Inge Winter - Academia.edu (original) (raw)

Papers by Inge Winter

The Lancet Psychiatry, 2018

The OPTiMiSE trial: a three-phase, double blind randomised switching study in first episode schiz... more The OPTiMiSE trial: a three-phase, double blind randomised switching study in first episode schizophrenia and schizophreniform disorder comparing amisulpride and olanzapine followed by open treatment with clozapine.

Schizophrenia Research, 2021

, C. (2021). The role of depression in the prediction of a "late" remission in first-episode psyc... more , C. (2021). The role of depression in the prediction of a "late" remission in first-episode psychosis: An analysis of the OPTiMiSE study. Schizophrenia Research,

Psychological Medicine

Background Negative symptoms are one of the most incapacitating features of Schizophrenia but the... more Background Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES). Methods T1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were com...

Social psychiatry and …, 2007

Knowledge of moderators of symptom improvement over time in acute mania improves predictability o... more Knowledge of moderators of symptom improvement over time in acute mania improves predictability of individual patient outcomes. This study attempted to identify such moderators of the rate of symptom improvement. In 3459 patients with high levels of mania in whom a change in psychotropic treatment was initiated and who were assessed six times over three months, clinical and social moderators of the rate of response were examined. Additionally, moderators of symptom improvement in individuals with high baseline levels of comorbid depression (n = 815) and psychosis (n = 1849) were identified. Within three months, mania symptoms were reduced by 52%, psychotic symptoms by 56% and depressive symptoms by 36%. High levels of baseline depression, greater illness severity in the past year, lower age of onset and rapid cycling reduced the rate of mania symptom improvement by 5-15%. Social variables indicating disadvantage similarly had negative contributions (5%-14%). Several reasons for change of medication involving patient choice, patient compliance, side effects and lack of effectiveness impacted negatively (reductions of 10%, 6%, 14% and 9% respectively). For the psychosis dimension, both low mania scores (22% reduction) and high depression scores (14% reduction) at baseline impacted negatively, whereas rate of reduction in depression was not conditional on baseline psychopathology. The rate of symptom improvement in acute mania is to a large extent conditional on the context as provided by the social, psychopathological and consumer environment. Understanding the context of treatment response offers valuable insights into treatment approaches aimed at moderation of traditional pharmacological interventions.

Schizophrenia Bulletin Open

Background Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation as dem... more Background Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation as demonstrated by elevated levels of C reactive protein (CRP) and pro-inflammatory cytokines. Aims The primary goal of this study was to investigate the association between pro-inflammatory biomarkers and clinical outcomes in unmedicated FEP patients. Method We used clinical data and biological samples from 289 FEP patients participating to the Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE) clinical trial. Patients were assessed at baseline and 4-5 weeks after treatment with amisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, Tumor Necrosis Factor (TNF)-α and CRP were measured. We first used multivariable regression to investigate the association between each of the four tested biomarkers and the following clinical outcomes: Positive And Negative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS), remission according to Andrea...

Biological Psychiatry Global Open Science

BMC Psychiatry

Background Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect o... more Background Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. Methods In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 alloca...

Journal of Affective Disorders Reports

European Neuropsychopharmacology

Schizophrenia Bulletin

Background An increasing body of evidence suggests that immune dysregulation is involved in the p... more Background An increasing body of evidence suggests that immune dysregulation is involved in the pathophysiology of psychotic disorders. Some, but not all, anti-inflammatory drugs have shown positive effects on symptom severity. Given the need for new treatment options in psychosis, anti-inflammatory medication should be explored as a potential treatment to improve outcome. Being a potent glucocorticosteroid that adequately passes through the blood-brain barrier, prednisolone qualifies as a potential candidate. This proof-of-concept study aims to explore the effect of prednisolone, compared to placebo, on symptom severity in patients with a psychotic disorder who are on a stable dose of antipsychotic medication. Methods The study was conducted from July 2015 until April 2019 in four centers in the Netherlands and Belgium. Patients with a psychotic disorder were randomized, double blind, 1:1 to prednisolone or placebo in addition to their antipsychotic treatment. Patients randomized t...

