Background and Hypothesis:Affective disturbances are a core feature of schizophrenia, yet patients' capacity to experience momentary affective shifts in real-world settings remains underexplored. Although consummatory pleasure appears preserved, studies suggest low levels of positive affect and high levels of negative affect in daily life. Physical exercise provides an ecologically valid context for probing short-term affective reactivity. This study examined whether high-intensity interval training (HIIT) elicited greater affective change than an active control condition (ACC), whether baseline symptom levels were associated with affective state, and whether baseline symptoms moderated affective reactivity. Study Design:In a randomized controlled trial, 69 outpatients with schizophrenia were randomized to a 12-week intervention involving either supervised HIIT or an ACC involving low-intensity, interactive video gaming. Affective state was assessed immediately before and after the 12th session using the Positive and Negative Affect Schedule (PANAS). Depressive (CDSS), negative symptoms (PANSS-N), and apathy (AES) were measured at baseline. Linear mixed-effects models tested Group × Time effects. Study Results:HIIT did not produce significantly greater changes in positive or negative affect than the active control. Across interventions, participants showed increases in positive affect and decreases in negative affect. Higher baseline symptom levels were associated with lower pre-session positive affect. Exploratory analyses indicated that participants with more severe negative symptoms showed greater positive affective gains following HIIT. Conclusions:A single session of structured activity, regardless of intensity, was associated with small but measurable affective improvements. These findings highlight the value of accessible activity-based interventions for enhancing affective well-being in schizophrenia.

OBJECTIVE:Antipsychotic drugs are to varying degrees associated with hematological side-effects and peripheral metabolic and immunological changes. Here, we aimed to characterize the initial transcriptional changes in peripheral leukocytes from individuals with schizophrenia spectrum disorder (SSD) after starting antipsychotic treatment with amisulpride, aripiprazole, or olanzapine. METHODS:We analyzed RNA sequencing data obtained from peripheral whole blood samples from 100 individuals with SSD (41 antipsychotic-naïve [AP-naïve], 10 AP-free, and 49 AP-switching at inclusion) collected at baseline and after 1 and 3 weeks of antipsychotic drug use. Data from 36 healthy controls (HC) collected at baseline and after 3 weeks without any intervention were included. We analyzed age- and sex-adjusted differentially expressed genes between SSD and HC before and after treatment and stratified by previous antipsychotic use. A linear mixed model was applied to study longitudinal gene expression changes associated with the antipsychotic drug that was used. RESULTS:After 3 weeks of antipsychotic use, the AP-switching group had the most significant transcriptional changes, characterized by increased expression of genes typically transcribed by immature erythroid cells and immature neutrophil cells. This gene profile showed no correlation with symptoms score. Interestingly, the immature neutrophil-associated gene signature was more pronounced in participants receiving olanzapine, and partly also amisulpride, but not aripiprazole. In contrast, only minor transcriptional changes were observed in the AP-naïve participants. CONCLUSIONS:These findings suggest that prior antipsychotic exposure may have a priming effect on leukocyte gene expression, which results in a transcriptional response indicative of stress erythropoiesis and neutropoiesis when switching to a new antipsychotic drug. This response appears to be independent of psychosis symptom severity.

Background Schizophrenia is associated with inflammation. Antipsychotic drugs have anti-inflammatory properties but few antipsychotics have been compared head-to head. The aim of this study was to evaluate the immunomodulatory effects of three pharmacologically different atypical antipsychotics, amisulpiride, aripiprazole and olanzapine, in patients with schizophrenia-spectrum disorders. Methods The study reports a predefined secondary outcome of the BeSt InTro-study, a double blind randomized head-to-head trial comparing amisulpride, aripiprazole and olanzapine. Patients with a schizophrenia-spectrum disorder (N=144) were randomized to the different treatment arms, and serum levels of nine cytokines (interleukin [IL]-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were assessed at baseline and weeks 1, 3, 6, 12, 26, 39 and 52. A combined pro-inflammatory variable was constructed from IL1-β and TNF-α. The primary analyses were done in per protocol (PP) data in the drug-naïve sample (n = 56). Changes in cytokine levels between baseline and the end of the study were analyzed in a mixed effects model with amisulpride as the reference drug. Results Treatment with amisulpride was associated with a reduction in pro-inflammatory IL-1β levels over 12 months, this change was statistically different compared to the change in aripiprazole and olanzapine. A significant difference between the influence of amisulpride compared to aripiprazole on the anti-inflammatory cytokine IL-10 was detected. Aripiprazole reduced IL-12p70 more than amisulpride. The combined pro-inflammatory variable decreased from baseline to week 52 with a magnitude of 0.52 standard deviation (SD) after treatment with amisulpride.. Conclusion Patients treated with amisulpride showed greater anti-inflammatory changes in cytokine serum levels than those treated with aripiprazole or olanzapine. Funding The Research Council of Norway, the Western Norway Regional Health Trust, and Klinbeforsk supported the study.

