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AIM: Reduction of duration of untreated psychosis (DUP) remains a key goal of early intervention programs. While a significant body of literature suggests that a short DUP has a positive impact on outcome, little is known regarding the threshold above which various dimensions of outcome are impaired. In this study, we explore the DUP threshold that best discriminates subgroups with poorer outcome regarding global functioning and quality of life after 3 years of treatment. METHOD: A total of 432 patients were followed-up prospectively over 3 years. Several hypothetical cut-off points for DUP were tested in order to maximize differences in effect size for quality of life and general functioning. RESULTS: While a DUP cut-off of 86 weeks defined two subpopulations with a difference of greatest effect size in quality of life after 3 years, it is already at a cut-off of 3 weeks of DUP that two subpopulations with a difference in global functioning of the greatest effect size was reached. CONCLUSION: DUP seems to have a differential impact on the various components of outcome, and in particular on quality of life and global functioning. Our data suggest that aiming at very short DUP is justified, but that DUP over 3 weeks are still compatible with good quality of life after 3 years of treatment.

Background: Given the likelihood of progressive illness in bipolar disorder (BD), it is important to understand the benefits and risks of interventions administered early in illness course. We conducted a systematic review of the effectiveness of interventions in the early course of BD I or II. Methods: We completed a systematic search on MEDLINE, PsycINFO, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL and Google Scholar from 1/1/1979 till 14/9/2022. We included controlled trials examining intervention effects on symptomatic, course, functional and tolerability outcomes of patients in the ‘early course’ of BD I or II. We classified patients to be in early course if they (a) were seeking help for the first time for a manic episode, (b) had a lifetime history of up to 3 manic episodes, or (c) had up to 6 lifetime mood episodes. Evidence quality was assessed using the GRADE approach. Results: From 4135 unique publications we included 25 reports representing 2212 participants in 16 randomized studies, and 17,714 participants from nine non-randomized studies. Available evidence suggested that in early illness course, lithium use was associated with lower recurrence risk compared with other mood stabilizers. Mood stabilizers were also associated with better global functioning, compared with the use of antipsychotics in the medium term. While summative findings regarding psychological therapies were limited by heterogeneity, family-focused and cognitive-behavioral interventions were associated with reduced recurrence risk or improved symptomatic outcomes. There was some evidence that the same pharmacological interventions were more efficacious in preventing recurrences when utilized in earlier rather than later illness course. Conclusions and recommendations: While there are promising initial findings, there is a need for more adequately powered trials to examine the efficacy and tolerability of interventions in youth and adults in early illness cou

AIM: Defining diagnosis is complex in early psychosis, which may delay the introduction of an appropriate treatment. The dichotomy of affective and non-affective psychosis is used in clinical setting but remains questioned on a scientific basis. In this study, we explore the clinical relevance of this dichotomy on the basis of clinical variables in a sample of first-episode psychosis patients. METHOD: We conducted a prospective study in a sample of 330 first-episode psychosis treated at an early intervention program. Affective and non-affective psychosis patients were compared on premorbid history, baseline data, outcomes and course of symptoms over the 3 years of treatment. RESULTS: Affective psychosis patients (22.42%) were more likely to be female, and had a shorter duration of untreated psychosis. The longitudinal analyses revealed that positive symptoms remained higher over the entire follow-up in the non-affective sub-group. A higher degree of variability of manic symptoms and a significantly better insight after 6 months were observed in the affective sub-group. No difference was observed regarding depressive and negative symptoms. At discharge, only the environmental quality of life and insight recovery were better in affective psychosis. CONCLUSIONS: Our study suggests that despite marginal differences at baseline presentation, these sub-groups differ regarding outcome, which may require differentiation of treatment and supports the utility of this dichotomy.

AIM: Premorbid history may have a major influence on the way patients cope with the onset of psychosis. This issue has been widely studied in the context of early intervention in schizophrenia but considerably less is known regarding affective psychosis. Our first goal was to investigate if subgroups could be identified among affective psychosis patients based on premorbid factors. Our second goal was to compare these subtypes according to the evolution of mood symptoms and outcomes at the end of the program. METHODS: We conducted a 3-year prospective study on a sample of 74 adults aged 18-35 with a first episode of affective psychosis. Latent class analysis (LCA) was used to reveal distinct exploratory subgroups within affective psychosis patients. RESULTS: Three distinct subgroups could be distinguished. One with later onset of psychosis mainly including women with more severe depressive symptoms in the first 6 months contrasting with two other subgroups with more severe manic symptoms all along the follow-up and earlier onset of psychosis, with or without many serious antecedents. The subgroup with many serious antecedents was more likely to require several hospitalizations, less likely to achieve recovery, especially regarding professional integration and return to premorbid general functioning. CONCLUSIONS: This study provides further evidence of poor functional recovery in the early phase of affective psychosis and shows that premorbid characteristics allow the identification of subgroups with distinct outcome which may require specification of treatment.

