Obesity and sarcopenic obesity characterized by low-grade inflammation are associated with increased risk for major depression in women

Julie A Pasco; Michael Berk; Brenda Penninx; Natalie K Hyde; Kara L Holloway-Kew; Emma C West; Mark A Kotowicz; Kara B Anderson; Adrienne O'Neil; Pamela G Rufus-Membere; Lana J Williams

doi:10.3389/fnut.2023.1222019

Obesity and sarcopenic obesity characterized by low-grade inflammation are associated with increased risk for major depression in women

Front Nutr. 2023 Sep 28:10:1222019. doi: 10.3389/fnut.2023.1222019. eCollection 2023.

Authors

Julie A Pasco^{1

2

3}, Michael Berk^{1

4

5}, Brenda Penninx⁶, Natalie K Hyde¹, Kara L Holloway-Kew¹, Emma C West¹, Mark A Kotowicz^{1

2}, Kara B Anderson¹, Adrienne O'Neil¹, Pamela G Rufus-Membere¹, Lana J Williams¹

Affiliations

¹ Deakin University, IMPACT - Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, VIC, Australia.
² Department of Medicine-Western Health, The University of Melbourne, St. Albans, VIC, Australia.
³ Department of Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁴ The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
⁵ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.
⁶ Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Centre, Amsterdam, Netherlands.

Abstract

Background: We aimed to determine women's risk of major depressive disorder (MDD) in relation to obesity phenotypes characterized by levels of circulating high-sensitivity C-reactive protein (hsCRP).

Methods: This population-based retrospective cohort study comprised 808 women (ages 20-84 y) recruited 1994-1997 and followed for a median 16.1 y (IQR 11.9-16.8). At baseline, body fat and lean tissue mass were measured by whole body dual-energy x-ray absorptiometry (DXA). Obesity was identified as high fat mass index (>12.9 kg/m²), body fat percentage (≥35%) and body mass index (≥30 kg/m²); sarcopenic obesity referred to a high ratio fat mass/fat-free mass (≥0.80). Systemic inflammation was operationalized as serum hsCRP concentration in the upper tertile (>2.99 mg/L). Obesity phenotypes were: non-obese + lowCRP, non-obese + highCRP, obese + lowCRP, and obese + highCRP. During follow-up, the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP) was used to identify lifetime history of MDD and age of onset. Poisson regression models were used to estimate the MDD rate for each obesity phenotype during follow-up. Demographic, health and lifestyle factors were tested as potential confounders.

Results: During 11,869 p-y of follow-up, 161 (19.9%) women experienced an MDD episode. For obesity phenotypes based on fat mass index, models adjusted for baseline age and prior MDD, and non-obese + lowCRP as reference, RR for non-obese + highCRP was 1.21 (95% CI 0.80, 1.82), obese + lowCRP 1.46 (0.86, 2.47) and obese + highCRP 1.56 (1.03, 2.37). Patterns were similar for obesity by body fat percentage, body mass index and sarcopenic obesity.

Conclusion: Consistently across different obesity definitions, this longitudinal study reports that women with both obesity and systemic inflammation are at increased risk of subsequent MDD. Future research should examine whether tackling this metabolically unhealthy obesity type - through, for example, lifestyle or medication approaches - can reduce depression risk.

Keywords: depression; high-sensitivity C-reactive protein; immunometabolic dysregulation; inflammation; major depressive disorder; mental disorders; obesity; sarcopenic obesity.

Grants and funding

This work was supported by the Victorian Health Promotion Foundation (VHPF) and the National Health and Medical Research Council (NHMRC) (251638, 454356, 509103, and 628582). MB was supported by a NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator grant (1156072 and 2017131); NH by an Executive Dean’s Postdoctoral Research Fellowship (Deakin); KH-K by an Alfred Deakin Postdoctoral Research Fellowship; EW and KA by Australian Government Research Training Program Scholarships; AO’N by an NHMRC Emerging Leader 2 Fellowship (2009295); PR-M by a Deakin University Postgraduate Industry Research Scholarship; and LW by a NHMRC Emerging Leadership Fellowship (1174060).