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Stephen R. Dager, MD; Seth D. Friedman, PhD; Aaron Heide, MD; Matthew E. Layton, MD, PhD; Todd Richards, PhD; Alan Artru, MD; Wayne Strauss, PhD; Cecil Hayes, PhD; Stefan Posse, PhD

Arch Gen Psychiatry. 1999;56:70-77.

Background  A fast, proton echo-planar spectroscopic imaging (PEPSI) technique, capable of simultaneously measuring metabolites from multiple brain regions, was used to investigate the anatomical distribution and magnitude of brain lactate responses to intravenous lactate infusion among subjects with panic disorder and control subjects.

Methods  Fifteen subjects with panic disorder and 10 control subjects were studied. All subjects were medication free and met DSM-IV criteria for panic disorder, or, for controls, no Axis I psychiatric disorder. Two-dimensional axial metabolite images having 1-cm³ spatial resolution were acquired at 6-minute intervals during 3 conditions: a 20-minute baseline, 20-minute 0.5-mol/L sodium lactate infusion, and 15-minute postinfusion period.

Results  Intravenous lactate infusion increased brain lactate levels throughout the axial brain section studied in all subjects. Panic-disordered subjects had significantly greater global brain lactate increases in response to lactate infusion. Lateralization of brain lactate response did not occur, nor were discrete regional loci of elevated lactate observed. Cerebrospinal fluid lactate changes corresponded to lactate changes in brain tissue. Severity of symptoms provoked by lactate infusion did not directly correlate with brain lactate response.

Conclusions  Greater overall rises in brain lactate among subjects with panic disorder compared with controls occurred in response to lactate infusion. We were unable to detect a distinct regional pattern for magnitude differences in brain lactate rise by which to identify a specific neuroanatomical substrate underlying a lactate-induced panic response. The wide anatomical distribution of these brain lactate increases suggest metabolic and/or neurovascular mechanisms for the abnormal rise in subjects with panic disorder.

From the Departments of Psychiatry (Drs Dager, Friedman, and Layton), Bioengineering (Drs Dager, Richards, and Strauss), Radiology (Drs Richards and Hayes), and Anesthesiology (Dr Artru), and Diagnostic Imaging Sciences Center (Drs Dager, Heide, Richards, and Hayes), University of Washington School of Medicine, Seattle; and Center for MR Research, Institut for Medizin, Jülich, Germany (Dr Posse).

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