Schizophrenia Bulletin

Background Autistic phenotypic profiles in patients with schizophrenia are reportedly associated ... more Background Autistic phenotypic profiles in patients with schizophrenia are reportedly associated with poor outcomes, including higher odds of antipsychotic treatment failure. The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Autism Severity Scale (PAUSS) has been validated as a tool to identify “autistic profiles” in adolescents and adults with schizophrenia. We used the PAUSS (total score and subscores) to quantify autistic symptom load at different time points in a sample of patients with first episode schizophrenia (FES). We sought to investigate whether showing “prominent and persistent” autistic symptom load was associated with not achieving clinical remission at week 4 after the FES. Methods We analysed a subsample of FES patients from the OPTiMiSE study that was treated with amisulpride in an open-label design and had completed 4 weeks of follow-up. The selected subsample was composed of 55 individuals (27.3% female, mean age 25.6 (6.2) years) at “high-risk o...

European Neuropsychopharmacology

Schizophrenia Bulletin

Background: Very few prospective, sequential studies are available that could guide decisions whi... more Background: Very few prospective, sequential studies are available that could guide decisions which have to be made in every day clinical routine. Some of the simplest questions of clinicians remain unanswered. For example: If the first antipsychotic used has not worked, is switching to another drug effective? Or should we perhaps increase the dose? And when should we start clozapine, the most efficacious drug? These questions are most urgent for patients with a first episode of psychosis. Methods: OPTiMiSE is an international clinical trial, conducted in 27 research centers located in 14 countries across Europe and Israel. Among other purposes, OPTiMiSE was designed to test a three-stage treatment algorithm. The 446 participants of OPTiMiSE were diagnosed with a first episode of schizophrenia, schizophreniform or schizoaffective disorder. Each participant started with a 4-week open label amisulpride treatment. After these 4 weeks, non-remitters are randomized to switch to another antipsychotic versus continuation of amisulpride for 6 weeks, in a double-blind fashion (phase 2). After these additional 6 weeks, non-remitters were switched to clozapine for another 12 weeks. Results: Description of the sample: Mean age at inclusion was 26 years, 30% of the patient sample was female. The median duration of illness was 4 months and none of the participants had been using antipsychotic medication for more than 2 weeks. All patients were treated on a voluntarily basis. The patient sample was moderately ill at baseline, with a mean score on the Positive And Negative Syndrome Scale (PANSS) of 78 (sd 19). Phase 1 Patients started on 200-800 mg/day amisulpride treatment, with a target dose of 400 mg/day. Drop-out rate was 20%. Out of the 446 patients who were initiated on amisulpride, 56% met remission criteria, based on the eight remission items of the PANSS. Side effects were mild, with a mean weight increase of 2.7 kg (sd 3.3). Phase 2 At the end of phase 1, 121 patients did not meet remission criteria. Out of the 93 patients who continued into the double-blind treatment phase, 72 patients completed the 6-week treatment phase. Remission rate in phase 2 was 35%. There was no significant difference between the two treatment arms regarding remission rate, nor regarding the drop out rate. Patients randomized to olanzapine gained significantly more weight compared to amisulpride. Phase 3 At the end of phase 2, 40 patients did not meet remission criteria. Out of the 28 patients who continued into the open-label clozapine treatment phase, 18 patients completed this 12-week treatment from which only 5 patients met remission criteria, translating into a remission rate of only 18%. Non-remitters generally did improve to a great extent but failed to meet the stringent remission criteria. Discussion: Amisulpride is confirmed to be a good option for initiating pharmacotherapy in first episode patients, resulting in a high remission rate. There was no advantage related to remission rates or drop out rates for switching non-responders after 4 week of treatment to another antipsychotic versus continuing the initiated antipsychotic for another 6 weeks; continuing the first antipsychotic may have the benefit of avoiding new side effects related to introducing a new antipsychotic. Despite a low remission rate following clozapine treatment, non-remitters generally did show a substantial reduction in symptoms, demonstrating that clozapine should be an option for non-responding psychotic patients early in the illness.

