title: Abnormal activity-dependent brain lactate and glutamate+glutamine responses in panic disorder.
abstract: BACKGROUND
  Prior evidence suggests panic disorder (PD) is characterized by neurometabolic abnormalities, including increased brain lactate responses to neural activation. Increased lactate responses could reflect a general upregulation of metabolic responses to neural activation. However, prior studies in PD have not measured activity-dependent changes in brain metabolites other than lactate. Here we examine activity-dependent changes in both lactate and glutamate plus glutamine (glx) in PD.
  
  
  METHODS
  Twenty-one PD patients (13 remitted, 8 symptomatic) and 12 healthy volunteers were studied. A single-voxel, J-difference, magnetic resonance spectroscopy editing sequence was used to measure lactate and glx changes in visual cortex induced by visual stimulation.
  
  
  RESULTS
  The PD patients had significantly greater activity-dependent increases in brain lactate than healthy volunteers. The differences were significant for both remitted and symptomatic PD patients, who did not differ from each other. Activity-dependent changes in glx were significantly smaller in PD patients than in healthy volunteers. The temporal correlation between lactate and glx changes was significantly stronger in control subjects than in PD patients.
  
  
  CONCLUSIONS
  The novel demonstration that glx responses are diminished and temporally decoupled from lactate responses in PD contradicts the model of a general upregulation of activity-dependent brain metabolic responses in PD. The increase in activity-dependent brain lactate accumulation appears to be a trait feature of PD. Given the close relationship between lactate and pH in the brain, the findings are consistent with a model of brain metabolic and pH dysregulation associated with altered function of acid-sensitive fear circuits contributing to trait vulnerability in PD.
authors: Department of Psychiatry, University of California Davis Medical Center, Sacramento, California 95817, USA. rjmaddock@ucdavis.edu
authors: Richard J
authors: RJ
authors: Maddock
authors: Michael H
authors: MH
authors: Buonocore
authors: Amber R
authors: AR
authors: Miller
authors: Jong H
authors: JH
authors: Yoon
authors: Steffan K
authors: SK
authors: Soosman
authors: April M
authors: AM
authors: Unruh
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010775:Photic Stimulation; D013001:Somatoform Disorders / Q000473:pathology*; D014316:Tritium; D014793:Visual Cortex / Q000378:metabolism*
chemical_list: D005973:Glutamine; D014316:Tritium; D019344:Lactic Acid; D018698:Glutamic Acid