Publications
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Prestmo, Astrid; Høyen, Karina Sagmo; Vaaler, Arne Einar; Torgersen, Terje; Kvithyld, Tuva Prestmo & Cohen, Lisa Janet
[Show all 7 contributors for this article]
(2023).
Post-discharge suicide among high-risk psychiatric inpatients: Risk factors and warnings signs.
Journal of Affective Disorders Reports.
ISSN 2666-9153.
12.
doi:
10.1016/j.jadr.2023.100506.
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Abstract
Background
The present study explored the predictive value of a novel suicide risk assessment with regard to suicide deaths within three years of discharge from an acute inpatient unit. The contributions of the different components of the assessment to overall determination of suicide risk were also explored.
Methods
A total of 380 acute psychiatric inpatients were analysed in a 3- year prospective study. At admission, the physician on duty performed a suicide risk assessment based on national guidelines and clinical state variables. A dichotomous variable reflecting high/low suicide risk level was determined by the clinician and recorded in the chart. Information on the number and causes of deaths was obtained from the Norwegian Cause of Death Registry.
Results
Eleven (2.9%) patients died by suicide within three years after discharge, eight high-risk patients and three low risk patients (OR = 8.7, 95% CI: 2.2–33, p = 0.002). In multivariable analysis, recent suicidal ideation (SI) (OR = 3.6, 95% CI: 1.5–8.7, p = 0.004), and affective disturbance (OR = 4.3, 95% CI: 1.5–12.6, p = 0.008) were significantly associated with rating of high suicide risk.
Limitations
The sample size was rather small, which in conjunction with the low base rate of suicide, reduces power and limits generalizability of the findings.
Conclusion
We found that a novel suicide risk assessment at admission to an acute psychiatric service was a powerful predictor of suicide post-discharge. The components of the risk assessment that were statistically significant with high suicide risk were affective disturbance and recent SI.
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Sheikh, Mashhood Ahmed; O'Connell, Kevin Sean; Lekva, Tove; Szabo, Attila; Akkouh, Ibrahim Ahmed & Osete, Jordi Requena
[Show all 31 contributors for this article]
(2022).
Systemic cell adhesion molecules in severe mental illness: Potential role of intercellular CAM-1 in linking peripheral and neuroinflammation.
Biological Psychiatry.
ISSN 0006-3223.
93,
p. 187–196.
doi:
10.1016/j.biopsych.2022.06.029.
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Background
Cell adhesion molecules (CAMs) orchestrate leukocyte trafficking and could link peripheral and neuroinflammation in patients with severe mental illness (SMI), by promoting inflammatory and immune-mediated responses and mediating signals across blood-brain barrier. We hypothesized that CAMs would be dysregulated in SMI and evaluated plasma levels of different vascular and neural CAMs. Dysregulated CAMs in plasma were further evaluated in vivo in leukocytes and brain tissue and in vitro in induced pluripotent stem cells.
Methods
We compared plasma soluble levels of different vascular (VCAM-1, ICAM-1, P-SEL) and neural (JAM-A, NCAD) CAMs in circulating leukocytes in a large SMI sample of schizophrenia (SCZ) spectrum disorder (n = 895) and affective disorder (n = 737) and healthy control participants (n = 1070) controlling for age, sex, body mass index, C-reactive protein, and freezer storage time. We also evaluated messenger RNA expression of ICAM1 and related genes encoding ICAM-1 receptors in leukocytes using microarray (n = 842) and in available RNA sequencing data from the CommonMind Consortium (CMC) in postmortem samples from the dorsolateral prefrontal cortex (n = 474). The regulation of soluble ICAM-1 in induced pluripotent stem cell–derived neurons and astrocytes was assessed in patients with SCZ and healthy control participants (n = 8 of each).
Results
Our major findings were 1) increased soluble ICAM-1 in patients with SMI compared with healthy control participants; 2) increased ITGB2 messenger RNA, encoding the beta chain of the ICAM-1 receptor, in circulating leukocytes from patients with SMI and increased prefrontal cortex messenger RNA expression of ICAM1 in SCZ; and 3) enhanced soluble ICAM-1 release in induced pluripotent stem cell–derived neurons from patients with SCZ.
Conclusions
Our results support a systemic and cerebral dysregulation of soluble ICAM-1 expression in SMI and especially in patients with SCZ.
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Filosa, James; Omland, Petter Moe; Hagen, Knut; Langsrud, Knut; Brenner, Eiliv & Knutsen, Andreas
[Show all 11 contributors for this article]
(2022).
Validation of questionnaires for restless legs syndrome in the
general population: the Trøndelag Health Study (HUNT).
Journal of Sleep Research.
ISSN 0962-1105.
p. 1–10.
doi:
10.1111/jsr.13571.