Schizophrenia Bulletin

37 people with schizophrenia and 37 matched controls. In an independent living cohort, sICAM-1 wa... more 37 people with schizophrenia and 37 matched controls. In an independent living cohort, sICAM-1 was measured with a Luminex immunoassay from the plasma of 78 chronically ill patients with schizophrenia (all receiving antipsychotic medication) and 73 healthy controls. All participants from the living cohort received the following cognitive assessments: Wechsler Adult Intelligence Scale-3rd edition to assess current IQ, Controlled Oral Word Association Test verbal fluency and Wechsler Memory Scale-Revised to assess verbal memory. Pearson's or Spearman's correlations were performed between cognitive measures and sICAM1 levels as appropriate in schizophrenia patients and healthy controls. Results: ICAM-1 was elevated in the brains of people with schizophrenia relative to controls and CD163+ perivascular macrophages were found in the parenchyma. Peripheral sICAM1 was elevated by 29.2% in people with schizophrenia compared to healthy controls, t(140) =-3.988, p < 0.01. In people with schizophrenia, sICAM1 was inversely correlated with immediate verbal memory (r=-0.30, p=0.01), delayed verbal memory (rho=-0.29, p=0.01), verbal abstract reasoning (r=-0.23, p=0.05), and processing speed (rho=-0.28, p=0.02). In healthy controls, sICAM1 levels were inversely correlated with verbal fluency (r=-0.27, p=0.03) and processing speed (rho=-0.26, p=0.03). Discussion: The brain endothelium of people with schizophrenia can attract more immune cells via increased ICAM-1. sICAM-1, a cleavage product of ICAM which enables white blood cell migration into tissue (including brain) is significantly elevated in peripheral blood of patients with schizophrenia. sICAM-1 is associated with poor verbal memory, reasoning and processing speed in people with schizophrenia and accounts for variation in cognition of healthy controls. This suggests that increased inflammatory processes, measured in blood, may reflect brain related cognitive deficits that are the hallmark of schizophrenia. Anti-inflammatory treatments may reverse cognitive impairment in schizophrenia.

Acta Psychiatrica Scandinavica

factors associated with amisulpride-induced weight gain in first-episode psychosis patients (from... more factors associated with amisulpride-induced weight gain in first-episode psychosis patients (from the OPTiMiSE cohort). Objective: Antipsychotic-induced weight gain (AiWG) is a debilitating adverse effect of most antipsychotics. First-episode psychosis patients are particularly vulnerable to the detrimental consequences of AiWG. Amisulpride has good efficacy and tolerability. We here aimed to identify the phenotypic factors associated with amisulpride-induced weight gain in first-episode psychosis patients. Method: Data were collected from the Optimization of Treatment and Management of Schizophrenia in Europe trial. Multivariable regression models with various phenotypic variables (N = 305) were performed with absolute AiWG and clinically relevant AiWG (≥7% AiWG) as outcomes. Results: Four weeks of amisulpride treatment increased body weight from 69.7 to 72.4 kg (P < 0.001). In the regression model of absolute AiWG, unemployment (b = 0.94, P = 0.016), younger age (b = À0.07, P = 0.031) and absence of current comorbid major depression disorder (b = À1.61, P = 0.034) were positively associated with absolute AiWG. In the regression model of clinically relevant AiWG, unemployment (OR = 2.83, P = 0.001), schizophreniform disorder (OR = 2.00, P = 0.025) and low baseline weight (OR = 0.97, P = 0.032) increased the likelihood of clinically relevant AiWG. Conclusions: Clinicians prescribing amisulpride should consider the relatively high susceptibility to AiWG in unemployed first-episode patients with psychosis, in particular young subjects with a diagnosis of

The Lancet Psychiatry, 2018

The OPTiMiSE trial: a three-phase, double blind randomised switching study in first episode schiz... more The OPTiMiSE trial: a three-phase, double blind randomised switching study in first episode schizophrenia and schizophreniform disorder comparing amisulpride and olanzapine followed by open treatment with clozapine.

