Journal of Affective Disorders Reports (Apr 2024)
Circulating levels of brain-derived neurotrophic factor (BDNF) in patients with bipolar disorders may be influenced by mitochondrial dysfunction, inflammation, and history of childhood trauma
Abstract
Background: Bipolar disorders are underpinned by deregulated immune processes including chronic inflammation. The crosstalk between immune factors and homeostatic molecules remains scarcely studied. The brain-derived neurotrophic factor is a neurotrophic molecule essential for neuronal and synaptic homeostasis. We explored correlations between BDNF levels and factors known to contribute to sustained inflammation, namely mitochondrial dysfunction (mtDNAcn), inflammation, and history of childhood maltreatment (CM). Methods: 175 patients with BD assessed either during acute mood episode or when euthymic and 85 healthy controls were included. CM history was assessed by the Childhood Trauma Questionnaire. Circulating levels of inflammatory molecules, BDNF and mitochondrial DNA copy number were determined. Correlations between the studied parameters were analyzed. Results: Low levels of BDNF were observed during acute mood episodes (mania/mixed/depression). We observed that IL-12/23p40 levels and history of CM were negatively correlated with circulating BDNF levels in acutely ill patients. In euthymic patients we found that while TNFα levels correlate negatively with BDNF levels, that of IL16, VEGF and mtDNAcn were positively correlated. Linear regression showed that: (i) in the whole BD sample, low mtDNAcn levels were associated with low BDNF levels (ii) in acutely ill BD patients, high CTQ-AE scores, and high IL-12/23p40 levels were associated with low BDNF levels. (ⅲ) in euthymic BD patients, low mtDNAcn levels were associated with low BDNF levels. Limitations: We acknowledge the relatively low sample size. Conclusions: We identified some of the immune factors possibly influencing the levels of BDNF. Future studies involving larger cohorts are warranted.
