A survey into the influence of dopaminergic drug exposure on ‘sense of presence’ symptoms in patients with parkinson's disease

AimsThe first objective was to estimate prevalence of sense of presence (SoP) experiences in patients with Parkinson's Disease (PD), including whether onset was prior to or after commencing dopaminergic medication. The second objective was to explore the relationship between frequency of SoP experiences and dopaminergic drug, drug dosage and length of drug exposure. The experimental hypothesis was that SoP symptoms in PD would present more frequently in patients treated longer and with higher dopaminergic drug doses.BackgroundPD is a debilitating neurodegenerative disorder. Psychiatric symptoms are common and associated with impaired quality of life and higher treatment costs. PD psychosis often starts with ‘minor hallucinations’, the most common being a false ‘sense of presence’ (SoP), the vivid sensation that someone else is nearby when nobody is there. SoP symptoms typically do not cause significant distress but may act as a prognostic marker for future severe psychosis and may prompt alteration of treatment or reduction in dopaminergic drug dosage. This study aimed to extend prior research by characterizing SoP further and investigating the link with dopaminergic medication.MethodThis was a retrospective, cross-sectional study. Twenty-one patients diagnosed with PD completed a questionnaire to identify presence of SoP symptoms, duration of symptoms, timing of onset related to dopaminergic treatment and the frequency of symptoms in relation to current levodopa equivalent dose (LED). Descriptive frequencies were compared using a two-tailed t-test. Multiple regression analysis was conducted to assess the relationship between frequency of SP experiences, levodopa equivalent dose and length of drug exposure.ResultSixteen of twenty-one patients reported experiencing SoP symptoms. Patients who had not experienced SoP symptoms had a significantly lower LED than those who had experienced these symptoms. There were no other significant differences between the groups. No statistical significance was shown on regression analysis; however our study was not adequately powered for the regression analysis as the number of participants was too low.ConclusionThis study confirms that SoP symptoms are common among patients with PD and supports a correlation between the total daily equivalent dose of levodopa and SoP symptoms. It does not provide evidence for a temporal relationship between onset of SoP symptoms and duration of dopaminergic treatment. The study was insufficiently powered and a larger study is required to investigate further.

Serotonergic and catecholaminergic (dopaminergic) oscillations in the reproductive regulation of Japanese quail

Specific temporal phase relation of serotonergic and dopaminergic oscillations alters reproductive responses in many species. Aim of the study was to confirm whether effect of serotonergic drug (5-HTP) and dopaminergic drug (L-DOPA) is due to their conversion into serotonin and dopamine respectively or other products. For this study, PCPA (p-chlorophenylalanine, a long lasting inhibitor of serotonin synthesis), DDC (Diethyldithiocarbamate, which inhibits biosynthesis of nor-adrenaline), α-MT (Methyl-p-tyrosine, an inhibitor for the conversion of tyrosine to DOPA) and DOPS (Dihydroxyphenylserine, a specific precursor for noradrenaline) were used in different groups in addition to 5-HTP and L-DOPA given at specific time interval. Reproductive responses monitored at 10 weeks post treatment indicate that gonadal activity was significantly low in HTP:DOPA (8-hr quail), HTP+PCPA:DOPA and HTP:DOPA+DDC quail compare to control (S:S). However, gonadal activity of HTP:S(HTP control), S:DOPA(DOPA control) and HTP: α-MT+DOPS was not different from S:S control and remained in active condition. These findings indicate that it is not the dose of neurotransmitter precursor drugs (5-HTP and L-DOPA) and the neurotransmitters (serotonin and dopamine itself) that cause the effect, instead it is the function of interval between the drug administration which induces or entrains specific phase relation between serotonergic and dopaminergic oscillations. Further, gonadal suppression observed in HTP:DOPA, HTP+PCPA:DOPA and HTP:DOPA+DDC group three groups is not due to injection of 5-HTP or L-DOPA (alone) but due to conversion of administered 5-HTP into serotonin and conversion of L-DOPA (administered) into dopamine; not due to their further conversion into catecholamines other than dopamine i.e. noradrenaline or adrenaline.

Dopaminergic drug effects on probability weighting during risky decision-making

Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioural addiction characterized by excessive risk-taking behaviour. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighing during decision-making. Healthy controls (n = 21) and pathological gamblers (n = 16) played a decision-making task involving choices between sure monetary options and risky gambles both in the gain and loss domains. Each participant played the task twice, either under placebo or the dopamine D2/D3 receptor antagonist sulpiride, in a double-blind, counter-balanced, design. A prospect theory modelling approach was used to estimate subjective probability weighting and sensitivity to monetary outcomes. Consistent with prospect theory, we found that participants presented a distortion in the subjective weighting of probabilities, i.e. they overweighted low probabilities and underweighted moderate to high probabilities, both in the gain and loss domains. Compared with placebo, sulpiride attenuated this distortion in the gain domain. Across drugs, the groups did not differ in their probability weighting, although in the placebo condition, gamblers consistently underweighted losing probabilities. Overall, our results reveal that dopamine D2/D3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision-making.Significance statementDopamine has been implicated in risky decision-making and gambling addiction, but the exact mechanisms underlying this influence remain partly elusive. Here we tested the hypothesis that dopamine modulates subjective probability weighting, by examining the effect of a dopaminergic drug on risk-taking behaviour, both in healthy individuals and pathological gamblers. We found that selectively blocking dopamine D2/D3 receptors diminished the typically observed distortion of winning probabilities, characterized by an overweighting of low probabilities and underweighting of high probabilities. This made participants more linear in their subjective estimation of probabilities, and thus more rational in their decision-making behaviour. Healthy participants and pathological gamblers did not differ in their risk-taking behaviour, except in the placebo condition in which gamblers consistently underweighted losing probabilities.