Riluzole effectively treats psychotic symptoms and improves cognition in 22q11.2 deletion syndrome: A clinical case

• Published in: European journal of medical genetics Vol. 62; no. 8; p. 103705
• Main Authors: Vingerhoets, Claudia, Tse, Desmond H.Y., van Amelsvoort, Therese
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Masson SAS 01.08.2019
• Subjects: Adult; Chromosomes, Human, Pair 22 - genetics; DiGeorge Syndrome - drug therapy; DiGeorge Syndrome - genetics; DiGeorge Syndrome - pathology; Female; Glutamic Acid - metabolism; Humans; Proline - metabolism; Proline Oxidase - genetics; Psychotic Disorders - drug therapy; Psychotic Disorders - genetics; Psychotic Disorders - pathology; Riluzole - administration & dosage; Young Adult
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2019.103705

22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a hemizygous microdeletion on the long arm of chromosome 22 and is associated with a high risk for psychosis and cognitive impairment. One of the genes located in the deleted region of 22q11DS is Proline Dehydrogenase (PRODH) which is important for conversion of proline to glutamate. Glutamate is the primary excitatory neurotransmitter and is involved in the pathophysiology of psychosis as well as in cognition. Excessive concentrations are toxic. Possibly, neuroprotective drugs modulating glutamatergic neurotransmission could be effective in treating psychotic symptoms and cognitive enhancement in patients with 22q11DS. Riluzole is a potent anti-glutamatergic drug that reduces glutamatergic neurotransmission. Here we report acute (single dose) and long-term effects of riluzole on glutamate and GABA levels in the anterior cingulate cortex (ACC) and striatum (measured with magnetic resonance spectroscopy, 1H-MRS) as well as on psychotic symptoms and cognitive functioning in a medication-free 23-year old woman with 22q11DS. Patient presented with frequent auditory and visual hallucinations and mild paranoid ideas. The 1H-MRS measurements showed that after a single dose riluzole (50 mg), glutamate in the ACC and striatum was reduced whereas striatal GABA increased compared to baseline. Strikingly, hallucinations and paranoia disappeared. Therefore, riluzole treatment was initiated and patient was followed up after 18 months of treatment. At follow-up, patient reported no hallucinations or paranoia and several cognitive functions were improved. Furthermore, glutamate concentrations in the ACC and striatum decreased whereas GABA concentrations increased in the striatum but decreased in the ACC. These results suggests that riluzole may be an effective treatment option for psychotic symptoms and cognitive enhancement in 22q11DS. Results warrant replication in a bigger sample.