The Discovery of Clinically Applicable Biomarkers for Bipolar Disorder: A Review of Candidate and Proteomic Approaches

Abstract

Bipolar disorder (BD) is a severe psychiatric condition which affects innumerable people across the globe. The etiopathogenesis of BD is multi-faceted with genetic, environmental and psychosocial factors playing a role. Hitherto, the diagnosis and management of BD are purely on empirical grounds as we lack confirmed biomarkers for this condition. In this regard, hypothesis-driven investigations have been unable to identify clinically applicable biomarkers, steering the field towards newer technologies. Innovative, state-of-the-art techniques like multiplex immunoassays and mass spectrometry can potentially investigate the entire proteome. By detecting up or down regulated proteins, novel biomarkers are identified and new postulates about the etiopathogenesis of BD are specified. Hence, biological pathways are uncovered which are involved in the initiation and advancement of the disease and new therapeutic targets are identified. In this manuscript, the extant literature is thoroughly reviewed and the latest findings on candidate BD biomarkers are provided, followed by an overview of the proteomic approaches. It was found that due to the heterogeneous nature of BD no single biomarker is feasible, instead a panel of tests is more likely to be useful. With the application of latest technologies, it is expected that validated biomarkers will be discovered which will be useful as diagnostic tools and help in the delivery of individually tailored therapies to the patients.

Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients

“…To avoid recurrences of mood episodes in BD, lifetime treatment is frequently needed and is essentially pharmacological, using mood stabilizers (e.g., lithium and valproate) or atypical antipsychotics (e.g., quetiapine and aripiprazole); antidepressants are also useful for acute depressive phases [ 2 ]. Notwithstanding advances in neuroscientific research, no clinical or laboratorial biomarker has been clearly identified that allows for an early and accurate diagnosis of BD [ 5 , 6 ]. Thus, a better knowledge of the underlying mechanisms of BD pathophysiology is still an unmet need.…”

Proteomic Analysis of Plasma Markers in Patients Maintained on Antipsychotics: Comparison to Patients Off Antipsychotics and Normal Controls

“…Previous blood/plasma/serum proteomic studies showed that 202 proteins were significantly altered in SZ and 99 in BD ( 6 ). Most of these proteins are involved in glucose homeostasis, lipid metabolism, inflammatory and immune processes, or the role of growth factors ( 6 , 10 , 11 ).…”

“…Previous blood/plasma/serum proteomic studies showed that 202 proteins were significantly altered in SZ and 99 in BD ( 6 ). Most of these proteins are involved in glucose homeostasis, lipid metabolism, inflammatory and immune processes, or the role of growth factors ( 6 , 10 , 11 ). While some proteins are likely associated with the disease pathophysiology, others might be related to the non-therapeutic effects of medications.…”

“…The phenomenological approach resulted in a clear symptom overlap between these conditions and a significant within-group heterogeneity ( 3 , 4 ). This variability is primarily due to the absence of reliable biomarkers in clinical practice ( 5 , 6 ). In addition, biomarkers can add to the current knowledge about the mechanism of action of antipsychotics (APs) ( 7 ).…”

“…While some proteins are likely associated with the disease pathophysiology, others might be related to the non-therapeutic effects of medications. Other proteins might also predict the response to individual pharmacological interventions ( 6 , 12 ). Thus, proteomic studies might be a step toward personalized psychiatry treatment ( 13 ).…”