Twenty-nine ATP1A3 mutation–positive individuals were examined; 26 exhibited motor symptoms (MMC), and 3 did not exhibit any evidence of movement disorder (nonmotor manifesting carrier [NMC]). Twenty-seven ATP1A3 mutation–negative participants (NC) from the same RDP families were studied with the same battery. The data were examined in terms of disorder categories: mood, anxiety, psychosis, and substance use disorders.
shows demographic characteristics of the 56 individuals interviewed for the present study. Among the MMCs, 77% had onset of motor symptoms by age 25, and 77% had initial symptom presentation in the upper body, mouth, and arm. UPDRS and Dystonia Rating Scale scores clearly indicate the absence of dystonic or parkinsonism features in the NMC and NC groups, with very distinct differences in mean scores. Those with motor symptoms reported more impact on daily living activities. In both carrier groups (MMC and NMC), 62% have smoked, not appreciatively different from the 67% who have smoked in the NC group.
Demographic characteristics and motor symptoms
shows rates of mood, anxiety, psychotic, and substance use disorders among MMC, NMC, and NC groups. The 3 NMC participants did not report any history of psychiatric disorder. Subsequent comparisons between MMC and NC groups indicated no appreciable difference in rates of anxiety (48% vs 41%), although substance abuse/dependence (38% vs 27%) and mood disorders (50% vs 22%) appeared more to be prevalent in the MMC group. Exactly half of the MMC group had a mood disorder compared with only 20.8% in the general population.17
Most striking, however, were the rates of psychotic disorder seen in the MMC group. No participant in the noncarrier group was diagnosed with a psychotic disorder, but 19% (5 participants) in the MMC group exhibited some form of psychotic disorder (p = 0.02 in case-control families having one or more members with psychosis), although none of those met the criteria for schizophrenia. Three patients from 3 separate families with 3 distinct ATP1A3 mutations received a diagnosis of psychotic disorder not otherwise specified (NOS). Two patients from 2 of the 3 families mentioned above received a diagnosis of brief psychotic disorder. Psychotic disorder NOS is characterized by psychotic symptomatology with inadequate information to make a specific diagnosis or about which there is contradictory information.18
Psychotic disorder NOS also includes patients with psychotic symptoms who do not meet the criteria for any specific psychotic disorder. Brief psychotic disorder is characterized by the presence of delusions, hallucinations, disorganized speech, or grossly disorganized or catatonic behavior for at least 1 day, but lasting less than 1 month.18
In addition, symptoms eventually remit to premorbid functioning.
Affective disorders by mutation statusa
To explore current severity, the Hamilton scores were compared across carrier and noncarrier groups (). The results suggested slightly greater severity of current anxiety (p = 0.068) and depressive symptoms (p = 0.025) in the MMC group relative to that in the NC control group. The NC group did not report or exhibit appreciable levels of current depression, although the MMC group, as a whole, reported mild levels of current depressive symptoms on average. Groups did not differ in scores on the Y-BOCS.
Hamilton Anxiety and Depression and Y-BOCS scores
Although we are unable to distinguish whether mood or psychotic disorders are an independent expression of ATP1A3 mutation or result from other sources (familial or the disease itself), age at onset of psychotic disorder in 2 individuals preceded that of motor disease (), suggesting the possibility that psychotic symptoms may be expressed independently from the motor disease in some cases. Two participants reported onset of psychotic symptoms occurring in the same year of movement symptoms, whereas the age at onset is not known for the fifth participant. The finding across 3 families decreases the likelihood that environment played a role.
Age of psychiatric disorder onset for participants with RDP who met reviewer diagnostic criteriaa
further characterizes the 5 patients with a psychotic disorder. Mean age at onset of psychosis within the MMC group (12.5 years) appears to be early compared with age for prototypical psychosis, which tends to occur between 15 and 24 years.19
Two siblings had onset of psychosis symptoms at ages 4 and 8 years. The other patients with known age at onset come from separate families and have a more typical onset of 15 and 23 years. Co-occurring disorders including anxiety, mood disorders, and substance abuse/dependence appear in all but 1 of the 5 patients.
Characteristics of RDP psychosis