Exploring levels of TSH and FT4 in patients with chronic fatigue syndrome (CFS), fibromyalgia (FM) and healthy controls did not reveal any associations between fatigue score and level of thyroid hormones.

AIM: The diagnoses of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are highly associated with fatigue and pain, respectively. Physiologically and clinically an effect of thyroid status on fatigue and pain is expected. There may be clinically relevant differences in thyroid hormone axes though within values of reference in both patients with normal thyroid hormones, or in patients with well-regulated thyroid disease. These potential differences are explored in this study. MATERIALS AND METHODS: In the present study, female patients with CFS (n = 49) and FM (n = 58) as well as female healthy controls (n = 53) were included. We explored plasma levels of TSH and FT4 between the groups using Kruskall-Wallis, and the relation between fatigue score and levels of TSH and FT4 by means of Spearman's rho. RESULTS: There were no group differences between CFS patients, FM patients, and healthy controls in levels of TSH and FT4. CONCLUSION: As one might clinically and physiologically expect an association between thyroid function and fatigue, which may be associated with clinical disorders such as CFS and FM, we suggest future studies to examine the field further by exploring the influence of thyroid receptors and responses of the thyroid hormone cascade.

Transdiagnostic Associations between Anger Hostility and Chemokine Interferon-gamma Inducible Protein 10.

Objective: Many psychiatric disorders are linked to low grade systemic inflammation as measured by systemic cytokine levels. Exploration of cytokines and immune activity and their role in psychiatric symptoms may inform pathobiology and treatment opportunities. The aim of this study is to explore if there are associations between cytokines and psychiatric symptom clusters. Comparison between patients regularly using and those not using psychotropic medication is also conducted. Methods: This was a cross sectional naturalistic study with 132 participants from a general open inpatient psychiatric ward at the Nordland Hospital Trust, Norway. Serum levels of 28 different cytokines were assessed. Psychiatric symptoms the last week were assessed by a self-rating scale (Symptom check list, SCL-90-R) and grouped in defined clusters. Multiple linear regression model was used for statistical analyses of associations between levels of cytokines and symptoms, adjusting for possible confounding factors. Results: We found a positive association (p = 0.009) between the chemokine interferon-gamma inducible protein 10 (CXCL 10; IP-10) and the anger hostility cluster. No associations were found between the other symptom clusters and cytokines. IP-10 and the anger hostility cluster were positively associated (p = 0.002) in the subgroup of patients using psychotropic medication, not in the subgroup not using psychotropic medication. Conclusion: Our analyses revealed a significant positive association between the symptom cluster anger hostility in SCL-90-R and the chemokine IP-10 in the subgroup of patients using psychotropic medications.

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders.

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.

Measuring the Effect of the Early assessment Team (MEET) for patients referred to outpatient mental health care: a study protocol for a randomised controlled trial.

BACKGROUND: Referrals to specialised mental health care (such as community mental health centres; CMHC) have increased over the last two decades. Patients often have multifaceted problems, which cannot only be solved by such care. Resources are limited, and triaging is challenging. A novel method which approaches patients early and individually upon referral to a CMHC-possibly with a brief intervention-is an Early assessment Team (EaT). In an EaT, two therapists meet the patient early in the process and seek to solve the present problem, often involving community services, primary health care, etc.; attention is paid to symptoms and functional strife, rather than diagnoses. This is in contrast to treatment as usual (TAU), where the patient (after being on a waiting list) meets one therapist, who focuses on history and situation to assign a diagnosis and eventually start a longitudinal treatment. The aim of this study is to describe and compare EaT and TAU regarding such outcomes as work and social adjustment, mental health, quality of life, use of health services, and patient satisfaction. The primary outcome is a change in perceived function from baseline to 12-month follow-up, measured by the Work and Social Adjustment Scale. METHOD: Patients (18 years and above; n = 588) referred to outpatient health care at a CMHC are randomised to EaT or TAU. Measures (patient self-reports and clinician reports, patients' records, and register data) are collected at baseline, after the first and last meeting, and at 2, 4, 8, 12, and 24 months after inclusion. Some participants will be invited to participate in qualitative interviews. TRIAL DESIGN: The study is a single-centre, non-blinded, RCT with two conditions involving a longitudinal and mixed design (quantitative and qualitative data). DISCUSSION: This study will examine an intervention designed to determine early on which patients will benefit from parallel or other measures than assessment and treatment in CMHC and whether these will facilitate their recovery. Findings may potentially contribute to the development of the organisation of mental health services. TRIAL REGISTRATION: ClinicalTrials.gov NCT05087446. Registered on 21 October 2021.

