Coello Klara, Stanislaus Sharleny, Forman Julie Lyng, Kjærstad Hanne Lie, Ormstrup Sletved Kimie Stefanie, Miskowiak Kamilla Woznica, Faurholt-Jepsen Maria, Munkholm Klaus, Poulsen Henrik Enghusen, Vinberg Maj, Lykkesfeldt Jens, Kessing Lars V
Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark.
Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark.
Free Radic Biol Med. 2025 Jun;233:186-195. doi: 10.1016/j.freeradbiomed.2025.03.041. Epub 2025 Mar 28.
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).
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.
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.
Against expectations, our findings did not support increased lipid oxidation being a trait phenomenon in BD.
氧化应激增加所导致的组织损伤似乎在双相情感障碍(BD)的病理生理学和病程发展中起关键作用。丙二醛(MDA)作为脂质氧化的产物,可能是与家族风险相关的双相情感障碍的一种特质标记物。然而,在新诊断的双相情感障碍(BD)患者及其未患病亲属(UR)中,对丙二醛的研究很少。
在这项前瞻性的“双相情感障碍发病研究”中,我们对371例新诊断/首发双相情感障碍患者(1016次访视)、139例其未患病的一级亲属(307次访视)和199名无情感障碍个人或一级家族史的健康对照个体(HC)(537次访视)进行了丙二醛的重复测量,双相情感障碍患者的中位随访时间为2.0[0.1;3.8]年,未患病亲属为1.4[0;2.4]年,健康对照个体为2.5[1.1;3.9]年。在双相情感障碍患者中,我们进一步研究了7年内丙二醛与情感阶段以及药物和疾病变量之间的关联。
在针对性别和年龄进行校正并对多重比较进行校正的分析中,未患病亲属在基线时的丙二醛水平比健康对照个体高42.3%(B = 1.423,95%CI = 1.139,1.777,p = <0.044)。然而,这种差异并未随时间持续存在。双相情感障碍患者与健康对照个体或未患病亲属之间,随着时间推移,丙二醛水平未观察到统计学上的显著差异。此外,丙二醛水平与精神药物使用、疾病变量或情感阶段改变无关。
与预期相反,我们的研究结果不支持脂质氧化增加是双相情感障碍的一种特质现象。