Altered prefrontal glutamate-glutamine-γ-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus

Department of Psychiatry and Interdisciplinary Program in Brain Science, Seoul National University, 28 Yongon-dong, Jongno-gu, Seoul 110-744, South Korea.
Archives of general psychiatry (Impact Factor: 13.75). 09/2009; 66(8):878-87. DOI: 10.1001/archgenpsychiatry.2009.86
Source: PubMed

ABSTRACT 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.
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.
Cross-sectional study.
General clinical research center.
One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants.
With the use of proton magnetic resonance spectroscopy, prefrontal glutamate-glutamine-gamma-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.
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.
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.

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    • "Regarding potential neurochemical alterations, a recent magnetic resonance spectroscopy (MRS) study determined that glutamate-glutamine-γ-aminobutyric acid (Glx) levels were elevated in the PFC of T1DM patients (Lyoo et al., 2009). In addition, higher PFC Glx concentrations were associated with impaired cognitive performance and depressed mood in these patients. "
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    Experimental Neurology 02/2011; 233(1):68-78. DOI:10.1016/j.expneurol.2011.02.004 · 4.62 Impact Factor
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    • "Additionally, glutamatergic alterations in the prefrontal cortex have been thought to be involved in the pathogenesis of this disorder in children [9] [10] as well as in adults [11]. At the same time glutamatergic disturbances in prefrontal cortex and in particular in the anterior cingulated cortex (ACC) have been reported in MDD [12] [13] and in some disorders in association with depressive symptoms [14] [15]. Proton-Magnet-Resonanz-Spectroscopy ( 1 H-MRS) is a non-invasive method which allows to detecting signals from neurometabolites in vivo. "
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