Schizophrenia Research, 2021

, C. (2021). The role of depression in the prediction of a "late" remission in first-episode psyc... more , C. (2021). The role of depression in the prediction of a "late" remission in first-episode psychosis: An analysis of the OPTiMiSE study. Schizophrenia Research,

Psychological Medicine

Background Negative symptoms are one of the most incapacitating features of Schizophrenia but the... more Background Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES). Methods T1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were com...

Social psychiatry and …, 2007

Knowledge of moderators of symptom improvement over time in acute mania improves predictability o... more Knowledge of moderators of symptom improvement over time in acute mania improves predictability of individual patient outcomes. This study attempted to identify such moderators of the rate of symptom improvement. In 3459 patients with high levels of mania in whom a change in psychotropic treatment was initiated and who were assessed six times over three months, clinical and social moderators of the rate of response were examined. Additionally, moderators of symptom improvement in individuals with high baseline levels of comorbid depression (n = 815) and psychosis (n = 1849) were identified. Within three months, mania symptoms were reduced by 52%, psychotic symptoms by 56% and depressive symptoms by 36%. High levels of baseline depression, greater illness severity in the past year, lower age of onset and rapid cycling reduced the rate of mania symptom improvement by 5-15%. Social variables indicating disadvantage similarly had negative contributions (5%-14%). Several reasons for change of medication involving patient choice, patient compliance, side effects and lack of effectiveness impacted negatively (reductions of 10%, 6%, 14% and 9% respectively). For the psychosis dimension, both low mania scores (22% reduction) and high depression scores (14% reduction) at baseline impacted negatively, whereas rate of reduction in depression was not conditional on baseline psychopathology. The rate of symptom improvement in acute mania is to a large extent conditional on the context as provided by the social, psychopathological and consumer environment. Understanding the context of treatment response offers valuable insights into treatment approaches aimed at moderation of traditional pharmacological interventions.

Schizophrenia Bulletin Open

Background Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation as dem... more Background Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation as demonstrated by elevated levels of C reactive protein (CRP) and pro-inflammatory cytokines. Aims The primary goal of this study was to investigate the association between pro-inflammatory biomarkers and clinical outcomes in unmedicated FEP patients. Method We used clinical data and biological samples from 289 FEP patients participating to the Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE) clinical trial. Patients were assessed at baseline and 4-5 weeks after treatment with amisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, Tumor Necrosis Factor (TNF)-α and CRP were measured. We first used multivariable regression to investigate the association between each of the four tested biomarkers and the following clinical outcomes: Positive And Negative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS), remission according to Andrea...

Biological Psychiatry Global Open Science

BMC Psychiatry

Background Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect o... more Background Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. Methods In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 alloca...

Journal of Affective Disorders Reports

European Neuropsychopharmacology

Schizophrenia Bulletin

Background An increasing body of evidence suggests that immune dysregulation is involved in the p... more Background An increasing body of evidence suggests that immune dysregulation is involved in the pathophysiology of psychotic disorders. Some, but not all, anti-inflammatory drugs have shown positive effects on symptom severity. Given the need for new treatment options in psychosis, anti-inflammatory medication should be explored as a potential treatment to improve outcome. Being a potent glucocorticosteroid that adequately passes through the blood-brain barrier, prednisolone qualifies as a potential candidate. This proof-of-concept study aims to explore the effect of prednisolone, compared to placebo, on symptom severity in patients with a psychotic disorder who are on a stable dose of antipsychotic medication. Methods The study was conducted from July 2015 until April 2019 in four centers in the Netherlands and Belgium. Patients with a psychotic disorder were randomized, double blind, 1:1 to prednisolone or placebo in addition to their antipsychotic treatment. Patients randomized t...

