Understanding treatment-resistant depression using “omics” techniques: A systematic review

Nare Amasi-Hartoonian; Carmine Maria Pariante; Annamaria Cattaneo; Luca Sforzini

doi:10.1016/j.jad.2022.09.011

Understanding treatment-resistant depression using “omics” techniques: A systematic review

Nare Amasi-Hartoonian^*, Carmine Maria Pariante, Annamaria Cattaneo, Luca Sforzini

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

10 Citations (Scopus)

Abstract

Background: Treatment-resistant depression (TRD) results in huge healthcare costs and poor patient clinical outcomes. Most studies have adopted a “candidate mechanism” approach to investigate TRD pathogenesis, however this is made more challenging due to the complex and heterogeneous nature of this condition. High-throughput “omics” technologies can provide a more holistic view and further insight into the underlying mechanisms involved in TRD development, expanding knowledge beyond already-identified mechanisms. This systematic review assessed the information from studies that examined TRD using hypothesis-free omics techniques. Methods: PubMed, MEDLINE, Embase, APA PsycInfo, Scopus and Web of Science databases were searched on July 2022. 37 human studies met the eligibility criteria, totalling 17,518 TRD patients, 571,402 healthy controls and 62,279 non-TRD depressed patients (including antidepressant responders and untreated MDD patients). Results: Significant findings were reported that implicate the role in TRD of various molecules, including polymorphisms, genes, mRNAs and microRNAs. The pathways most commonly reported by the identified studies were involved in immune system and inflammation, neuroplasticity, calcium signalling and neurotransmitters. Limitations: Small sample sizes, variability in defining TRD, and heterogeneity in study design and methodology. Conclusions: These findings provide insight into TRD pathophysiology, proposing future research directions for novel drug targets and potential biomarkers for clinical staging and response to antidepressants (citalopram/escitalopram in particular) and electroconvulsive therapy (ECT). Further validation is warranted in large prospective studies using standardised TRD criteria. A multi-omics and systems biology strategy with a collaborative effort will likely deliver robust findings for translation into the clinic.

Original language	English
Pages (from-to)	423-455
Number of pages	33
Journal	Journal of Affective Disorders
Volume	318
DOIs	https://doi.org/10.1016/j.jad.2022.09.011
Publication status	Published - 1 Dec 2022

Keywords

Genome-wide
Genomics
High-troughput “omics” techniques
Major depressive disorder (MDD) treatment
Transcriptomics
Treatment-resistant depression (TRD)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jad.2022.09.011

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@article{177e3af4085b466db3d7003fb3d8eb12,

title = "Understanding treatment-resistant depression using “omics” techniques: A systematic review",

abstract = "Background: Treatment-resistant depression (TRD) results in huge healthcare costs and poor patient clinical outcomes. Most studies have adopted a “candidate mechanism” approach to investigate TRD pathogenesis, however this is made more challenging due to the complex and heterogeneous nature of this condition. High-throughput “omics” technologies can provide a more holistic view and further insight into the underlying mechanisms involved in TRD development, expanding knowledge beyond already-identified mechanisms. This systematic review assessed the information from studies that examined TRD using hypothesis-free omics techniques. Methods: PubMed, MEDLINE, Embase, APA PsycInfo, Scopus and Web of Science databases were searched on July 2022. 37 human studies met the eligibility criteria, totalling 17,518 TRD patients, 571,402 healthy controls and 62,279 non-TRD depressed patients (including antidepressant responders and untreated MDD patients). Results: Significant findings were reported that implicate the role in TRD of various molecules, including polymorphisms, genes, mRNAs and microRNAs. The pathways most commonly reported by the identified studies were involved in immune system and inflammation, neuroplasticity, calcium signalling and neurotransmitters. Limitations: Small sample sizes, variability in defining TRD, and heterogeneity in study design and methodology. Conclusions: These findings provide insight into TRD pathophysiology, proposing future research directions for novel drug targets and potential biomarkers for clinical staging and response to antidepressants (citalopram/escitalopram in particular) and electroconvulsive therapy (ECT). Further validation is warranted in large prospective studies using standardised TRD criteria. A multi-omics and systems biology strategy with a collaborative effort will likely deliver robust findings for translation into the clinic.",

keywords = "Genome-wide, Genomics, High-troughput “omics” techniques, Major depressive disorder (MDD) treatment, Transcriptomics, Treatment-resistant depression (TRD)",

author = "Nare Amasi-Hartoonian and Pariante, {Carmine Maria} and Annamaria Cattaneo and Luca Sforzini",

note = "Funding Information: Dr. Sforzini and Prof. Pariante have received research funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2, as part of the EU-PEARL project. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. Prof. Pariante is also funded by a Senior Investigator award from the National Institute for Health Research (NIHR); the Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1); the European Commission (EARLYCAUSE grant SC1-BHC-01-2019); the NARSAD; the Psychiatry Research Trust; and the Wellcome Trust (SHAPER, Scaling-up Health-Arts Programme to scale up arts interventions, grant 219425/Z/19/Z). <10 % of his support in the last 10 years derives from commercial collaborations, including consultation and speakers fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and V{\"a}rde Partners. Funding Information: Research funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC), London, United Kingdom. This work was also supported by the Wellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer's Disease (NIMA) Consortium (104025), which is also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer. Funding Information: Dr. Sforzini and Prof. Pariante have received research funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2 , as part of the EU-PEARL project. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. Prof. Pariante is also funded by a Senior Investigator award from the National Institute for Health Research (NIHR); the Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1); the European Commission (EARLYCAUSE grant SC1-BHC-01-2019); the NARSAD; the Psychiatry Research Trust; and the Wellcome Trust (SHAPER, Scaling-up Health-Arts Programme to scale up arts interventions, grant 219425/Z/19/Z). Less than 10 % of his support in the last 10 years derives from commercial collaborations, including consultation and speakers fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and V{\"a}rde Partners. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = dec,

