The International Journal of Neuropsychopharmacology

Research Article

Gender-specific abnormalities in the serotonin transporter system in panic disorder

Dara M. Cannona1a2 c1, Jacqueline M. Klavera2, Summer A. Kluga2, Paul J. Carlsona3, David A. Luckenbaugha2, Masanori Ichisea4 and Wayne C. Drevetsa2a5a6

a1 Clinical Neuroimaging Laboratory, Departments of Anatomy and Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland

a2 National Institutes of Mental Health, Mood and Anxiety Disorders Program, Molecular Imaging Branch, NIMH, NIH, Bethesda, MD, USA

a3 The Brain Institute, University of Utah, USA

a4 Department of Radiology, Columbia University, New York, USA

a5 Laureate Institute for Brain Research, Tulsa, OK, USA

a6 Department of Psychiatry, The University of Oklahoma College of Medicine, Tulsa, OK, USA


The central serotonergic system has been implicated in the pathophysiology of panic disorder (PD) by evidence of abnormally elevated serotonin-turnover, reduced pre- and post-synaptic 5-HT1A−receptor sensitivity and binding and clinical improvement during administration of agents that enhance serotonergic transmission. Polymorphisms in genes that putatively influence serotonergic neurotransmission increase the vulnerability for developing PD specifically in males. We tested the hypotheses that serotonin transporter (5-HTT) binding is elevated in PD subjects vs. healthy controls in regions where in vivo evidence exists for both elevated 5-HTT and 5-HT1A receptor levels in PD and investigated whether the extent of this difference depends upon gender. Volunteers were out-patients with current PD (n=24) and healthy controls (n=24). The non-displaceable component of 5-HTT binding-potential (BPND) was measured using positron emission tomography and the 5-HTT selective radioligand, [11C]DASB. PD severity was assessed using the PD Severity Scale. The 5-HTT-BPND was increased in males with PD relative to male controls in the anterior cingulate cortex (F=8.96, p FDR=0.01) and midbrain (F=5.09, p FDR=0.03). In contrast, BPND did not differ between females with PD and female controls in any region examined. The finding that 5-HTT-binding is elevated in males but not in females with PD converges with other evidence suggesting that dysfunction within the central serotonergic system exists in PD, and also indicates that such abnormalities are influenced by gender. These findings conceivably may reflect a sexual dimorphism that underlies the greater efficacy of serotonin reuptake inhibitor treatment in females vs. males with PD.

(Received April 04 2012)

(Reviewed May 17 2012)

(Revised June 19 2012)

(Accepted June 21 2012)

(Online publication September 06 2012)

Key words

  • Cingulate cortex;
  • [C-11]DASB;
  • insula;
  • positron emission tomography;
  • 5-HTT