MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Neumeister, 2004 PubMed
Full Info	Neumeister, A., Nugent, A.C., Waldeck, T., Geraci, M., Schwarz, M., Bonne, O., Bain, E.E., Luckenbaugh, D.A., Herscovitch, P., Charney, D.S. et al. (2004) Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls. Arch Gen Psychiatry, 61, 765-773

Study

Hypothesis or Background	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.
Sample Information	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).
Method Detail	Randomized double-blind crossover study. 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. 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.
Method Keywords	positron emission tomography (PET); dose administration; psychometric method
Result	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.
Conclusions	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.

Relationships reported by Neumeister, 2004

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
Orbitofrontal cortex (orbitofrontal cortex)	brain morphology and function	Tryptophan (tryptophan)	molecule		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex in patients with remitted MDD but not in controls.	Positive
medial thalamus (medial thalamus)	brain morphology and function	Tryptophan (tryptophan)	molecule		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the medial thalamus in patients with remitted MDD but not in controls.	Positive
Anterior cingulate cortex (anterior cingulate cortices)	brain morphology and function	Tryptophan (tryptophan)	molecule		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the anterior cingulate cortices in patients with remitted MDD but not in controls.	Positive
MDD	syndrome	Ventral striatum (ventral striatum)	brain morphology and function		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the ventral striatum in patients with remitted MDD but not in controls.	Positive
Depressed mood (depressed mood)	symptoms	Tryptophan (tryptophan)	molecule	P-value<0.01	Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P<.001).	Positive
Ventral striatum (ventral striatum)	brain morphology and function	Tryptophan (tryptophan)	molecule		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the ventral striatum in patients with remitted MDD but not in controls.	Positive
Posterior cingulate cortex (posterior cingulate cortices)	brain morphology and function	Tryptophan (tryptophan)	molecule		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the posterior cingulate cortices in patients with remitted MDD but not in controls.	Positive
MDD	syndrome	Anterior cingulate cortex (anterior cingulate cortices)	brain morphology and function		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the anterior cingulate cortices in patients with remitted MDD but not in controls.	Positive
MDD	syndrome	medial thalamus (medial thalamus)	brain morphology and function		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the medial thalamus in patients with remitted MDD but not in controls.	Positive
MDD	syndrome	Orbitofrontal cortex (orbitofrontal cortex)	brain morphology and function		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex in patients with remitted MDD but not in controls.	Positive
MDD	syndrome	Posterior cingulate cortex (posterior cingulate cortices)	brain morphology and function		Compared with sham depletion, TD (tryptophan depletion) was associated with an increase in regional cerebral glucose utilization in the posterior cingulate cortices in patients with remitted MDD but not in controls.	Positive