Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients: a longitudinal magnetic resonance spectroscopy study

David J. Bond; Leonardo E. Silveira; Ivan J. Torres; Raymond W. Lam; Lakshmi N. Yatham

doi:10.1017/s0033291721000544

Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients: a longitudinal magnetic resonance spectroscopy study

David J. Bond, Leonardo E. Silveira, Ivan J. Torres, Raymond W. Lam, Lakshmi N. Yatham

Psychiatry & Behavioral Sciences

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Abstract

BACKGROUND: We previously reported that bipolar disorder (BD) patients with clinically significant weight gain (CSWG; ⩾7% of baseline weight) in the 12 months after their first manic episode experienced greater limbic brain volume loss than patients without CSWG. It is unknown whether CSWG is also a risk factor for progressive neurochemical abnormalities.

METHODS: We investigated whether 12-month CSWG predicted greater 12-month decreases in hippocampal N-acetylaspartate (NAA) and greater increases in glutamate + glutamine (Glx) following a first manic episode. In BD patients (n = 58) and healthy comparator subjects (HS; n = 34), we measured baseline and 12-month hippocampal NAA and Glx using bilateral 3-Tesla single-voxel proton magnetic resonance spectroscopy. We used general linear models for repeated measures to investigate whether CSWG predicted neurochemical changes.

RESULTS: Thirty-three percent of patients and 18% of HS experienced CSWG. After correcting for multiple comparisons, CSWG in patients predicted a greater decrease in left hippocampal NAA (effect size = -0.52, p = 0.005). CSWG also predicted a greater decrease in left hippocampal NAA in HS with a similar effect size (-0.53). A model including patients and HS found an effect of CSWG on Δleft NAA (p = 0.007), but no diagnosis effect and no diagnosis × CSWG interaction, confirming that CSWG had similar effects in patients and HS.

CONCLUSION: CSWG is a risk factor for decreasing hippocampal NAA in BD patients and HS. These results suggest that the well-known finding of reduced NAA in BD may result from higher body mass index in patients rather than BD diagnosis.

Original language	English (US)
Pages (from-to)	3783-3791
Number of pages	9
Journal	Psychological medicine
Volume	52
Issue number	16
Early online date	Mar 12 2021
DOIs	https://doi.org/10.1017/s0033291721000544
State	Published - Dec 12 2022

Bibliographical note

Funding Information:
The authors thank the BD patients and HS who enrolled in STOP-EM. A modified version of this report was presented at the 16th Annual Meeting of the International Society for Bipolar Disorders, July 13–16, 2016, Amsterdam, the Netherlands. The data for this manuscript were generated from the Systematic Treatment Optimization Program for Early Mania (STOP-EM), which was supported by an unrestricted grant to LNY from AstraZeneca Canada. The sponsor had no input into the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Publisher Copyright:
© The Author(s), 2021. Published by Cambridge University Press.

Keywords

Bipolar disorder
N-acetylaspartate
body mass index
glutamate
hippocampus
magnetic resonance spectroscopy

PubMed: MeSH publication types

Journal Article

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10.1017/s0033291721000544

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@article{e61da80a4a4144c29e0b63f0e63348b7,

title = "Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients: a longitudinal magnetic resonance spectroscopy study",

abstract = "BACKGROUND: We previously reported that bipolar disorder (BD) patients with clinically significant weight gain (CSWG; ⩾7% of baseline weight) in the 12 months after their first manic episode experienced greater limbic brain volume loss than patients without CSWG. It is unknown whether CSWG is also a risk factor for progressive neurochemical abnormalities.METHODS: We investigated whether 12-month CSWG predicted greater 12-month decreases in hippocampal N-acetylaspartate (NAA) and greater increases in glutamate + glutamine (Glx) following a first manic episode. In BD patients (n = 58) and healthy comparator subjects (HS; n = 34), we measured baseline and 12-month hippocampal NAA and Glx using bilateral 3-Tesla single-voxel proton magnetic resonance spectroscopy. We used general linear models for repeated measures to investigate whether CSWG predicted neurochemical changes.RESULTS: Thirty-three percent of patients and 18% of HS experienced CSWG. After correcting for multiple comparisons, CSWG in patients predicted a greater decrease in left hippocampal NAA (effect size = -0.52, p = 0.005). CSWG also predicted a greater decrease in left hippocampal NAA in HS with a similar effect size (-0.53). A model including patients and HS found an effect of CSWG on Δleft NAA (p = 0.007), but no diagnosis effect and no diagnosis × CSWG interaction, confirming that CSWG had similar effects in patients and HS.CONCLUSION: CSWG is a risk factor for decreasing hippocampal NAA in BD patients and HS. These results suggest that the well-known finding of reduced NAA in BD may result from higher body mass index in patients rather than BD diagnosis.",

keywords = "Bipolar disorder, N-acetylaspartate, body mass index, glutamate, hippocampus, magnetic resonance spectroscopy",

author = "Bond, {David J.} and Silveira, {Leonardo E.} and Torres, {Ivan J.} and Lam, {Raymond W.} and Yatham, {Lakshmi N.}",

note = "Funding Information: The authors thank the BD patients and HS who enrolled in STOP-EM. A modified version of this report was presented at the 16th Annual Meeting of the International Society for Bipolar Disorders, July 13–16, 2016, Amsterdam, the Netherlands. The data for this manuscript were generated from the Systematic Treatment Optimization Program for Early Mania (STOP-EM), which was supported by an unrestricted grant to LNY from AstraZeneca Canada. The sponsor had no input into the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} The Author(s), 2021. Published by Cambridge University Press.",

year = "2022",

month = dec,

day = "12",

doi = "10.1017/s0033291721000544",

language = "English (US)",

volume = "52",

pages = "3783--3791",

journal = "Psychological medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "16",

