Brain Serotonin1A Receptor Binding in Major Depression Is Related to Psychic and Somatic Anxiety

Background The anxious phenotype of the 5-HT1A receptor knockout mouse and the anxiolytic properties of 5-HT1A agonists suggest that the 5-HT1A receptor modulates anxiety. We investigated the relationship of anxiety expressed in major depressive disorder (MDD) to regional 5-HT1A binding. Methods Positron emission tomography with [carbonyl-11C]WAY-100635 was used to estimate regional 5-HT1A binding potential (BP) in 28 medication-free MDD subjects. Stepwise linear regression assessed the predictive capacity of three anxiety components, derived from a larger MDD sample and termed psychic, somatic, and motoric anxiety, on regional 5-HT1A BP. Results Higher psychic (β ≥ .63) and lower somatic (β ≤ –.70) anxiety predicted over 50% of the variance in 5-HT1A BP in multiple cortical regions, but not in amygdala, hippocampus, or autoreceptors of the raphe nuclei. The psychic and somatic anxiety components were not related to depression severity. Comorbid panic disorder was associated with lower cortical and subcortical 5-HT1A BP. Conclusions The 5-HT1A receptor in the same brain regions has different relationships to psychic anxiety versus somatic anxiety. Lower 5-HT1A BP in panic disorder may be accounted for by higher somatic and lower psychic anxiety. Further study of the pathobiology of these anxiety components may identify distinct therapeutic targets or mechanisms.