Elsevier

Biological Psychiatry

Volume 77, Issue 3, 1 February 2015, Pages 295-303
Biological Psychiatry

Archival Report
Type 2 Diabetes Mellitus: A Potentially Modifiable Risk Factor for Neurochemical Brain Changes in Bipolar Disorders

https://doi.org/10.1016/j.biopsych.2013.11.007Get rights and content

Abstract

Background

Neuroimaging changes in bipolar disorder (BD) may be secondary to the presence of certain clinical factors. Type 2 diabetes mellitus (T2DM) damages the brain and frequently co-occurs with BD. Studying patients with both T2DM and BD could help identify preventable risk factors for neuroimaging changes in BD.

Methods

We used 1.5T magnetic resonance spectroscopy to measure prefrontal N-acetylaspartate (NAA), which is mainly localized in neurons, and total creatine (tCr), an energy metabolite, in 19 BD patients with insulin resistance/glucose intolerance (BD + IR/GI), 14 BD subjects with T2DM (BD + T2DM), 15 euglycemic BD participants, and 11 euglycemic, nonpsychiatric control.

Results

The levels of NAA and tCr were lowest among BD + T2DM, intermediate in the BD + IR/GI, and highest among the euglycemic BD and control subjects (F3,55 = 4.57, p = .006; F3,55 = 2.92, p = .04, respectively). Even the BD + IR/GI subjects had lower NAA than the euglycemic participants (t43 = 2.13, p = .04). Total Cr was associated with NAA (β = .52, t56 = 5.57, p = .000001). Both NAA and tCr correlated with Global Assessment of Functioning scores (r46 = .28, p = .05; r46 = .48, p = .0004, respectively).

Conclusions

T2DM, but also prediabetes, may be risk factors for prefrontal neurochemical alterations in BD. These changes were associated with poor psychosocial functioning and could indicate impaired energy metabolism. The findings emphasize the importance of improving diabetes care in BD and suggest potential options for treatment of neuroimaging alterations.

Section snippets

Methods and Materials

This was a cross-sectional study of BD subjects recruited from the Maritime Bipolar Registry (13) and control subjects recruited through advertisement. The study was approved by the Ethics Committee of Capital District Health Authority and all included subjects signed the informed consent.

Description of the Participants

We analyzed data from 59 subjects: 33 participants with BD and impaired glucose metabolism (15 with IR, 4 with GI, and 14 with T2DM), 15 euglycemic BD patients, and 11 euglycemic, psychiatrically healthy control subjects. The BD + T2DM subjects had higher BMI, greater proportion of participants with dyslipidemia, and lower proportion of Li treated subjects than the other groups (F3,55 = 3.81, p = .02, χ23 = 24.5, p < .001, χ22 = 7.37, p = .03, respectively). The average age at T2DM diagnosis

Discussion

The main findings of this study are that BD patients with impaired glucose metabolism showed lower prefrontal NAA levels than euglycemic BD subjects, who had comparable NAA with euglycemic, nonpsychiatric control subjects. The largest extent of changes were found in BD + T2DM subjects, but even the BD + IR/GI group had significantly lower NAA than the euglycemic participants. The NAA was positively associated with tCr, which showed a similar pattern of between-group differences as the NAA. Both

Acknowledgments and Disclosures

This study was supported by funding from the Canadian Institutes of Health Research (103703, 106469, and 64410), the Nova Scotia Health Research Foundation, the Dalhousie Clinical Research Scholarship to Dr. Hajek and NARSAD Young Investigator Award to Dr. Calkin. The sponsors of the study had no role in the design or conduct of this study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

We thank Julie

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