Self-reported mental health difficulties were of limited use when screening for psychiatric diagnoses in adults born small for gestational age at term.

AIM: Being born small for gestational age (SGA) at term increases the risk of adverse health outcomes. We examined whether self-reported mental health differed between adults born SGA and non-SGA at term and could be used to screen for psychiatric diagnoses. METHODS: We used the Strengths and Difficulties Questionnaire to gather data from 68 participants born SGA and 88 non-SGA controls at a mean age of 26.5 years. Group differences were analysed by linear regression. We calculated the area under the curve and the sensitivity, specificity and predictive values for psychiatric diagnoses. RESULTS: The mean total difficulties score was 1.9 (95% confidence interval 0.4-3.5) points higher for participants born SGA. They also reported more internalising and emotional problems (p < 0.05). The areas under the curve were 0.82 and 0.68 in the SGA and control groups, respectively. Among participants born SGA, the 90th percentile cut-off had a sensitivity of 0.38, a specificity of 0.93 and positive and negative predictive values of 0.75 and 0.71. The 80th percentile cut-off had higher sensitivity and lower specificity. CONCLUSION: Adults born SGA reported more mental health difficulties than non-SGA controls. The low sensitivity using the 90th percentile cut-off suggests that a lower cut-off should be considered.

Mental health services in Norway, 2023.

Norway has, according to the World Health Organization, more psychiatrists engaged in public health services per head of population than any other country, and the proportionate numbers of psychologists and others engaged in mental healthcare are also among the world's highest. Approximately 10% of Norway's gross domestic product is spent on health, expenditure per capita that is the fourth highest internationally. We discuss how this wealth of expertise translates into the delivery of services to the public.

Are symptoms assessed differently for schizophrenia and other psychoses in legal insanity evaluations of violent crimes?

BACKGROUND: Forensic evaluations of legal insanity include the experts' assessment of symptoms present at the mental state examination (MSE) and the mental state at the time of offense (MSO). Delusions and hallucinations are most important. We explored how often symptoms were recorded in written forensic reports. DESIGN: This exploratory, cross-sectional study included 500 reports of legal insanity written in 2009-2018 from cases of violent crimes in Norway. The first author read all reports and coded symptoms recorded from the experts' assessments of the offenders. Two co-authors repeated this procedure for 50 randomly selected reports. Interrater reliability was calculated with Gwet's AC1. Generalized Linear Mixed Models with Wald tests for fixed effects and Risk Ratios as effect sizes were used for the statistical analyses. RESULTS: Legal insanity was the main conclusion in 23.6% of the reports; 71.2% of these were diagnosed with schizophrenia while 22.9% had other psychotic disorders. Experts recorded few symptoms from MSO, but more from MSE, although MSO is important for insanity. We found a significant association between delusions and hallucinations recorded present in the MSO and legal insanity for defendants with other psychotic disorders, but no association for defendants with schizophrenia. The differences in symptom recordings between diagnoses were significant. CONCLUSION: Few symptoms were recorded from the MSO. We found no association between presence of delusions or hallucinations and legal insanity for defendants with schizophrenia. This may indicate that a schizophrenia diagnosis is more important to the forensic conclusion than the symptoms recorded in the MSO.

Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study.

OBJECTIVES: Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use. METHODS: The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score. RESULTS: At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients. CONCLUSION: The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.

