Reductions in Occipital Cortex GABA Levels in Panic Disorder Detected With 1H-Magnetic Resonance Spectroscopy

Abstract

DYSREGULATION in brain γ-aminobutyric acid (GABA) neuronal function might contribute to the pathophysiology of human panic disorder. For example, lowered brain GABA levels are associated with anxietylike behaviors in animals,%^1,2 and elevated brain GABA levels tend to be associated with anxiolysis.%^2,3 Although clinical studies of GABA levels in patients with panic disorder have shown normal plasma%^4,5 and cerebrospinal fluid GABA levels,%⁶ to date there have been no in vivo studies, to our knowledge, evaluating brain GABA levels in this patient population. Other components of the GABA system, such as the benzodiazepine (BZD) receptor, have been implicated in the pathophysiology of panic. For instance, impaired brain GABA_A/BZD receptor functioning has been directly linked to neophobic behaviors in mice,%^7,8 behaviors that resemble human agoraphobia. Furthermore, a generalized cortical reduction in BZD receptor binding in patients with panic disorder was recently observed using a positron emission tomographic technique, with effects being most pronounced in the right orbitofrontal and insular cortices,%⁹ although, subsequently, other groups%^10,11 also using positron emission tomography did not detect these abnormalities. In addition, regional cortical reductions in BZD receptor binding have been identified with single-photon emission computed tomographic techniques in frontal,%^12-14 temporal,%^12,13 left hippocampal, precuneus,%¹⁵ and occipital%¹² areas of patients with panic disorder.