Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression

Abstract

Introduction This study aimed to find the expression biomarkers of pharmacological treatment response in a naturalistic hospital setting. Through gene expression profiling, we were able to find differentially-expressed genes (DEGs) in unipolar (UD) and bipolar (BD) depressed women. Methods We performed gene expression profiling in hospitalized women with unipolar (n=24) and bipolar depression (n=32) who achieved clinical improvement after pharmacological treatment (without any restriction). To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. Results After pharmacological treatment, UD and BD varied in the number of regulated genes and ontological pathways. Also, the pathways of neurogenesis and synaptic transmission were significantly up-regulated. Our research focused on DEGs with a minimum fold change (FC) of more than 2. For both types of depression, 2 up-regulated genes, OPRM1 and CELF4 (p=0.013), were significantly associated with treatment response (defined as a 50% reduction on the Hamilton Depression Rating Scale [HDRS]). We also uncovered the SHANK3 (p=0.001) gene that is unique for UD and found that the RASGRF1 (p=0.010) gene may be a potential specific biomarker of treatment response for BD. Conclusion Based on transcriptomic profiling, we identified potential expression biomarkers of treatment outcomes for UD and BD. We also proved that the Ras-GEF pathway associated with long-term memory, female stress response, and treatment response modulation in animal studies impacts treatment efficacy in patients with BD. Further studies focused on the outlined genes may help provide predictive markers of treatment outcomes in UD and BD.

DRD1 Gene Polymorphism Predict Therapeutic Responses in Patients With Bipolar Mania Treated by Combination of Lithium and Olanzapine

“…/-48A/1403C, BD patients have a positive correlation with DRD1 mononucleotide polymorphism (800T/C, 48A/G, 1403T/C), and the most common haploid type is 800C/48G/1403T (C-G-T), which is very similar to study result of Ni [19]. Dmitrzak-Weglarz and their colleague also reported that 48A/G genotype, G/G and allele G are signi cantly increased, especially in female patients with BDII, and it is speculated that BD is more inherited from the mother (non-father) to the offspring [20]. However, this study did not nd any difference in the gene polymorphism of rs4532 and rs686 sites in bipolar manic patients and the normal control.…”

Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder

“…One promising way to markedly increase the accuracy of diagnosis is to identify disease biomarkers for objectively diagnosing MDD. In recent decades, much work has been done to identify potential biomarkers for MDD ( Dmitrzak-Weglarz et al., 2021 ; Bai et al., 2021 ; Huang et al., 2022 ; Travica et al., 2022 ). However, few studies have taken the severity of MDD into consideration.…”

Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis

“…In our meta-analysis, we noted that Rasgrf1 was one of the most consistent downregulated genes by FLX activity ( Table 6 , Table 7 , Table 8 and Table 10 ). Consistently, it has been shown that Rasgrf1 knockdown reversed the effect of UCMS on mice [ 140 ], and it has been shown in humans that RASGRF1 may be a potential specific biomarker of treatment response for bipolar disorder [ 141 ]. Concerning the NMDAR-positive modulation underlying AD action, one identified initial trigger of such an effect is Drd1-pyramidal cell signaling [ 142 , 143 ].…”