Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates

Alessandro Miola; Neri A. Alvarez-Villalobos; Fernando Gerardo Ruiz-Hernandez; Eleanna De Filippis; Marin Veldic; Miguel L. Prieto; Balwinder Singh; Jorge A. Sanchez Ruiz; Nicolas A. Nunez; Manuel Gardea Resendez; Francisco Romo-Nava; Susan L. McElroy; Aysegul Ozerdem; Joanna M. Biernacka; Mark A. Frye; Alfredo B. Cuellar-Barboza

doi:10.1016/j.jad.2023.04.068

Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates

Alessandro Miola, Neri A. Alvarez-Villalobos, Fernando Gerardo Ruiz-Hernandez, Eleanna De Filippis, Marin Veldic, Miguel L. Prieto, Balwinder Singh, Jorge A. Sanchez Ruiz, Nicolas A. Nunez, Manuel Gardea Resendez, Francisco Romo-Nava, Susan L. McElroy, Aysegul Ozerdem, Joanna M. Biernacka, Mark A. Frye, Alfredo B. Cuellar-Barboza^*

^*Corresponding author for this work

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

Abstract

Background: Although insulin resistance (IR) and cardiometabolic syndrome are prevalent in patients with bipolar disorder (BD), only a few studies have attempted to precisely assess the degree and clinical impact of IR in BD. Methods: A comprehensive search was conducted from multiple research databases through May 2022, following a pre-defined protocol (PROSPERO: CRD42022359259). We extracted neuroimaging, cognition, illness course, and treatment response findings from individuals with BD with evidence of IR compared with euglycemic BD individuals. Results: Of 1436 identified articles, 10 reports fulfilling inclusion criteria were included (n = 1183). BD patients with IR displayed worse composite verbal memory scores and worse executive function and exhibited smaller hippocampal volumes along with prefrontal neurochemical alterations compared to euglycemic BD patients. Fixed-effect meta-analysis revealed that BD patients with impaired glucose metabolism (IGM) were more likely to develop a chronic and rapid cycling course when compared with euglycemic BD patients (k = 2, OR = 2.96, 95 % CI 1.69–5.17, OR = 2.88, 95 % CI 1.59–5.21, p < 0.001, respectively), with a trend for significantly lower Global Assessment of Functioning scores (k = 5, MD = −4, 95 % CI −8.23–0.23, p = 0.06). BD patients with IGM displayed a higher rate of poor response to mood stabilizers when compared with euglycemic BD patients (k = 2, OR = 6.74, 95 % CI 1.04–43.54, p = 0.04). Limitations: Cross-sectional design and small sample sizes of studies included limit the generalizability of results. Conclusion: IR is associated with worse clinical outcomes of BD and inadequate treatment response. Implementing strategies to prevent and treat IR in BD is crucial to improve the prognosis of such a difficult-to-treat population.

Original language	English
Pages (from-to)	1-11
Number of pages	11
Journal	Journal of Affective Disorders
Volume	334
DOIs	https://doi.org/10.1016/j.jad.2023.04.068
State	Published - 1 Aug 2023

Bibliographical note

Funding Information:
This study was supported, in part, by benefactor support, the Marriott Family Foundation , and the Mayo Clinic Center for Individualized Medicine .

Funding Information:
Dr. Romo-Nava is supported in part by a National Institute of Mental Health K23 Award (K23MH120503) and a 2017 NARSAD Young Investigator Award from the Brain and Behavior Research Foundation; has a U.S. Patent and Trademark Office patent # 10,857,356; receives consultant fees from Otsuka Pharmaceutical and has received non-financial research support from Soterix Medical.Dr. Prieto served on an advisory board of Janssen and received grant support from ANID FONDECYT Regular 1181365, FONDEF ID19I10116 and Basal Funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024.Dr. Nuñez is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685.Dr. Frye is supported by a grant from the Assurex Health, Mayo Foundation and Intellectual property licensed to Chymia LLC. He received honoraria from the Carnot Laboratories and the American Physician Institute.This study was supported, in part, by benefactor support, the Marriott Family Foundation, and the Mayo Clinic Center for Individualized Medicine.

Publisher Copyright:
© 2023 Elsevier B.V.

Keywords

Bipolar disorder
Clinical course
Insulin resistance
Systematic review
Treatment response

UN SDGs

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

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10.1016/j.jad.2023.04.068

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Miola, A., Alvarez-Villalobos, N. A., Ruiz-Hernandez, F. G., De Filippis, E., Veldic, M., Prieto, M. L., Singh, B., Sanchez Ruiz, J. A., Nunez, N. A., Resendez, M. G., Romo-Nava, F., McElroy, S. L., Ozerdem, A., Biernacka, J. M., Frye, M. A., & Cuellar-Barboza, A. B. (2023). Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates. Journal of Affective Disorders, 334, 1-11. https://doi.org/10.1016/j.jad.2023.04.068

