Predictors of Mood Response to Acute Tryptophan Depletion A Reanalysis

Abstract

Acute tryptophan depletion (ATD) induces depressive symptoms in 50-Acute tryptophan depletion (ATD) is a technique used to study serotonin (5-hydroxytryptamine; 5-HT) brain function in mood disorders. In this paradigm, 5-HT function is temporarily lowered by deprivation of its precursor L -Tryptophan (Trp), an amino acid essential for 5-HT synthesis. It has been suggested that behavioral response to ATD might be informative about the pathophysiology of clinical depression and the mechanisms mediating antidepressant efficacy.A number of studies have demonstrated that ATD temporarily induces depressive symptoms in remitted depressive patients treated with antidepressant medication (Delgado et al. 1990; Spillman et al. 2001). The recurrence of symptoms appears to be highest in subjects treated with a selective serotonin reuptake inhibitor (SSRI) (Delgado et al. 1990(Delgado et al. , 1994(Delgado et al. , 1999.However, not all patients react to ATD; even in SSRItreated patients, ATD exacerbates symptoms in 50-60% of investigated patients (Van der Does 2001a). This raises the question of what factors determine response to ATD. It has been argued that induced depressive

Cognitive and serotonergic vulnerability to depression: Convergent findings.

“…Although the present study found no significant relationship between recurrent depression and response to ATD, recurrent depression was the most powerful predictor of ATD response in a previous study (Booij et al, 2002). Other ATD studies also support this association (Neumeister et al, 2004;Smith et al, 1997).…”

Lack of Effect of Tyrosine Depletion on Mood in Recovered Depressed Women

“…Against this we have demonstrated that the related procedure of TRP depletion, administered in an identical placebocontrolled crossover design, causes significant depressive relapse in a similar group of recovered depressed subjects (Smith et al, 1997). Indeed a recent review of the effects of TRP depletion in recovered depressed patients suggested that female subjects with a history of multiple episodes were particularly at risk of clinical depressive relapse (Booij et al, 2002).…”

“…The women in the present study had mostly been recovered for long periods of time and it is possible that long duration of remission may make subjects less vulnerable to the mood lowering effects of monoamine depletion. However, the literature on TRP depletion does not support this possibility (Booij et al, 2002). All our subjects had at some time point met criteria for the melancholic subtype of depression because we predicted that subjects who had experienced anhedonia might be more vulnerable to lowered DA function.…”

The Effect of Acute Tryptophan Depletion on the Neural Correlates of Emotional Processing in Healthy Volunteers

“…This reduction is achieved by selectively excluding the essential amino acid tryptophan, the precursor to 5-HT, from the diet (Young et al, 1985). The most well-known effect of ATD is to produce a temporary recurrence of some depressive symptoms in a proportion of patients who have previously experienced a major depressive episode but who are euthymic at the time of testing (Booij et al, 2002). This effect appears to be most marked in patients maintained on selective serotonin reuptake inhibitors (SSRIs), though mood change in unmedicated remitted major depressive disorder patients has also been reported (Neumeister et al, 2004).…”