The effects of tryptophan depletion on neural responses to emotional words in remitted depression.
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 > or =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.
Roiser
Jonathan P
JP
Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London WC1N 3AR, United Kingdom. j.roiser@ucl.ac.uk
Levy
Jamey
J
Fromm
Stephen J
SJ
Nugent
Allison C
AC
Talagala
S Lalith
SL
Hasler
Gregor
G
Henn
Fritz A
FA
Sahakian
Barbara J
BJ
Drevets
Wayne C
WC
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D018592:Cross-Over Studies; D003863:Depression / Q000175:diagnosis / Q000503:physiopathology*; D004311:Double-Blind Method; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D010919:Placebos; D011597:Psychomotor Performance; D012039:Regional Blood Flow / Q000502:physiology; D012075:Remission, Spontaneous; D012701:Serotonin / Q000096:biosynthesis / Q000502:physiology*; D014364:Tryptophan / Q000097:blood*
D010919:Placebos; D012701:Serotonin; D014364:Tryptophan