Brain Serotonin 1A Receptor Binding in Major Depression Is Related to Psychic and Somatic Anxiety

• Published in: Biological psychiatry (1969) Vol. 58; no. 12; pp. 947 - 954
• Main Authors: Sullivan, Gregory M., Oquendo, Maria A., Simpson, Norman, Van Heertum, Ronald L., Mann, J. John, Parsey, Ramin V.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2005
• Subjects: Depression; hypochondriacal; panic; psychic; serotonin 1A (5-HT 1A); somatic; serotonin 1A (5-HT 1A); Depression; somatic; psychic; hypochondriacal; panic
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2005.05.006

The anxious phenotype of the 5-HT 1A receptor knockout mouse and the anxiolytic properties of 5-HT 1A agonists suggest that the 5-HT 1A receptor modulates anxiety. We investigated the relationship of anxiety expressed in major depressive disorder (MDD) to regional 5-HT 1A binding. Positron emission tomography with [carbonyl- 11C]WAY-100635 was used to estimate regional 5-HT 1A 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-HT 1A BP. Higher psychic (β ≥ .63) and lower somatic (β ≤ –.70) anxiety predicted over 50% of the variance in 5-HT 1A 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-HT 1A BP. The 5-HT 1A receptor in the same brain regions has different relationships to psychic anxiety versus somatic anxiety. Lower 5-HT 1A 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.