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3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[(11) C]methyl-l-tryptophan ((11) C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional (11) C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized (11) C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized (11) C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized (11) C-AMT trapping in the brainstem and pre-frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms., (© 2014 International Society for Neurochemistry.)

Negative affect in healthy populations regulates the appraisal of demanding situations, which tunes subsequent effort mobilization and adjustments in cognitive control. In the present study, we hypothesized that dysphoria in depressed individuals similarly modulates this adaptation, possibly through a neural mechanism involving serotonergic regulation. We tested the effect of dysphoria induced by acute tryptophan depletion (ATD) in remitted depressed patients on conflict adaptation in a Simon task. ATD temporarily lowers the availability of the serotonin precursor L-Tryptophan and is known to increase depressive symptoms in approximately half of remitted depressed participants. We found that depressive symptoms induced by ATD were associated with increased conflict adaptation. Our finding extends recent observations implying an important role of affect in regulating conflict-driven cognitive control.

Acute tryptophan depletion (ATD) in currently depressed patients has no immediate effect on symptoms, but leads to transient symptom improvement or worsening the next day. In view of recent findings concerning the cognitive effects of serotonin manipulations, we used ATD in fourteen depressed patients to investigate whether cognitive effects following ATD predict symptom changes. We found that symptom improvement 24h after ATD was associated with an improved recall of positive words and with less attentional bias and recall of negative words, 5h after ATD. These results indicate that serotonergic alterations affect emotional processing which may subsequently lead to symptom changes., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Depression is a major risk factor for cardiovascular disease. An important risk factor for cardiovascular disease, low heart rate variability, often has been found in depressed patients and has been associated with impulsivity. The present study investigated whether experimental lowering of serotonin would decrease heart rate variability and increase impulsivity in remitted depressed patients, in particular in those patients with disturbed impulse control., Methods: Nineteen patients in remission from depression received high-dose and low-dose acute tryptophan depletion in a randomized, counterbalanced, double-blind crossover design. Heart rate variability and impulsivity were assessed during each acute tryptophan depletion session and during a baseline session. Suicidal ideation during past depression was used as an index for individual differences in impulse control., Results: High-dose acute tryptophan depletion led to a larger increase in depressive symptoms than did low-dose acute tryptophan depletion. High-dose acute tryptophan depletion decreased heart rate variability and increased impulsivity and anxiety, but only in patients with a history of suicidal ideation. Symptom effects of high-dose acute tryptophan depletion correlated with low heart rate variability at baseline., Conclusions: Depressed patients who have problems with controlling impulsivity might be more at risk for developing cardiovascular disease, possibly related to increased vulnerability to impaired 5-hydroxytryptamine function.

Background: Acute tryptophan depletion (ATD) induces depressive symptoms in remitted depressed patients treated with serotonergic medications, but not in patients treated with noradrenergic medications or electroconvulsive therapy. A recent study suggests that cognitive therapy (CT) protects against the effects of ATD, but the evidence is questionable. The present study compared the effect of ATD in patients who were treated with antidepressant medication and CT (n = 17) versus antidepressant medication alone (n = 23) during their latest episode., Methods: Forty remitted depressed patients underwent high-dose and low-dose ATD in a randomized double-blind crossover design., Results: There were no differences in response to ATD between treatment groups. This applied to groups defined by lifetime and by recent CT experience., Conclusions: Cognitive therapy does not protect against the effects of rapidly lowered plasma tryptophan levels in remitted depressed patients who are also treated with antidepressant medication.

Background: Acute tryptophan depletion transiently induces symptoms in those with remitted depression. The behavioural specificity is uncertain, however. Recently, symptom provocation studies have become controversial, particularly in the USA., Aims: To assess the specificity of acute tryptophan depletion. To investigate systematically the subjective experiences of those taking part in a symptom provocation study., Method: Twenty individuals with remitted depression underwent acute tryptophan depletion in a double-blind, crossover trial. Psychiatric symptoms and self-schemata relevant to depression were assessed. The quality of the informed consent procedure and subjective experiences were also evaluated., Results: Acute tryptophan depletion induced a specific depressive response. The effects were more pronounced in females than in males. Participants were quite satisfied with the informed consent procedure. They had understood that this was a fundamental research project and personal benefits were not expected. However, some participants still found it a positive experience., Conclusions: Acute tryptophan depletion is a suitable model of vulnerability to depression, from both a scientific and an ethical perspective.

Background: It has frequently been demonstrated that experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50-60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression. In unmedicated depressed patients, ATD has no immediate effect on symptoms. The effects in currently depressed medicated patients have not been investigated., Methods: Fourteen currently depressed patients (seven patients treated with a selective serotonin-noradrenalin reuptake inhibitor (SSNRI); seven other treatment, non-SSNRI) received ATD in a double-blind, crossover design. Different strengths of the ATD mixture (aimed at 50% and 90% reduction of tryptophan) were used on separate days. Psychiatric symptoms were assessed at both sessions prior to, at +6.5 h, and at +24 h after ATD., Results: The ATD mixtures induced the expected reductions of plasma tryptophan levels. Full but not partial depletion improved mood and other psychiatric symptoms at +24 h in patients who received SSNRI treatment, as indicated by clinical ratings and self-report. Subjective sleep quality also improved., Conclusions: The effects of ATD on psychiatric symptoms in currently depressed patients are remarkably different from the results in recently remitted SSRI-treated patients. ATD in currently depressed patients treated with serotonergic antidepressants possibly provides important information about the mechanism of action of SSRIs.

