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BackgroundGiven 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.MethodsWe 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.ResultsFrom 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 recommendationsWhile 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 course. Specifically, there is a compelling need to compare the relative benefits of lithium with other pharmacological agents in preventing recurrences. In addition to symptomatic outcomes, there should be a greater focus on functional impact and tolerability. Effective pharmacological and psychological interventions should be offered to those in early course of BD, balancing potential risks using shared decision-making approaches.

This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this case‒control 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for Treatment Response and Resistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICS Consensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27% female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serine racemase and serine-hydroxymethyltransferase 1, and higher levels of the glutamate-cysteine transporter 3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteine transporter 3 levels only in responders; this association was disrupted in the treatment resistant group. Treatment resistant patients and limited responders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials., (© 2024. The Author(s).)

Introduction: Some aspects of gender differences in patients with schizophrenia spectrum disorders (SSD) have been studied, especially in cross-sectional designs and with a short-term follow-up. However, only a few studies have considered the evolution during the follow-up of SSD patients according to their gender. In this study, we explore gender differences from the time of entry in an early intervention program for psychosis, up to three years follow-up., Methods: We conducted a prospective study including a cohort of 474 patients treated at the Treatment and Early Intervention in Psychosis (TIPP) program, 319 men and 155 women, having presented a first episode of psychosis (FEP). Data regarding premorbid and baseline sociodemographic, psychopathological and patient functioning, were collected. These data were reassessed longitudinally after 2, 6, 12, 18, 24, 30 and 36 months after entry in TIPP., Results: Regarding premorbid and baseline characteristics, woman developed threshold symptoms of a FEP 1 year later than men on average. Women were more likely to be married, men were more likely to live in pension or care home facility or to be homeless. Women displayed a higher rate of history of suicide attempts and exposure to childhood trauma, while men were more likely to have a forensic history, a history of abuse of alcohol and cannabis as well as a dependency to cannabis at the time of entry in TIPP. Regarding evolution, men were more prone to violent acts and were less likely to decrease their usage of substances. The longitudinal analysis highlighted that men displayed greater negative symptoms over the entire treatment period, lower functioning after 6 months and on all assessment points after. Both genders displayed similar rate of improvement in these 3 dimensions over time., Conclusion: Our study confirms that there are some gender differences in the early phase of psychosis that may require differentiation of assessment and treatment to improve recovery., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Frequently associated with early psychosis, depressive and manic dimensions may play an important role in its course and outcome. While manic and depressive symptoms can alternate and co-occur, most of the studies in early intervention investigated these symptoms independently. The aim of this study was therefore to explore the co-occurrence of manic and depressive dimensions, their evolution and impact on outcomes., Methods: We prospectively studied first-episode psychosis patients ( N = 313) within an early intervention program over 3 years. Based on latent transition analysis, we identified sub-groups of patients with different mood profiles considering both manic and depressive dimensions, and studied their outcomes., Results: Our results revealed six different mood profiles at program entry and after 1.5 years follow-up (absence of mood disturbance, co-occurrence, mild depressive, severe depressive, manic and hypomanic), and four after 3 years (absence of mood disturbance, co-occurrence, mild depressive and hypomanic). Patients with absence of mood disturbance at discharge had better outcomes. All patients with co-occurring symptoms at program entry remained symptomatic at discharge. Patients with mild depressive symptoms were less likely to return to premorbid functional level at discharge than the other subgroups. Patients displaying a depressive component had poorer quality of physical and psychological health at discharge., Conclusions: Our results confirm the major role played by mood dimensions in early psychosis, and show that profiles with co-occurring manic and depressive dimensions are at risk of poorer outcome. An accurate assessment and treatment of these dimensions in people with early psychosis is crucial.

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., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

