Beneficial Effects of Lithium on Severe Irritability in a Patient with Rett Syndrome

Abstract

To The Editor:

Rett syndrome (RS) is a neurodevelopmental disorder that causes severe cognitive and physical impairment. Its predominant features include social withdrawal and loss of previously acquired skills. Currently, new targeted therapies are being investigated in RS (Wang et al., 2015). Here, we present a case of RS with severe irritability that improved with lithium.

Case Presentation

A 20-month-old girl was first brought with symptoms of speech delay, social withdrawal, repetitive hand stereotypies (hand washing, clapping, and twisting), shouting, feeding problems, insomnia, and bruxism. Her psychomotor development was considered to be normal till 8 months; however, significant delay was observed in communication and social interaction on the admission examination. Her Denver/Ankara Development Screening Instrument results are as follows: motor skills 13-month level, ego adaptation:10-month level, language development: 7-month level, and social development:13-month level. Genetic investigation revealed an MECP2 gene mutation and she was diagnosed as having RS. The patient had no family history of mood disorders. The patient was brought to our clinic at the age of 8 with complaints of aggressive behavior, impulsivity, and problems with sleep initiation/maintenance. Daily doses of melatonin 3 mg, valproic acid 200 mg, and risperidone 0.75 mg were initiated. Melatonin had minimal benefit and risperidone had to be stopped due to severe weight gain. After a relatively stable period, severe irritability and agitation emerged at the age of 10. The patient also had increased energy and self-mutilative behaviors such as arm-biting, disruptive and aggressive behaviors such as hitting people, breaking objects, and shouting. The patient was administered Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode and mania was excluded. The irritability was considered as a symptom of RS. Zuclopenthixol and haloperidol did not improve these symptoms and minimal amelioration was observed with quetiapine 900 mg. Subsequently, lithium was initiated and titrated up to 1200 mg and clinically significant benefit was observed. The score of Aberrant Behavior Checklist diminished from 105 to 41 and the score of hyperactivity subscale diminished from 43 to 13. The symptoms did not reemerge in the 10-month follow-up.

Discussion

Therapeutic mechanism of lithium in RS is unclear. It may be associated with Brain Derived Neurotrophic Factor (BDNF), which is a neurotrophic factor that has been recently implicated in the pathophysiology of RS (Li and Pozzo-Miller, 2014). BDNF levels have been found to be lower in human brain samples (Deng et al., 2007). A possible explanation of the beneficial effect of lithium in the present case might be the enhancement of the BDNF release (Tsai, 2006). Moreover, it has been reported that lithium both increased the expression of BDNF, BCL2, and BCL-XL genes and decreased the expression of proapoptotic genes such as Bax, Bad, and Caspases (Dwivedi and Zhang, 2015).

In conclusion, lithium may be a treatment choice for patients with RS and severe irritability. Beneficial effects of lithium in RS should be evaluated in larger series to confirm our observations.

Footnotes

Disclosures

The authors transfer all copyright ownership of the article entitled “Beneficial Effects of Lithium on Severe Irritability in a Patient with Rett Syndrome” to the Journal of Child and Adolescent Psychopharmacology. The authors warrant that the article is original, is not for consideration by another journal, has not been previously published, and has been prepared according to the article rules. The authors warrant that they have no conflicts of interest in general or in connection with the submitted article and no financial relationships with any pharmaceutical company.

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