TY - JOUR
T1 - Altered prefrontal glutamate-glutamine-γ-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus
AU - Lyoo, In Kyoon
AU - Yoon, Sujung J.
AU - Musen, Gail
AU - Simonson, Donald C.
AU - Weinger, Katie
AU - Bolo, Nicolas
AU - Ryan, Christopher M.
AU - Kim, Jieun E.
AU - Renshaw, Perry F.
AU - Jacobson, Alan M.
PY - 2009/8
Y1 - 2009/8
N2 - 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-γ-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.
AB - 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-γ-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.
UR - http://www.scopus.com/inward/record.url?scp=68149180517&partnerID=8YFLogxK
U2 - 10.1001/archgenpsychiatry.2009.86
DO - 10.1001/archgenpsychiatry.2009.86
M3 - Article
C2 - 19652127
AN - SCOPUS:68149180517
SN - 0003-990X
VL - 66
SP - 878
EP - 887
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
IS - 8
ER -