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: The factorial structure of schizophrenia symptoms has been much debated but little is known on its degree of unicity, specificity as well as its dynamic over time. Symptom differentiation is a phenomenon according to which patients' symptoms could differentiate from one another during illness to form more independent, distinct dimensions. On the contrary, symptom dedifferentiation is an increase in the correlations between those symptoms over time. The goal of this study was to investigate symptom differentiation or dedifferentiation over time in recent onset psychosis using the Positive and Negative Syndrome Scale., Methods: A confirmatory factor analysis model based on the consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia was estimated on seven different time points over a three-year period. A general factor capturing common variance between every symptom was also included. Explained common variance was computed for the general factor and each specific factor., Results: Three hundred and sixty-two recent onset psychosis patients were assessed. Results showed no evidence for either symptom differentiation or dedifferentiation over time. Specific symptoms accounted for >70 % of the variance suggesting a high degree of specificity of the symptomatology., Conclusions: Overall, this study adds support for a highly multidimensional approach to clinical symptom assessment with an explicit focus on depression. The premise behind the staging approach being inherently one-dimensional, implications for further research is discussed., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The concept of affective psychosis regroups psychotic disorders with mood syndrome. Previous studies provided evidence to support a dichotomy between affective and non-affective psychoses although questions remain regarding the utility and validity of such a category to develop clinical guidelines. The aim of this study is to explore similarities and differences within affective psychoses to question whether strategies would apply to all the diagnoses falling under this umbrella term. Using Bayesian model comparison methods, we explored the homogeneity of the characteristics of first-episode affective patients (N = 77) treated in a specialized 3-year early intervention in psychosis programme. Our analysis revealed affective psychoses display many similarities regarding socio-demographic variables, the course of positive and manic symptoms over three years, and outcome at discharge. Our results did not support the heterogeneous model. However, despite no significant differences in the course of symptoms with the major depressive disorder group, the schizoaffective disorder group displayed a more severe clinical picture at the beginning of the programme and a poorer functional outcome than the two other groups. Absence of clear boundaries and the several similarities within affective psychoses suggest they can usefully be grouped to define treatment strategies that are easily legible by clinicians., (Copyright © 2022. Published by Elsevier B.V.)

Background: Considerable evidence on general population suggests that an "Affective pathway to psychosis", involving depression and anxiety dimensions, mediates the abuse-psychosis association. However, this has never been tested in Early Psychosis (EP) patients. We aim at testing whether severity of depressive and anxiety mediates the abuse-positive symptoms dyad in an EP prospective sample., Methods: 330 EP subjects aged 18-35 were assessed for psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Abuse was considered as facing at least one experience of physical, sexual, or emotional abuse before age 16. Positive psychotic symptoms and anxiety were measured with the Positive and Negative Syndrome Scale and depressive symptoms with the Montgomery-Asberg Depression Rating Scale. Mediation analyses were performed to study whether the abuse-positive symptom's link was mediated by depressive, anxiety, and a combination of anxiety/mood symptoms., Results: Among the 330 EP patient included, 104 (31.5% of the total) were exposed to abuse. Analyses across the 36 months of follow-up showed that depression and anxiety partially mediated 26.7% of the total effect of the abuse-positive symptoms association (indirect effects (IE) = 0.392 and 0.421 respectively), while the combined anxiety/mood model mediated 28.9% (IE = 0.475). Subanalyses at two and 36 months revealed a consistent role of depression, while that of anxiety was only present at baseline., Conclusion: Our work confirms a mediating role of mood and anxiety in the association between abuse and positive symptoms during the first three years of treatment., (Copyright © 2021. Published by Elsevier Ltd.)

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., (© 2021 John Wiley & Sons Australia, Ltd.)

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., (© 2021 John Wiley & Sons Australia, Ltd.)

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., (© 2021 John Wiley & Sons Australia, Ltd.)

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., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Service disengagement is a frequent problem in early intervention in psychosis. The goal of this study was to evaluate the rate and variables associated with service disengagement in a three year specialized program that allows treatment intensification on a case to case basis., Methods: 328 early psychosis patients were assessed at baseline on a large set of socio-demographic and clinical variables and were followed-up over 36 months. Patients who left the program for reasons related to engagement with care were compared to patients who completed the program., Results: Rates of disengagement were low (6.3%). Patients with lower socio-economic status, who committed offences during the program or with a diagnosis of Schizophreniform/brief psychotic disorder were more likely to disengage from the program., Conclusions: The engagement strategies implemented in the context of our early intervention programs have allowed to keep disengagements to a relatively low level. In this context, only 3 variables emerged to guide adaptation of the intervention in order to improve this already good engagement rate., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Substance-use disorder (SUD) was found to be an aggravating factor to delinquency and is closely related to personality disorders (PDs)., Objectives: The aim of this study was to investigate sex differences in the relationship between PD traits and SUD in adolescents institutionalized in child welfare and juvenile justice institutions., Methods: PD traits were measured dimensionally in a sample of 282 boys (69 with an SUD diagnosis) and 143 girls (45 with an SUD diagnosis) from child welfare and juvenile-justice institutions., Results: Logistic regressions showed that antisocial, borderline, and paranoid personality traits were positively associated with SUD, while obsessive compulsive personality traits were negatively related with SUD. Additionally, in institutionalized girls, self-defeating personality traits were associated with less risk of SUD., Conclusion: This study provides a relative evidence for sex specificities in the relation between PD traits and SUD.

