Panic disorder is a potentially disabling anxiety disorder affecting 1.5% to 3.5% of the population. Twin studies show that panic disorder has a significant heritable component. However, the underlying pathophysiology of this condition is not well understood. The long-term goal of this study is to apply new concepts of brain metabolism to advance understanding of the causes of panic disorder. In an attempt to distinguish underlying causes from the many physiological effects of panic disorder, Klein (1993) proposed the """"""""suffocation false alarm"""""""" theory. Among the observations supporting this theory are the consistent findings of increased lactic acid responses to a variety of metabolic challenges in patients with panic disorder (reviewed in Maddock 2001). Brain lactate has recently been shown to have a previously unappreciated and significant role in brain energy metabolism under aerobic conditions. Recent studies using proton magnetic resonance spectroscopy (1 H-MRS) have shown increased lactate responses to alkalosis in the brain parenchyma of patients with panic disorder. Understanding the mechanism of this effect may shed light on the underlying pathophysiology of this condition. Several mechanisms have been proposed, including 1) a disturbance in the intrinsic dynamics of lactate metabolism; and 2) hypoxia due to increased cerebral vasoconstriction. These two models make distinctly different predictions about the brain lactate response to sensory stimulation in panic disorder. This study aims to reject one of these two models. The brain lactate response to photic stimulation will be studied with 1H-MRS in 16 patients with panic disorder and 16 matched normal volunteers. Prior studies show that photic stimulation leads to lactate accumulation in the visual cortex despite adequate oxygen supplies. Our pilot studies confirm this increase in lactate. The hypothesis that hypoxia is a necessary condition for the increased brain lactate responses in panic disorder would be falsified by a finding of increased lactate responses to photic stimulation in the panic patients. Conversely, the hypothesis that panic patients have a disturbance in the intrinsic dynamics of lactate metabolism would be falsified by finding no difference in the lactate response between the panic and control groups. The results of this study will constrain the possible models that can account for this phenomenon and guide future studies of the underlying pathophysiology of panic disorder.
|Maddock, R J; Buonocore, M H; Copeland, L E et al. (2009) Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study. Mol Psychiatry 14:537-45|
|Maddock, Richard J; Buonocore, Michael H; Lavoie, Shawn P et al. (2006) Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla. Psychiatry Res 148:47-54|