Time estimation in a case of Tourette's syndrome: Effect of antipsychotic medications

Abstract Aims Dopamine (DA) hyperactivity causes overestimation of time, whereas DA hypoactivity produces its underestimation. DA activity also provides neurochemical substrates pertinent to several psychiatric conditions, such as schizophrenia and Tourette's syndrome. The overestimation of time sometimes exists in patients with Tourette's syndrome, but no reports have addressed time perception in relation to antipsychotic medications which typically act as DA receptor antagonists. We herein report a case of Tourette's syndrome, in which time estimation was differentially affected by risperidone (a DA antagonist) and aripiprazole (a DA partial agonist). Case A 27‐year‐old man who suffered from verbal and motor tics was treated with risperidone. His tic symptoms disappeared; however, he began to experience a strange feeling that “time is going too fast.” For example, “people walk more quickly compared to a normal pace.” These complaints were thought to represent underestimation of time. Then, risperidone was switched to oral aripiprazole to optimize DA transmissions, which resulted in the amelioration of these subjective feelings. Conclusion Our observations indicate that the underestimation of time may occur in patients with Tourette's syndrome who receive antipsychotic drugs with high DA D2 receptor blocking potency. This may support the concept that the estimation of time is influenced by DA activity.


| INTRODUC TI ON
The underestimation of time is represented by the feeling of "time going fast," whereas its overestimation is described as "time going Tourette's syndrome, but no reports have addressed time perception in relation to antipsychotic medications which typically act as DA receptor antagonists. We herein report a case of Tourette's syndrome, in which time estimation was differentially affected by risperidone (a DA antagonist) and aripiprazole (a DA partial agonist).
Case: A 27-year-old man who suffered from verbal and motor tics was treated with risperidone. His tic symptoms disappeared; however, he began to experience a strange feeling that "time is going too fast." For example, "people walk more quickly compared to a normal pace." These complaints were thought to represent underestimation of time. Then, risperidone was switched to oral aripiprazole to optimize DA transmissions, which resulted in the amelioration of these subjective feelings.

Conclusion:
Our observations indicate that the underestimation of time may occur in patients with Tourette's syndrome who receive antipsychotic drugs with high DA D 2 receptor blocking potency. This may support the concept that the estimation of time is influenced by DA activity.

K E Y W O R D S
dopamine, time perception, Tourette's syndrome syndrome, we report a case of this disorder in which time estimation was improved by a switch from risperidone (DA antagonist) to aripiprazole (DA partial agonist).

| C A S E REP ORT
A 27-year-old man was suffering from uncomfortable feelings. He had no family history of Tourette's syndrome or physical comorbidities. At age six, he started calling out "Je [dʒə]" and "I [i]," spitting, and touching his body. Around the age of 10, his doctor told him that his symptoms would improve without any treatment by the age of 20.
After having graduated from university, he began working in sales to the age of 25, when he retired and started attending a school for comedy. At this time, his symptoms remained, so he visited another children's clinic, where he was diagnosed with Tourette's syndrome. He was prescribed 1 mg of oral risperidone, but his verbal and motor tics continued.
When he was 27, he decided to visit our hospital in April 2017.
His doctor prescribed 1.5 mg oral risperidone, to be taken just before bed. Within 1 week, his family members reported that he stopped calling out "Je" and "I," spitting, and touching his body. However, he still wanted to call out, in some occasions, especially when he felt stressed. After increasing the dose of risperidone to 2 mg, he was moved to another hospital because his doctor assessed that his tic symptoms were successfully treated. However, the symptoms reappeared one month later. In July 2017, his doctor increased the dose of risperidone to 2.5 mg. Thereafter, he experienced no tics.
In February 2018, he began to experience a strange feeling for approximately 15 minutes that people seemed to walk quickly, but then return to a normal pace. His family told him that people had been walking at a normal pace. He experienced this feeling at least twice a week for 6 months. This usually appeared when he looked at the window after he went to bed at night. He was still taking 2.5 mg of oral risperidone. In July 2018, he visited our hospital again to treat these symptoms. He also suffered from ejaculation difficulty. At that time, he was neither depressed nor manic.
In September 2018, the dose of risperidone was decreased to 1.5 mg and coadministration of 6 mg oral aripiprazole was initiated.
From October 2018 onwards, he has no longer experienced the abnormal feeling of "time going fast." His ejaculation disorder has also improved. On the basis of these observations, we gradually reduced the dose of risperidone, whereas the dose of aripiprazole was increased.
Since December 2018, he has been taking 15 mg of oral aripiprazole alone and has never experienced the feeling of "time is going too fast" again or suffered from tics. Currently, he is attending a school for comedy. Aripiprazole, with its partial agonistic effect, may partially activate F I G U R E 1 Interval timing in Tourette's syndrome in relation to antipsychotic treatments. A, Timing in normal cases. B, Interval timing in Tourette's syndrome. Patients with the disorder tend to overestimate time and feel that "time goes slowly." C, Interval timing after the administration of risperidone. Antipsychotic drugs with a high dopamine-D 2 receptor blocking potency, such as risperidone, may cause overestimation of time, so the patients feel "time goes fast." D, Interval timing after switching from risperidone to aripiprazole. Aripiprazole, a D 2 receptor partial agonist, is less potent in blocking D 2 receptor compared to risperidone, so that patients feel "time goes more slowly" striatal DA transmissions ( Figure 1D), contributing to the normaliza- This may support the concept that the estimation of time is influenced by DA activity.

ACK N OWLED G M ENTS
This study received support from Grants-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology (Early-Career Scientists, Basic Section 52030: Psychiatry-related).

CO N FLI C T O F I NTE R E S T
TI and NU declare no conflict of interest. TS reports personal fees from Otsuka Pharmaceuticals outside the submitted work. KN reports grants from research funding, personal fees from speaker's honoraria, and personal fees from attending an advisory board meeting from Otsuka Pharmaceuticals outside the submitted work.

AUTH O R CO NTR I B UTI O N S
TI treated the patient and drafted the manuscript. NU, KN, and TS critically reviewed the draft and revised it. All authors made substantial contributions, drafted the manuscript, and approved the final manuscript.

I N FO R M E D CO N S E NT
The patient gave informed consent, and their anonymity has been preserved.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are included in this article.