Antidepressive Effectiveness of Amisulpride, Aripiprazole, and Olanzapine in Patients With Schizophrenia Spectrum Disorders: A Secondary Outcome Analysis of a Pragmatic, Randomized Trial (BeSt InTro).

BACKGROUND: Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum. METHODS: Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling. RESULTS: Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization. CONCLUSIONS: There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs.

Giant Cell Arteritis Presenting with Mania, Psychosis, and Cognitive Dysfunction: A Case Report.

Background: Giant cell arteritis (GCA) is an autoimmune vasculitis affecting medium- and large-sized arteries. Vascular inflammation may lead to narrowing of the arterial lumen, and acute occlusion may result in vision loss and stroke. The classical symptoms include headache, fever, and jaw claudication. However, there is an increasing recognition of atypical presentations. Case Presentation. We report a case of a 70-year-old woman presenting with fluctuating manic symptoms and confusion, in addition to headache and musculoskeletal pain. After diagnosis of GCA, treatment with corticosteroids gradually improved the somatic symptoms. Conclusion: Corticosteroids led to a temporary exacerbation of manic symptoms, which improved after 3 to 4 weeks of continuous treatment, indicating that the symptoms were most likely associated with GCA. The patient manifested with clinical features and a clinical course that has, to our knowledge, not been described or published before. Therefore, GCA may be an underdiagnosed disease in psychiatric populations and should be considered in case of atypical, new-onset psychiatric disorders in the elderly.

Trajectories of response in schizophrenia-spectrum disorders: A one-year prospective cohort study of antipsychotic effectiveness.

BACKGROUND: Antipsychotic drugs remain the mainstay of schizophrenia treatment; however, their effectiveness has been questioned, and it is not possible to predict the response to a specific antipsychotic drug in an individual patient. Thus, it is important to compare the effectiveness of the various antipsychotics and search for possible response predictors. AIM: To investigate the effectiveness of antipsychotic drugs, we examined response trajectories and predictors for belonging to different trajectory groups. METHODS: The Bergen-Stavanger-Innsbruck-Trondheim (BeSt InTro) trial compared the effectiveness of three atypical antipsychotics-amisulpride, aripiprazole, and olanzapine-in a prospective, semirandomized, rater-blind, head-to-head design. Adult participants with a schizophrenia spectrum disorder diagnosis, according to international classification of diseases, Tenth Revision (ICD-10) F20-29, were included. Participants were followed for a period of 12 mo, with assessments at baseline; after one, three and six weeks; and after three, six, nine and 12 mo. A latent class mixed model was fitted to our data. The three-trajectory model based on the Positive and Negative Syndrome Scale (PANSS) total score reduction was found to have adequate fit, and the study drugs, as well as various demographic and clinical parameters, were tested as predictors for belonging to the different trajectory groups. RESULTS: Overall, 144 participants were included, and 41% completed the 12-mo study period. The largest trajectory group, consisting of 74% of participants, showed a PANSS total score reduction of 59% from baseline to 12 mo (Good response group). A trajectory group comprising 13% of participants had their PANSS total score reduced by 82.5% at 12 mo (Strong response group), while the last response trajectory group comprising 13% of the participants had a PANSS total score reduction of 13.6% (Slight response group). The largest part of the total reduction for the Good and Strong response groups occurred at six weeks of treatment, amounting to 45% and 48% reductions from baseline, respectively. The use of amisulpride predicted belonging to the Strong response group, while unemployment, depression, and negative psychotic symptoms at baseline increased the chance of belonging to the Slight response group, indicating a poor response to antipsychotic drug treatment. CONCLUSION: Most of the participants (87%) had a good outcome after one year. Amisulpride users, more often than aripiprazole and olanzapine users, belonged to the response trajectory group with a strong response.

Use of assessment instruments in forensic evaluations of criminal responsibility in Norway.