BACKGROUND:Schizophrenia patho-etiology may involve endothelial inflammation and blood-brain barrier (BBB) dysregulation with cellular adhesion molecules (CAMs) as important mediators. CAMs are essential for cellular integrity but can show increased levels in inflammation. Cognitive dysfunction precedes and exists independently of psychotic symptoms in schizophrenia patients. CAMs could impact cognition through influence on BBB integrity. To gain insights into disease mechanisms and potential therapeutic targets, we explored the relationship between CAMs protein levels and neurocognitive tests in schizophrenia-spectrum disorders in the BeSt InTro study. METHODS:Seventy-one in- and out-patients underwent CAMs measurements and neuropsychological testing on a minimum of one time point: baseline, 6, 26, or 52 weeks. Cognitive domains included working memory, processing speed, verbal abilities, executive functions, and overall cognition. CAMs analyzed were neural CAMs: junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD); vascular CAMs: intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), and platelet (P)-selectin from fasting blood samples. Linear mixed effects models, adjusted for age, sex, body mass index, smoking, education, and drug naivety, estimated CAMs effect on cognitive outcome measures. RESULTS:N-CAD levels correlated positively with overall cognition (p = 0.002), working memory (p = 0.034), and executive functions (p = 0.0011). ICAM-1 levels correlated positively with overall cognition (p = 0.037). Conversely, JAM-A levels correlated negatively with executive functions (p = 0.021). CONCLUSION:Associations between CAMs (N-CAD, ICAM-1, JAM-A) and neurocognitive tests suggest CAMs may impact cognition in schizophrenia. Contrary to our hypothesis, most associations between CAMs levels and cognitive tests were positive. Future research on mechanisms is mandatory.

BACKGROUND:Impaired clinical insight is common in schizophrenia spectrum disorders (SSDs) and predicts poor treatment adherence and outcomes. It is linked to disorganised, positive, negative, and hostility symptoms. However, few studies repeatedly assess insight after antipsychotic initiation while comparing pharmacologically distinct agents. This study examined how symptom levels and changes predict the development and endpoint of clinical insight over 6 weeks, contrasting the partial dopamine agonist aripiprazole (PDA) with two dopamine antagonists (DAs). METHODS:Data from 144 SSD patients in the Bergen-Stavanger-Innsbruck-Trondheim (BeSt InTro) trial, a pragmatic, semi-randomised study of amisulpride, aripiprazole, and olanzapine, were analysed using latent growth curve models. Insight was measured by PANSS Item G12; symptom factors (positive, negative, hostility, cognitive/disorganised) were derived from PANSS. RESULTS:Lower baseline symptoms and greater improvement between weeks 3 and 6 predicted better insight at 6 weeks across all factors. For positive symptoms, improvement between weeks 1 and 3 (b = 0.57, p = 0.009) also predicted better insight. Patients on aripiprazole showed less improvement in insight, though some findings lost significance after correction. CONCLUSION:Symptom reduction is associated with improved insight, with early changes in positive symptoms exerting the fastest effect. Despite symptom improvement, aripiprazole PDA treatment was linked to less insight gain than DA treatment. These preliminary findings warrant further study.

