Lipid Alteration Signature in the Blood Plasma of Individuals With Schizophrenia, Depression, and Bipolar Disorder
Authors: Tkachev Anna , Stekolshchikova Elena , Vanyushkina Anna , Zhang Hanping , Morozova Anna , Zozulya Svetlana , Kurochkin Ilia , Anikanov Nickolay , Egorova Alina , Yushina Ekaterina , Vogl Thomas , Senner Fanny , Schaupp Sabrina K. , Reich-Erkelenz Daniela , Papiol Sergi , Kohshour Mojtaba Oraki , Klöhn-Saghatolislam Farahnaz , Kalman Janos L. , Heilbronner Urs , Heilbronner Maria , Gade Katrin , Comes Ashley L. , Budde Monika , Anderson-Schmidt Heike , Adorjan Kristina , Wiltfang Jens , Reininghaus Eva Z. , Juckel Georg , Dannlowski Udo , Fallgatter Andreas , Spitzer Carsten , Schmauß Max , von Hagen Martin , Zorkina Yana , Reznik Alexander , Barkhatova Aleksandra , Lisov Roman , Mokrov Nikita , Panov Maxim , Zubkov Dmitri , Petrova Daria , Zhou Chanjuan , Liu Yiyun , Pu Juncai , Falkai Peter , Kostyuk Georgiy , Klyushnik Tatiana , Schulze Thomas G. , Xie Peng , Schulte Eva C. , Khaitovich Philipp 
Published: January 2023

Importance

No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers.

Objective

To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD).

Design, Setting, and Participants

This was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria [DE-AT]), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health–related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020.

Main Outcomes and Measures

Plasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry.

Results

Blood lipid levels were assessed in 980 individuals (mean [SD] age, 36 [13] years; 510 male individuals [52%]) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean [SD] age, 34 [13] years; 323 male individuals [56%]). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: [Pearson correlation] r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P &amp;lt; 10−38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P &amp;lt; 10−79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids.

Conclusions and Relevance

In this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.