day = "1",

doi = "10.1016/j.jad.2022.09.011",

language = "English",

volume = "318",

pages = "423--455",

journal = "Journal of Affective Disorders",

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TY - JOUR

T1 - Understanding treatment-resistant depression using “omics” techniques

T2 - A systematic review

AU - Amasi-Hartoonian, Nare

AU - Pariante, Carmine Maria

AU - Cattaneo, Annamaria

AU - Sforzini, Luca

N1 - Funding Information: Dr. Sforzini and Prof. Pariante have received research funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2, as part of the EU-PEARL project. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. Prof. Pariante is also funded by a Senior Investigator award from the National Institute for Health Research (NIHR); the Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1); the European Commission (EARLYCAUSE grant SC1-BHC-01-2019); the NARSAD; the Psychiatry Research Trust; and the Wellcome Trust (SHAPER, Scaling-up Health-Arts Programme to scale up arts interventions, grant 219425/Z/19/Z). <10 % of his support in the last 10 years derives from commercial collaborations, including consultation and speakers fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and Värde Partners. Funding Information: Research funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC), London, United Kingdom. This work was also supported by the Wellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer's Disease (NIMA) Consortium (104025), which is also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer. Funding Information: Dr. Sforzini and Prof. Pariante have received research funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2 , as part of the EU-PEARL project. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. Prof. Pariante is also funded by a Senior Investigator award from the National Institute for Health Research (NIHR); the Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1); the European Commission (EARLYCAUSE grant SC1-BHC-01-2019); the NARSAD; the Psychiatry Research Trust; and the Wellcome Trust (SHAPER, Scaling-up Health-Arts Programme to scale up arts interventions, grant 219425/Z/19/Z). Less than 10 % of his support in the last 10 years derives from commercial collaborations, including consultation and speakers fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and Värde Partners. Publisher Copyright: © 2022 The Authors

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Background: Treatment-resistant depression (TRD) results in huge healthcare costs and poor patient clinical outcomes. Most studies have adopted a “candidate mechanism” approach to investigate TRD pathogenesis, however this is made more challenging due to the complex and heterogeneous nature of this condition. High-throughput “omics” technologies can provide a more holistic view and further insight into the underlying mechanisms involved in TRD development, expanding knowledge beyond already-identified mechanisms. This systematic review assessed the information from studies that examined TRD using hypothesis-free omics techniques. Methods: PubMed, MEDLINE, Embase, APA PsycInfo, Scopus and Web of Science databases were searched on July 2022. 37 human studies met the eligibility criteria, totalling 17,518 TRD patients, 571,402 healthy controls and 62,279 non-TRD depressed patients (including antidepressant responders and untreated MDD patients). Results: Significant findings were reported that implicate the role in TRD of various molecules, including polymorphisms, genes, mRNAs and microRNAs. The pathways most commonly reported by the identified studies were involved in immune system and inflammation, neuroplasticity, calcium signalling and neurotransmitters. Limitations: Small sample sizes, variability in defining TRD, and heterogeneity in study design and methodology. Conclusions: These findings provide insight into TRD pathophysiology, proposing future research directions for novel drug targets and potential biomarkers for clinical staging and response to antidepressants (citalopram/escitalopram in particular) and electroconvulsive therapy (ECT). Further validation is warranted in large prospective studies using standardised TRD criteria. A multi-omics and systems biology strategy with a collaborative effort will likely deliver robust findings for translation into the clinic.

AB - Background: Treatment-resistant depression (TRD) results in huge healthcare costs and poor patient clinical outcomes. Most studies have adopted a “candidate mechanism” approach to investigate TRD pathogenesis, however this is made more challenging due to the complex and heterogeneous nature of this condition. High-throughput “omics” technologies can provide a more holistic view and further insight into the underlying mechanisms involved in TRD development, expanding knowledge beyond already-identified mechanisms. This systematic review assessed the information from studies that examined TRD using hypothesis-free omics techniques. Methods: PubMed, MEDLINE, Embase, APA PsycInfo, Scopus and Web of Science databases were searched on July 2022. 37 human studies met the eligibility criteria, totalling 17,518 TRD patients, 571,402 healthy controls and 62,279 non-TRD depressed patients (including antidepressant responders and untreated MDD patients). Results: Significant findings were reported that implicate the role in TRD of various molecules, including polymorphisms, genes, mRNAs and microRNAs. The pathways most commonly reported by the identified studies were involved in immune system and inflammation, neuroplasticity, calcium signalling and neurotransmitters. Limitations: Small sample sizes, variability in defining TRD, and heterogeneity in study design and methodology. Conclusions: These findings provide insight into TRD pathophysiology, proposing future research directions for novel drug targets and potential biomarkers for clinical staging and response to antidepressants (citalopram/escitalopram in particular) and electroconvulsive therapy (ECT). Further validation is warranted in large prospective studies using standardised TRD criteria. A multi-omics and systems biology strategy with a collaborative effort will likely deliver robust findings for translation into the clinic.

KW - Genome-wide

KW - Genomics

KW - High-troughput “omics” techniques

KW - Major depressive disorder (MDD) treatment

KW - Transcriptomics

KW - Treatment-resistant depression (TRD)

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U2 - 10.1016/j.jad.2022.09.011

DO - 10.1016/j.jad.2022.09.011

M3 - Review article

AN - SCOPUS:85138039296

SN - 0165-0327

VL - 318

SP - 423

EP - 455

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -

Understanding treatment-resistant depression using “omics” techniques: A systematic review

Abstract

Keywords

UN SDGs

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