Alternations of Plasma Fatty Acids in Patients With Bipolar Depression Under Acute Treatment of rTMS Combined With Quetiapine and Mood Stabilizer

Abstract

Purpose: Repetitive transcranial magnetic stimulation (rTMS) represents a potential clinical tool in treating bipolar disorder (BD). However, the intervention of rTMS combined with pharmacotherapy on the plasma fatty acids (FAs) in patients with bipolar depression has not been reported yet.

Method: In this study, we assessed the clinical symptoms and evaluated plasma FAs from 30 inpatients with bipolar depression at baseline phase (BD group), after 2 weeks of treatment with rTMS combined with quetiapine and mood stabilizer (BD-2w group), and 32 healthy controls (HCs).

Finding: We found that acetic acid, propionic acid, isovaleric acid, isobutyric acid, and valeric acid, as well as levels of total short-chain fatty acids (SCFAs), were decreased in both BD and BD-2w groups, and levels of several medium- and long-chain fatty acids (MLCFAs) were altered in BD when compared with HC. Moreover, 2 weeks of treatment increased the levels of various MLCFAs. Finally, we developed combinational FAs panels that could distinguish BD from HC (area under the curve [AUC] = 0.961), BD-2w from HC (AUC = 0.978), and BD from BD-2w (AUC = 0.891) effectively.

Conclusion: These findings might provide a basis for developing diagnostic methods and reveal the potential relationship between bipolar depression and plasma FAs.

Keywords: acute treatment; bipolar depression; fatty acids; quetiapine combined with mood stabilizers; rTMS.

FIGURE 1

The differential concentration of fatty acids (FAs) among healthy control (HC), bipolar disorder (BD), and BD‐2w participants. (A) Short‐chain fatty acids, (B) polyunsaturated fatty acids, (C) saturated fatty acids, (D) monounsaturated fatty acids, (E) total SFAs, total MUFAs, total PUFAs, total N6‐PUFAs, and total N3‐PUFAs. The black circle, blue circle, and red circle represent one value from an individual in the HC, BD, and BD‐2w, respectively. C18:2n6c, cis‐linoleic acid; C20:4n6, arachidonic acid (AA); C18:3n3, α‐linolenic acid; C18:3n6, gamma‐linolenic acid; C20:3n6, gamma dihomo linoleic acid; C20:2, 11,14‐eicosadienoate; C20:5n3, eicosapentaenoic acid (EPA); C22:6n3, docosahexaenoic acid (DHA); C22:5n3, docosapentaenoic acid (DPA); C20:3n3, eicosatrienoic acid; C22:4, docosatetraenoate; C22:5n6, docosapentaenoic acid; C16:0, palmitic acid; C18:0, stearic acid; C17:0, heptadecanoic acid; C14:0, myristic acid; C15:0, pentadecanoic acid; C13:0, tridecanoic acid; C20:0, arachidic acid; C12:0, lauric acid; C22:0, behenic acid; C8:0, caprylic acid; C10:0, decanoate acid; 18:1n9c, cis‐oleic acid; C18:1n11c, cis‐vaccenic acid; C16:1, palmitoleic acid; C20:1, eicosenoic acid; C22:1T, trans‐erucic acid; C20:1T, trans‐eicosenoic acid; MUFAs, monounsaturated fatty acids; N3 PUFAs, omega‐3 polyunsaturated fatty acids; N6 PUFAs, omega‐6 polyunsaturated fatty acids; PUFAs, polyunsaturated fatty acids; SFAs, saturated fatty acids. *p < 0.05; **p < 0.01.

FIGURE 2

Potential biomarker panels and the correlation between levels of identified fatty acid (FA) species and clinical variables. Top 10 differential FAs identified from random forest classifiers, and area under the curve (AUC) value of receiver operating characteristic (ROC) analysis for discriminating the bipolar disorder (BD) from healthy control (HC) (A, B), BD‐2w from HC (D, E), and BD from BD‐2w (G, H). (C, F, and I) Correlation between concentrations of identified FA species and levels of LDL, BMI, HAMA, HAMD or BRMS, Age, HDL, GLU, gender, TG, and CHOL. Red and blue squares indicate positive and negative correlations, respectively, and the intensities of the colors are proportional to the degree of correlation. BMI, body mass index; BRMS, Bech–Rafaelsen Mania Rating Scale; CHOL, cholesterol; CI, confidence interval; GLU, blood glucose; HAMA, Hamilton Anxiety Scale; HAMD, Hamilton Depression Rating Scale; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; TG, triglyceride. *p < 0.05; **p < 0.01; ***p < 0.001.