Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I-FP-CIT study: reply to comment by Erro et al.

Dear Sir,We appreciate the interest of Erro and colleagues in our work and are grateful for their comments [1], giving us the opportunity to add further details and discuss the results of our study [2]. We also thank them for having brought to our attention their recently published article focusing on patients with newly diagnosed or untreated Parkinson’s disease (PD), which unfortunately had not been published at the time of our submission.The main objective of our study was not to address the relationship between asymmetry of motor signs and psychiatric symptoms in PD patients but to investigate a possible correlation between DAT availability and affective symptoms in the most common movement disorders, including for the first time patients with essential tremor and primary dystonia. We also included PD patients in order to contribute to the debate in the literature on the role of dopamine in PD-related affective symptoms, a subject on which several published studies have shown unclear results [3, 4]. However, Erro and colleagues raise this interesting issue of motor asymmetry, as they enrolled a sample of patients balanced for laterality of parkinsonian signs (17 patients for each group). By contrast, we enrolled 21 consecutive PD patients: 11 patients with left side predominant motor symptoms, 6 with right side predominant motor symptoms, and 4 with only mild asymmetry on the motor scale score (3 left side and 1 right side). We found an inverse significant correlation between depression symptom levels (evaluated by means of the Hamilton Depression Rating Scale) and DAT availability in the left caudate. This result is additionally strengthened by our unbalanced patient sample, as the majority of patients had a lower DAT availability on the right side, corresponding to the most affected hemisphere. By contrast, Erro and colleagues found a significant inverse correlation between anxiety levels (evaluated by means of the Hospital Anxiety Depression Scale, HADS, anxiety subscale, HADS-A) and DAT availability in the right caudate.Their findings stimulated an additional analysis of our data: in PD patients, Hamilton Anxiety Rating Scale (HARS) scores did not correlate with age (r = 0.18, p = 0.47), duration of disease (r = 0.39, p = 0.11), H&Y stage (r = 0.16, p = 0.52) or UPDRS III score (r = 0.11, p = 0.65). HARS scores did not correlate with DAT availability in the right and left caudate after controlling for these factors (partial correlation coefficients: right caudate r = −0.06, p = 0.80; left caudate r = −0.26, p = 0.29). In addition, while we did not find any correlation between anxiety levels and DAT availability in the bilateral caudate of the right side predominant motor group (n = 7), a trend towards a correlation between anxiety levels and DAT availability in both the right and the left caudate was detected in patients with left side predominant motor signs (n = 14; r = −0.48, p = 0.08, for both analyses). This result supports the importance of enrolling large patient samples also balanced for motor side involvement, as correctly stated by Erro and colleagues. Such balance could not have been achieved in our study due to its consecutive enrolment. The study by Erro and colleagues was instead a retrospective one.Two previous SPECT studies that used similar methods to ours [3, 4] did not include motor laterality in their analysis. However, in line with our results, both studies found an inverse correlation between affective symptoms and DAT availability in the left hemisphere. On the other hand, the correlation with the caudate nucleus does not necessarily reflect the predominance of motor signs on a hemibody over the opposite one, as it has been reported that motor signs mainly correlate with the uptake in the putamen [5]. Moreover, this trend of reasoning well explains why the literature on motor side onset and non-motor symptoms has been so inconclusive to date [6].In our opinion, further major factors other than motor laterality, should be considered as potential causes of discrepancies between the two papers: (1) our sample included PD patients with a disease duration longer than those reported by Erro and colleagues (i.e. less than 2 years as an inclusion criterion); (2) the timing of rating scale administration (on the day of SPECT in our study, “within 3 months” in the paper by Erro and colleagues); (3) different rating scales were used: a clinician/observer scale (HARS in our study) and a self-rated scale (HADS-A in the study of Erro and colleagues). While at present none of the available anxiety scales can be recommended for use in PD populations, but only suggested [7, 8], it has already been clarified that for depression in PD patients observer-rated scales are preferred if the study or clinical setting permits [9].Finally, with regard to the caution suggested by Erro and colleagues in interpreting our results in essential tremor and primary dystonia, we clearly stated in the discussion that any interpretation explaining psychiatric manifestations in these two disorders may at present be merely speculative. Nevertheless, alterations in DAT availability have been reported in patients with primary psychiatric disorders without motor manifestations. Furthermore, we considered a “floor effect” of rating scales as a possible reason for the lack of correlation between affective symptoms and DAT availability only in the healthy controls, in line with other studies [3]. It is not clear to us how “the latter result drove the overall interpretation” (as stated by Erro and colleagues in their letter), as we did not include normative data in the analysis of the patient results.In conclusion, we are aware that the role played by dopamine dysfunction in PD-related affective symptoms is still far from being fully elucidated and—more importantly—that our findings, obtained for the first time in a small sample of patients with essential tremor and primary dystonia, are preliminary and need to be replicated in larger series.