Effects of acute tryptophan depletion on neuropsychological and motor function in Parkinson’s disease

Abstract

Interactions between the 5-HT system and the dopaminergic system and cholinergic system may be important in determining cognitive function and motor function in Parkinson's disease (PD). Previous studies have shown effects of reducing serotonin function, by acute tryptophan depletion (ATD), on neuropsychological function. In particular, an adverse effect on verbal memory has been demonstrated. This study compared with the effects of ATD on cognitive and motor function in PD and healthy control subjects. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, cross-over, randomised design in 20 patients with PD and 35 healthy controls matched for age, gender and premorbid IQ. There was a differential group effect of ATD on global cognitive function whereby the mean score on the modified mini mental state examination during ATD was lower than placebo in PD but higher in controls. There was a similar pattern of effects on verbal recognition. In a visual recognition task, ATD improved performance in the PD but not in the control group. In terms of psychomotor speed, there was also a group-specific effect with reduced latency of response during ATD in the PD group but increased latency in the control group. ATD has subtle neuropsychological effects, which differ significantly between PD and healthy control subjects. This suggests that the dopaminergic and cholinergic deficit of PD significantly modulates the effects of serotonin depletion, resulting in positive effects in some domains. Further investigation on the effects of specific serotonin antagonists may be merited in PD.

The effects of acute tryptophan depletion on neuropsychological function, mood and movement in the healthy elderly

“…We have previously reported an increase in latency of response on the motor screening task in healthy elderly controls during ATD (Mace et al, 2009). The current study represents an expansion of the control group in that report, both in terms of numbers and an older mean age.…”

“…In previous studies in elderly subjects with neuropsychological disease, we have suggested that the combination of the serotonergic deficit induced by ATD interacts with cholinergic deficit to give rise to reduced cognitive function during ATD (Mace et al, 2009; Porter et al, 2003, 2005). There is some evidence of cholinergic change with aging in healthy subjects (Court et al, 1997), suggesting that the same interaction may be seen during ATD in the elderly.…”

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

“…Manipulating central tryptophan levels using acute tryptophan depletion is also used as a tool to investigate the role of serotonin in neurological disorders. In Parkinson’s disease patients, a demonstrable reduction in global cognitive function and verbal recognition during acute tryptophan depletion is observed compared with placebo and control patients suggesting an interaction between serotonergic and cholinergic impairment [ 63 ]. No deficits in memory were observed in tryptophan-depleted young persons with attention deficit hyperactivity disorder [ 64 ], in reward response tests with alcoholic males [ 65 ], or in cognitive testing of Alzheimer’s patients that could not be attributed to old age [ 66 ].…”

Acute tryptophan depletion and Lewy body dementias

“…Individual results for complete assessments Figure 1. Effects of ATD on global cognitive function in DLB/PDD (current data), PD (Mace et al, 2010b), senile dementia of the Alzheimer's type (SDAT) (Porter et al, 2000) and recovered depression in the elderly (RD) (Porter et al, 2005).…”

“…ATD studies used to examine the effects of a rapid reduction in serotonin function have investigated the role of serotonin function in AD (Porter et al, 2000;2003), PD (Scholtissen et al, 2006;Mace et al, 2010a;2010b), and recovered depression in the elderly (Porter et al, 2005;2007). These studies have found that ATD generally decreased global cognitive status (as measured by the MMSE) in patients compared with healthy controls.…”