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Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and cont

Posted on 05/09/2010
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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.

About the Authors

Neumeister A, Nugent AC, Waldeck T, Geraci M, Schwarz M, Bonne O, Bain EE, Luckenbaugh DA, Herscovitch P, Charney DS, Drevets WC. (2004) Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls. Arch Gen Psychiatry. 2004 Aug;61(8):765-73. Section on Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892-2670, USA.

Comments

Dr_Abram_Hoffer

Posted on 05/16/2010 05:45 pm

This new work with NAD Therapy is very exciting and I think is right on target. It is indeed an energy-metabolic-deficiency (EMD) because in the absence of this coenzyme cycle almost all the reactions in the body run down... I congratulate Theo Verwey and his colleagues for this remarkable advance in using this concept and in using a simple test, the ratio of pyruvate to lactate as a diagnostic measure, to indicate the dose, duration of treatment etc.

NAD_Blood_Tests

Posted on 05/09/2010 06:22 am

It is known that dietary tryptophan can be converted to nicotinamide nucleotides in the body. Both the level of tryptophan and the energy content of the diet have been shown to influence the efficiency of conversion. The rate at which tryptophan is converted to nicotinamide nucleotides in the body may be expected to be influenced by the activities of the enzymes concerned with the tryptophan-NAD pathway.