Schizophrenia Bulletin

Background Autistic phenotypic profiles in patients with schizophrenia are reportedly associated ... more Background Autistic phenotypic profiles in patients with schizophrenia are reportedly associated with poor outcomes, including higher odds of antipsychotic treatment failure. The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Autism Severity Scale (PAUSS) has been validated as a tool to identify “autistic profiles” in adolescents and adults with schizophrenia. We used the PAUSS (total score and subscores) to quantify autistic symptom load at different time points in a sample of patients with first episode schizophrenia (FES). We sought to investigate whether showing “prominent and persistent” autistic symptom load was associated with not achieving clinical remission at week 4 after the FES. Methods We analysed a subsample of FES patients from the OPTiMiSE study that was treated with amisulpride in an open-label design and had completed 4 weeks of follow-up. The selected subsample was composed of 55 individuals (27.3% female, mean age 25.6 (6.2) years) at “high-risk o...

European Neuropsychopharmacology

Schizophrenia Bulletin

Background: Very few prospective, sequential studies are available that could guide decisions whi... more Background: Very few prospective, sequential studies are available that could guide decisions which have to be made in every day clinical routine. Some of the simplest questions of clinicians remain unanswered. For example: If the first antipsychotic used has not worked, is switching to another drug effective? Or should we perhaps increase the dose? And when should we start clozapine, the most efficacious drug? These questions are most urgent for patients with a first episode of psychosis. Methods: OPTiMiSE is an international clinical trial, conducted in 27 research centers located in 14 countries across Europe and Israel. Among other purposes, OPTiMiSE was designed to test a three-stage treatment algorithm. The 446 participants of OPTiMiSE were diagnosed with a first episode of schizophrenia, schizophreniform or schizoaffective disorder. Each participant started with a 4-week open label amisulpride treatment. After these 4 weeks, non-remitters are randomized to switch to another antipsychotic versus continuation of amisulpride for 6 weeks, in a double-blind fashion (phase 2). After these additional 6 weeks, non-remitters were switched to clozapine for another 12 weeks. Results: Description of the sample: Mean age at inclusion was 26 years, 30% of the patient sample was female. The median duration of illness was 4 months and none of the participants had been using antipsychotic medication for more than 2 weeks. All patients were treated on a voluntarily basis. The patient sample was moderately ill at baseline, with a mean score on the Positive And Negative Syndrome Scale (PANSS) of 78 (sd 19). Phase 1 Patients started on 200-800 mg/day amisulpride treatment, with a target dose of 400 mg/day. Drop-out rate was 20%. Out of the 446 patients who were initiated on amisulpride, 56% met remission criteria, based on the eight remission items of the PANSS. Side effects were mild, with a mean weight increase of 2.7 kg (sd 3.3). Phase 2 At the end of phase 1, 121 patients did not meet remission criteria. Out of the 93 patients who continued into the double-blind treatment phase, 72 patients completed the 6-week treatment phase. Remission rate in phase 2 was 35%. There was no significant difference between the two treatment arms regarding remission rate, nor regarding the drop out rate. Patients randomized to olanzapine gained significantly more weight compared to amisulpride. Phase 3 At the end of phase 2, 40 patients did not meet remission criteria. Out of the 28 patients who continued into the open-label clozapine treatment phase, 18 patients completed this 12-week treatment from which only 5 patients met remission criteria, translating into a remission rate of only 18%. Non-remitters generally did improve to a great extent but failed to meet the stringent remission criteria. Discussion: Amisulpride is confirmed to be a good option for initiating pharmacotherapy in first episode patients, resulting in a high remission rate. There was no advantage related to remission rates or drop out rates for switching non-responders after 4 week of treatment to another antipsychotic versus continuing the initiated antipsychotic for another 6 weeks; continuing the first antipsychotic may have the benefit of avoiding new side effects related to introducing a new antipsychotic. Despite a low remission rate following clozapine treatment, non-remitters generally did show a substantial reduction in symptoms, demonstrating that clozapine should be an option for non-responding psychotic patients early in the illness.

