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Schizophrenia is a severe mental disorder and one of its characteristics is cognitive impairments. Findings regarding levels of the heme metabolite and plasma antioxidant bilirubin in schizophrenia are inconclusive. However, a recently published study indicate that low levels of bilirubin may be implicated in the memory impairments seen in the disorder. The aim of this cross-sectional study was to investigate the levels of bilirubin in individuals with a first-episode psychosis (FEP) and to examine if bilirubin levels were associated to cognitive impairments, symptoms and duration of untreated psychosis (DUP). Bilirubin levels were reduced in 39 individuals with FEP compared with 20 HC (median [IQR]: 11.0 [9.0–13.0] µM vs. 15.0 [11.5–18.5] µM). In individuals with FEP, bilirubin levels were also positively correlated to two working memory tests (r = 0.40 and r = 0.32) and inversely correlated to DUP (r = − 0.36). Findings were not influenced by confounding factors. The results confirm the antioxidant deficit previously seen in schizophrenia, but also indicate that these changes may be related to DUP. The study also confirms that bilirubin may be implicated in the cognitive deficits that accompanies the disorder, here for the first time presented in individuals with FEP.

IntroductionPatient-controlled admissions (PCAs) represent a change in psychiatric inpatient care where patients are allowed to decide for themselves when hospitalisation might be required. Prior research has demonstrated that PCA increase the number of admissions, but decrease days in inpatient care, while both the admissions to and days in involuntary care decrease. However, investigations have been restricted to specific patient groups and have not examined other possible benefits, such as effects on symptoms, quality of life and autonomy.Methods and analysisThis study explores the implementation process and effects of PCA in Region Stockholm, who is currently introducing PCA for all patients with severe psychiatric conditions and extensive healthcare utilisation. In total, the study comprises approximately 45 inpatient wards, including child and adolescent psychiatry. In a naturalistic evaluation, patients assigned PCA will be followed up to 36 months, both with regard to hospitalisation rates and self-reported outcomes. In addition, qualitative studies will explore the experiences of patients, caregivers of adolescents and healthcare providers.Ethics and disseminationApproval has been granted by the Swedish Ethical Review Authority (Dnr: 2020-06498). The findings from this study will be disseminated via publications in international peer-reviewed journals, at scientific conferences, as part of two doctoral theses, and through the Swedish Partnership for Mental Health.Trial registration numberNCT04862897.

Purpose: Emotional instability and self-harm pose major problems for society and health care. There are effective interventions in outpatient care, but when patients need inpatient care, nurses often struggle meeting their patient's needs. Brief admission (BA) is a newly implemented crisis intervention and novel form of inpatient care. The aim of this study is to describe nurses' experiences working with BA related to patients with emotional instability and self-harm. Methods: Eight nurses were interviewed according to a semi-structured interview guide. The data was analysed using qualitative content analysis. Results: Four main categories emerged regarding nurses' experiences with BA: provides security and continuity, fosters caring relationships, shifts focus towards patient's health and empowers the patient. The nurse's role shifted from \"handling problems\" to establishing caring relationships with a focus on the person's health and possibilities for recovering instead of psychiatric symptoms. Conclusions: Previous studies on patients' perspective of BA describe positive experiences such as increased autonomy and participation in the healthcare process. This study supports those findings, albeit from the perspective of nurses. Our findings suggest that BA may reduce work-related stress experienced by nurses while caring for persons with emotional instability and self-harm. BA may also support nurses in their ability to provide more meaningful and constructive psychiatric inpatient care.

Patients with schizophrenia have a threefold higher mortality from cardiovascular disease than people in the general population. Atherosclerosis is linked to immune activation, a process tentatively entwined with the underlying pathophysiological mechanisms of schizophrenia. The aim of the present study was to investigate an extensive array of cardiovascular biomarkers in individuals experiencing their first episode of psychosis (FEP), either drug-naïve or exposed to short-term antipsychotic treatment, alongside a group of healthy controls (HC). Using the OLINK Proximity Extension Assay, Cardiovascular II Panel, we analyzed plasma from 72 FEP patients, including 42 later diagnosed with schizophrenia and 54 HCs. Biomarker levels, that significantly differed between patients and controls, were correlated with symptom severity, cognitive performance and cardiovascular risk factors. Fifteen out of 92 cardiovascular biomarkers were higher in individuals with FEP compared to HC, and one biomarker was lower in FEP patients compared to HC. BMI, waist size, blood pressure, fp-glucose, HbA1c and serum lipid levels were similar between the groups. No correlations that held for multiple comparisons were seen between biomarker concentrations and symptom severity, cognitive performance or cardiovascular risk factors in FEP patients. Higher concentrations of several cardiovascular biomarkers were observed in individuals with FEP compared to in HC. This suggests that patients with FEP are at an increased risk of developing cardiovascular disease from the onset of psychosis, even before changes in traditional biomarkers are detectable. It underscores the need for innovative approaches to detect and monitor this risk early.

Using structural MRI data from 45,615 individuals aged 3–96 years, Kaufmann and colleagues reveal that common brain disorders are associated with heritable patterns of apparent aging of the brain.

Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.

To our knowledge, there is no consensus regarding when individuals who repeatedly self-harm and are at risk of suicide should be hospitalized. To evaluate a new alternative, we examined the effects of brief admission (BA) to hospital by self-referral. To determine the effects of BA on inpatient service use and on secondary outcomes of daily life functioning, nonsuicidal self-injuries, and attempted suicide among individuals who self-harm and are at risk of suicide. The single-masked Brief Admission Skåne Randomized Clinical Trial was conducted from September 2015 to June 2018 at 4 psychiatric health care facilities in southern Sweden. Data were collected 6 months retrospectively at baseline and at 6-month and 12-month follow-ups. Participants were randomized to either BA and treatment as usual (BA group) or treatment as usual (control group). The sample was a referral population, with the most important inclusion criteria being current episodes of self-harm and/or recurrent suicidality, at least 3 diagnostic criteria for borderline personality disorder, and hospitalization in the last 6 months. Self-referred BA was offered for 12 months, with standard limits for duration and frequency, after the negotiation of a contract outlining the intervention. Prespecified main outcome measures were days admitted to the hospital, including voluntary admission, BA, and compulsory admission. The 125 participants had a mean (SD) age of 32.0 (9.4) years, 106 (84.8%) were women, and 63 were randomized to the BA group and 62 to the control group. No significant advantage was observed in the number of days in the hospital for the BA group compared with the control group. Within-group analyses demonstrated significant decreases in both groups regarding days admitted to the hospital (BA group: χ2 = 22.71; P < .001; control group: χ2 = 23.01; P < .001) and visits to the emergency department (BA group: χ2 = 13.95; P < .001; control group: χ2 = 21.61; P < .001), but only the BA group showed a reduction in days with compulsory admission (χ2 = 7.67; P = .02) and nonsuicidal self-injuries (χ2 = 6.13; P = .047). The BA group showed significantly greater improvements in the mobility domain of daily life functioning (z = -2.39; P = .02) and significant within-group improvements in 3 other domains (cognition: F = 9.02; P < .001; domestic responsibilities: F = 3.23; P = .049; and participation: F = 3.79; P = .03). Brief admission appears no more efficacious in reducing use of inpatient services than usual care for individuals who self-harm and are at risk of suicide. Future studies should explore other possible beneficial effects. ClinicalTrials.gov identifier: NCT02985047.

Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [11C]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (β = 0.013–0.074, partial r = −0.037–0.273, p = 0.131–0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3–8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.

Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.