@article{c77a52ad69794c55a50f7d1ddf29e996,

title = "Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates",

abstract = "Background: Although insulin resistance (IR) and cardiometabolic syndrome are prevalent in patients with bipolar disorder (BD), only a few studies have attempted to precisely assess the degree and clinical impact of IR in BD. Methods: A comprehensive search was conducted from multiple research databases through May 2022, following a pre-defined protocol (PROSPERO: CRD42022359259). We extracted neuroimaging, cognition, illness course, and treatment response findings from individuals with BD with evidence of IR compared with euglycemic BD individuals. Results: Of 1436 identified articles, 10 reports fulfilling inclusion criteria were included (n = 1183). BD patients with IR displayed worse composite verbal memory scores and worse executive function and exhibited smaller hippocampal volumes along with prefrontal neurochemical alterations compared to euglycemic BD patients. Fixed-effect meta-analysis revealed that BD patients with impaired glucose metabolism (IGM) were more likely to develop a chronic and rapid cycling course when compared with euglycemic BD patients (k = 2, OR = 2.96, 95 % CI 1.69–5.17, OR = 2.88, 95 % CI 1.59–5.21, p < 0.001, respectively), with a trend for significantly lower Global Assessment of Functioning scores (k = 5, MD = −4, 95 % CI −8.23–0.23, p = 0.06). BD patients with IGM displayed a higher rate of poor response to mood stabilizers when compared with euglycemic BD patients (k = 2, OR = 6.74, 95 % CI 1.04–43.54, p = 0.04). Limitations: Cross-sectional design and small sample sizes of studies included limit the generalizability of results. Conclusion: IR is associated with worse clinical outcomes of BD and inadequate treatment response. Implementing strategies to prevent and treat IR in BD is crucial to improve the prognosis of such a difficult-to-treat population.",

keywords = "Bipolar disorder, Clinical course, Insulin resistance, Systematic review, Treatment response",

author = "Alessandro Miola and Alvarez-Villalobos, {Neri A.} and Ruiz-Hernandez, {Fernando Gerardo} and {De Filippis}, Eleanna and Marin Veldic and Prieto, {Miguel L.} and Balwinder Singh and {Sanchez Ruiz}, {Jorge A.} and Nunez, {Nicolas A.} and Resendez, {Manuel Gardea} and Francisco Romo-Nava and McElroy, {Susan L.} and Aysegul Ozerdem and Biernacka, {Joanna M.} and Frye, {Mark A.} and Cuellar-Barboza, {Alfredo B.}",

note = "Funding Information: This study was supported, in part, by benefactor support, the Marriott Family Foundation , and the Mayo Clinic Center for Individualized Medicine . Funding Information: Dr. Romo-Nava is supported in part by a National Institute of Mental Health K23 Award (K23MH120503) and a 2017 NARSAD Young Investigator Award from the Brain and Behavior Research Foundation; has a U.S. Patent and Trademark Office patent # 10,857,356; receives consultant fees from Otsuka Pharmaceutical and has received non-financial research support from Soterix Medical.Dr. Prieto served on an advisory board of Janssen and received grant support from ANID FONDECYT Regular 1181365, FONDEF ID19I10116 and Basal Funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024.Dr. Nu{\~n}ez is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685.Dr. Frye is supported by a grant from the Assurex Health, Mayo Foundation and Intellectual property licensed to Chymia LLC. He received honoraria from the Carnot Laboratories and the American Physician Institute.This study was supported, in part, by benefactor support, the Marriott Family Foundation, and the Mayo Clinic Center for Individualized Medicine. Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

year = "2023",

month = aug,

day = "1",

doi = "10.1016/j.jad.2023.04.068",

language = "English",

volume = "334",

pages = "1--11",

journal = "Journal of Affective Disorders",

issn = "0165-0327",

publisher = "Elsevier",

}

Miola, A, Alvarez-Villalobos, NA, Ruiz-Hernandez, FG, De Filippis, E, Veldic, M, Prieto, ML, Singh, B, Sanchez Ruiz, JA, Nunez, NA, Resendez, MG, Romo-Nava, F, McElroy, SL, Ozerdem, A, Biernacka, JM, Frye, MA & Cuellar-Barboza, AB 2023, 'Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates', Journal of Affective Disorders, vol. 334, pp. 1-11. https://doi.org/10.1016/j.jad.2023.04.068

TY - JOUR

T1 - Insulin resistance in bipolar disorder

T2 - A systematic review of illness course and clinical correlates

AU - Miola, Alessandro

AU - Alvarez-Villalobos, Neri A.

AU - Ruiz-Hernandez, Fernando Gerardo

AU - De Filippis, Eleanna

AU - Veldic, Marin

AU - Prieto, Miguel L.

AU - Singh, Balwinder

AU - Sanchez Ruiz, Jorge A.

AU - Nunez, Nicolas A.

AU - Resendez, Manuel Gardea

AU - Romo-Nava, Francisco

AU - McElroy, Susan L.

AU - Ozerdem, Aysegul

AU - Biernacka, Joanna M.

AU - Frye, Mark A.

AU - Cuellar-Barboza, Alfredo B.