Objectives: To evaluate tolerance and diagnostic yield of colonoscopy in elderly patients., Methods: We studied retrospectively 200 consecutive colonoscopies performed in patients older than 80 years (mean age: 83.5 +/- 3.1). We analyzed the following factors: indication, type and tolerance of the preparation, analgesia, tolerance of the procedure, information provided by the examination and therapeutic consequences., Results: The indications were: anaemia in 81 cases, change in bowel habits in 58 cases, rectal bleeding in 26 cases and others in 35 cases. Preparation (4.2 +/- 1.3 L Polyethylene-glycol) was good 150 times (75%), moderate 27 times and poor 23 times. It was tolerated well 122 times (61%) and poorly 78 times (39%). Sixty-six colonoscopies were performed without any analgesia, diazanalgesia was used in 108 cases, general anesthesia in 8 and diazepam and/or antispasmodics in 18. Tolerance of colonoscopy was good in 140 cases (70%), moderate in 37 cases and poor in 23 cases. Tolerance was better with analgesia than without (p < 0.001). The caecum was reached in 167 cases (83.5%). Colonoscopy was normal in 68 cases (34%). The lesions discovered were: 40 polyps larger than 10 mm, 41 diverticulosis, 29 cancers, 7 ischaemic colitis, 5 angiodysplasias, 5 sigmoiditis, 3 villous adenomas, 1 Bothriocephalus and 1 thermometric ulceration. A lesion responsible for the symptoms was diagnosed in 80 cases (40%). Diagnostic yield was better when indication was anaemia (52%) than change in bowel habits (24%) (p < 0.001). The lesions were treated endoscopically in 41 cases (38 polypectomies, 3 electrocoagulations) and surgically in 22 cases. Colonoscopy as well as its preparation were well tolerated in 93 cases (46.5%)., Conclusion: In a selected elderly population, colonoscopy was better tolerated with analgesia; large bowel preparation was often difficult. The diagnostic yield was relatively good. A multicentric prospective study is underway in order to determine the predictive criterias allowing an improvement of colonoscopic yield in the elderly.

We report two new cases, in the same family, of type B Niemann-Pick disease associated with sea-blue histiocytes syndrome. In one patient the disease was revealed by spontaneous rupture of the spleen. The sea-blue histiocytes syndrome is due to the histiocytes being overloaded by ceroids, and it usually occurs in a context of blood disease or thesaurismosis. Twenty-five cases of sea-blue histiocytes syndrome associated with type B Niemann-Pick disease have been reported, with rupture of the spleen in two of them. The link between the two conditions is the transformation into ceroids of the sphyngomyelin accumulated in histiocytes.

Thirty cases of clometacin-induced hepatitis were retrospectively collected over a nine-year period in hepatogastroenterological units of non university, public hospitals. There was a strong female predominance (90 percent). Clometacin (Dupéran) was taken because of arthritis in 8 out of 10 cases. Administration was continuous in 85 percent of cases and median duration was 445 days. median dose was 450 mg per day. Jaundice, fatigue, and weight loss were the most frequent symptoms, but edema, ascites and palmar erythema were not uncommon. Thrombopenia (38 percent) was the most frequent hematologic abnormality. Renal failure, always with benign course, was present in 1/4 of cases. Biochemical disorders indicated hepatocellular and cholestatic hepatitis in 3/4 and 1/4 of cases respectively. Hypoprothrombinemia below 50 percent was noted in 1 out of 6 cases, and was associated with death in half cases. Gamma-globulins were increased in 80 percent of cases, with a predominant increase of IgG. Antinuclear or anti-smooth muscle antibodies were present in 60 percent of cases, whereas antimitochondrial and antimicrosomes were absent. Histopathological examination of the liver biopsy specimens obtained in 25 patients showed acute hepatitis in 8 and chronic active hepatitis with fibrosis in 17--including 6 patients with cirrhosis; there were no epidemiological, clinical (except ascites), or biochemical differences between these two groups. Four of the 7 patients tested had HLA B8 antigens; they all had chronic active hepatitis, with autoantibodies in 3 cases. Median duration of hospitalization was 21 days. Hepatitis was directly responsible for death in 3 patients; biochemical sequelae (hypergammaglobulinemia or anicteric cholestasis) were present in 8 patients, 2 of whom most likely had cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)