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Gut Microbes Volume 15, 2023 - Issue 2
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Research Paper

Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome

S. Brushetta Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;b Department of Health Sciences, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0002-5445-2972View further author information
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R. Gacesaa Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;c Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0003-2119-0539View further author information
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A. Vich Vilad Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium;e VIB-KU Leuven Center for Microbiology, Leuven, BelgiumORCID Iconhttps://orcid.org/0000-0003-4691-5583View further author information
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M.F. Brandao Goisa Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0001-7918-2481View further author information
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S. Andreu-Sáncheza Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;f Department of Pediatrics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0002-3503-9971View further author information
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J.C. Swartea Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;c Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0002-3709-9193View further author information
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M.A.Y. Klaassena Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;c Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsView further author information
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V. Collija Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;c Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0003-3743-1544View further author information
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T. Sinhaa Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0002-0992-7983View further author information
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L.A. Boltea Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;c Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0001-6036-0831View further author information
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J. Wua Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsView further author information
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M. Swertza Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;g Genomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0002-0979-3401View further author information
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M.L.A. de Kroonb Department of Health Sciences, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0003-1730-4994View further author information
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S.A. Reijneveldb Department of Health Sciences, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0002-1206-7523View further author information
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C. Wijmengaa Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0002-5635-1614View further author information
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R.K. Weersmac Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0001-7928-7371View further author information
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J. Fua Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;f Department of Pediatrics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0001-5578-1236View further author information
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H.M. van Looh Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsView further author information
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A. Kurilshikova Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsORCID Iconhttps://orcid.org/0000-0003-2541-5627View further author information
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A. Zhernakovaa Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsCorrespondence[email protected] [email protected]
ORCID Iconhttps://orcid.org/0000-0002-4574-0841View further author information
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Article: 2281360 | Received 27 Jun 2023, Accepted 06 Nov 2023, Published online: 28 Nov 2023

Figures & data

Figure 1. Schematic of study design.

This cross-sectional study explored the relationship between several internalizing disorders (range: 70–385 cases), psychotropic drug (PTD) use and the gut microbiome. Data on internalizing disorders and medication use was available from around the time of stool sample collection. The disorders in white boxes were not analyzed individually. *Controls included participants (n = 5,522) without any internalizing disorders. **One or more internalizing disorders were observed in 491 participants (see Figure S1 for more details).
Figure 1. Schematic of study design.

Figure 2. Bacterial species associated with internalizing disorders and psychotropic drugs.

Heatmap depicting the effect sizes (β coefficients) of bacterial taxa associations at species level with internalizing disorders and use of any psychotropic drugs (incl. SSRI) in the unadjusted model. * indicates nominal significance (P < 0.05). ** indicates both nominal and FDR significance (P < 0.05, FDR < 0.05). Abbreviations – DYS: dysthymia, MDD: major depressive disorder, AnyDep: any depression, GAD: generalized anxiety disorder, AnyAnx: any anxiety, PTDs: all psychotropic drugs, SSRI: selective serotonin-reuptake inhibitors.
Figure 2. Bacterial species associated with internalizing disorders and psychotropic drugs.

Figure 3. Bacterial species associated with internalizing disorders, adjusted for the use of SSRIs or of any PTDs and vice versa.

Forest plots depicting the confidence intervals of effect sizes (β ± 1.96*SE) of associations between CLR-transformed bacterial species and i) internalizing disorders adjusted for SSRIs (purple) or any PTDs (green) and ii) SSRIs (blue) and any PTDs (orange) adjusted for internalizing disorders. Abbreviations – AnyDep: any depression, DYS: dysthymia, MDD: major depressive disorder, AnyAnx: any anxiety, GAD: generalized anxiety disorder, PTDs: all psychotropic drugs, SSRI: selective serotonin-reuptake inhibitors.
Figure 3. Bacterial species associated with internalizing disorders, adjusted for the use of SSRIs or of any PTDs and vice versa.

Figure 4. Bacterial gut – brain modules associated with internalizing disorders and psychotropic drugs.

Heatmap depicting the effect sizes (β coefficients) of bacterial gut – brain modules associations with internalizing disorders and use of any psychotropic drugs (incl. SSRI) in the unadjusted model. * indicates nominal significance (P < 0.05). ** indicates both nominal and FDR significance (P < 0.05, FDR < 0.05). Abbreviations – DYS: dysthymia, AnyDep: any depression, MDD: major depressive disorder, AnyAnx: any anxiety, GAD: generalized anxiety disorder, PTDs: all psychotropic drugs, SSRI: selective serotonin-reuptake inhibitors, SAM: S-Adenosyl Methionine, DOPAC: 3,4-Dihydroxyphenylacetic acid.
Figure 4. Bacterial gut – brain modules associated with internalizing disorders and psychotropic drugs.

Figure 5. Bacterial gut – brain modules associated with internalizing disorders, adjusted for the use of SSRIs or of any PTDs and vice versa.

Forest plots depicting the confidence intervals of effect sizes (β ± 1.96*SE) of associations between CLR-transformed bacterial gut – brain modules and i) internalizing disorders adjusted for SSRIs (purple) or any PTDs (green) and ii) SSRIs (blue) and any PTDs (orange) adjusted for internalizing disorders. Abbreviations – AnyDep: any depression, DYS: dysthymia, MDD: major depressive disorder, PTDs: all psychotropic drugs, SSRI: selective serotonin-reuptake inhibitors, SAM: S-Adenosyl Methionine, DOPAC: 3,4-Dihydroxyphenylacetic acid.
Figure 5. Bacterial gut – brain modules associated with internalizing disorders, adjusted for the use of SSRIs or of any PTDs and vice versa.
Supplemental material

Supplemental Material

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Data availability statement

Scripts used for data analysis can be found at:

https://github.com/GRONINGEN-MICROBIOME-CENTRE/DMP and https://github.com/GRONINGEN-MICROBIOME-CENTRE/DMP_MentalHeath

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