N1 - Funding Information: This study was supported, in part, by benefactor support, the Marriott Family Foundation , and the Mayo Clinic Center for Individualized Medicine . Funding Information: Dr. Romo-Nava is supported in part by a National Institute of Mental Health K23 Award (K23MH120503) and a 2017 NARSAD Young Investigator Award from the Brain and Behavior Research Foundation; has a U.S. Patent and Trademark Office patent # 10,857,356; receives consultant fees from Otsuka Pharmaceutical and has received non-financial research support from Soterix Medical.Dr. Prieto served on an advisory board of Janssen and received grant support from ANID FONDECYT Regular 1181365, FONDEF ID19I10116 and Basal Funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024.Dr. Nuñez is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685.Dr. Frye is supported by a grant from the Assurex Health, Mayo Foundation and Intellectual property licensed to Chymia LLC. He received honoraria from the Carnot Laboratories and the American Physician Institute.This study was supported, in part, by benefactor support, the Marriott Family Foundation, and the Mayo Clinic Center for Individualized Medicine. Publisher Copyright: © 2023 Elsevier B.V.

PY - 2023/8/1

Y1 - 2023/8/1

N2 - Background: Although insulin resistance (IR) and cardiometabolic syndrome are prevalent in patients with bipolar disorder (BD), only a few studies have attempted to precisely assess the degree and clinical impact of IR in BD. Methods: A comprehensive search was conducted from multiple research databases through May 2022, following a pre-defined protocol (PROSPERO: CRD42022359259). We extracted neuroimaging, cognition, illness course, and treatment response findings from individuals with BD with evidence of IR compared with euglycemic BD individuals. Results: Of 1436 identified articles, 10 reports fulfilling inclusion criteria were included (n = 1183). BD patients with IR displayed worse composite verbal memory scores and worse executive function and exhibited smaller hippocampal volumes along with prefrontal neurochemical alterations compared to euglycemic BD patients. Fixed-effect meta-analysis revealed that BD patients with impaired glucose metabolism (IGM) were more likely to develop a chronic and rapid cycling course when compared with euglycemic BD patients (k = 2, OR = 2.96, 95 % CI 1.69–5.17, OR = 2.88, 95 % CI 1.59–5.21, p < 0.001, respectively), with a trend for significantly lower Global Assessment of Functioning scores (k = 5, MD = −4, 95 % CI −8.23–0.23, p = 0.06). BD patients with IGM displayed a higher rate of poor response to mood stabilizers when compared with euglycemic BD patients (k = 2, OR = 6.74, 95 % CI 1.04–43.54, p = 0.04). Limitations: Cross-sectional design and small sample sizes of studies included limit the generalizability of results. Conclusion: IR is associated with worse clinical outcomes of BD and inadequate treatment response. Implementing strategies to prevent and treat IR in BD is crucial to improve the prognosis of such a difficult-to-treat population.

AB - Background: Although insulin resistance (IR) and cardiometabolic syndrome are prevalent in patients with bipolar disorder (BD), only a few studies have attempted to precisely assess the degree and clinical impact of IR in BD. Methods: A comprehensive search was conducted from multiple research databases through May 2022, following a pre-defined protocol (PROSPERO: CRD42022359259). We extracted neuroimaging, cognition, illness course, and treatment response findings from individuals with BD with evidence of IR compared with euglycemic BD individuals. Results: Of 1436 identified articles, 10 reports fulfilling inclusion criteria were included (n = 1183). BD patients with IR displayed worse composite verbal memory scores and worse executive function and exhibited smaller hippocampal volumes along with prefrontal neurochemical alterations compared to euglycemic BD patients. Fixed-effect meta-analysis revealed that BD patients with impaired glucose metabolism (IGM) were more likely to develop a chronic and rapid cycling course when compared with euglycemic BD patients (k = 2, OR = 2.96, 95 % CI 1.69–5.17, OR = 2.88, 95 % CI 1.59–5.21, p < 0.001, respectively), with a trend for significantly lower Global Assessment of Functioning scores (k = 5, MD = −4, 95 % CI −8.23–0.23, p = 0.06). BD patients with IGM displayed a higher rate of poor response to mood stabilizers when compared with euglycemic BD patients (k = 2, OR = 6.74, 95 % CI 1.04–43.54, p = 0.04). Limitations: Cross-sectional design and small sample sizes of studies included limit the generalizability of results. Conclusion: IR is associated with worse clinical outcomes of BD and inadequate treatment response. Implementing strategies to prevent and treat IR in BD is crucial to improve the prognosis of such a difficult-to-treat population.

KW - Bipolar disorder

KW - Clinical course

KW - Insulin resistance

KW - Systematic review

KW - Treatment response

UR - http://www.scopus.com/inward/record.url?scp=85154614571&partnerID=8YFLogxK

U2 - 10.1016/j.jad.2023.04.068

DO - 10.1016/j.jad.2023.04.068

M3 - Review article

C2 - 37086806

AN - SCOPUS:85154614571

SN - 0165-0327

VL - 334

SP - 1

EP - 11

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -

Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates

Abstract

Bibliographical note

Keywords

UN SDGs

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