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- Göteson, Andreas, 1991, et al.
(author)
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A serum proteomic study of two case-control cohorts identifies novel biomarkers for bipolar disorder
- 2022
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Journal article (peer-reviewed)abstract
- We set out to identify novel protein associations with potential as clinically viable biomarkers for bipolar disorder. To this end, we used proximity extension assay to analyze 201 unique proteins in blood serum from two independent cohorts comprising patients with bipolar disorder and healthy controls (total n = 493). We identified 32 proteins significantly associated with bipolar disorder in both case-control cohorts after adjusting for relevant covariates. Twenty-two findings are novel to bipolar disorder, but 10 proteins have previously been associated with bipolar disorder: chitinase-3-like protein 1, C-C motif chemokine 3 (CCL3), CCL4, CCL20, CCL25, interleukin 10, growth/differentiation factor-15, matrilysin (MMP-7), pro-adrenomedullin, and TNF-R1. Next, we estimated the variance in serum protein concentrations explained by psychiatric drugs and found that some case-control associations may have been driven by psychiatric drugs. The highest variance explained was observed between lithium use and MMP-7, and in post-hoc analyses and found that the serum concentration of MMP-7 was positively associated with serum lithium concentration, duration of lithium therapy, and inversely associated with estimated glomerular filtration rate in an interaction with lithium. This is noteworthy given that MMP-7 has been suggested as a mediator of renal tubulointerstitial fibrosis, which is characteristic of lithium-induced nephropathy. Finally, we used machine learning to evaluate the classification performance of the studied biomarkers but the average performance in unseen data was fair to moderate (area under the receiver operating curve = 0.72). Taken together, our serum biomarker findings provide novel insight to the etiopathology of bipolar disorder, and we present a suggestive biomarker for lithium-induced nephropathy. © 2022, The Author(s).
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| 2. |
- Göteson, Andreas, 1991, et al.
(author)
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Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 7446-53
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Journal article (peer-reviewed)abstract
- The etiopathology of bipolar disorder is largely unknown. We collected cerebrospinal fluid (CSF) samples from two independent case-control cohorts (total n = 351) to identify proteins associated with bipolar disorder. A panel of 92 proteins targeted towards central nervous system processes identified two proteins that replicated across the cohorts: the CSF concentrations of testican-1 were lower, and the CSF concentrations of C-type lectin domain family 1 member B (CLEC1B) were higher, in cases than controls. In a restricted subgroup analysis, we compared only bipolar type 1 with controls and identified two additional proteins that replicated in both cohorts: draxin and tumor necrosis factor receptor superfamily member 21 (TNFRSF21), both lower in cases than controls. This analysis additionally revealed several proteins significantly associated with bipolar type 1 in one cohort, falling just short of replicated statistical significance in the other (tenascin-R, disintegrin and metalloproteinase domain-containing protein 23, cell adhesion molecule 3, RGM domain family member B, plexin-B1, and brorin). Next, we conducted genome-wide association analyses of the case-control-associated proteins. In these analyses, we found associations with the voltage-gated calcium channel subunit CACNG4, and the lipid-droplet-associated gene PLIN5 with CSF concentrations of TNFRSF21 and CLEC1B, respectively. The reported proteins are involved in neuronal cell-cell and cell-matrix interactions, particularly in the developing brain, and in pathways of importance for lithium's mechanism of action. In summary, we report four novel CSF protein associations with bipolar disorder that replicated in two independent case-control cohorts, shedding new light on the central nervous system processes implicated in bipolar disorder.
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| 3. |
- Isgren, Anniella, et al.
(author)
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Cerebrospinal fluid proteomic study of two bipolar disorder cohorts
- 2022
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27:11, s. 4568-4574
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Journal article (peer-reviewed)abstract
- The pathophysiology of bipolar disorder remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, we analyzed 201 proteins in cerebrospinal fluid (CSF) from mood stable bipolar disorder patients and control subjects sampled from two independent cohorts, amounting to a total of 204 patients and 144 controls. We used three Olink Multiplex panels, whereof one specifically targets immune biomarkers, to assess a broad set of CSF protein concentrations. After quality control and removal of proteins with a low detection rate, 105 proteins remained for analyses in relation to case-control status and clinical variables. Only case-control differences that replicated across cohorts were considered. Results adjusted for potential confounders showed that CSF concentrations of growth hormone were lower in bipolar disorder compared with controls in both cohorts. The effect size was larger when the analysis was restricted to bipolar disorder type 1 and controls. We found no indications of immune activation or other aberrations. Growth hormone exerts many effects in the central nervous system and our findings suggest that growth hormone might be implicated in the pathophysiology of bipolar disorder.
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| 4. |
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| 5. |
- Lööw, Joel, et al.
(author)
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A CHANGING WORK ENVIRONMENT IN THE WAKE OF THE COVID-19 PANDEMIC? – OBSERVATIONS FROM MANAGERS IN A SWEDISH MINING COMPANY
- 2023
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In: Occupational Safety and Hygiene – SHO2023 Proceedings Book. - : Portuguese Society of Occupational Safety and Hygiene (SPOSHO). - 9789895486342 ; , s. 376-389, s. 376-389
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Conference paper (peer-reviewed)abstract
- Background: The Covid-19 pandemic has changed work life in many ways for many people; however, it is still an open question as to what changes will become permanent and what aspects of work life will return to that which was considered “normal” before the pandemic.Objective: In this study, the authors describe and analyse the effects of Covid-19 on managers in a large Swedish mining company.Method: This study is based on both quantitative and qualitative methods. Empirical material is used to explore the effects of the pandemic on the work environments of managers. Results are based on interviews in combination with a self-assessment process regarding how the managers allocated their work time during a work week.Results: The results describe the work activities of the studied managers supported with quotes from interview studies to illustrate to most central observations of how work has changed due to the Covid-19 pandemic.Conclusion: The results are summarized into six hypotheses: 1) the workday was densified due to remote meetings; 2) "double work" during meetings was the rule, rather than the exception; 3) meetings became more focused; 4) meetings became more accessible; 5) the manager became less operational; and 6) a new work culture was created.Application: This is an exploratory study of consequences and effects of Covid-19 pandemic summarized in six hypotheses that can befruitful for further and future studies.
