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Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study

Molecular Psychiatry volume 14, pages 537–545 (2009)Cite this article

Abstract

Converging evidence suggests that patients with panic disorder have a metabolic disturbance that may influence the regulation of arousal systems and confer vulnerability to ‘spontaneous’ panic attacks. The consistent finding of elevated brain lactate responses to various metabolic challenges in panic disorder appears to support this model, although the mechanism of this effect is not understood. Several mechanisms have been proposed to account for elevated brain lactate responses in panic disorder, including (1) brain hypoxia due to excessive cerebral vasoconstriction, and (2) a metabolic disturbance affecting lactate metabolism. Recent studies have shown that neural activation (for example, sensory stimulation) causes local lactate accumulation in the presence of increased oxygen availability. The current study used proton magnetic resonance spectroscopic measures of visual cortex lactate changes during visual stimulation in 15 untreated patients with panic disorder and 15 matched volunteers to critically test these two proposed mechanisms of elevated brain lactate responses in panic disorder. Visual cortex lactate/N-acetylaspartate increased during visual stimulation in both groups. The increase was significantly greater in the panic patients than in the comparison group. There were no group differences in end-tidal pCO2. The finding that visual stimulation leads to significantly greater visual cortex lactate responses in panic patients is not predicted by the hypoxia model. These results suggest that a metabolic disturbance affecting the production or clearance of lactate is the cause of the elevated brain lactate responses consistently observed in panic disorder and provide further support for metabolic models of vulnerability to this illness.

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Acknowledgements

This research was supported by grant no. R21MH69699 to RJM from the National Institute of Mental Health. We thank Shawn Lavoie for his help with data analysis.

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Authors and Affiliations

  1. Department of Psychiatry, University of California Davis Medical Center, Sacramento, CA, USA

    R J Maddock, L E Copeland & A L Richards

  2. Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA

    M H Buonocore

  3. Imaging Research Center, University of California Davis Medical Center, Sacramento, CA, USA

    R J Maddock, M H Buonocore, L E Copeland & A L Richards

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Correspondence to R J Maddock.

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Maddock, R., Buonocore, M., Copeland, L. et al. Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study. Mol Psychiatry 14, 537–545 (2009). https://doi.org/10.1038/sj.mp.4002137

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