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Pharmacopsychiatry 2023; 56(01): 25-31
DOI: 10.1055/a-1936-3580
Original Paper

Metformin is Protective Against the Development of Mood Disorders

Jacqueline Lake
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Chiara C. Bortolasci
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Amanda L. Stuart
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Julie A. Pasco
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
2   Department of Medicine-Western Health, University of Melbourne, St Albans, Australia
3   Department of Epidemiology and Preventive Medicine, Monash University, Prahran, Australia
4   Barwon Health, Geelong, Australia
,
Srisaiyini Kidnapillai
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Briana Spolding
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Trang T. T. Truong
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Bruna Panizzutti
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Zoe S. J. Liu
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
,
Olivia M. Dean
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
5   The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
,
Tamsyn Crowley
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
6   Bioinformatics Core Research Facility (BCRF), Deakin University, Geelong, Australia
,
Mark Richardson
6   Bioinformatics Core Research Facility (BCRF), Deakin University, Geelong, Australia
,
Jee Hyun Kim
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
5   The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
,
Michael Berk
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
5   The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
7   Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Australia
,
Lana J. Williams   *
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
4   Barwon Health, Geelong, Australia
,
Ken Walder   *
1   Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, VIC, Australia
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Abstract

Introduction Mood disorders are a major cause of disability, and current treatment options are inadequate for reducing the burden on a global scale. The aim of this project was to identify drugs suitable for repurposing to treat mood disorders.

Methods This mixed-method study utilized gene expression signature technology and pharmacoepidemiology to investigate drugs that may be suitable for repurposing to treat mood disorders.

Results The transcriptional effects of a combination of drugs commonly used to treat mood disorders included regulation of the steroid and terpenoid backbone biosynthesis pathways, suggesting a mechanism involving cholesterol biosynthesis, and effects on the thyroid hormone signaling pathway. Connectivity Map analysis highlighted metformin, an FDA-approved treatment for type 2 diabetes, as a drug having global transcriptional effects similar to the mood disorder drug combination investigated. In a retrospective cohort study, we found evidence that metformin is protective against the onset of mood disorders.

Discussion These results provide proof-of-principle of combining gene expression signature technology with pharmacoepidemiology to identify potential novel drugs for treating mood disorders. Importantly, metformin may have utility in the treatment of mood disorders, warranting future randomized controlled trials to test its efficacy.

Key words

metformin - mood disorder - pharmacoepidemiology - drug repurposing - gene expression signature

* These authors contributed equally.


Supplementary Material



Publication History

Received: 09 May 2022
Received: 25 August 2022

Accepted: 09 August 2022

Article published online:
28 September 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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