Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review

Abstract

Background: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. Methods: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. Results: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti- inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro- inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. Conclusion: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.