Schoemaker Gwendolyn, Mocking Roel J T, Medema Suzanne, Koeter Maarten W J, de Haan Lieuwe, van Beveren Nico J M
Antes Centre for Mental Health Care, Rotterdam, the Netherlands.
Academic Medical Centre, Department of Psychiatry, University of Amsterdam, Amsterdam, the Netherlands.
Schizophr Res. 2025 Jul;281:275-285. doi: 10.1016/j.schres.2025.05.025. Epub 2025 May 27.
Schizophrenia is a heterogeneous disorder. Conflicting findings concerning abnormal levels of red blood cell fatty acids (RBC FA) in schizophrenia patients compared to healthy controls have been found. This stimulated research on the possible presence of a bimodal distribution of RBC FA. Bimodality suggests subgroups of the disease, including different endophenotypes and/or clinical characteristics. However, to date only a small number of publications reported on bimodality. The evidence whether fatty acids in red blood cells are bimodally distributed in schizophrenia is conflicting and data on bimodality in healthy controls are limited. The aim of current study was to investigate whether bimodal distributions of RBC FA concentrations are present in stable patients as compared to controls, and if so whether these distributions differ in form or size between patients and healthy controls.
From the GROUP study, a multisite, longitudinal, naturalistic cohort study, we investigated a subset of 215 patients, between 16 and 50 years, with a psychotic disorder and 98 healthy controls, between 16 and 50 years, for which RBC FA measurements were available. We studied a panel of 28 RBC FAs; 7 saturated fatty acids (SFAs), 9 monounsaturated fatty acids (MUFAs) and 12 polyunsaturated fatty acids (PUFAs). We did not investigate underlying genetics. The Likelihood Ratio Test was used to compare the goodness of fit of a bimodal or a unimodal distribution of each of the 28 FA concentrations. Hierarchical regressions were used to investigate whether belonging to the lower end of the distribution was associated with higher positive or negative symptom severity.
At baseline, 19 out of 28 FAs are significantly bimodally distributed in patients versus 11 out of 28 FAs in controls (p < .05). As a group, RBC FAs in patients are borderline significant more often bimodally distributed as compared to controls. In contrast to previous studies, for AA, DHA and EPA we did not find a bimodal distribution in patients and an unimodal distribution in controls. Belonging to the lower end of the RBC FA distribution was not associated with positive or negative symptom severity.
Our findings do not support the existence of a unique bimodality of RBC FA distribution in relatively stable patients with schizophrenia spectrum disorders compared to controls. Bimodality may be more pronounced in the acute phase of the disease, further research into bimodality should focus on the influence of oxidative stress on levels of FAs and bimodality in (partly) remitted patients as well as acutely ill patients.
精神分裂症是一种异质性疾病。与健康对照相比，精神分裂症患者红细胞脂肪酸（RBC FA）水平异常的研究结果相互矛盾。这激发了对RBC FA可能存在双峰分布的研究。双峰分布提示该疾病存在亚组，包括不同的内表型和/或临床特征。然而，迄今为止，仅有少数出版物报道了双峰分布情况。关于红细胞脂肪酸在精神分裂症中是否呈双峰分布的证据相互矛盾，且健康对照中双峰分布的数据有限。本研究的目的是调查与对照组相比，稳定期患者的RBC FA浓度是否存在双峰分布，如果存在，患者与健康对照之间这些分布在形式或大小上是否存在差异。
从一项多中心、纵向、自然主义队列研究GROUP研究中，我们调查了215例年龄在16至50岁之间患有精神障碍的患者和98例年龄在16至50岁之间的健康对照的一个子集，这些对象均有RBC FA测量数据。我们研究了一组28种RBC FA；7种饱和脂肪酸（SFA）、9种单不饱和脂肪酸（MUFA）和12种多不饱和脂肪酸（PUFA）。我们未研究潜在的遗传学。似然比检验用于比较28种FA浓度中每一种的双峰或单峰分布的拟合优度。分层回归用于研究属于分布较低端是否与更高的阳性或阴性症状严重程度相关。
在基线时，28种FA中有19种在患者中显著呈双峰分布，而在对照组中为28种中的11种（p <.05）。作为一个整体，与对照组相比，患者的RBC FA更常呈双峰分布，差异接近显著。与先前研究不同，对于花生四烯酸（AA）、二十二碳六烯酸（DHA）和二十碳五烯酸（EPA），我们未发现患者中存在双峰分布而对照组中存在单峰分布。属于RBC FA分布较低端与阳性或阴性症状严重程度无关。
我们的研究结果不支持与对照组相比，相对稳定的精神分裂症谱系障碍患者中存在独特的RBC FA分布双峰性。双峰性在疾病急性期可能更明显，对双峰性的进一步研究应关注氧化应激对脂肪酸水平的影响以及（部分）缓解期患者和急性期患者的双峰性。
