Cerebrospinal fluid proteomic study of two bipolar disorder cohorts

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.

Large-Scale Mendelian Randomization Study Reveals Circulating Blood-based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance

“…More broadly, blood-based inflammatory markers identified in the present study should be tested as potential early indicators of the risk of developing psychiatric disorders and cognitive impairment. It is worth noting that most prior case-control studies have utilized low-throughput methods to assess circulating proteins; only three very recent studies have utilized the Olink or SomaScan platform to assess a large panel of proteins in serious mental illness [58][59][60] . Studies in patients at clinical high risk for psychosis, or in the first episode of psychosis, may be particularly informative due to relative lack of cumulative medication exposure, as well as providing information on the potential prognostic value of such blood-based proteomic biomarkers 61 .…”

“…Random-effects meta-analysis is more conservative than fixed-effects meta-analysis in the presence of heterogeneity across instruments without sacrificing power in the absence of heterogeneity 68 . Moreover, multiplicative random-effect meta-analysis is more conservative in the presence of pleiotropy 34 than an additive random-effects approach. (For comparison purposes and as a technical replication, we also performed MR analyses with standard fixed-effects IVW, using the commonly utilized TwoSampleMR package 17 ; results of this comparison are available in the supplementary materials.)…”

Pioneering Changes in Psychiatry: Biomarkers, Psychedelics, and AI

“…Current knowledge of biomarkers in psychiatry, the therapeutic use of psychedelics, and the application of AI techniques is still developing and is not without limitations. Identifying valid and reliable biomarkers in psychiatry has been challenging due to the complex and heterogeneous nature of psychiatric disorders . While the field has progressed, it still requires a comprehensive panel of biomarkers that can reliably guide clinical decisions.…”

T cells: an emerging cast of roles in bipolar disorder

“…As an essential component in maintaining the homeostasis of the internal environment, the immune system has typically evolved to protect humans from infection and malignancy; nonetheless, it is not without effects on the central nervous system, which can lead to changes in mood, cognition, and behavior [ 4 ]. The role of immune dysfunction in BD is currently unclear, with low-grade chronic inflammation (increased plasma cytokines, soluble cytokine receptors, chemokines, acute phase reactants) and T-cell activation features that may be associated with BD, but the results are controversial [ 5 – 9 ]. Stressful situations can trigger emotional episodes in individuals with BD, and T cells are associated with the physiological stress response [ 10 , 11 ].…”