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


METHODS
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.
Parsey
Ramin V
RV
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA. rparsey@neuron.cpmc.columbia.edu
Hastings
Ramin S
RS
Oquendo
Maria A
MA
Huang
Yung-yu
YY
Simpson
Norman
N
Arcement
Julie
J
Huang
Yiyun
Y
Ogden
R Todd
RT
Van Heertum
Ronald L
RL
Arango
Victoria
V
Mann
J John
JJ
D000328:Adult; D000553:Ambulatory Care; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007546:Isoquinolines; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D012720:Severity of Illness Index; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data
D000928:Antidepressive Agents; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D050486:Serotonin Plasma Membrane Transport Proteins; C058079:McN 5652