Psychosis Linked to More Severe Cognitive, Functional and Behavioral Symptoms, But Less Chorea, Study Finds

People with Huntington’s disease who develop psychosis tend to have worse cognitive and behavioral disturbances, reduced ability to function, and fewer involuntary movements than patients who do not experience these psychiatric symptoms, a new study reports.

The study, titled “Psychosis and longitudinal outcomes in Huntington disease: the COHORT Study,” was published in the Journal of Neurology, Neurosurgery and Psychiatry.

Psychosis is defined as experiencing hallucinations — things that are not really happening — and delusions, or believing things that are demonstrably untrue. Psychiatric symptoms are estimated to affect up to 11% of people with Huntington’s.

In other neurodegenerative conditions, such as Alzheimer’s, psychosis is associated with a poorer clinical course and with a distinct genetic basis. However, it is not clear to what extent Huntington’s patients who experience psychosis differ from those who do not.

To address this question, a team of Australian researchers analyzed data from the international Cooperative Huntington Observational Research Trial, or COHORT (NCT00313495), which included 1,082 participants (mean age 51.6 years, 52.9% women) with Huntington’s.

A total of 994 patients had been diagnosed with Huntington’s at baseline, while the remaining 88 received this diagnosis during the study. Overall, the group had had Huntington’s for approximately eight years.

Physical and neurological examinations were conducted annually over five years. The Unified Huntington’s Disease Rating Scale was used to assess ability to function, motor disturbances, and behavioral symptoms, while the Mini-Mental State Examination measured cognition.

Results showed that 190 participants (17.6%) experienced symptoms of psychosis during the course of their disease, 97 of whom already had a history of psychosis before the study.

Among the 141 patients who showed such symptoms during the study, 121 (85.8%) developed delusions, 39 (27.7%) had hallucinations, and 19 (13.5%) developed both.

Compared with those who never experienced psychosis, participants who previously had psychiatric symptoms scored significantly lower, on average, on measurements of total functional capacity (6.98 vs. 8.50) and cognition (24.19 vs. 25.32). They also had higher (worse) scores for behavioral symptoms (20.11 vs. 11.87), which were maintained over time.

Regarding motor disturbances, participants with psychosis had significantly lower scores for chorea (9.13 vs. 10.18) — a type of involuntary movement associated with Huntington’s — indicating lower frequency of this symptom. This difference was sustained after accounting for medications used, including antipsychotics. The researchers noted that chorea usually occurs during the early to intermediate stage of the disease, reducing thereafter.

There were no differences between those who did or did not develop psychosis in terms of age, sex, time since Huntington’s diagnosis, or number of CAG repeats — the hallmark genetic change in Huntington’s, which correlates with age of disease onset and with its progression.

“The current study provides evidence that patients with psychosis have a distinct clinical course characterised by more severe cognitive, functional and behavioural deficits, yet also relatively less chorea,” the researchers said.

If these findings are replicated in other studies, the team added, they “point to an important direction for future research in terms of clarifying the genetic and neurobiological underpinnings of [psychosis in Huntington’s].”