Search

Quetiapine use is on the rise, leading to a corresponding increase in acute intoxications, some of which have fatal outcomes. When assessing whole-blood quetiapine concentrations during forensic autopsies, interpretations are primarily based on toxicity data from studies of serum concentrations. To our knowledge, there are only two previous studies that have attempted to establish the ratio between whole blood and serum quetiapine concentrations with limited populations and high variability of results. Paired specimens of whole blood and serum from 16 quetiapine users recruited from the Psychiatric Clinic, St. Olav University Hospital were analyzed using LC-MS-MS. Quetiapine concentrations in both matrices were determined and compared. The mean blood:serum ratio of quetiapine was 0.74 (standard deviation (SD) = 0.05, 95% confidence interval (CI) 0.71-0.76, P < 0.001), range 0.66-0.85. Simple linear regression showed strong linear correlation between quetiapine concentrations in the two matrices (B = 0.774, P > 0.001, r = 0.999). Our results imply that quetiapine occurs at lower concentrations within erythrocytes than in plasma. This is most likely due to a high degree of plasma protein binding. Other factors which may influence the distribution of quetiapine between these compartments are solubility, metabolism and passive or active efflux mechanisms. We did not observe any covariation between blood:serum ratios and serum concentrations. Quetiapine was consistently present at lower concentrations in whole blood than in serum. If so inclined to, a conversion factor of ∼0.7 may be considered for extrapolation of concentrations from serum to whole blood, at least in cases with therapeutic quetiapine concentration levels., (© The Author(s) 2024. Published by Oxford University Press.)

Central nervous system inflammation might play a role in patients with depressive disorders. This hypothesis is supported by studies reporting increased cerebrospinal fluid levels of the inflammatory markers interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNF-α) in patients with ongoing depression. In this case-control study, we aimed to examine whether these findings also applied to depressed patients in a geriatric population . Cerebrospinal fluid cytokine analyses were performed on 15 patients (age >60 years) with depressive disorders and 45 age- and sex matched controls (patients with headache or idiopathic facial palsy). IL-6, IL-8, IL-10, TNF-α, monocyte chemoattractant protein-1 and transforming growth factor beta 1 were included in the statistical analyses. Patients with depression had significantly lower cerebrospinal fluid levels of IL-6 as compared to controls ( p = 0.014) in the univariate analysis. The finding was, however, no longer statistically significant after correction for age and body mass index ( p = 0.097). Overall, this study indicates that the cytokines included in this study are not significantly altered in geriatric patients with depression. Future studies exploring cerebrospinal fluid cytokine levels should include corrections for possible confounding factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schou, Larsen, Stunes and Sæther.)

Aims: This open-label study in patients with alcohol dependence and evidence of elevated liver stiffness and/or hepatic steatosis was designed to explore the efficacy of nalmefene (18 mg) in reducing alcohol consumption and its subsequent effects on a variety of clinically relevant liver parameters., Methods: Adult patients with a diagnosis of alcohol dependence and evidence of elevated liver stiffness and/or hepatic steatosis (liver stiffness >6 kPa or controlled attenuation parameter (CAP) >215 dB/m as measured by transient elastography) were recruited at two study sites in Germany. During the 12-week treatment period, patients were instructed to take nalmefene each day they perceived a risk of drinking alcohol., Results: All 45 enrolled patients took at least one dose of nalmefene and 39 completed the study. After 12 weeks of study treatment with nalmefene patients showed a reduction in alcohol consumption of -13.5 days/month heavy drinking days and -45.8 g/day total alcohol consumption. Most liver parameters showed modest changes at Week 12; there was a 13% decrease in liver stiffness and 10% reduction in CAP values. Results indicated non-significant negative associations between alcohol consumption and liver stiffness and/or CAP over this 12-week study. Nalmefene was generally well tolerated, and most adverse events were mild or moderate, the most frequent being dizziness., Conclusions: Patients treated with nalmefene for 12 weeks had reductions in alcohol consumption by ~50% relative to baseline and showed trends to improvement in liver stiffness and CAP., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