Abstract Background Cardiometabolic diseases are the main causes of death in persons with severe mental illness (SMI), highlighting the need to improve management of cardiovascular risk factors in both primary and specialized health care. The “Healthy Heart Tool” aims at helping health care workers to identify persons at risk, and to initiate proper interventions. Here we investigate if the recommendations in the Healthy Heart Tool are followed one year after implementation and whether implementation of the tool improved cardiometabolic risk factors in SMI. Methods Data from 270 individuals with SMI from six Norwegian hospitals were collected at baseline and at 12 months after implementation of the Healthy Heart Tool throughout the health care services. Changes from baseline to 12 months follow-up were analyzed using chi-square and independent t-tests, whereas implementation effects were analyzed using logistic general linear mixed models. Results After implementing the Healthy Heart Tool, significantly more persons received dietary advice and/or salt restriction advice (75.5% vs. 84.8%, p = 0.035). After controlling for Body Mass Index (BMI) ≥ 30 and sex, there was an odds ratio (OR) of 8.9 (95% CI 1.42–55.77) for receiving dietary advice and/or advice on salt reduction. There was a significant reduction (p = 0.016) in numbers of participants with high levels of total serum cholesterol ≥ 5 mmol/ (54.4% vs. 46.3%). Conclusions Implementing the Healthy Heart Tool can increase awareness of cardiovascular risk factors in patients with SMI. The intervention increased the proportion of individuals who received dietary and salt reduction advice and decreased the proportion of individuals with high cholesterol levels. However, due to the small numbers, these results should be interpreted with caution. Nonetheless, the findings suggest that the Healthy Heart Tool may be an effective means for improving the management of cardiovascular risk factors in individuals with SMI in typical clinical settings. Trial registrations The trial was retrospectively registered in ClinicalTrials.gov 29.01.25, ID NCT 06807242.

OBJECTIVE:Folate and cobalamin deficiency or impaired function due to genetic variants in key enzymes have been associated with neuropsychiatric symptoms. The aim of this study was to compare folate and cobalamin status in patients admitted to an acute psychiatric unit to patients from primary health care in order to reveal factors which may be important in the follow-up of patients with mental disorders. METHODS:Anonymous blood samples tested for folate, cobalamin, the metabolic marker total homocysteine (tHcy), creatinine and glomerular filtration rate as well as age and gender in patients admitted to a psychiatric acute unit (n = 981) and patients from primary health care (controls) (n = 32,201) were reviewed retrospectively. RESULTS:Median serum folate was 18% lower and median serum cobalamin was 11% higher in patients with mental disorders compared to controls. Folate deficiency was associated with 54% higher median tHcy levels among patients with mental disorders compared to controls. The prevalence of folate deficiency was 31% and of cobalamin deficiency 6% in patients admitted to a psychiatric acute unit in a Norwegian hospital in 2024. CONCLUSION:Folate, but not cobalamin deficiency, was prevalent in Norwegian patients with mental disorders. The higher tHcy levels in folate-deficient patients with mental disorders indicate an impaired folate metabolism, which might be related to genetic factors, such as polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Ensuring a serum folate concentration above 15 nmol/L and a serum cobalamin above 250 pmol/L might improve symptoms in patients with mental disorders.

The perception of a voice in the absence of an external auditory source-an auditory verbal hallucination-is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate + Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task.

Childhood maltreatment and trauma (CMT) increase the risk for schizophrenia spectrum disorders (SSDs) and the severity of psychosis symptoms. Few studies have considered the possible influence of parental mental health on the relationship between CMT and symptoms of psychosis. Possibly, parental mental health problems (MHP) confound this relationship by increasing both the genetic vulnerability for psychosis and the potential for sub-optimal childhood environments. The aim was to examine the potential influence of parental MHP on the relationship between CMT and symptoms of psychosis. We hypothesized a positive and dose-dependent association between overall CMT and symptoms of psychosis not moderated by parental MHP. Patients with SSDs (N = 133) from the Bergen-Stavanger-Innsbruck-Trondheim (BeStInTro) study were included and assessed for CMT by the Childhood Trauma Questionnaire - Short Form, psychosis symptoms by The Positive and Negative Syndrome Scale and parental mental health by means of focused patient interviews. Regression analyses showed a dose-response relationship between CMT and overall psychosis symptom severity and negative symptom severity, further supported by t-tests showing that SSD patients with CMT showed more psychosis symptoms compared to SSD patients with no CMT. Multiple regression analysis with interaction term showed that the association between CMT and psychosis symptom severity was independent, and not moderated, by parental MHP. A dose-dependent relationship between CMT and psychosis symptoms emerged, not moderated by parental MHP, suggesting that CMT has an independent and true effect on psychosis symptoms.

