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


METHODS
Cross-sectional study.


METHODS
General clinical research center.


METHODS
One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants.


METHODS
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.


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.
Lyoo
In Kyoon
IK
Department of Psychiatry and Interdisciplinary Program in Brain Science, Seoul National University, 28 Yongon-dong, Jongno-gu, Seoul 110-744, South Korea. inkylyoo@snu.ac.kr
Yoon
Sujung J
SJ
Musen
Gail
G
Simonson
Donald C
DC
Weinger
Katie
K
Bolo
Nicolas
N
Ryan
Christopher M
CM
Kim
Jieun E
JE
Renshaw
Perry F
PF
Jacobson
Alan M
AM
D000328:Adult; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D003863:Depression / Q000175:diagnosis* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D005973:Glutamine / Q000032:analysis / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000737:chemistry* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
D018698:Glutamic Acid; D005973:Glutamine; D006442:Glycated Hemoglobin; D005680:gamma-Aminobutyric Acid