%) and older at illness onset (36 years old), reported better premorbid adjustment, presented less severe positive symptoms and better functioning; and showed higher premorbid intelligence quotient and better performance on all the explored cognitive domains. Ten years later the FEP patients in the medium- and high-education groups had good global functioning and a neurocognitive performance within the normal limits. CONCLUSIONS: Higher education is associated with better initial conditions and more favourable outcomes after an FEP. Sharing this information with the world's educational systems is essential to targeting resources and designing innovative programs or strategies to compensate for student difficulties.

Cognitive reserve as a moderator of outcomes in five clusters of first episode psychosis patients: a 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes. METHODS: Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups. RESULTS: The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning. CONCLUSIONS: CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Ten-year course of cognition in first-episode non-affective psychosis patients: PAFIP cohort.

BACKGROUND: A large body of research states that cognitive impairment in schizophrenia is static. Nevertheless, most previous studies lack a control group or have small study samples or short follow-up periods. METHOD: We aimed to address these limitations by studying a large epidemiological cohort of patients with first-episode schizophrenia spectrum disorders and a comparable control sample for a 10-year period. RESULTS: Our results support the generalized stability of cognitive functions in schizophrenia spectrum disorders considering the entire group. However, the existence of a subgroup of patients characterized by deteriorating cognition and worse long-term clinical outcomes must be noted. Nevertheless, it was not possible to identify concomitant factors or predictors of deterioration (all Ps > 0.05). CONCLUSIONS: Cognitive functions in schizophrenia spectrum disorder are stable; however, a subgroup of subjects that deteriorate can be characterized.

Overlap between genetic variants associated with schizophrenia spectrum disorders and intelligence quotient: a systematic review.

BACKGROUND: To study whether there is genetic overlap underlying the risk for schizophrenia spectrum disorders (SSDs) and low intelligence quotient (IQ), we reviewed and summarized the evidence on genetic variants associated with both traits. METHODS: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and preregistered it in PROSPERO. We searched the Medline databases via PubMed, PsycInfo, Web of Science and Scopus. We included studies in adults with a diagnosis of SSD that explored genetic variants (single nucleotide polymorphisms [SNPs], copy number variants [CNVs], genomic insertions or genomic deletions), estimated IQ and studied the relationship between genetic variability and both traits (SSD and IQ). We synthesized the results and assessed risk of bias using the Quality of Genetic Association Studies (Q-Genie) tool. RESULTS: Fifty-five studies met the inclusion criteria (45 case-control, 9 cross-sectional, 1 cohort), of which 55% reported significant associations for genetic variants involved in IQ and SSD. The SNPs more frequently explored through candidate gene studies were in COMT, DTNBP1, BDNF and TCF4. Through genome-wide association studies, 2 SNPs in CHD7 and GATAD2A were associated with IQ in patients with SSD. The studies on CNVs suggested significant associations between structural variants and low IQ in patients with SSD. LIMITATIONS: Overall, primary studies used heterogeneous IQ measurement tools and had small samples. Grey literature was not screened. CONCLUSION: Genetic overlap between SSD and IQ supports the neurodevelopmental hypothesis of schizophrenia. Most of the risk polymorphisms identified were in genes relevant to brain development, neural proliferation and differentiation, and synaptic plasticity.

Dissecting the functional outcomes of first episode schizophrenia spectrum disorders: a 10-year follow-up study in the PAFIP cohort.

BACKGROUND: The aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach. METHOD: A large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored. RESULTS: The cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes. CONCLUSIONS: The current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.

Neuroanatomical abnormalities in first-episode psychosis across independent samples: a multi-centre mega-analysis.

BACKGROUND: Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples. METHODS: Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. RESULTS: FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease - gyrus rectus - was negatively correlated with the severity of positive and negative symptoms. CONCLUSIONS: This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.

Stability of schizophrenia diagnosis in a 10-year longitudinal study on first episode of non-affective psychosis: Conclusions from the PAFIP cohort.

OBJECTIVE: To evaluate the 10-year stability of schizophrenia diagnosis in a cohort of first-episode psychosis (FEP) patients and the factors associated with it. METHODS: Changes in diagnosis of 209 FEP patients were described during 10 years of follow-up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through binary logistic regressions, ROC and survival curves. RESULTS: Out of the 209 patients, 126 were diagnosed of schizophrenia 6 months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126 schizophrenia patients had changed to a different diagnosis after 10 years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow-up. Retrospectively, out of the 154 patients with schizophrenia in the 10-year assessment, 36 had a different diagnosis at baseline, and those factors related to a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis. CONCLUSIONS: Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after 10 years.

Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone.

BACKGROUND: Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. METHOD: From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. CONCLUSIONS: Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.

