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Schizophrenia (SZ), schizoaffective disorder (SZA), bipolar disorder (BD), and psychotic depression (PD) are associated with premature death due to preventable general medical comorbidities (GMCs). The interaction between psychosis, risk factors, and GMCs is complex and should be elucidated. More research particularly among those with SZA or PD is warranted. We evaluated the association between registry-based psychotic disorders and GMC diagnoses in a large national sample of participants with different psychotic disorders. In addition, we examined whether body mass index (BMI) and smoking as risk factors for GMCs explain differences between diagnostic groups. This was a cross-sectional study of a clinical population of participants (n = 10,417) in the Finnish SUPER study. Registry-based diagnoses of psychotic disorders and hypertension, diabetes, chronic obstructive pulmonary disease (COPD), cancers, ischemic heart disease, and liver disorders were obtained. Participants’ BMI and self-reported smoking were recorded. Total effect of diagnostic category adjusted for age and sex as well as direct effect including known risk factors was calculated using logistic regression. Regardless of diagnostic category, participants had high BMI (average 30.3 kg/m2), and current smoking was common (42.4%). Diabetes and COPD were more common in SZ than in other diagnostic categories. The differences between psychotic disorders were not explained by obesity or smoking status only. Obesity and smoking were prevalent in all diagnostic categories of psychotic disorders, and continued efforts at prevention are warranted. Additional differences in GMC prevalence exist between psychotic disorders that are not explained by obesity and smoking.

Delusion is the most characteristic symptom of psychosis, occurring in almost all first-episode psychosis patients. The motivational salience hypothesis suggests delusion to originate from the experience of abnormal motivational salience. Whether the motivation-related brain circuitries are activated during the actual delusional experience remains, however, unknown. We used a forced-choice answering tree at random intervals during functional magnetic resonance imaging to capture delusional and non-delusional spontaneous experiences in patients with first-episode psychosis (n = 31) or clinical high-risk state (n = 7). The motivation-related brain regions were identified by an automated meta-analysis of 149 studies. Thirteen first-episode patients reported both delusional and non-delusional spontaneous experiences. In these patients, delusional experiences were related to stronger activation of the ventral striatum in both hemispheres. This activation overlapped with the most strongly motivation-related brain regions. These findings provide an empirical link between the actual delusional experience and the motivational salience hypothesis. Further use and development of the present methods in localizing the neurobiological basis of the most characteristic symptoms may be useful in the search for etiopathogenic pathways that result in psychotic disorders.

BackgroundPsychotic disorders, including schizophrenia (SZ), schizoaffective disorder (SZA), bipolar disorder (BD), psychotic depression (PD), and other nonaffective psychoses (ONAP), are associated with increased risk of suicidal acts. Few studies have compared suicidal act prevalence across psychotic disorders using both self-report and register data. The impact of hospitalization duration on subsequent suicidal acts is unclear.MethodsWe used data from the SUPER-Finland study, involving 7067 participants with register-based ICD-10 diagnoses of psychotic disorders (SZ, SZA, BD, PD, ONAP). Lifetime suicidal acts were identified through self-report and register-based records of intentional self-harm events requiring medical treatment. Associations between diagnostic categories and suicidal acts were assessed using logistic regression, adjusted for sex, duration of illness, socioeconomic status, childhood abuse, and substance use. Survival analysis was used to examine the impact of hospital stay length on postdischarge self-harm.ResultsLifetime suicide attempts (39.1%) and register self-harm (19.3%) were prevalent. of those with self-reported suicide attempts, 40.5% also had register-based self-harm. Self-harm and suicide attempts were significantly more prevalent in SZA, BD, and PD compared to schizophrenia, with large differences between groups (24.1–46.4% for suicide attempts, 11.1–23.9% for self-harm). Adjusted odds of self-harm were higher for disorders with a mood component. Shorter hospitalizations were associated with an elevated hazard ratio for subsequent self-harm.ConclusionsPrevalence of register-based self-harm and self-reported suicide attempts differ markedly. Suicidal acts are common in psychotic disorders, particularly in those with a mood component. Very short inpatient stays may not be adequate in these disorders.

