title: Brain circuits in panic disorder.
abstract: This paper reviews the pathophysiology of panic disorder (PD), within the context of newly described "fear circuitries," which have been well characterized in preclinical models. Substantial advances in the neurosciences have made it possible for clinical neuroscientists to refine our understanding of the pathophysiology of PD and the mechanisms of currently effective treatment. These advances have in turn helped generate testable hypotheses for future neurobiological and psychopharmacologic research. Perturbation of mutual modulation ("cross talk") between key brain transmitter systems (serotonin, norepinephrine, gamma-aminobutyric acid, corticotropin-releasing factor, and others) may underlie the pathogenesis of panic-anxiety. Restoration of normal homeostasis may be an important therapeutic component of antipanic therapy and may provide information about underlying neurocircuits. Neuroimaging, an important new tool, has already begun to bridge the gap between the preclinical and clinical neurosciences through confirmation of hypothesized dysfunction of the complex human prefrontal cortex and its subcortical components. In higher species, such as humans, dysfunction of cortical inhibition or excessive cortical activation of caudal limbic structures is postulated to lead to activation of the phylogenetically conserved amygdalofugal pathways. Consistent with probable subtypes of PD, overlapping theoretical models of panic neurocircuitries are proposed, including ventilatory dysregulation, which is coupled with neurovascular instability in a critical area of the panic neurocircuitry--the amygdalohippocampus. Neuroimaging appears a critical tool in guiding further elaboration of the interaction of cortical and subcortical components of the panic neurocircuitry, whereas challenge studies appear crucial in gathering further information regarding brain stem dysfunction.
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Coplan
authors.forename: R B
authors.initials: RB
authors.lastname: Lydiard
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D005239:Fear / Q000502:physiology; D006801:Humans; D009434:Neural Pathways / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000502:physiology; D016584:Panic Disorder / Q000473:pathology / Q000503:physiopathology*
chemical_list: D018377:Neurotransmitter Agents