OBJECTIVES: Assessment instruments are often used to enhance quality and objectivity in therapeutic and legal settings. We aimed to explore the use of instruments in Norwegian reports of forensic evaluations of criminal responsibility; specifically, whether this use was associated with diagnostic and forensic conclusions. METHODS: Our study has an exploratory cross-sectional design. We examined 500 reports filed with the Norwegian Board of Forensic Medicine in 2009-2018 regarding defendants indicted for the most serious violent crimes. The first author coded data from all reports according to a registration form developed for this study. Two co-authors then coded a random sample of 50 reports, and inter-rater reliability measures were calculated. The first author coded 41 reports for calculation of intra-rater reliability. Descriptive statistics are presented for the use of assessment instruments, and a generalized linear mixed model (GLMM) was used to estimate associations between the use of instruments and diagnostic and forensic conclusions. RESULTS: Instruments were used in 50.0% of reports. The Wechler's Adult Intelligence Scale (WAIS), Historical Clinical Risk-20 (HCR-20), and the Structured Clinical Interview for DSM disorders (SCID I), were used in 15.8, 13.8, and 9.0% of reports, respectively. The use of instruments increased from 36% in 2009 to 58% in 2015; then decreased to 49% in 2018. Teams of two experts wrote 98.0% of reports, and 43.4% of these teams comprised two psychiatrists. In 20.0% of reports, the diagnostic conclusion was schizophrenia, and in 8.8% it was other psychotic disorders. A conclusion of criminal irresponsibility was given in 25.8% of reports. Instruments were more often used in reports written by teams that comprised both a psychiatrist and a psychologist, compared to reports by two psychiatrists. The use of instruments was strongly associated with both diagnostic and forensic conclusions. CONCLUSION: Instruments were used in 50% of reports on forensic evaluations of criminal responsibility in Norway, and their use increased during the study period. Use of instruments was associated with diagnostic and forensic conclusions.

High-sensitivity C-reactive protein is related to age and gender in an acute psychiatric inpatient population.

Increased levels of high-sensitivity C-reactive protein (hsCRP) is associated with several psychiatric disorders. Demographic factors such as age and gender might affect this association, but the results are conflicting. The aim of this study was to explore a relationship between age, gender and hsCRP in an acute psychiatric inpatient population. We included 484 patients admitted to an acute psychiatric ward. Based on age distribution percentiles (25%, 50% and 75 %), we categorized patients into three age groups; ≦31 years old, 31-47 years old and ≧ 48 years old. Differences in serum levels of hsCRP between the age groups were assessed in the total sample, within males and females, and within diagnostic groups. There were significant differences in hsCRP across age groups. The effect was stronger in males than females. The significant differences between age groups were kept among patients with substance use disorders and bipolar disorders, but not among schizophrenia spectrum disorders, unipolar depression, neurotic disorders and personality disorders. Our findings suggest that the previously known association between age and hsCRP is present within an acute psychiatric population. However, this association was not found for all psychiatric diagnoses.

Association between C-reactive protein levels and antipsychotic treatment during 12 months follow-up period after acute psychosis.

BACKGROUND: A potential role of inflammatory pathways in the pathology of schizophrenia has been suggested for at least a subgroup of patients. Elevated levels of the inflammatory marker C-reactive protein (CRP) have been observed, with associations to pathogenesis and symptoms. The current evidence regarding effects of antipsychotics on CRP levels is ambiguous. OBJECTIVES: To examine and compare the influence on CRP levels of three pharmacologically diverse new generation antipsychotics during a one-year follow-up in schizophrenia spectrum disorder. METHODS: In a multicenter, pragmatic and rater-blinded randomized trial, the effects of amisulpride, aripiprazole and olanzapine were compared in 128 patients with schizophrenia spectrum disorder. All had positive symptoms of psychosis at study entry. Clinical and laboratory assessments including the measurement of CRP levels were conducted at baseline, and 1, 3, 6, 12, 26, 39, and 52 weeks thereafter. RESULTS: For all antipsychotic drugs analysed together, there was an increase in CRP levels during the one-year follow-up. Aripiprazole, as opposed to amisulpride and olanzapine, was associated with a reduced CRP level after one week, after which the CRP level caught up with the other drugs. Compared to those previously exposed to antipsychotic drugs, antipsychotic-naïve patients had lower CRP levels at all follow-up time points, but with the same temporal patterns of change. CONCLUSION: Treatment with amisulpride, aripiprazole and olanzapine showed different effects on CRP levels in patients with schizophrenia spectrum disorders, modified by previous antipsychotics exposure status. This finding suggests that antipsychotic drugs may vary with respect to their influence on pro-inflammatory pathways. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01446328; URL: http://www. CLINICALTRIALS: gov/.