The clinical significance of anti-neuronal antibodies for psychiatric disorders is controversial. We investigated if a positive anti-neuronal antibody status at admission to acute psychiatric inpatient care was associated with a more severe neuropsychiatric phenotype and more frequent abnormalities during clinical work-up three years later. Patients admitted to acute psychiatric inpatient care who tested positive for N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2) and/or glutamic acid decarboxylase 65 (GAD65) antibodies (n = 24) were age - and sex matched with antibody-negative patients (1:2) from the same cohort (n = 48). All patients were invited to follow-up including psychometric testing (e.g. Symptom Checklist-90-Revised), serum and cerebrospinal fluid (CSF) sampling, EEG and 3 T brain MRI. Twelve antibody-positive (ab+) and 26 antibody-negative (ab-) patients consented to follow-up. Ab+ patients had more severe symptoms of depression (p = 0.03), psychoticism (p = 0.04) and agitation (p = 0.001) compared to ab- patients. There were no differences in CSF analysis (n = 6 ab+/12 ab-), EEG (n = 7 ab+/19 ab-) or brain MRI (n = 7 ab+/17 ab-) between the groups. In conclusion, anti-neuronal ab+ status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at three-year follow-up. This supports the hypothesis that anti-neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients.

Background: Norwegian national guidelines recommend that clozapine be offered to patients with schizophrenia after two failed attempts with other antipsychotic drugs. One of the main objectives for the introduction of clinical pathways in mental health care is to provide an equal service to patients irrespective of where in the country they live. We wished to investigate the prescribing level of clozapine in various Norwegian counties., Material and Method: We retrieved aggregated data from the Norwegian Prescription Database, the Norwegian Patient Registry and Statistics Norway on prescribing of clozapine, number of patients in contact with the specialist health service with the diagnosis schizophrenia, and population figures for 2016., Results: Nationwide in 2016, there were 50 users of clozapine per 100 000 inhabitants (95 % confidence interval (CI) 48-52). The number of users was highest in Troms county (76 (95 % CI 63-89) per 100 000 inhabitants) and lowest in Akershus county (38 (95 % CI 33-43) per 100 000 inhabitants). We found no significant correlation between the prescribing rate for clozapine and the proportion of the population in the county who were undergoing treatment for schizophrenia in the specialist health service., Interpretation: Prescribing of clozapine varies among Norwegian counties and is not correlated with the proportion of the population who are undergoing treatment for schizophrenia in the specialist health service. Different levels of implementation of the national guidelines constitute a possible explanation for the geographic differences.

Objective: To identify the specific domains of the presynaptic protein synapsin targeted by recently described autoantibodies to synapsin., Methods: Sera of 20 and CSF of two patients with different psychiatric and neurological disorders previously tested positive for immunoglobulin (Ig)G antibodies to full-length synapsin were screened for IgG against synapsin I domains using HEK293 cells transfected with constructs encoding different domains of rat synapsin Ia. Additionally, IgG subclasses were determined using full-length synapsin Ia. Serum and CSF from one patient were also screened for IgA autoantibodies to synapsin I domains. Sera from nine and CSF from two healthy subjects were analyzed as controls., Results: IgG in serum from 12 of 20 IgG synapsin full-length positive patients, but from none of the healthy controls, bound to synapsin domains. Of these 12 sera, six bound to the A domain, five to the D domain, and one to the B- (and possibly A-), D-, and E-domains of synapsin I. IgG antibodies to the D-domain were also detected in one of the CSF samples. Determination of IgG subclasses detected IgG1 in two sera and one CSF, IgG2 in none of the samples, IgG3 in two sera, and IgG4 in eight sera. One patient known to be positive for IgA antibodies to full-length synapsin had IgA antibodies to the D-domain in serum and CSF., Conclusions: Anti-synapsin autoantibodies preferentially bind to either the A- or the D-domain of synapsin I., Competing Interests: The authors have declared that no competing interests exist.