Schizophrenia Bulletin

37 people with schizophrenia and 37 matched controls. In an independent living cohort, sICAM-1 wa... more 37 people with schizophrenia and 37 matched controls. In an independent living cohort, sICAM-1 was measured with a Luminex immunoassay from the plasma of 78 chronically ill patients with schizophrenia (all receiving antipsychotic medication) and 73 healthy controls. All participants from the living cohort received the following cognitive assessments: Wechsler Adult Intelligence Scale-3rd edition to assess current IQ, Controlled Oral Word Association Test verbal fluency and Wechsler Memory Scale-Revised to assess verbal memory. Pearson's or Spearman's correlations were performed between cognitive measures and sICAM1 levels as appropriate in schizophrenia patients and healthy controls. Results: ICAM-1 was elevated in the brains of people with schizophrenia relative to controls and CD163+ perivascular macrophages were found in the parenchyma. Peripheral sICAM1 was elevated by 29.2% in people with schizophrenia compared to healthy controls, t(140) =-3.988, p < 0.01. In people with schizophrenia, sICAM1 was inversely correlated with immediate verbal memory (r=-0.30, p=0.01), delayed verbal memory (rho=-0.29, p=0.01), verbal abstract reasoning (r=-0.23, p=0.05), and processing speed (rho=-0.28, p=0.02). In healthy controls, sICAM1 levels were inversely correlated with verbal fluency (r=-0.27, p=0.03) and processing speed (rho=-0.26, p=0.03). Discussion: The brain endothelium of people with schizophrenia can attract more immune cells via increased ICAM-1. sICAM-1, a cleavage product of ICAM which enables white blood cell migration into tissue (including brain) is significantly elevated in peripheral blood of patients with schizophrenia. sICAM-1 is associated with poor verbal memory, reasoning and processing speed in people with schizophrenia and accounts for variation in cognition of healthy controls. This suggests that increased inflammatory processes, measured in blood, may reflect brain related cognitive deficits that are the hallmark of schizophrenia. Anti-inflammatory treatments may reverse cognitive impairment in schizophrenia.

Acta Psychiatrica Scandinavica

factors associated with amisulpride-induced weight gain in first-episode psychosis patients (from... more factors associated with amisulpride-induced weight gain in first-episode psychosis patients (from the OPTiMiSE cohort). Objective: Antipsychotic-induced weight gain (AiWG) is a debilitating adverse effect of most antipsychotics. First-episode psychosis patients are particularly vulnerable to the detrimental consequences of AiWG. Amisulpride has good efficacy and tolerability. We here aimed to identify the phenotypic factors associated with amisulpride-induced weight gain in first-episode psychosis patients. Method: Data were collected from the Optimization of Treatment and Management of Schizophrenia in Europe trial. Multivariable regression models with various phenotypic variables (N = 305) were performed with absolute AiWG and clinically relevant AiWG (≥7% AiWG) as outcomes. Results: Four weeks of amisulpride treatment increased body weight from 69.7 to 72.4 kg (P < 0.001). In the regression model of absolute AiWG, unemployment (b = 0.94, P = 0.016), younger age (b = À0.07, P = 0.031) and absence of current comorbid major depression disorder (b = À1.61, P = 0.034) were positively associated with absolute AiWG. In the regression model of clinically relevant AiWG, unemployment (OR = 2.83, P = 0.001), schizophreniform disorder (OR = 2.00, P = 0.025) and low baseline weight (OR = 0.97, P = 0.032) increased the likelihood of clinically relevant AiWG. Conclusions: Clinicians prescribing amisulpride should consider the relatively high susceptibility to AiWG in unemployed first-episode patients with psychosis, in particular young subjects with a diagnosis of