Association between brain-derived neurotropic factor (BDNF), high-sensitivity C-reactive protein (hs-CRP) and psychiatric symptoms in medicated and unmedicated patients.

BACKGROUND: There is evidence that brain-derived neurotropic factor (BDNF) plays a protective role in the brain. Peripheral levels of BDNF correlate with its concentration in the brain. Previous studies have revealed lower serum BDNF levels in patients with mental illnesses. In most studies serum BDNF correlates negatively with psychiatric disorders and disease severity. Most studies in this field are on psychiatric diagnosis and personality traits. The aim of our study is to explore associations between general psychiatric symptoms, independent of diagnostic groups, and serum BDNF as well as the inflammatory biomarker high-sensitive CRP (hs-CRP). Comparison between the group regularly using psychotropic medication and those not using psychotropic medication is conducted. METHODS: The study is a cross sectional study with 132 participants from a general open inpatient psychiatric ward at the Nordland Hospital Trust, Bodoe, Norway. Participants were assessed on serum levels of BDNF and hs-CRP. Psychiatric symptoms were assessed by a self-rating scale (Symptom check list, SCL-90- R). Multiple linear regression model was used for statistical analyses of associations between levels of BDNF, hs-CRP and symptoms. RESULTS: We found a positive association (p < 0.05), for most SCL-90 symptom clusters with BDNF in the psychotropic medication-free group. No associations were found in the group of patients using psychotropic medication, except one, the paranoid ideation cluster (p 0.022). No associations were found between hs-CRP and symptom clusters. CONCLUSION: We found no relation between symptom clusters and the inflammatory biomarker hs-CRP. Serum BDNF levels were positively associated with intensity of psychiatric symptoms in the group of patients not using psychotropic medication. Our findings are in conflict with several previous studies reporting increased hs-CRP as well as decreased rather than increased BDNF in mental suffering. Patients on psychotropic medication may not require the same upregulation because the medication is modulating the underlying biological pathology.

Neurocognitive function and associations with mental health in adults born preterm with very low birthweight or small for gestational age at term.

Objectives: To assess neurocognitive function in adults born with low birthweight compared with controls and to explore associations between neurocognitive function and psychopathology in these groups. Methods: In this prospective cohort study, one group born preterm with very low birthweight (VLBW: birthweight <1,500 g, n = 53), one group born small for gestational age at term (SGA: birthweight <10th percentile, n = 63) and one term-born control group (birthweight ≥10th percentile, n = 81) were assessed with neurocognitive tests, diagnostic interviews, and self-report questionnaires at 26 years of age. Results: The VLBW group scored significantly below the control group on several neurocognitive measures, including IQ measures, psychomotor speed, verbal fluency, aspects of visual learning and memory, attention, social cognition, working memory and fine motor speed. The SGA group consistently scored at an intermediate level between the VLBW and the control group and had significantly lower scores than controls on Performance IQ and psychomotor speed, including switching. In the VLBW group, associations were found between lower spatial working memory and the presence of anxiety disorders, internalizing and attention problems, and autistic traits. Furthermore, lower Full scale IQ was associated with attention problems when adjusting for sex and parental socioeconomic status. Conclusion: Adults born preterm with VLBW or born term SGA displayed neurocognitive difficulties. Spatial working memory was associated with difficulties with attention, anxiety, and social function of VLBW adults. The finding and its clinical applicability should be further explored.