The present functional magnetic resonance imaging (fMRI) study investigated neural correlates of switching between task-processing and periods of rest in a conventional ON-OFF block-design in patients with auditory verbal hallucinations (AVHs) and healthy controls. It has been proposed that auditory hallucinations are a failure of top-down control of bottom-up perceptual processes which could be due to aberrant up- and down regulation of brain networks. A version of the Eriksen Flanker task was used to assess cognitive flexibility and conflict control. BOLD fMRI with alternating blocks of task engagement and rest was collected using a 3T MR scanner. The objective of the study was to explore how patients would dynamically modulate relevant brain networks in response to shifting environmental demands, while transitioning from a resting state to active task-processing. Analysis of performance data found significant behavioral effects between the groups, where AVH patients performed the Flanker task significantly less accurately and with longer reaction times (RTs) than the healthy control group, indicating that AVH patients displayed reduced top-down guided conflict control. A network connectivity analysis of the fMRI data showed that both groups recruited similar networks related to task-present and task-absent conditions. However, the controls displayed increased network variability across task-present and task-absent conditions. This would indicate that the controls were better at switching between networks and conditions when demands changed from task-present to task-absent, with the consequence that they would perform the Flanker task better than the AVH patients.

Background:New pharmacological treatment strategies are urgently needed for schizophrenia since current antipsychotic medications have limitations related to efficacy, tolerability, and disease course modification. Different lines of evidence converge on aberrant activity of the immune system, but translation into new treatment is still pending. Studies investigating the antipsychotic properties of less potent anti-inflammatory drugs have provided equivocal findings. A potent agent like prednisolone might be better suited for establishing proof-of-concept that dampening of inflammation may be beneficial in schizophrenia. Methods:In this double-blind multicentre pilot study, 12 patients (aged 18-39) with schizophrenia maintained on stable antipsychotic regimens were randomized to prednisolone or placebo. Study medication was initiated with 40 mg/day and gradually tapered to zero over a period of 6 weeks. The primary outcome was difference in the Positive and Negative Syndrome Scale (PANSS) total score 6 weeks after baseline. Outcomes:In patients randomized to prednisolone (N = 6), a clear trend towards more pronounced reduction of psychotic symptoms was observed compared to the placebo group (N = 6). Difference in symptom severity per the PANSS total score after 6 weeks of add-on treatment was 15·4 (SD = 8·5, p = 0·101). For the PANSS general score, we observed a statistically significant difference of 12·5 (SD = 4·6, p = 0·021) at week 6. Safety and tolerability were acceptable for the duration of prednisolone treatment. Interpretation:These findings suggest beneficial effect of add-on prednisolone. However, this needs further replication in a larger sample for confirmation and to identify the mechanisms of action.

Treatment with antipsychotics (APs) for schizophrenia spectrum disorders (SSDs) is generally effective, however, a significant proportion does not respond favorably. Childhood trauma (CT) subtypes (physical, sexual, and emotional abuse, physical and emotional neglect) could influence treatment effectiveness; however, research is scarce. Heterogeneity in AP response could be explained by differentiating by CT subtype. The present study was based on the Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study. CTQ-SF assessed CT subtypes in SSDs (n = 98). CT subtypes were examined in relation to psychosis symptoms measured by PANSS during one year of treatment with APs, by means of linear mixed effects (LME) models. Results were significant for CT subtypes, where increased levels of sexual abuse and physical neglect were associated with increased mean levels of psychosis symptoms throughout the course of treatment from baseline to 52 weeks. AP effectiveness may thus be influenced by CT subtype in SSDs. The results support clinical guidelines recommending a focus on assessment and treatment of trauma in SSDs.