Show summary
Questionnaires for restless legs syndrome have rarely been validated against face-to-face interviews in the general population. We aimed to validate the modified Norwegian, seven-item Cambridge-Hopkins restless legs syndrome questionnaire and a single diagnostic question for restless legs syndrome. We also aimed to stratify validity at 65 years of age. Among a random sample of 1,201 participants from the fourth wave of the Trøndelag Health Study, 232 (19%) agreed to participate, out of whom 221 had complete data for analyses. Participants completed the questionnaires for restless legs syndrome immediately before attending a face-to-face interview using the latest diagnostic criteria. We calculated sensitivity, specificity, and Cohen’s kappa statistic (κ) of questionnaire- versus interview-based diagnoses. We found acceptable validity of the seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome (κ = 0.37, 95% confidence interval [CI] 0.23–0.51) and good validity of the single diagnostic question (κ = 0.47, 95% CI 0.35–0.58). We also found good validity through the combination of modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome items 2 and 5, while item 1 or 2 alone showed only acceptable validity. The single diagnostic question was significantly more valid among those aged <65 years (κ = 0.60 versus κ = 0.26). Both single- and two-item questionnaire-based diagnoses overestimated interview-based restless legs syndrome prevalence. The seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome will be useful for epidemiological studies although low sensitivity may cause underestimation of true restless legs syndrome prevalence in the general population, especially among elderly. Brief questionnaire-based diagnoses of up to three items seem best utilised as an initial screen. Future studies should identify brief and even more valid questionnaire-based diagnoses for restless legs syndrome in order to estimate prevalence accurately in large epidemiological studies.
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Mullins, Niamh; Forstner, Andreas J.; O'Connell, Kevin Sean; Coombes, Brandon; Coleman, Jonathan R. I. & Qiao, Zhen
[Show all 59 contributors for this article]
(2021).
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.
Nature Genetics.
ISSN 1061-4036.
53,
p. 817–829.
doi:
10.1038/s41588-021-00857-4.
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Nakken, Erlend Iversen; Grinde, Frithjof; Vaaler, Arne; Drange, Ole Kristian; Brodtkorb, Eylert & Sæther, Sverre Georg
(2021).
Epilepsy and other seizure disorders in acute psychiatric inpatients.
BMC Psychiatry.
ISSN 1471-244X.
21.
doi:
10.1186/s12888-021-03619-y.
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Background: It is well known that patients with epilepsy have a high rate of psychiatric comorbidity. However, studies exploring epilepsy in psychiatric cohorts are scarce. The aim of this study was to examine the prevalence of seizure disorders in acute psychiatric inpatients.
Methods: This is a cross-sectional study performed in a catchment-area based acute psychiatric department. All patients (age > 18) admitted during September 2011 - March 2012 were eligible for inclusion. Consenting patients were screened for a life-time history of epilepsy or seizures using self-reported questionnaire data and diagnostic codes for epilepsy in hospital and National registries. Patients scoring positive to one or more of these screening criteria underwent a thorough diagnostic validation (chart review), and the seizure disorders were classified as epilepsy, acute symptomatic seizures and/or psychogenic non-epileptic seizures according to current definitions.
Results: A total of 380 out of 591 (64.3%) consecutively admitted patients consented to participate in the study. Eighty-nine patients (23.4%) scored positive to one or more screening criteria. Fifteen (3.9%) were classified with epilepsy, 21 (5.5%) with acute symptomatic seizures and 9 (2.4%) with psychogenic non-epileptic seizures.
Conclusions: This is the first study to report on the prevalence of seizure disorders in acute psychiatric inpatients. The life-time prevalence of epilepsy in this cohort of patients is five - six times as high as reports in the general population. These findings underscore the need for the clinical psychiatrist to have comprehensive knowledge on the interface between epileptology and psychiatry.
Trials registration: ClinicalTrials.gov identifier NCT01415323.
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Szabo, Attila; O'Connell, Kevin Sean; Ueland, Thor; Sheikh, Mashhood Ahmed; Agartz, Ingrid & Andreou, Dimitrios
[Show all 31 contributors for this article]
(2021).
Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation.
Brain, Behavior, and Immunity.
ISSN 0889-1591.
99,
p. 299–306.
doi:
10.1016/j.bbi.2021.10.017.
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Background
Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients.
Methods
We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (n = 1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; n = 1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers.
Results
We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA, IL-18R1), and increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol types and the expression of inflammasome system elements in SMI.
Conclusions
Based on these results, we suggest a role for inflammasome activation/dysregulation in SMI. Our findings further the understanding of possible underlying inflammatory mechanisms and may expose important therapeutic targets in SMI.
