Investigation of malondialdehyde as a trait marker associated with familial risk in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives – A longitudinal cohort study

Aims
Increased oxidative stress-generated tissue damage seems to play a pivotal role in the pathophysiology and progression of bipolar disorder (BD). Malondialdehyde (MDA), a product of lipid oxidation, may represent a trait marker in BD associated with familial risk. However, MDA is scarcely studied in patients with newly diagnosed bipolar disorder (BD) and their unaffected relatives (UR).
Methods
In this prospective "the Bipolar Illness Onset study", we investigated repeated measurements of MDA in a cohort of 371 patients with newly diagnosed/first-episode BD (1016 visits), 139 of their unaffected first-degree relatives (307 visits) and 199 healthy control individuals (HC) with no personal or first-degree family history of affective disorder (537 visits) with a median follow-up time of 2.0. [0.1; 3.8] years for patients with BD, 1.4 [0; 2.4] years for UR, and 2.5 [1.1; 3.9] years for HC. Amongst patients with BD, we further investigated associations of MDA with affective phases and medicine- and illness variables over a period of 7 years.
Results
Unaffected relatives had 42.3 % higher levels of MDA at baseline compared with HC in analyses adjusted for sex and age corrected for multiple comparisons (B = = 1.423, 95 % CI = 1.139, 1.777, p = <0.044). However, this difference did not persist over time. No statistically significant differences in MDA levels were observed over time between BD patients and either HC or UR. Additionally, MDA levels were not associated with psychotropic use, illness variables, or affective phase alterations.
Conclusions
Against expectations, our findings did not support increased lipid oxidation being a trait phenomenon in BD.