It has frequently been demonstrated that acute tryptophan depletion (ATD) induces a transient depressed mood in some patients who are in remission from depression. However, the effects of ATD on cognitive processes in remitted depressed patients have not been investigated. The aim of the present study was to investigate the effects of different extents of depletion on mood and cognitive tasks involving neutral and emotional stimuli. Twenty patients in remission or in partial remission from depression received ATD in a double-blind, crossover design. Mood was assessed at both sessions before, at +6.5 h and +24 h after depletion. Cognitive assessment in both sessions started at +4.75 h, and also before and after the whole procedure. The ATD mixtures induced the expected reductions of plasma tryptophan levels. High-dose ATD induced a depressive response in a subsample of patients and impaired the processing of positive information independent of mood change. Attention for neutral stimuli (Stroop interference) improved in a dose-dependent manner. ATD may affect mood and cognition via different pathways: one implicated in mood regulation and the processing of emotional information, and one for the processing of neutral information. The first pathway may be more important for discriminating vulnerability to impaired serotonin function. The comparison of the effects of high-dose and low-dose ATD is useful for those studies aiming to investigate the relationships among 5-HT, mood and cognition.

Acute tryptophan depletion (ATD) induces depressive symptoms in 50-60% of selective serotonin reuptake inhibitor (SSRI) treated, recovered depressed patients. However, no reliable predictors of mood response to ATD have been established. In the present study, individual subject data of six ATD studies were pooled ('mega-analysis') in order to investigate the mediating role of clinical, demographic and biochemical characteristics in the mood response to ATD. A procedure was developed to make different versions of the Hamilton scale comparable. Recurrent depressive episodes, female gender, prior exposure to SSRI antidepressant treatment and previous serious suicidal thoughts/attempts all appear to be independent predictors of mood response to ATD. Chronicity of illness is the most powerful predictor. Residual symptoms of depression were not found to predict response to ATD. ATD may be useful to study the mechanism of action of SSRI antidepressants and individual biological vulnerability of the serotonin system. Whether the effects of ATD represent a reversal of the action of SSRI antidepressants or individual vulnerability probably depends upon the timing of the procedure in the course of remission of a depressive episode.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[11C]methyl-Ltryptophan (11C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional 11C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized 11C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized 11C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized 11C-AMT trapping in the brainstem and prefrontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms. [ABSTRACT FROM AUTHOR]

Negative affect in healthy populations regulates the appraisal of demanding situations, which tunes subsequent effort mobilization and adjustments in cognitive control. In the present study, we hypothesized that dysphoria in depressed individuals similarly modulates this adaptation, possibly through a neural mechanism involving serotonergic regulation. We tested the effect of dysphoria induced by acute tryptophan depletion (ATD) in remitted depressed patients on conflict adaptation in a Simon task. ATD temporarily lowers the availability of the serotonin precursor L-Tryptophan and is known to increase depressive symptoms in approximately half of remitted depressed participants. We found that depressive symptoms induced by ATD were associated with increased conflict adaptation. Our finding extends recent observations implying an important role of affect in regulating conflict-driven cognitive control. [ABSTRACT FROM AUTHOR]

Cognitive reactivity (CR) is a psychological vulnerability marker of depression, whereas response to acute tryptophan depletion (ATD; a serotonergic challenge procedure) is a biological vulnerability marker. The aim of this study was to investigate the relationship between these markers. Thirty-nine remitted depressed patients participated in 2 ATD sessions in a double-blind crossover design. CR, assessed prior to the ATD sessions, predicted depressive response to high-dose ATD. CR also diminished the effects of 2 known predictors of ATD response: gender and residual symptoms. Neuroticism and behavioral inhibition were unrelated to ATD response. CR is associated with an increased sensitivity to reductions of serotonin concentrations. These findings present a small step toward unifying cognitive and neurobiological theories of depression. [ABSTRACT FROM AUTHOR]

Depression is associated with reduced brain serotonin (5-hydroxytryptamine; 5-HT) function and with cognitive dysfunctions. A diet rich in α-lactalbumin protein has been found to increase the ratio tryptophan/large neutral amino acids (Trp/∑LNAA), and to improve cognitive functioning in individuals with high neuroticism scores. Since cognitive dysfunctions sometimes persist after remission of depression, the present study investigated the effects of α-lactalbumin-enriched diet on cognition in recovered depressed patients. Twenty-three recovered depressed patients and 20 healthy matched controls without a history of depression consumed meals rich in α-lactalbumin or casein protein in a double-blind crossover design. Mood, cognitive function and plasma amino acids were assessed at both sessions before and after dietary intake. Alpha-lactalbumin protein had no effect on mood, but improved abstract visual memory and impaired simple motor performance. These effects were independent of history of depression. Supplements of α-lactalbumin may be useful for nutrition research in relation to age- or disease-related memory decline. The present findings should be further examined in different (e.g. medicated) samples. The long-term effects of α-lactalbumin should also be investigated. [ABSTRACT FROM AUTHOR]