Expression and Functionality Study of 9 Toll-Like Receptors in 33 Drug-Naïve Non-Affective First Episode Psychosis Individuals: A 3-Month Study.

Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-naïve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1-9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1-9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-α) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory response.

Premorbid adjustment as predictor of long-term functionality: Findings from a 10-year follow-up study in the PAFIP-cohort.

The literature indicates that patients with schizophrenia spectrum disorders often show deficits in premorbid adjustment. Additionally, these impairments have been correlated with critical disease parameters, evident in both early and advanced stages. The principal objective of this study was to investigate the association between premorbid adjustment and functional outcomes a decade following the initial episode of psychosis. A cluster analysis was performed to group patients according to their premorbid adjustment scores as assessed with the Premorbid Adjustment Scale (PAS). The measurements of The Disability Assessment Scale (DAS), The Global Assessment of Function (GAF) scale, ​​and The Quality of Life Scale (QLS) were used to compare the functionality of the groups at a 10-year follow-up. A total of 231 patients were classified into three groups based on their premorbid adjustment: "good PAS", "deteriorating PAS", and "chronically poor PAS". The three groups differed significantly in their sociodemographic and cognitive baseline characteristics. At the 10-year follow-up, "good PAS" group had better scores than the other groups in the variables of functionality and quality of life. The relationship found between premorbid adjustment and long-term functional results in patients with psychosis can help us predict the evolution of patients and act accordingly.

Familiality of the Intelligence Quotient in First Episode Psychosis: Is the Degree of Family Resemblance Associated With Different Profiles?

BACKGROUND AND HYPOTHESIS: There is uncertainty about the relationship between the family intelligence quotient (IQ) deviation and the risk for schizophrenia spectrum disorders (SSD). This study tested the hypothesis that IQ is familial in first episode psychosis (FEP) patients and that their degree of familial resemblance is associated with different profiles. STUDY DESIGN: The participants of the PAFIP-FAMILIAS project (129 FEP patients, 143 parents, and 97 siblings) completed the same neuropsychological battery. IQ-familiality was estimated through the Intraclass Correlation Coefficient (ICC). For each family, the intra-family resemblance score (IRS) was calculated as an index of familial similarity. The FEP patients were subgrouped and compared according to their IRS and IQ. STUDY RESULTS: IQ-familiality was low-moderate (ICC = 0.259). A total of 44.9% of the FEP patients had a low IRS, indicating discordancy with their family-IQ. Of these patients, those with low IQ had more schizophrenia diagnosis and a trend towards poorer premorbid adjustment in childhood and early adolescence. Whereas FEP patients with low IQ closely resembling their family-IQ were characterized by having the lowest performance in executive functions. CONCLUSIONS: The deviation from the familial cognitive performance may be related to a particular pathological process in SSD. Individuals with low IQ who do not reach their cognitive familial potential show difficulties in adjustment since childhood, probably influenced by environmental factors. Instead, FEP patients with high phenotypic family resemblance might have a more significant genetic burden for the disorder.

Sex differences in cognitive reserve among first episode of psychosis patients.

INTRODUCTION: Cognitive reserve (CR) has recently been considered a key factor in the onset of a first episode of psychosis (FEP). However, the differences in CR in FEP patients according to sex have not yet been investigated. MATERIAL AND METHODS: CR was estimated among 443 FEP patients (246 men and 197 women) and 156 healthy controls (96 men and 60 women) by using the proxies premorbid IQ, years of education and employment status. A neuropsychological battery was administrated to measure neurocognitive specific domains. Analyses of variance were used to make comparisons between groups. RESULTS: FEP women had greater CR than FEP men. This circumstance was not observed in healthy controls. Among the group of patients with low CR, FEP women outperformed FEP men in the cognitive domains verbal memory and processing speed. Meanwhile, among the FEP patients with high CR, men showed better performance in attention than women. CONCLUSIONS: Differences in CR observed between FEP men and women could be related to a number of specific factors, such as, age at illness onset, education level, and variability in performance in verbal memory, processing speed, and attention domains. These results provide background information about CR in FEP patients that will be useful in the design of sex specific cognitive remediation interventions.

A Proxy Approach to Family Involvement and Neurocognitive Function in First Episode of Non-Affective Psychosis: Sex-Related Differences.

Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a subdomain of family support, namely, family involvement (estimated through a proxy measure), cognitive functioning, and sex in first-episode psychosis (FEP) patients. The sample included 308 patients enrolled in the Program for Early Phases of Psychosis (PAFIP), divided into 4 groups based on their estimated family involvement (eFI) level and sex, and compared on various variables. Women presented lower rates of eFI than men (37.1% and 48.8%). Higher eFI was associated with better cognitive functioning, particularly in verbal memory. This association was stronger in women. The findings suggest that eFI may be an important factor in FEP patients' cognitive functioning. This highlights the importance of including families in treatment plans for psychotic patients to prevent CD. Further research is needed to better understand the complex interplay between family support, sex, and cognitive functioning in psychotic patients and develop effective interventions that target these factors.

