WFRF:(Jakobsson Joel)
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A serum proteomic study of two case-control cohorts identifies novel biomarkers for bipolar disorder
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- Göteson, Andreas, 1991 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Isgren, Anniella (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Sparding, Timea (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- (creator_code:org_t)
- 2022-02-08
- 2022
- English.
- In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
- Journal article (peer-reviewed)
Abstract
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- 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).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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