Louisa J. Steinberg, MD, PhD; Mark D. Underwood, PhD; Mihran J. Bakalian, BA; Suham A. Kassir, BSc; J. John Mann, MD; Victoria Arango, PhD
Background: Serotonergic system abnormalities are implicated in many psychiatric disorders, including major depression. The temporal lobe receives a high density of serotonergic afferent projections, and responses in the primary auditory cortex to sound are modulated by serotonergic tone. However, the associations between changes in serotonergic tone, disease state and changes in auditory cortical function remain to be clarified.
Methods: We quantified serotonin 1A (5-HT1A) receptor binding, serotonin 2A (5-HT2A) receptor binding, and serotonin transporter (SERT) binding in Brodmann areas (BA) 41/42, 22, 9 and 4 from postmortem brain sections of 40 psychiatrically healthy controls and 39 individuals who had a history of a major depressive episode (MDE).
Results: There was 33% lower 5-HT2A receptor binding in BA 41/42 in individuals who had an MDE than in controls (p = 0.0069). Neither 5-HT1A nor SERT binding in BA 41/42 differed between individuals who had an MDE and controls. We also found 14% higher 5-HT1A receptor binding (p = 0.045) and 21% lower SERT binding in BA 9 of individuals who had an MDE (p = 0.045).
Limitations: The study was limited by the small number of postmortem brain samples including BA 41/42 available for binding assays and the large overlap between suicide and depression in the MDE sample.
Conclusion: Depression may be associated with altered serotonergic function in the auditory cortex involving the 5-HT2A receptor and is part of a wider view of the pathophysiology of mood disorders extending beyond psychopathology.
Submitted Oct. 15, 2018; Revised Feb. 4, 2019; Accepted Feb. 17, 2019; Published online on May 23, 2019
Acknowledgements: The authors thank Dr. Steve Ellis for his feedback on the statistical analysis of the data.
Affiliations: From the Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA (Steinberg, Underwood, Bakalian, Kassir, Mann, Arango); the Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA (Steinberg, Underwood, Mann, Arango); and the Department of Radiology, Columbia University, New York, NY, USA (Mann).
Competing interests: J. Mann receives royalties from the Research Foundation of Mental Hygiene for commercial use of the C-SSRS. No other competing interests declared.
Contributors: L. Steinberg, M. Underwood, J. Mann and V. Arango designed the study. M. Underwood, M. Bakalian, S. Kassir, J. Mann and V. Arango acquired the data, which L. Steinberg, M. Underwood, M. Bakalian, J. Mann and V. Arango analyzed. L. Steinberg and M. Bakalian wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: L.J. Steinberg, 1051 Riverside Dr, New York, NY 10032; Louisa.Steinberg@nyspi.columbia.edu