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TY - JOUR

T1 - Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients

T2 - a longitudinal magnetic resonance spectroscopy study

AU - Bond, David J.

AU - Silveira, Leonardo E.

AU - Torres, Ivan J.

AU - Lam, Raymond W.

AU - Yatham, Lakshmi N.

N1 - Funding Information: The authors thank the BD patients and HS who enrolled in STOP-EM. A modified version of this report was presented at the 16th Annual Meeting of the International Society for Bipolar Disorders, July 13–16, 2016, Amsterdam, the Netherlands. The data for this manuscript were generated from the Systematic Treatment Optimization Program for Early Mania (STOP-EM), which was supported by an unrestricted grant to LNY from AstraZeneca Canada. The sponsor had no input into the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Publisher Copyright: © The Author(s), 2021. Published by Cambridge University Press.

PY - 2022/12/12

Y1 - 2022/12/12

N2 - BACKGROUND: We previously reported that bipolar disorder (BD) patients with clinically significant weight gain (CSWG; ⩾7% of baseline weight) in the 12 months after their first manic episode experienced greater limbic brain volume loss than patients without CSWG. It is unknown whether CSWG is also a risk factor for progressive neurochemical abnormalities.METHODS: We investigated whether 12-month CSWG predicted greater 12-month decreases in hippocampal N-acetylaspartate (NAA) and greater increases in glutamate + glutamine (Glx) following a first manic episode. In BD patients (n = 58) and healthy comparator subjects (HS; n = 34), we measured baseline and 12-month hippocampal NAA and Glx using bilateral 3-Tesla single-voxel proton magnetic resonance spectroscopy. We used general linear models for repeated measures to investigate whether CSWG predicted neurochemical changes.RESULTS: Thirty-three percent of patients and 18% of HS experienced CSWG. After correcting for multiple comparisons, CSWG in patients predicted a greater decrease in left hippocampal NAA (effect size = -0.52, p = 0.005). CSWG also predicted a greater decrease in left hippocampal NAA in HS with a similar effect size (-0.53). A model including patients and HS found an effect of CSWG on Δleft NAA (p = 0.007), but no diagnosis effect and no diagnosis × CSWG interaction, confirming that CSWG had similar effects in patients and HS.CONCLUSION: CSWG is a risk factor for decreasing hippocampal NAA in BD patients and HS. These results suggest that the well-known finding of reduced NAA in BD may result from higher body mass index in patients rather than BD diagnosis.

AB - BACKGROUND: We previously reported that bipolar disorder (BD) patients with clinically significant weight gain (CSWG; ⩾7% of baseline weight) in the 12 months after their first manic episode experienced greater limbic brain volume loss than patients without CSWG. It is unknown whether CSWG is also a risk factor for progressive neurochemical abnormalities.METHODS: We investigated whether 12-month CSWG predicted greater 12-month decreases in hippocampal N-acetylaspartate (NAA) and greater increases in glutamate + glutamine (Glx) following a first manic episode. In BD patients (n = 58) and healthy comparator subjects (HS; n = 34), we measured baseline and 12-month hippocampal NAA and Glx using bilateral 3-Tesla single-voxel proton magnetic resonance spectroscopy. We used general linear models for repeated measures to investigate whether CSWG predicted neurochemical changes.RESULTS: Thirty-three percent of patients and 18% of HS experienced CSWG. After correcting for multiple comparisons, CSWG in patients predicted a greater decrease in left hippocampal NAA (effect size = -0.52, p = 0.005). CSWG also predicted a greater decrease in left hippocampal NAA in HS with a similar effect size (-0.53). A model including patients and HS found an effect of CSWG on Δleft NAA (p = 0.007), but no diagnosis effect and no diagnosis × CSWG interaction, confirming that CSWG had similar effects in patients and HS.CONCLUSION: CSWG is a risk factor for decreasing hippocampal NAA in BD patients and HS. These results suggest that the well-known finding of reduced NAA in BD may result from higher body mass index in patients rather than BD diagnosis.

KW - Bipolar disorder

KW - N-acetylaspartate

KW - body mass index

KW - glutamate

KW - hippocampus

KW - magnetic resonance spectroscopy

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DO - 10.1017/s0033291721000544

M3 - Article

C2 - 33706825

AN - SCOPUS:85102430241

SN - 0033-2917

VL - 52

SP - 3783

EP - 3791

JO - Psychological medicine

JF - Psychological medicine

IS - 16

ER -

Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients: a longitudinal magnetic resonance spectroscopy study

Abstract

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