Background: Despite increasing evidence of cognitive dysfunctions in bipolar I disorder, there is no specific neuropsychological profile of the disorder. Sampling and Method: The aim of the present study was to investigate the effect of processing speed on other cognitive functions in a population-based sample of 32 familial bipolar I disorder patients, their 40 unaffected first-degree relatives and 55 controls. A neuropsychological test battery was administered to all participants, and the effect of processing speed on other cognitive functions was analyzed with the digit symbol subtest of the Wechsler Adult Intelligence Scale-Revised both in within- and between-group comparisons. Results: After adjusting for the effect of processing speed, only small differences were detected in short-delay cued recall and in long-delay memory between patients and controls, as well as between patients and relatives. Relatives scored better than controls only in verbal ability. Processing speed had a significant effect on nearly all scores, differing by group when patients, relatives and controls were examined separately, the effect being most extensive in patients. Conclusions: These results support the view that impaired processing speed in particular contributes to a range of cognitive dysfunctions in bipolar disorder. However, it may not be specific to bipolar I disorder and can possibly be considered a shared endophenotype with other mental disorders.

IntroductionInsomnia is a common symptom among patients with schizophrenia and schizoaffective disorder, negatively impacting symptom severity, functioning and well-being; however, it is rarely the direct focus of treatment. The main recommended treatment for insomnia is cognitive behavioural therapy (CBT-I). There is some evidence that CBT-I can also be used to treat insomnia in patients with schizophrenia, but only a few randomised controlled trials (RCTs) have been published. The aim of this ongoing RCT is to determine whether we can alleviate symptoms of insomnia and improve the quality of life in patients with schizophrenia and schizoaffective disorder through CBT-I delivered via the internet or in a group mode.Methods and analysesThe aim of this study is to recruit 84–120 outpatients from the Psychosis Clinics of Helsinki University Hospital and the City of Helsinki Health Services. The main inclusion criteria are a diagnosis of schizophrenia or schizoaffective disorder and self-reported sleep problems. The study will be performed on a cyclic basis, with a target of 12–24 patients per cycle. Participants are randomly assigned into three groups: (1) a group receiving only treatment as usual (TAU), (2) internet-based individual therapy for insomnia (iCBT-I)+TAU or (3) group therapy for insomnia (GCBT-I) conducted via a virtual platform+TAU. The primary outcome measures are quantitative changes in the Insomnia Severity Index score and/or changes in health-related quality of life using the 15D quality of life measure. Secondary outcomes include self-reported variables for sleep, health, stress and the severity of psychotic and depressive symptoms; objective outcomes include actigraphy and bed sensor data to evaluate circadian rhythms and motor activity. Outcome measures are assessed at baseline and after the treatment period at weeks 12, 24 and 36.Ethics and disseminationThe Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, approved the study protocol. The results will be published in peer-reviewed journals.Trial registration number NCT04144231.

First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1- and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFα, CXCL1, CCL7, IFN-α2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum level of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate an association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.

The purpose of this study was to explore the association of cognition with hazardous drinking Polygenic Scores (PGS) in 2649 schizophrenia, 558 schizoaffective disorder, and 1125 bipolar disorder patients in Finland. Hazardous drinking PGS was computed using the LDPred program. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: the 5-choice serial reaction time task, or Reaction Time (RT) test, and the Paired Associative Learning (PAL) test. The association between hazardous drinking PGS and cognition was measured using four cognition variables. Log-linear regression was used in Reaction Time (RT) assessment, and logistic regression was used in PAL assessment. All analyses were conducted separately for males and females. After adjustment of age, age of onset, education, household pattern, and depressive symptoms, hazardous drinking PGS was not associated with reaction time or visual memory in male or female patients with schizophrenia, schizoaffective, and bipolar disorder.

