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Altered Prefrontal Glutamate–Glutamine– -Aminobutyric Acid Levels and Relation to Low Cognitive Performance and Depressive Symptoms in Type 1 Diabetes Mellitus
In Kyoon Lyoo, MD, PhD, MMS;
Sujung J. Yoon, MD, PhD;
Gail Musen, PhD;
Donald C. Simonson, MD, MPH, ScD;
Katie Weinger, EdD;
Nicolas Bolo, PhD;
Christopher M. Ryan, PhD;
Jieun E. Kim, MD, MS;
Perry F. Renshaw, MD, PhD;
Alan M. Jacobson, MD
Arch Gen Psychiatry. 2009;66(8):878-887.
Context Neural substrates for low cognitive performance and depression, common long-term central nervous system–related changes in patients with type 1 diabetes mellitus, have not yet been studied.
Objective To investigate whether prefrontal glutamate levels are higher in patients with type 1 diabetes and whether an elevation is related to lower cognitive performance and depression.
Design Cross-sectional study.
Setting General clinical research center.
Participants One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants.
Main Outcome Measures With the use of proton magnetic resonance spectroscopy, prefrontal glutamate–glutamine– -aminobutyric acid (Glx) levels were compared between patients and control subjects. Relationships between prefrontal Glx levels and cognitive function and between Glx levels and mild depressive symptoms were assessed in patients with type 1 diabetes.
Results Prefrontal Glx concentrations were 9.0% (0.742 mmol/L; P = .005) higher in adult patients with type 1 diabetes than in healthy control subjects. There were positive linear trends for the effects of lifetime glycemic control on prefrontal Glx levels (P for trend = .002). Cognitive performances in memory, executive function, and psychomotor speed were lower in patients (P = .003, .01, and <.001, respectively) than in control subjects. Higher prefrontal Glx concentrations in patients were associated with lower performance in assessment of global cognitive function (0.11 change in z score per 1-mmol/L increase in Glx) as well as with mild depression.
Conclusions The high prefrontal glutamate levels documented in this study may play an important role in the genesis of the low cognitive performance and mild depression frequently observed in patients with type 1 diabetes. Therapeutic options that alter glutamatergic neurotransmission may be of benefit in treating central nervous system–related changes in patients with adult type 1 diabetes.
Author Affiliations: Department of Psychiatry and Interdisciplinary Program in Brain Science, Seoul National University, Seoul, South Korea (Drs Lyoo and Kim); Department of Psychiatry, Harvard Medical School, Boston, Massachusetts (Drs Lyoo, Musen, Weinger, Bolo, and Jacobson); Department of Psychiatry, Catholic University of Korea School of Medicine, Seoul (Dr Yoon); Research Division, Joslin Diabetes Center, Boston (Drs Musen, Weinger, and Jacobson); Department of Internal Medicine, Brigham and Women's Hospital, Boston (Dr Simonson); Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Dr Ryan); and Department of Psychiatry and the Brain Institute, University of Utah, and Department of Veterans Affairs Veterans Integrated Service Network 19 Mental Illness Research, Education, and Clinical Center, Salt Lake City, Utah (Dr Renshaw).
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