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| 6. |
- Sandberg, Johan V, et al.
(author)
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Proteins associated with future suicide attempts in bipolar disorder: A large-scale biomarker discovery study
- 2022
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578.
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Journal article (peer-reviewed)abstract
- Suicide is a major cause of death worldwide. Several biological systems have been implicated in suicidal behavior but studies of candidate biomarkers have failed to produce clinically relevant biomarkers for suicide prediction. The objective of the present study was to identify novel candidate biomarkers for suicidal behavior. We used a nested case-control study design where a large cohort of patients with bipolar disorder (N = 5 110) were followed up to 8 years after blood sampling. We included patients that attempted suicide during follow-up (N = 348) and matched bipolar disorder patients from the same cohort who did not attempt suicide during the study period (N = 348) and analyzed a total of 92 proteins with a neuro exploratory multiplex panel. Using a multivariate classification algorithm devised to minimize bias in variable selection, we identified a parsimonious set of proteins that best discriminated bipolar disorder patients with and without prospective suicide attempts. The algorithm selected 16 proteins for the minimal-optimal classification model, which outperformed 500 models with permuted outcome (p = 0.0004) but had low sensitivity (53%) and specificity (64%). The candidate proteins were then entered in separate logistic regression models to calculate protein-specific associations with prospective suicide attempts. In individual analyses, three of these proteins were significantly associated with prospective suicide attempt (SCGB1A1, ANXA10, and CETN2). Most of the candidate proteins are novel to suicide research.
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| 7. |
- Vinberg, Stig, 1954-, et al.
(author)
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Do leadership behaviours, work environments and the health of managers in Sweden and outside Sweden differ?—a study of a large international mining company
- 2023
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In: Mineral Economics. - : Springer Nature. - 2191-2203 .- 2191-2211. ; 36:4, s. 655-666
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Journal article (peer-reviewed)abstract
- The mining industry faces specific challenges related to the working conditions and safety of employees. Studies indicate that the leadership behaviours, working conditions and health of managers are of importance for the working conditions and health of subordinates. Therefore, the aim here is to study these factors in a large international mining company with its head office in Sweden. The specific focus is on identifying similarities and differences that may exist between managers in Sweden and managers outside Sweden. An online survey with validated questions has been distributed to all managers in the company. The main findings are that both managers in and outside of Sweden report relatively high values regarding relation-, structure- and change-oriented leadership behaviours. In addition, managers also rated HEL (healthy and effective leadership) behaviours with relatively high values. The managers in Sweden rate relation orientation with the highest value and the managers outside Sweden rate structure orientation with the highest value. These differences have been confirmed by a regression analysis that identified significant associations between the group of managers based outside Sweden and higher structure orientated leadership behaviours. Both manager groups rate relatively high values regarding job satisfaction and self-rated health. However, they rate relatively high work demand values. The main conclusions are that there are different patterns in leadership behaviours between these two manager groups that can be related to cross-culture factors. Further investigation of the reasons for these differences is important in this industrial sector.
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| 8. |
- Zhang, R. Y., et al.
(author)
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Genome-wide study of immune biomarkers in cerebrospinal fluid and serum from patients with bipolar disorder and controls
- 2020
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1
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Journal article (peer-reviewed)abstract
- Bipolar disorder is a common, chronic psychiatric disorder. Despite high heritability, there is a paucity of identified genetic risk factors. Immune biomarkers are under more direct genetic influence than bipolar disorder. To explore the genetic associations with immune biomarker levels in cerebrospinal fluid (CSF) and blood serum which previously showed differences in bipolar disorder, we performed a study involving 291 individuals (184 bipolar disorder patients and 107 controls). The biomarkers assayed in both CSF and serum were: chitinase-3-like protein-1 (YKL-40), monocyte chemoattractant protein-1 (MCP-1), soluble cluster of differentiation (sCD14), tissue inhibitor of metalloproteinases-1 and 2 (TIMP-1 and TIMP-2). C-reactive protein (CRP) was only quantified in serum, and interleukin 8 (IL-8) measures were only available in CSF. Genome-wide association studies were conducted using PLINK for each of three genotyping waves and incorporated covariates for population substructure, age, sex, and body mass index (BMI). Results were combined by meta-analysis. Genome-wide significant associations were detected for all biomarkers except TIMP-1 and TIMP-2 in CSF. The strongest association in CSF was found for markers within the CNTNAP5 gene with YKL-40 (rs150248456, P=2.84x10(-10)). The strongest association in serum was also for YKL-40 but localized to the FANCI gene (rs188263039, P=5.80x10(-26)). This study revealed numerous biologically plausible genetic associations with immune biomarkers in CSF and blood serum. Importantly, the genetic variants regulating immune biomarker levels in CSF and blood serum differ. These results extend our knowledge of how biomarkers showing alterations in bipolar disorder are genetically regulated.
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