Lower serotonin transporter binding potential in the human brain during major depressive episodes

Am J Psychiatry. 2006 Jan;163(1):52-8. doi: 10.1176/appi.ajp.163.1.52.


Objective: CSF analysis, neuroendocrine challenges, serotonin depletion studies, and treatment studies implicate the serotonergic system in the pathophysiology of major depressive disorder. On the basis of postmortem and imaging studies, the authors hypothesized that subjects with major depressive disorder in a major depressive episode have fewer serotonin transporter sites, compared with healthy subjects.

Method: Serotonin transporter binding potential (f(1)B(max)/K(d)) was determined using positron emission tomography with [(11)C]McN 5652 in six brain regions in 25 medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and in 43 healthy volunteer comparison subjects. All subjects had arterial lines placed to determine metabolite-corrected arterial input functions.

Results: Serotonin transporter binding potential differed significantly by brain region and group. Post hoc analysis revealed lower binding potential in subjects with major depressive disorder, relative to the comparison subjects, in the amygdala and midbrain. The lower binding potential was more pronounced in the depressed subjects who had never received antidepressants. No correlation was found between binding potential in the midbrain and severity of depression or number of days without medication. Binding potential did not differ between suicide attempters and nonattempters.

Conclusions: Subjects in a major depressive episode have lower serotonin transporter binding potential in the amygdala and midbrain, compared to healthy subjects.

Publication types

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

MeSH terms

  • Adult
  • Ambulatory Care
  • Amygdala / diagnostic imaging
  • Amygdala / metabolism
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / metabolism*
  • Female
  • Hospitalization
  • Humans
  • Isoquinolines
  • Male
  • Mesencephalon / diagnostic imaging
  • Mesencephalon / metabolism
  • Positron-Emission Tomography / statistics & numerical data
  • Psychiatric Status Rating Scales
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Severity of Illness Index
  • Suicide, Attempted / psychology
  • Suicide, Attempted / statistics & numerical data


  • Antidepressive Agents
  • Carbon Radioisotopes
  • Isoquinolines
  • Serotonin Plasma Membrane Transport Proteins
  • McN 5652