Kjelby, Eirik PhD; Gjestad, Rolf PhD; Fathian, Farivar PhD; Sinkeviciute, Igne PhD; Alisauskiene, Renata MD; Anda, Liss-Gøril PhD; Løberg, Else-Marie PhD; Reitan, Solveig Klæbo PhD; Joa, Inge PhD; Larsen, Tor Ketil PhD; Rettenbacher, Maria PhD; Berle, Jan Øystein PhD; Fasmer, Ole Bernt PhD; Kroken, Rune Andreas PhD; Johnsen, Erik PhD Author Information

Schizophrenia is a serious mental disorder, and monitoring remission is a widely used measure of effectiveness of the treatment provided. It is very important to identify possible factors correlating with remission. In our substudy of BeSt InTro, a randomized controlled trial of three antipsychotic drugs, 126 patients with ICD-10 diagnoses F20 -29 (F23 excluded) were randomized to one of the second-generation antipsychotic drugs amisulpride, aripiprazole or olanzapine. Remission rate was calculated at seven assessment points, with and without using the time criterion of six months included in the consensus remission criteria. Because of drop-out ( n = 77), we had data for 49 patients at one-year follow-up. These data were used to calculate the one-year remission rate to 55 % (27/49), without taking into consideration the 6-month time criterion. When we applied the consensus remission criteria with the 6-month time criterion included, the one-year remission rate was calculated for 59 patients: 29 % (17/59). Antipsychotic drug naivety and low negative symptom load at baseline correlated highly with belonging to the remission group. Use of amisulpride was more probable to lead to remission than that of aripiprazole, but it was not more probable than the use of olanzapine (in per-protocol analyses). Negative symptoms showed the largest resistance to treatment. The lack of remission for the majority of the participants in this closely monitored antipsychotic drug trial is alarming and could act as a reminder that novel treatment principles are needed, especially targeted towards the negative symptoms in schizophrenia.

INTRODUCTION:Associations between psychiatric disorders and mortality have been extensively studied, but limited evidence exists regarding influence of clinical characteristics on mortality risk, at the time of acute psychiatric hospitalization. METHODS:A prospective total-cohort study included all patients consecutively admitted to Haukeland University Hospital's psychiatric acute ward in Bergen, Norway between 2005 and 2014 (n = 6125). Clinical interviews were conducted at the first admission within the study period, and patients were subsequently followed for up to 15 years in the Norwegian Cause of Death Registry. Competing risks regression models were used to investigate associations between clinical characteristics at first admission and the risk of natural and unnatural death during follow-up. RESULTS:The mean age at first admission and at time of death was 42.5 and 62.8 years, respectively, and the proportion of women in the sample was 47.2%. A total of 1381 deaths were registered during follow-up, of which 65.5% had natural, 30.4% unnatural, and 4.1% unknown causes. Higher age, male sex, unemployment, cognitive deficits, and physical illness were associated with increased risk of natural death. Male sex, having no partner, physical illness, suicide attempts, and excessive use of alcohol and illicit substances were associated with increased risk of unnatural death. CONCLUSION:Psychiatric symptoms, except suicide attempts, were unrelated to increased mortality risk. In the endeavor to reduce the increased mortality risk in people with mental disorders, focus should be on addressing modifiable risk factors linked to physical health and excessive use of alcohol and illicit substances.

Background. The lifetime prevalence of suicide is around 5% in patients with schizophrenia. Non-adherence to antipsychotic medication is an important risk factor, but prospective studies investigating joint effects of antipsychotic drugs, antidepressants, and benzodiazepines on suicidality are scarce. We aimed to investigate how use and non-use of psychotropic medications are associated with suicidality in schizophrenia. Methods. An open cohort study followed all patients consecutively admitted to a psychiatric acute unit during a 10-year period with a diagnosis of schizophrenia (n = 696). Cox multiple regression analyses were conducted with use of antipsychotics, antidepressants, and benzodiazepines as time-dependent variables. Adjustments were made for age, gender, depressive mood, agitated behavior, and use of alcohol and illicit substances. Results. A total of 32 (4.6%) suicide events were registered during follow-up. Of these, 9 (28%) were completed suicides and 23 (72%) were attempted suicides. A total of 59 (8.5%) patients were readmitted with suicidal plans during the follow-up. Compared to non-use, use of anti- psychotics was associated with 70% lower risk of attempted or completed suicide (adjusted hazard ratio [AHR] = 0.30, p <0.01, CI 0.14-0.65) and 69% reduced risk of readmission with suicidal plans (AHR = 0.31, p < 0.01, CI 0.18-0.55). Use of prescribed benzodiazepines was associated with 126% increased risk of readmission with suicidal plans (AHR = 2.26, p = 0.01, CI 1.24-4.13). Conclusions. Adherence to antipsychotic medication is strongly associated with reduced suicidal risk in schizophrenia. The use of prescribed benzodiazepines was identified as a significant risk factor for being readmitted with suicidal plans.