Intelligence quotient changes over 10 years: Diversity of cognitive profiles in first episode of psychosis and healthy controls.

OBJECTIVE: This study aimed to analyse whether intelligence quotient (IQ) improves, declines, or remains stable over 10 years among FEP patients and healthy subjects. METHODS: A group of FEP patients enrolled in a Program of First Episode Psychosis in Spain called PAFIP, and a sample of Healthy Controls (HC) completed the same neuropsychological battery at baseline and approximately 10 years later, which included the WAIS vocabulary subtest to estimate premorbid IQ and 10-year IQ. Cluster analysis was performed separately in the patient group and the HC group to determine their profiles of intellectual change. RESULTS: One hundred and thirty-seven FEP patients were grouped into five clusters: "Improved low IQ" (9.49 % of patients), "Improved average IQ" (14.6 %), "Preserved low IQ" (17.52 %), "Preserved average IQ" (43.06 %), and "Preserved high IQ" (15.33 %). Ninety HC were grouped into three clusters: "Preserved low IQ" (32.22 % of the HC), "Preserved average IQ" (44.44 %), and "Preserved high IQ" (23.33 %). The first two clusters of FEP patients, characterized by a low IQ, earlier age at illness onset, and lower educational attainment, showed a substantial cognitive improvement. The remaining clusters demonstrated cognitive stability. CONCLUSIONS: The FEP patients showed intellectual improvement or stability, but no decline post-onset of psychosis. However, their profiles of intellectual change are more heterogeneous than that of HC over 10 years. Particularly, there is a subgroup of FEP patients with a significant potential for long-term cognitive enhancement.

Longitudinal effects of cannabis use on attentional processes in patients with first episode of psychosis.

BACKGROUND: Attention deficits have been considered to be a central characteristic of schizophrenia-spectrum disorders. However, the specific interactions with, and longitudinal effects of, cannabis use at the different stages of the disorder remain unknown. Due to the high percentage of patients who are cannabis users at the onset of the disease, our objective was to explore this relationship and how it evolves in the first three years of the disease. METHOD: A total of 461 patients with a first episode of psychosis (FEP) and 187 healthy controls were studied. The differences between cannabis users and non-users at baseline were explored based on both sociodemographic variables and performance in neuropsychological tests of attention. The interaction between cannabis, attentional, and clinical variables was followed up at 3 years. RESULTS: Of the 648 participants included in this study, 229 (35.34%) were cannabis users. Of them, 187 (40.6%) were patients and 42 (22.5%) were healthy controls. At baseline, control groups [cannabis users (N = 42); non-users (N = 145)] outperformed the patient groups [cannabis users (N = 187); non-users (N = 274)] in all attention tasks. Longitudinal analyses showed significant improvements in the attentional domains at 3-year follow-up, mainly in the group of patients who had never used cannabis (N = 238), followed by ex-users (N = 105), and persistent users (N = 43). At 3-year follow-up, the group of ex-users was the one that achieved scores closer to those of healthy controls. CONCLUSION: FEP patients, both cannabis users and non-users, showed attention deficits. However, the patients who had never used cannabis fared better than cannabis users.

Trauma and psychosis: The mediating role of premorbid adjustment and recent stressful events in a 3-year longitudinal study.

BACKGROUND: Some of the most-studied environmental factors that can contribute to the development of psychosis are the adversities experienced at an early age. Among these, childhood interpersonal trauma (CIT) has been considered especially influential in the onset of the disease. The aim of the study was to explore the relationship between CIT and the first episode of psychosis (FEP), as well as the relationship between CIT and clinical and functional outcomes 3 years after illness onset. METHODS: A total of 278 patients with a FEP and 52 healthy controls were studied. Logistic regression analysis was carried out to examine the explained variation by CIT at the beginning of psychosis. Recent stressful events and premorbid adjustment related to CIT, were introduced in path analyses to determine their mediating effects between CIT and the disease and its clinical and functional results. RESULTS: Mediation analyses showed that CIT was indirectly associated with belonging to the FEP group through recent stressful events (Effect = 0.981; SE = 0.323; CI = 0.485 to 1.761). Premorbid academic adjustment in late adolescence mediated the relationship between CIT and clinical and functional outcomes, specifically in the measurements of the Scales for Assessment of Positive and Negative Symptoms, in the Brief Psychiatric Rating Scale, and in the Disability Assessment Scale. CONCLUSIONS: These findings suggest that early traumatic experiences play an important role in the FEP. Early intervention that promotes good academic adjustment during adolescence and/or avoids retraumatisation could positively impact both the onset and the course of psychotic illness.