Context: Brain neurotransmitter changes characterising panic disorder remain uncertain.
Objective: To quantify brain norepinephrine and serotonin turnover in patients with panic disorder, in the absence of a panic attack.
Methods: Consecutively recruited, untreated patients with panic disorder (n = 34) and 24 matched healthy volunteers were tested in a study of cross-sectional design. Internal jugular venous sampling was used to directly quantify brain monoamine turnover, by measuring overflow of norepinephrine and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity, and the influence of an SSRI drug, citalopram, were investigated.
Results: Brain norepinephrine turnover was unremarkable in panic disorder. In contrast, serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased 4-fold in subcortical brain regions and the cerebral cortex (P <0.01). Serotonin turnover was highest in patients with more severe disease, was unrelated to transporter genotype, and was reduced by citalopram (P <0.01).
Conclusion: The marked increase in serotonin turnover, in the absence of a panic attack, probably represents the underlying neurotransmitter substrate for the disorder, given the direct relationship between serotonin turnover and illness severity, and the reduction in serotonin turnover with SSRI administration. Serotonin transporter genotyping demonstrated that increased whole brain serotonin turnover most likely derived, not from impaired serotonin reuptake, but from increased firing of seroto-nergic midbrain raphe neurons projecting to both the cerebral cortex and subcortical brain regions.
