RT Journal
A1 Neumeister A, Nugent AC, Waldeck T, et al
T1 NEural and behavioral responses to tryptophan depletion in unmedicatedpatients with remitted major depressive disorder and controls
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2004
FD August 1
VO 61
IS 8
SP 765
OP 773
DO 10.1001/archpsyc.61.8.765
UL http://dx.doi.org/10.1001/archpsyc.61.8.765
AB Context 
    An instructive paradigm for investigating the relationship between brain
serotonin function and major depressive disorder (MDD) is the response to
tryptophan depletion (TD) induced by oral loading with all essential amino
acids except the serotonin precursor tryptophan.Objective 
    To determine whether serotonin dysfunction represents a trait abnormality
in MDD in the context of specific neural circuitry abnormalities involved
in the pathogenesis of MDD.Design 
    Randomized double-blind crossover study.Setting 
    Outpatient clinic.Participants 
    Twenty-seven medication-free patients with remitted MDD (18 women and
9 men; mean ± SD age, 39.8 ± 12.7 years) and 19 controls (10
women and 9 men; mean ± SD age, 34.4 ± 11.5 years).Interventions 
    We induced TD by administering capsules containing an amino acid mixture
without tryptophan. Sham depletion used identical capsules containing hydrous
lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were
performed 6 hours after TD. Magnetic resonance images were obtained for all
participants.Main Outcome Measures 
    Quantitative positron emission tomography of regional cerebral glucose
utilization to study the neural effects of sham depletion and TD. Behavioral
assessments used a modified (24-item) version of the Hamilton Depression Rating
Scale.Results 
    Tryptophan depletion induced a transient return of depressive symptoms
in patients with remitted MDD but not in controls (P<.001).
Compared with sham depletion, TD was associated with an increase in regional
cerebral glucose utilization in the orbitofrontal cortex, medial thalamus,
anterior and posterior cingulate cortices, and ventral striatum in patients
with remitted MDD but not in controls.Conclusion 
    The pattern of TD-induced regional cerebral glucose utilization changes
in patients with remitted MDD suggests that TD unmasks a disease-specific,
serotonin system–related trait dysfunction and identifies a circuit
that probably plays a key role in the pathogenesis of MDD.