A positron emission tomography study of the serotonergic system in relation to anxiety in depression

Zafer Iscan, Gopalkumar Rakesh, Samantha Rossano, Jie Yang, Mengru Zhang, Jeffrey Miller, Gregory M. Sullivan, Priya Sharma, Matthew McClure, Maria A. Oquendo, J. John Mann, Ramin V. Parsey, Christine DeLorenzo

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Symptoms of anxiety are highly comorbid with major depressive disorder (MDD) and are known to alter the course of the disease. To help elucidate the biological underpinnings of these prevalent disorders, we previously examined the relationship between components of anxiety (somatic, psychic and motoric) and serotonin 1A receptor (5-HT1A) binding in MDD and found that higher psychic and lower somatic anxiety was associated with greater 5-HT1A binding. In this work, we sought to examine the correlation between these anxiety symptom dimensions and 5-HTT binding. Positron emission tomography with [11C]-3-amino-4-(3-dimethylamino-methylphenylsulfanyl)-benzonitrile ([11C]DASB) and a metabolite-corrected arterial input function were used to estimate regional 5-HTT binding in 55 subjects with MDD and anxiety symptoms. Somatic anxiety was negatively correlated with 5-HTT binding in the thalamus (β=−.33, p=.025), amygdala (β=−.31, p=.007) and midbrain (β=−.72, p<.001). Psychic anxiety was positively correlated with 5-HTT binding in midbrain only (β=.46, p=.0025). To relate to our previous study, correlation between 5-HT1A and 5-HTT binding was examined, and none was found. We also examined how much of the variance in anxiety symptom dimensions could be explained by both 5-HTT and 5-HT1A binding. The developed model was able to explain 68% (p<.001), 38% (p=.012) and 32% (p=.038) of the total variance in somatic, psychic, and motoric anxiety, respectively. Results indicate the tight coupling between the serotonergic system and anxiety components, which may be confounded when using aggregate anxiety measures. Uncovering serotonin's role in anxiety and depression in this way may give way to a new generation of therapeutics and treatment strategies.

Original languageEnglish
Pages (from-to)1011-1021
Number of pages11
JournalEuropean Neuropsychopharmacology
Issue number10
StatePublished - Oct 2017

Bibliographical note

Funding Information:
This study was supported with the following grants: J.J.M.: R01 MH40695 , P50 MH62185 , R.V.P.: R01 MH074813-01 (NIMH), NARSAD - PTSD—Serotonin and Stress System Interactions, AFSP - Suicide in Depression Comorbid with PTSD: Serotonin and Stress System Interactions, RFMH - Localization of Selective Attention Deficits in High Lethality Suicide Attempters. CD: K01 MH91354 ( NIMH ). Moreover, the study has been partly funded by the Russian Academic Excellence Project '5–100'. Funding sources had no further role.

Funding Information:
We would like to thank Tony Jin, Hao Chen, Ruofeng Wen, Mala Ananth, Judith Crowell, Laura Kunkel, Mohammad Zia, Greg Perlman, Joshua Kaufman from Stony Brook University and Francesca Zanderigo from Columbia University for their comments and help in data acquisition and processing. We acknowledge the biostatistical consultation and support from the Biostatistical Consulting Core at the School of Medicine, Stony Brook University.

Publisher Copyright:
© 2017 Elsevier B.V. and ECNP


  • Anxiety
  • Depression
  • Positron emission tomography
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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