title: Altered prefrontal glutamate-glutamine-gamma-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus.
abstract: 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.
authors: 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
authors: In Kyoon
authors: IK
authors: Lyoo
authors: Sujung J
authors: SJ
authors: Yoon
authors: Gail
authors: G
authors: Musen
authors: Donald C
authors: DC
authors: Simonson
authors: Katie
authors: K
authors: Weinger
authors: Nicolas
authors: N
authors: Bolo
authors: Christopher M
authors: CM
authors: Ryan
authors: Jieun E
authors: JE
authors: Kim
authors: Perry F
authors: PF
authors: Renshaw
authors: Alan M
authors: AM
authors: Jacobson
mesh_terms: 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*
chemical_list: D018698:Glutamic Acid; D005973:Glutamine; D006442:Glycated Hemoglobin; D005680:gamma-Aminobutyric Acid