Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder

Göteson, Andreas; Isgren, Anniella; Jönsson, Lina; Sparding, Timea; Smedler, Erik; Pelanis, Aurimantas; Zetterberg, Henrik; Jakobsson, Joel; Pålsson, Erik; Holmén-Larsson, Jessica; Landén, Mikael

doi:10.1038/s41380-021-01236-5

Cited by 13 publications

(9 citation statements)

References 57 publications

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“…We conducted an exploratory proteomic study of bipolar disorder using CSF collected in two independent case-control cohorts. This is the second study using the PEA technology to measure CSF protein concentrations in these cohorts [7]. Here, we used three Olink protein biomarker discovery panels, whereof one was targeted toward immune markers.…”

Section: Discussionmentioning

confidence: 99%

“…The recruitment process and work-up procedures for patients and selection of control subjects have been described in detail previously [7,[12][13][14]. In brief, an adapted Swedish version of the semi-structured interview Affective Disorder Evaluation (ADE) was used to aid the diagnosis of bipolar disorder.…”

Section: Patients and Methods Study Populationmentioning

confidence: 99%

“…Combined, these panels include 201 unique protein assays. Six assays overlapped with a previous study conducted in the same study population [7]. Correlations for the overlapping assays are presented in Supplementary figure 1 and case-control comparisons for these proteins are shown in supplementary table 1.…”

Section: Immunoassays and Preprocessing Of Protein Datamentioning

confidence: 99%

“…We recently analyzed CSF samples from the same two independent bipolar cohorts used in the present study with a multiplex protein assay targeted for CNS processes [7]. Two proteins (testican-1 and C-type lectin domain family 1 member B) differed between patients and controls.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid proteomic study of two bipolar disorder cohorts

et al. 2022

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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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Section: Discussionmentioning

confidence: 99%

Section: Patients and Methods Study Populationmentioning

confidence: 99%

Section: Immunoassays and Preprocessing Of Protein Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid proteomic study of two bipolar disorder cohorts

et al. 2022

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“…Indeed, miRNA circulating levels are a promising field of investigation [ 56 - 60 ]. Access to cerebrospinal fluid could reduce this bias [ 61 , 62 ], however feasibility is obviously a strong limitation.…”

Section: Potential Limitations Of Biomarkersmentioning

confidence: 99%

Clinical Utility of Fluid Biomarker in Depressive Disorder

Serretti

2022

Clin Psychopharmacol Neurosci

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Major depressive disorders are ranked as the single largest contributor to non-fatal health loss and biomarkers could largely improve our routine clinical activity by predicting disease course and guiding treatment. However there is still a dearth of valid biomarkers in the field of psychiatry. The initial assumption that a single biomarker can capture the myriad of complex processes proved to be naive. The purpose of this paper is to critically review the field and to illustrate the possible practical application for routine clinical care. Biomarkers derived from DNA analysis are the ones that have received the most attention. Other potential candidates include circulating transcription products, proteins, and inflammatory markers. DNA polygenic risk scores proved to be useful in other fields of medicine and preliminary results suggest that they could be useful both as risk and diagnostic biomarkers also in depression and for the choice of treatment. A number of other possible fluid biomarkers are currently under investigation for diagnosis, outcome prediction, staging, and stratification of interventions, however research is still needed before they can be used for routine clinical care. When available, clinicians may be able to receive a lab report with detailed information about disease risk, outcome prediction, and specific indications about preferred treatments.

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Search for cerebrospinal fluid biomarkers in patients with major psychiatric disorders: Multiplex immunoassay findings and proximity extension assay prospects

Hidese

2024

Neuropsychopharm Rep

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Multiplex immunoassays have been developed to detect multiple proteins simultaneously and are used to search for biomarkers, including those present in major psychiatric disorders. This study aimed to review multiplex immunoassay studies on cerebrospinal fluid (CSF) biomarkers in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) and examine future research directions using improved proteomic techniques. According to the results of previous multiplex immunoassay studies, increased CSF IFN‐β, IL‐8, MCP‐2, MMP‐2, PAI‐1, sICAM‐1, and sVCAM‐1 and decreased CSF ACE, APP, fibrinogen, and GDNF were observed in patients with schizophrenia, while CSF HGF and S100B were positively correlated with psychotic symptom and CSF IL‐11, IL‐29/IFN‐λ1, and TSLP were negatively correlated. Increased CSF IFN‐β and IL‐1β and decreased CSF Aβ42, APP, IL‐6, and NCAM‐1 were observed, while CSF S100B was positively correlated with manic symptom in patients with BD. Increased CSF IL‐4, MCP‐1, MIP‐1β, and MMP‐2 were observed in patients with MDD, while CSF HGF and MMP‐2 were positively correlated with depressive symptom and CSF IL‐15 and MCP‐1 were negatively correlated. However, signal cross‐talk and cross‐reactivity problems have been observed in previous studies using multiplex immunoassay. The proximity extension assay can be used to overcome cross‐reactivity and enable ultrasensitive multiplexed detection and quantification of more than 1000 target proteins. However, proteomic studies using proximity extension assay technology in patients with schizophrenia, BD, or MDD are still scarce. Therefore, future high‐quality proteomic studies are required to identify CSF biomarkers for larger sets of target proteins in patients with major psychiatric disorders.

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Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder

Cited by 13 publications

References 57 publications

Cerebrospinal fluid proteomic study of two bipolar disorder cohorts

Cerebrospinal fluid proteomic study of two bipolar disorder cohorts

Clinical Utility of Fluid Biomarker in Depressive Disorder

Search for cerebrospinal fluid biomarkers in patients with major psychiatric disorders: Multiplex immunoassay findings and proximity extension assay prospects

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