BackgroundPatient satisfaction with care (PSC) is a valuable predictor in both quality of life and treatment outcomes with psychiatric patients. First episode psychosis (FEP) patients are a diverse group of usually young adults. Determining the factors behind PSC in FEP patients could be an important tool in planning better care programs and predictive tools for the outcome of FEP. Many FEP patients are still on the cusp of their adult lives. Achieving better treatment adherence by higher PSC could help many people back to their studies or work lives and enhance their quality of life and social and occupational functioning. Determining background factors and associations with better PSC would help tailoring treatment options for FEP patients.MethodsThe Helsinki Early Psychosis Study recruited FEP patients (aged 18 to 40 years old) who were having their first treatment of psychosis in the catchment area of the Helsinki University Hospital and the psychiatric services of Helsinki City in the time period from December 2010 to June 2016. The diagnoses of psychotic disorders were later verified using the Structured Diagnostic Interview for DSM-IV, Research Version, as well as a review of all medical records. Substance-induced psychotic disorders and psychotic disorders due to a general medical condition were excluded. Baseline assessment was conducted as soon as the patient had entered treatment and was able to give informed consent according to the treating personnel. Follow ups were conducted at 2 months after baseline.Data was gathered on symptoms, sociodemographic factors, functioning, overall health, aspects of treatment and medication. Duration of untreated psychosis was determined as accurately as possible with the help of patient records and diagnostic interview. Patient satisfaction was evaluated by PSQ (Patient satisfaction questionnaire) developed by Swedish researchers for their early intervention program for first episode psychosis patients. The questionnaire contains ten questions about different aspects of the patients’ care and was part of the 2-month follow-up protocol.Results97 patients were recruited in the study. Out of those patients, 72 patients participated in the 2-month follow up and 51 filled out the PSC questionnaire. The results of the PSQ were translated into a dichotomist scale of “satisfied” (very or rather satisfied) or “not satisfied” (neither satisfied nor dissatisfied; rather or very dissatisfied). Interestingly, DUP was not associated with higher or lower satisfaction with care unlike in other studies. Conversely, higher SOFAS score at the 2-month follow up was associated with better treatment satisfaction. Especially patients who felt they had been able to influence their care, who felt that the sessions with the psychiatric staff been helpful, and who were satisfied with the concern and understanding the psychiatric staff had shown had significantly higher SOFAS than those who were not satisfied with these aspects of care, whereas e.g. attitudes regarding medication were not significantly associated with SOFAS. A summary score of the PSQ correlated positively with the 2 month SOFAS scores (Spearman rho 0.40, p=0.007).DiscussionUnlike in many other studies, longer DUP was not associated with poorer PSC. Instead, satisfaction with qualitative aspects of treatment contact and being able to influence treatment decisions were associated with better functioning. This suggest that the staff-patient relationship and empowering patients in treatment decisions are important in the treatment of FEP.

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline ( p  < 0.0001; Cohen’s d  = 0.70) and at the 12-month follow-up ( p  = 0.0007) compared to controls. The group difference remained significant ( p  = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations ( ρ  = 0.20) and disorganization ( ρ  = 0.23), and with worse verbal performance ( ρ  = −0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [ 11 C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume ( V T ) of [ 11 C]PBR28 was lower in patients compared to controls ( p  = 0.026; Cohen’s d  = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels ( p  = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.

Sleep problems are common in psychotic disorders and are associated with worse quality of life and disease prognosis. Genome-wide association studies (GWAS) have revealed genetic influences for schizophrenia and sleep, but polygenic scores (PGSs) for sleep traits have not been evaluated systematically in patients with psychotic disorders. This study investigated the associations between PGSs for sleep traits (insomnia, PGS ; sleep duration, PGS ; short sleep duration, PGS ; long sleep duration; PGS ), diurnal preference (eveningness, PGS ), and schizophrenia (PGS ) with clinical features of psychotic disorders in the Finnish SUPER study comprising 8,232 patients with psychotic disorders. The measures included self-reported sleep and well-being, cognitive assessments, clozapine use, and functional outcomes. Using FinnGen data of 356,077 individuals, we analyzed the distributions of PGSs in psychotic and bipolar disorders and the general population. PGS associated with more sleep problems and worse well-being (e.g. worse health-related quality of life [β = -0.07, CI = -0.09, -0.05,  < .001]). High PGS is associated with better sleep quality, worse clinical outcomes, and performance in cognitive tests (e.g. more errors in paired-associated learning [β = 0.07, CI = 0.04, 0.09,  < .001]). PGS was higher in affective psychotic and bipolar disorders, while PGS and PGS were higher in schizophrenia as compared with individuals with no psychiatric disorders. Genetic risks for sleep and diurnal preference vary between non-affective psychosis, affective psychosis, and the general population. The findings in this study emphasize the heterogeneity in genetic etiology of the objective features of disease severity and the more subjective measures related to well-being and self-reported measures of sleep.