AIM: Personality disorder is a common co-occurrence ('comorbidity') among patients with bipolar disorder and appears to affect outcome negatively. However, there is little knowledge about the impact of this comorbidity in the early phases of bipolar disorder. We examined the prevalence and effect of personality disorder co-occurrence on outcome in a cohort of youth with first episode mania with psychotic features. METHODS: Seventy-one first episode mania patients, aged 15-29, were assessed at baseline, 6, 12, and 18 months as part of a randomized controlled trial of olanzapine and chlorpromazine as add-on to lithium in first episode mania with psychotic features. The current study involved secondary analysis of trial data. RESULTS: A co-occurring clinical personality disorder diagnosis was present in 16.9% of patients. Antisocial and narcissistic personality disorders were the most common diagnoses. Patients with co-occurring personality disorder had higher rates of readmission to hospital, lower rates of symptomatic recovery and poorer functional levels at 6 months, but these differences disappeared after 12 and 18 months. CONCLUSIONS: In the early phase of bipolar disorder, patients with personality disorder comorbidity display delayed symptomatic and functional recovery and increased likelihood to need hospital readmissions. These observations suggest that routine assessment for personality disorder and specific interventions are important in order to improve short-term treatment efficacy in this subgroup.

Traumatic events during childhood/early adolescence can cause long-lasting physiological and behavioral changes with increasing risk for psychiatric conditions including psychosis. Genetic factors and trauma (and their type, degree of repetition, time of occurrence) are believed to influence how traumatic experiences affect an individual. Here, we compared long-lasting behavioral effects of repeated social defeat stress (SD) applied during either peripuberty or late adolescence in adult male WT and Gclm-KO mice, a model of redox dysregulation relevant to schizophrenia. As SD disrupts redox homeostasis and causes oxidative stress, we hypothesized that KO mice would be particularly vulnerable to such stress. We first found that peripubertal and late adolescent SD led to different behavioral outcomes. Peripubertal SD induced anxiety-like behavior in anxiogenic environments, potentiated startle reflex, and increased sensitivity to the NMDA-receptor antagonist, MK-801. In contrast, late adolescent SD led to increased exploration in novel environments. Second, the long-lasting impact of peripubertal but not late adolescent SD differed in KO and WT mice. Peripubertal SD increased anxiety-like behavior in anxiogenic environments and MK-801-sensitivity mostly in KO mice, while it increased startle reflex in WT mice. These suggest that a redox dysregulation during peripuberty interacts with SD to remodel the trajectory of brain maturation, but does not play a significant role during later SD. As peripubertal SD induced persisting anxiety- and fear-related behaviors in male mice, we then investigated anxiety in a cohort of 89 early psychosis male patients for whom we had information about past abuse and clinical assessment during the first year of psychosis. We found that a first exposure to physical/sexual abuse (analogous to SD) before age 12, but not after, was associated with higher anxiety at 6-12 months after psychosis onset. This supports that childhood/peripuberty is a

BACKGROUND: While specialized early intervention programs represent the gold standard in terms of optimal management of first-episode psychosis (FEP), poor medication adherence remains a predominant unmet need in the treatment of psychosis. In this regard, an interaction between insight and adherence in FEP patients has been hypothesized but has been challenged by multiple pitfalls. METHODS: Latent profile analysis and trajectory modeling techniques were used to evaluate insight and adherence of 331 FEP patients engaged at the beginning, middle, and end of a 3-year specialized early psychosis program. A Bayesian model comparison approach was used to compare scores of clinical, functional, and socioeconomic outcomes at the end point of the study. RESULTS: Nearly one-third of the patients maintain a high level of insight and adherence during the entire program. At the end of the 3-year follow-up, more than three-quarters of patients are considered adherent to their medication. Patients with low levels of insight and adherence at the beginning of the program improve first in terms of adherence and then of insight. Furthermore, patients with high levels of insight and adherence are most likely to reach functional recovery and to experience an increase in environmental quality of life. CONCLUSIONS: Latent FEP subpopulations can be identified based on insight and adherence. Medication adherence was the first variable to improve, but a gain in insight possibly plays a role in the reinforcement of adherence.

BACKGROUND: Not all patients respond well to early interventions for their psychosis. The present study's goal was to evaluate whether patients' responses in the first six months of treatment in a specialised three-year programme could predict final outcomes. METHODS: 206 early psychosis patients were assessed at baseline, using a large set of sociodemographic and clinical variables, and then monitored for 36 months. Among those variables, changes in their Global Assessment of Functioning (GAF) scores during the first six months were used to predict outcomes after three years. RESULTS: Changes in GAF scores during the first six months were the only variables that predicted every symptom of functional outcome. GAF scores were also always the first or second most important predictor for every outcome. This finding held for both high- and low-functioning patients at baseline. CONCLUSIONS: Predicting poor long-term outcomes after only six months should help clinicians to improve treatments.

While first-episode schizophrenia has received extensive attention in the literature, few studies have focused on the first episode of affective psychoses. Considering the lack of structured data regarding this diagnostic grouping commonly used in clinical settings, our aim was to scope the literature on first-episode affective psychoses to consolidate current knowledge and to identify areas to be targeted in future studies. We also planned to investigate the relevance of the "affective psychosis" concept regarding diagnostic categories and specific needs of intervention. We conducted a search on the Embase, Medline, PubMed, PsycINFO and Web Of Science databases until October 2020. We selected studies and synthesized the key findings into a narrative review regarding major topics of early intervention research: diagnostic categorization, premorbid factors, intervention, duration of untreated illness, neurobiology and neurocognition. After screening 961 titles and abstracts and 193 full-text papers, we selected 77 studies for inclusion. Our results showed heterogeneity in diagnosis-related grouping under the concept of affective psychoses, especially variability regarding the inclusion of schizoaffective disorder. Nonetheless, this concept still encompasses patients with different psychopathological and neurocognitive profiles from the non-affective patients requiring specialized intervention. This study thus provided support for the relevance of this concept as well as a need for further investigation.