The myth of panic spontaneity: Consideration of behavioral and neurochemical sensitization.

Abstract

Panic disorder is characterized by a progression of panic symptom severity with repeated attacks. Repeated panic episodes evoke heightened anticipatory anxiety, phobic avoidance and are typically associated with comorbid symptoms of depression. Due to the heterogeneity of the disorder, reliable neurochemical correlates attending panic have not been identified. However, variable neuropeptide interfacing with major and minor transmitter systems may modulate individual vulnerability to panic and account for variable panic profiles. The extensive colocalization of cholecystokinin (CCK) with other neurotransmitters, including dopamine (DA), enkephalin (ENK) and GABA, in specific central sites may influence various aspects of anxiety and panic. The behavioral correlates attending panic likely follow from variable neurochemical release and conditioning/sensitization. Clinicians maintain that recurrent panic attacks are spontaneous (unexpected, uncued) and fail to acknowledge the wealth of information implicating a prominent role for stressful life events in panic. Conditioning and sensitization of both behavior (e.g., fear-motivated) and neurochemical events (e.g., DA and CCK) in response to uncontrollable stressors parallel the diverse heterogeneity of panic amongst clinical samples. Cholecystokinin-4, pentagastrin, lactate acid, and CO2 induce panic attacks that are dependent on subjective history, expectancy measures and panic profiles. Panic disorder is associated with chronic illness and familial sick-role modeling exacerbates the course of the illness. The current review outlines the evidence in support of a conditioning/sensitization model for panic, a model that may explain the variable efficacies of pharmacological interventions.