Background
Major depressive disorder (MDD) has been associated with both dysfunction of the central
serotonergic system and abnormal responses to emotional stimuli. We used acute tryptophan
depletion (ATD) to investigate the effect of temporarily reducing brain serotonin
synthesis on neural and behavioral responses to emotional stimuli in remitted MDD
subjects (rMDD) and healthy control subjects.
Methods
Twenty control subjects and 23 rMDD subjects who had been unmedicated and in remission
for ≥3 months completed the study. Following tryptophan or sham depletion, participants
performed an emotional-processing task during functional magnetic resonance imaging.
In addition, resting state regional blood flow was measured using arterial spin labeling.
Results
Neither group exhibited significant mood change following ATD. However, tryptophan
depletion differentially affected the groups in terms of hemodynamic responses to
emotional words in a number of structures implicated in the pathophysiology of MDD,
including medial thalamus and caudate. These interactions were driven by increased
responses to emotional words in the control subjects, with little effect in the patients
under the ATD condition. Following ATD, habenula blood flow increased significantly
in the rMDD subjects relative to the control subjects, and increasing amygdala blood
flow was associated with more negative emotional bias score across both groups.
Conclusions
These data provide evidence for elevated habenula blood flow and alterations in the
neural processing of emotional stimuli following ATD in rMDD subjects, even in the
absence of overt mood change. However, further studies are required to determine whether
these findings represent mechanisms of resilience or vulnerability to MDD.
Key Words
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Article info
Publication history
Published online: June 18, 2009
Accepted:
May 2,
2009
Received in revised form:
May 1,
2009
Received:
October 21,
2008
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