Background: The clinical significance of anti-neuronal antibodies in patients with psychiatric disorders, but without encephalitis, remains unknown. In patients admitted to acute psychiatric inpatient care we aimed to identify clinical features distinguishing anti-neuronal antibody positive patients from matched controls., Results: Patients who were serum-positive to N-methyl D-aspartate receptor (NMDAR) (n = 21), contactin-associated protein 2 (CASPR2) (n = 14) and/or glutamic acid decarboxylase 65 (GAD65) (n = 9) antibodies (cases) were age and sex matched (1:2) with serum-negative patients from the same cohort (controls). The prevalence and severity of psychiatric symptoms frequently encountered in NMDAR, CASPR2 and GAD65 antibody associated disorders were compared in cases and controls. NMDAR, CASPR2 and GAD65 antibody positive patients did not differ in their clinical presentation from matched serum negative controls., Conclusion: In this cohort, patients with and without NMDAR, CASPR2 and GAD65 antibodies admitted to acute psychiatric inpatient care had similar psychiatric phenotypes. This does not exclude their clinical relevance in subgroups of patients, and studies further investigating the clinical significance of anti-neuronal antibodies in patients with psychiatric symptomatology are needed.

Objective: To study the prevalence of autoantibodies to synapsin in patients with psychiatric and neurological disorders and to describe clinical findings in synapsin antibody positive patients., Methods: Sera of 375 patients with different psychiatric and neurological disorders and sera of 97 healthy controls were screened (dilution 1:320) for anti-synapsin IgG using HEK293 cells transfected with rat synapsin Ia. Positive sera were further analyzed by immunoblots with brain tissue from wild type and synapsin knock out mice and with HEK293 cells transfected with human synapsin Ia and Ib. Binding of synapsin IgG positive sera to primary neurons was studied using murine hippocampal neurons., Results: IgG in serum from 23 (6.1%) of 375 patients, but from none of the 97 healthy controls (p=0.007), bound to rat synapsin Ia transfected cells with a median (range) titer of 1:1000 (1:320-1:100,000). Twelve of the 23 positive sera reacted with a protein of the molecular size of synapsin I in immunoblots of wild type but not of synapsin knock out mouse brain tissue. Out of 19/23 positive sera available for testing, 13 bound to human synapsin Ia and 16 to human synapsin Ib transfected cells. Synapsin IgG positive sera stained fixed and permeabilized murine hippocampal neurons. Synapsin IgG positive patients had various psychiatric and neurological disorders. Tumors were documented in 2 patients (melanoma, small cell lung carcinoma); concomitant anti-neuronal or other autoantibodies were present in 8 patients., Conclusions: Autoantibodies to human synapsin Ia and Ib are detectable in a proportion of sera from patients with different psychiatric and neurological disorders, warranting further investigation into the potential pathophysiological relevance of these antibodies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Self-rated health is frequently used as a health outcome variable in population studies. The aim of this study was to investigate the association between self-rated health and mortality in a Norwegian population., Material and Methods: We used data from the first "Nord-Trøndelag Health Study" in 1984-1986 (HUNT 1), where 76,793 persons aged 20 years and older participated (90.7 % of the total adult county population). Average follow-up time was 16.4 years (median 18.9 years). Mortality risks in different groups were estimated using Cox' regression analyses, adjusted for age, education and chronic disease., Results: Compared to participants with very good self-rated health, men with poor self-rated health had a relative increased mortality risk (hazard ratio) of 2.37 (95 % CI 2,09-2,70) and women of 2.37 (95 % CI 2.05-2.76), when adjusted for age, education and chronic disease. Poor self-rated health gave a mortality risk of 2.99 (95 % CI 2.76-3.23), compared to self-reported myocardial infarction 2.02 (95 % CI 1.92-2.12) and diabetes 1.99 (95 % CI 1.90-2.09), adjusted for age and gender., Interpretation: Adults who participate in health surveys and rate their health to be poor have a higher mortality as a group than those with a good self-rated health, even higher than those with self-reported cardiac infarction or diabetes. Our findings strengthen the impression that self-rated health is a very important health indicator in population studies.