Psychiatric and Neurocognitive Morbidity in Rapid-Onset Dystonia Parkinsonism (P01.225)

Objective: Elevated rates of psychiatric disease and cognitive dysfunction have been found in primary dystonias. These features have not been studied in Rapid-Onset Dystonia-Parkinsonism (RDP), DYT12. Data are presented for 47 individuals (with or without gene mutation). Background RDP is a rare form of dystonia caused by mutation of the gene encoding the alpha-3 subunit of Na+/K+-ATPase ( ATP1A3 ). RDP is characterized by abrupt onset of dystonic symptoms with features of Parkinsonism and subsequent stabilization without recovery. Psychiatric and cognitive symptoms have not been systematically studied in RDP. Design/Methods: The SCID-I and CIDI-I were administered to 47 individuals, including 27 mutation carriers (24 motor-manifesting, 3 non-motor-manifesting) and 20 family members without ATP1A3 mutation. Discrepancies in diagnoses were adjudicated by a psychiatrist blinded to mutation status, who rendered final diagnoses. Cognitive data were obtained on 43 individuals, including 23 motor-manifesting carriers, 3 non-motor-manifesting carriers, and 17 non-carrier relatives. Results: Mood disorders appear more prevalent among carriers (44%) compared to non-carriers (25%). Anxiety (44% vs. 50%) and substance use (33% vs. 32%) were similar across groups. Five individuals from three families with ATP1A3 mutation (19%) exhibited psychotic disorder. Psychotic disorder was not present among non-carriers. One non-carrier exhibited evidence of visual memory dysfunction. Gene carriers exhibited visual (17%) and verbal (22%) memory deficits. More gene carriers exhibited impairment compared to non-carriers on Trail Making B (54% vs. 12%) and Trail Making A (42% vs. 29%). Self reported rates of childhood learning difficulties (post-RDP onset) were higher among gene carriers (69% vs. 24%). Conclusions: Anxiety disorders and substance use/abuse did not differ among individuals with and without ATP1A3 mutation. Increased mood and psychotic disorders for gene carriers illustrate comorbid mental illness. Impaired memory and executive functioning is consistent with findings in other dystonias. Higher prevalence of childhood learning difficulties in gene carriers suggests non-motor manifestations prior to motor onset. Supported by: NINDS 5R01NS058949-03. Disclosure: Dr. Brashear has received personal compensation for activities with Allergan, Inc., Merz Pharma, Ipsen as a consultant. Dr. Brashear has received personal compensation in an editorial capacity for the American Academy of Neurology. Dr. Brashear will receive future royalty payments for editing a book on spasticity. Dr. Brasher has received research support from Allergan, Inc., Merz Pharma, and Ipsen. Dr. Cook has nothing to disclose. Dr. Amponsah has nothing to disclose. Dr. Hill has nothing to disclose. Dr. Snively has nothing to disclose. Dr. Light has nothing to disclose. Dr. Suerken has nothing to disclose. Dr. McCall has received personal compensation for activities with Sepracor, Inc. Dr. Boggs has nothing to disclose. Dr. Stacy has received personal compensation for activities with Allergan, Inc., Biogen Idec, General Electric, Novartis, Osmotica, Teva Neuroscience, and Synosia. Dr. Stacy has received research support from Ceregene, Impax, Neuraltus, Novartis, Schering-Plough, and the Parkinson Study Group. Dr. Ozelius has nothing to disclose. Dr. Sweadner has nothing to disclose.