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Understanding treatment-resistant depression using "omics" techniques: A systematic review.

Nare Amasi-Hartoonian1, Carmine Maria Pariante2, Annamaria Cattaneo3

  • 1Institute of Psychiatry, Psychology and Neuroscience, King's College London, Department of Psychological Medicine, London, UK.

Journal of Affective Disorders
|September 14, 2022
PubMed
Summary

This review of omics studies in treatment-resistant depression (TRD) reveals key molecular pathways and suggests new biomarkers. Future research should use multi-omics approaches for better clinical translation.

Keywords:
Genome-wideGenomicsHigh-troughput “omics” techniquesMajor depressive disorder (MDD) treatmentTranscriptomicsTreatment-resistant depression (TRD)

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Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Treatment-resistant depression (TRD) presents significant clinical and economic challenges.
  • Traditional candidate mechanism approaches are limited by TRD's complexity and heterogeneity.
  • High-throughput omics technologies offer a holistic view of TRD pathogenesis.

Purpose of the Study:

  • To systematically review hypothesis-free omics studies investigating treatment-resistant depression.
  • To identify molecular mechanisms and pathways implicated in TRD development.
  • To explore potential biomarkers and therapeutic targets for TRD.

Main Methods:

  • Systematic literature search across major scientific databases (PubMed, MEDLINE, Embase, PsycInfo, Scopus, Web of Science) up to July 2022.
  • Inclusion of 37 human studies encompassing over 17,500 TRD patients, 571,000 controls, and 62,000 non-TRD depressed patients.
  • Analysis of findings from hypothesis-free omics techniques (genomics, transcriptomics, etc.).

Main Results:

  • Omics studies identified significant roles for various molecules, including polymorphisms, genes, mRNAs, and microRNAs in TRD.
  • Key implicated pathways include immune system/inflammation, neuroplasticity, calcium signaling, and neurotransmitter systems.
  • Common limitations include small sample sizes and heterogeneity in TRD definition and study design.

Conclusions:

  • Findings offer insights into TRD pathophysiology, highlighting potential novel drug targets and biomarkers.
  • Further validation in large prospective studies with standardized TRD criteria is essential.
  • A multi-omics and systems biology approach is recommended for robust clinical translation.