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Wightman, Douglas P.; Jansen, Iris E.; Savage, Jeanne E.; Shadrin, Alexey; Bahrami, Shahram & Holland, Dominic
[Show all 59 contributors for this article]
(2021).
A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease.
Nature Genetics.
ISSN 1061-4036.
53,
p. 1276–1282.
doi:
10.1038/s41588-021-00921-z.
Show summary
Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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Engh, John; Ueland, Thor; Agartz, Ingrid; Andreou, Dimitrios; Aukrust, Pål & Boye, Birgitte
[Show all 27 contributors for this article]
(2021).
Plasma Levels of the Cytokines B Cell-Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Schizophrenia, Bipolar, and Major Depressive Disorder: A Cross Sectional, Multisite Study.
Schizophrenia Bulletin.
ISSN 0586-7614.
48(1),
p. 37–46.
doi:
10.1093/schbul/sbab106.
Show summary
Background
Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection.
Methods
We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP.
Results
Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen’s d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10).
Conclusions
These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.
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Reponen, Elina Johanna; Dieset, Ingrid; Tesli, Martin Steen; Mørch, Ragni Helene; Aas, Monica & Vedal, Trude Seselie Jahr
[Show all 18 contributors for this article]
(2020).
Atherogenic lipid ratios related to myeloperoxidase and C-reactive protein levels in psychotic disorders.
Frontiers in Psychiatry.
ISSN 1664-0640.
11.
doi:
10.3389/fpsyt.2020.00672.
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Background: Cardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders, where dyslipidemia occurs frequently. In the pathogenesis of these serious mental disorders, a low-grade inflammation seems to be a possible contributor. Concurrently, systemic inflammation and its interplay with dyslipidemia is a central driver in the pathogenesis of CVD. We hypothesize that evaluation of atherogenic lipid ratios together with inflammatory markers reflecting different inflammatory pathways with relevance for atherogenesis, could give novel information on immune-related mechanisms involved in early CVD risk in patients with psychotic disorders.
Methods: As a measure for CVD risk we calculated atherogenic lipid ratios using established sex-specific cut-offs: Total cholesterol/high-density lipoprotein; HDL-c (TC/HDL) and triglyceride/HDL-c (TG/HDL) were evaluated in 571 schizophrenia (SCZ) and 247 bipolar disorder (BD) patients, and in 99 healthy controls (HC). In addition, as a measure of low-grade inflammation, we measured fasting plasma levels of nine stable atherogenic inflammatory markers in patients (SCZ, BD) and in HC. The elevated inflammatory markers and CVD risk in patients, as reflected by TC/HDL and TG/HDL, were further assessed in multivariable analyses adjusting for comorbid cardio-metabolic risk factors.
Results: A markedly higher proportion (26%-31%) of patients had increased TC/HDL and TG/HDL ratios compared with HC. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO) were higher (p<0.05, p<0.001) in patients with psychotic disorders than in HC, and hs-CRP and MPO were independently associated with atherogenic lipid ratios in the multivariable analyses.
Conclusions: Our findings suggest that low-grade inflammation and abnormal neutrophil activation may cause increased CVD risk in patients with psychotic disorders. These mechanisms should be further examined to determine the potential for development of novel risk evaluation strategies.
Keywords: CVD risk; bipolar disorder; dyslipidemia; inflammatory biomarkers; schizophrenia.
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Schou, Morten Brix; Drange, Ole Kristian & Sæther, Sverre Georg
(2019).
Fylkesvise forskjeller i forskrivning av klozapin.
Tidsskrift for Den norske legeforening.
ISSN 0029-2001.
139(13),
p. 1265–1270.
doi:
10.4045/tidsskr.19.0151.
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Drange, Ole Kristian; Smeland, Olav Bjerkehagen; Shadrin, Alexey A.; Finseth, Per Ivar; Witoelar, Aree & Frei, Oleksandr
[Show all 52 contributors for this article]
(2019).
Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes.
Frontiers in Neuroscience.
ISSN 1662-4548.
13.
doi:
10.3389/fnins.2019.00220.
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Background: Alzheimer’s disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected.
Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits.
Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer’s Project part 1 (17,008 AD cases and 37,154 controls) and
the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework.
Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and
nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect).
Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP.
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Schou, Morten Brix; Sæther, Sverre Georg; Drange, Ole Kristian; Reitan, Solveig Merete Klæbo; Stoecker, Winfried & Vaaler, Arne
[Show all 7 contributors for this article]
(2017).
Anti-neuronal antibodies and their significance for psychiatric and cognitive symptomatology: a 3 year prospective case-controlled follow up study.
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Published
Feb. 24, 2022 2:52 PM
- Last modified
Feb. 24, 2022 2:52 PM
