Serotonin-Related Abnormality Seen in Major Depressive Disorder
September 6, 2004
By Megan Rauscher

NEW YORK (Reuters Health) -- Tryptophan depletion studies in patients with and without a history of major depressive disorder (MDD) have revealed a disease-specific, serotonin-related process, researchers report in the August issue of Archives of General Psychiatry.

Dr. Alexander Neumeister from the National Institute of Mental Health in Bethesda, Maryland, told Reuters Health "we unmasked alterations in a circuit that is critical in the pathophysiology of MDD and showed metabolic differences in MDD patients relative to controls."

The circuit, he added, "involves cortical and subcortical areas of the brain and is involved in emotion processing and cognitive functions."

The researchers used the response to depletion of the serotonin precursor tryptophan to gauge the relationship between brain serotonin function and MDD. Depletion was induced by oral loading with all essential amino acids but tryptophan.

In 27 medication-free patients with remitted MDD (rMDD), tryptophan depletion led to a transient return to depressive symptoms. This was not the case in controls, who remained unaffected by tryptophan depletion.

Compared with sham depletion, tryptophan depletion 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 rMDD but not control patients.

"Genetic differences between MDD patients and controls," Dr. Neumeister continued, "may further enhance our knowledge about why people with depression differ from controls in their behavioral and neural responses to serotonin alterations and will lead to novel insight into the biology of MDD."

However, therapy can compensate for the underlying dysfunction in MDD," he emphasized, "and consequently maintenance treatment may be the key to ensure successful antidepressant treatment and a favorable treatment outcome."

Arch Gen Psychiatry 2004;61:765-773.

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