Sex differences in diencephalon serotonin transporter availability in major depression

Biol Psychiatry. 2006 Jan 1;59(1):40-7. doi: 10.1016/j.biopsych.2005.06.012. Epub 2005 Sep 1.


Background: Major depression is more prevalent in women than men. The present study evaluated if previous findings that demonstrated decreased 5-hydroxytryptamine (5-HT) transporter availability in depressed patients would be confirmed in a larger sample and also evaluated sex differences.

Methods: Depressed (n = 32) and healthy subjects (n = 32), including 16 pairs of women and men, participated in an iodine-123-2 beta-carbomethoxy-3beta-(4-iodophenyltropane) ([(123)I]beta-CIT) single photon emission computed tomography (SPECT) and a magnetic resonance imaging (MRI) scan. Participants were administered [(123)I]beta-CIT (225.7 +/- 3.7 MBq) and imaged 23.0 +/- 1.6 hours later. Statistical analyses included analysis of variance and a regression analysis of the main and interactive effects of age, sex, and depression.

Results: Overall, depressed patients demonstrated 12% lower diencephalon and no change in striatal or brainstem [(123)I]beta-CIT uptake. Significant age by sex, sex by depression, and age by sex by depression interactions were noted due to 22% lower diencephalon [(123)I]beta-CIT uptake in depressed women compared with less than a 1% decrease in depressed men.

Conclusions: As observed previously, diencephalon 5-HT transporter availability is decreased in depressed patients. However, the decrease appears to be sex-specific and age-dependent. These findings suggest that serotonergic mechanisms mediating depressed mood differ between men and women in an age-dependent manner and may explain why young women respond better to treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Mapping
  • Case-Control Studies
  • Cocaine / analogs & derivatives
  • Cocaine / pharmacokinetics
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / metabolism*
  • Diencephalon / diagnostic imaging
  • Diencephalon / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Iodine Isotopes / pharmacokinetics
  • Male
  • Middle Aged
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Sex Characteristics*
  • Statistics as Topic
  • Tomography, Emission-Computed, Single-Photon / methods


  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Isotopes
  • Serotonin Plasma Membrane Transport Proteins
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Cocaine