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

Monika Dmitrzak-Weglarz; Aleksandra Szczepankiewicz; Janusz Rybakowski; Paweł Kapelski; Karolina Bilska; Maria Skibinska; Edyta Reszka; Monika Lesicka; Ewa Jablonska; Edyta Wieczorek; Joanna Pawlak

doi:10.1055/a-1546-9483

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2021; 54(06): 261-268
DOI: 10.1055/a-1546-9483

Original Paper

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

Monika Dmitrzak-Weglarz

¹Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poland

,

Aleksandra Szczepankiewicz

²Laboratory of Molecular and Cell Biology, Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, Poland

,

Janusz Rybakowski

³Department of Adult Psychiatry, Poznan University of Medical Sciences, Poland

,

Paweł Kapelski

¹Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poland

,

Karolina Bilska

¹Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poland

,

Maria Skibinska

¹Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poland

,

Edyta Reszka

⁴Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland

,

Monika Lesicka

⁴Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland

,

Ewa Jablonska

⁴Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland

,

Edyta Wieczorek

⁴Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland

,

Joanna Pawlak

¹Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poland

› Author Affiliations

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.

Key words

transcriptomic profile - ontology analysis - unipolar depression - bipolar depression - pharmacological treatment

Full Text

References

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