Suicide is a common cause of death in all phases of schizophrenia spectrum disorder, particularly in the youngest patients. Clinical measures have demonstrated limited value in suicide prediction, spurring the search for potential biomarkers. The causes of suicidal behaviour are complex, but the immune system seems to be involved as it reflects or even causes mental suffering. We aimed to identify cytokines with associations to suicidality in a sample of patients with symptoms of active psychosis. Patients with schizophrenia spectrum disorder (N = 144) participating in a semi-randomized antipsychotic drug trial (the BeSt InTro study) were assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) at eight visits across 12 months. The Clinical Global Impression for Severity of Suicidality scale (CGI-SS) was used for assessing suicidality. Serum concentrations of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, and IL-10 were measured using immunoassays. A logistic regression model was used to investigate the association between cytokine levels and suicidality. To enhance clinical significance, the CGI-SS scores were dichotomized into two groups before analyses: low (=1) and high (≥2) risk for suicidality. Both uni- and multi-variate analyses revealed an inverse correlation between IL-2 and IL-10 serum levels and suicidality, where lower cytokine concentrations of IL-2 and IL-10 were associated with higher suicidality scores. The results were consistent when adjusted for depression and substance use. These results indicate that inflammatory processes are linked to the risk of suicidality in patients with schizophrenia spectrum disorders.

BACKGROUND AND PURPOSE:Most patients with isolated rapid eye movement sleep behaviour disorder (iRBD) progress to a parkinsonian alpha-synucleinopathy. However, time to phenoconversion shows great variation. The aim of this study was to investigate whether cholinergic and dopaminergic dysfunction in iRBD patients was associated with impending phenoconversion. METHODS:Twenty-one polysomnography-confirmed iRBD patients underwent baseline 11C-donepezil and 6-Fluoro-(18F)-l-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET). Potential phenoconversion was monitored for up to 8 years. PET images were analysed according to patients' diagnoses after 3 and 8 years using linear regression. Time-to-event analysis was made with Cox regression, dividing patients into low and high tracer uptake groups. RESULTS:Follow-up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (n = 4) or dementia with Lewy bodies (n = 4), while nine remained non-phenoconverters. Compared with non-phenoconverters, 8-year phenoconverters had lower mean 11C-donepezil uptake in the parietal (p = 0.032) and frontal cortex (p = 0.042), whereas mean 11C-donepezil uptake in 3-year phenoconverters was lower in the parietal cortex (p = 0.005), frontal cortex (p = 0.025), thalamus (p = 0.043) and putamen (p = 0.049). Phenoconverters within 3 years and 8 years had lower 18F-DOPA uptake in the putamen (p < 0.001). iRBD patients with low parietal 11C-donepezil uptake had a 13.46 (95% confidence interval 1.42;127.21) times higher rate of phenoconversion compared with those with higher uptake (p = 0.023). iRBD patients with low 18F-DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (p = 0.0002). CONCLUSIONS:These findings suggest that cortical cholinergic dysfunction, particularly within the parietal cortex, could be a biomarker candidate for predicting short-term phenoconversion in iRBD patients. This study aligns with previous reports suggesting dopaminergic dysfunction is associated with forthcoming phenoconversion.

BACKGROUND:Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. METHODS:The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. RESULTS:The total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. CONCLUSIONS:In our study, patients with schizophrenia - including the drug-naïve - have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.