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Review
. 2022 Aug:139:104758.
doi: 10.1016/j.neubiorev.2022.104758. Epub 2022 Jun 28.

Insulin resistance in depression: A large meta-analysis of metabolic parameters and variation

Brisa S Fernandes  1 , Estela Salagre  2 , Nitesh Enduru  1 , Iria Grande  3 , Eduard Vieta  3 , Zhongming Zhao  4
Affiliations
Review

Insulin resistance in depression: A large meta-analysis of metabolic parameters and variation

Brisa S Fernandes et al. Neurosci Biobehav Rev. 2022 Aug.

Abstract

Increased insulin resistance is recognized in psychiatric disorders, such as schizophrenia and bipolar disorder, but its occurrence in depression is less clear. Our aims were to verify if insulin resistance is altered in depression, to test the metabolic subgroup hypothesis of depression and if there are changes with antidepressants. Inclusion criteria were studies including adult subjects with depression and either a control group or follow-up after treatment with antidepressants, and assessing fasting insulin or glucose levels or the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Seventy studies with 240,704 participants were included. Both insulin levels and the HOMA-IR index were increased in acute depression. Neither insulin nor the HOMA-IR index were altered during remission. Insulin was increased in atypical, but not typical depression. There was higher variation in insulin in individuals with depression than in controls. Insulin resistance did not change with antidepressant treatment. Insulin resistance is increased in depression during acute episodes. Heterogeneity was high in most of the analyses. Laboratory assessment of insulin resistance might have clinical utility in people with depression for diagnosis of the metabolic subtype and treatment selection, following precision psychiatry standards.

Keywords: Biomarker; Depression; Major depressive disorder; Meta-analysis; Precision psychiatry; Systematic review.

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Conflict of interest statement

Conflict of Interest

The authors have no conflict of interest regarding this subject. IG has received grants and served as consultant, advisor or CME speaker for the following identities: Angelini, Casen Recordati, Ferrer, Janssen Cilag, and Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare outside the submitted work. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Novartis, Orion Corporation, Organon, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda, outside the submitted work.

Figures

Fig. 1.
Fig. 1.
Forest plot for random effects of the between-group meta-analysis on plasma and serum fasting insulin levels in people with acute depressive symptoms regardless of medication (with and without) and healthy controls. The sizes of the circles are proportional to the sample size. Adjusted p-values < 0.004 (0.05/12) are considered statistically significant.
Fig. 2.
Fig. 2.
Forest plot for random effects of the between-group meta-analysis on the HOMA-IR index in people with acute depressive symptoms regardless of medication (with and without) and healthy controls. The sizes of the circles are proportional to the sample size. Adjusted p-values < 0.004 (0.05/12) are considered statistically significant.
Fig. 3.
Fig. 3.
Forest plot for random effects of the between-group meta-analysis on plasma and serum fasting glucose levels in people with acute depressive symptoms regardless of medication (with and without) and healthy controls. The sizes of the circles are proportional to the sample size. Adjusted p-values < 0.004 (0.05/12) are considered statistically significant.
Fig. 4.
Fig. 4.
Forest plots for random effects of the between- and within-group meta-analyses. a) Forest plot for random effects on the between-group meta-analysis between remitted depression and healthy controls regarding fasting insulin levels. b) Forest plot for random effects on the between-group meta-analysis between subjects with remitted depression and healthy controls regarding the HOMA-IR index. c) Forest plot for random effects on the between-group meta-analysis between subjects with remitted depression and healthy controls regarding fasting glucose levels. d) Forest plot for changes in fasting insulin levels following treatment of an acute depressive episode with antidepressants according to response or non-response. e) Forest plot for changes in the HOMA-IR index following treatment of an acute depressive episode with antidepressants according to response or non-response. f) Forest plot for changes in fasting glucose levels following treatment of an acute depressive episode with antidepressants according to response or non-response. The sizes of the circles are proportional to the sample size. Adjusted p-values < 0.004 (0.05/12) are statistically significant.
Fig. 5.
Fig. 5.
Variability of insulin resistance in depression. a) Forest plot for random effects on the between-group meta-analysis according to the clinical features of depression (typical vs. atypical depression). b) Forest plot showing summary effect sizes for the coefficient of variation ratio (CVR) of the metabolic markers in individuals with acute depression with and without psychiatric medication. c) Forest plot showing summary effect sizes for the coefficient of variation ratio (CVR) of the metabolic markers in individuals with acute depression without psychiatric medication.
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