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The effects of tryptophan depletion on neural responses to emotional words in remitted depression.

ABSTRACT: 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.

SUBMITTER: Roiser JP

PROVIDER: S-EPMC2745906 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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The effects of tryptophan depletion on neural responses to emotional words in remitted depression.

Roiser Jonathan P JP 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

Biological psychiatry 20090617 5

<h4>Background</h4>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.<h4>Methods</h4>Twenty control subjects and 23 rMDD subjects who had been unmedicated and in ...[more]

PMID: 19539268

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Project description:BackgroundThe aim of this study was to improve our understanding of the underlying mechanisms in the maintenance of depression. We examined attentional bias (AB) for negative and positive adjectives and general threat words in strictly-defined clinical groups of participants with pure Major Depressive Disorder (MDD) without a history of anxiety disorders (AD), mixed MDD and AD, and remitted participants.MethodWe investigated both stimulus specificity and time course of AB in these groups, adopting a cross-sectional design. Data were drawn from the large scale Netherlands Study of Depression and Anxiety (NESDA), from which we selected all participants with pure current MDD without a history of AD (n = 29), all participants with current MDD and co-morbid AD(s) (n = 86), all remitted MDD participants (n = 294), and a comparison group without (a history of) MDD or ADs (n = 474). AB was measured with an Exogenous Cueing Task covering short and long presentation times (500 and 1250 ms) and 4 stimulus types (negative, positive, threat, neutral).ResultsBoth traditional and trial level (dynamic) AB scores failed to show an AB for negative adjectives in participants with MDD or mixed MDD/AD. Specifically for long duration trials (1250 ms), remitted participants showed a larger AB traditional score (albeit the actual score still being negative) than the comparison group. The mixed MDD/AD group showed a higher trial-level AB score away from positive adjectives (1250 ms) than the comparisons. In addition, the mixed MDD/AD group showed higher and more variable trial-level AB scores away from short and towards longer presented general threat words together with a non-significant tendency to show less negative traditional AB scores for threat trials (500 ms) than the comparison group.ConclusionsAll in all, the findings do not corroborate the view that an AB towards negative or away from positive adjectives is critically involved in currently depressed individuals. Yet, the relatively high (less negative) AB score for negative adjectives in remitted individuals points to the possibility that an AB for negative information may be involved as a risk factor in the recurrence of MDD.

Dataset Information

The effects of tryptophan depletion on neural responses to emotional words in remitted depression.

Publications

The effects of tryptophan depletion on neural responses to emotional words in remitted depression.

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