F56 Psychiatric symptoms in huntington’s disease: relationship to disease stage in the CAPIT-HD2 beta-testing study

Background Psychiatric symptoms are common in Huntington’s disease (HD) and contribute significantly to functional impairment. Low mood, anxiety and irritability can all occur many years before motor onset, but are also common in the general population. Apathy and perseveration (repetitive thinking or behavior) can occur before motor onset, but usually appear after diagnosis and are worst from stage 3 onwards. Previous studies have found that apathy correlates with motor and cognitive measures of disease progression, while the mood disorder does not. Methods One of the objectives of the Repair-HD study was to develop and validate a new Core Assessment Protocol for Intra-cerebral Transplantation in HD (CAPIT-HD2), which includes a psychiatric interview, the Problem Behaviours Assessment for HD (PBA-s), and several Patient-Reported Outcome (PRO) measures. The 12-month follow-up is now complete and analysis underway. We report a preliminary analysis of data from the baseline psychiatric measures. Results Cases (N=73) and controls (N=50) differed significantly for PBA-s apathy (p<0.001), anger (p<0.05), repetitive behavior (p<0.001), modified total PBA score (mPBA) (p<0.001) and the extended 7-item PBA-s composite apathy score (p<0.001), but not for the composite affect score. In patients, Total Functional Capacity (TFC) scores correlated significantly with apathy (rs=−0.415, p<0.001), composite apathy (rs=−0.459, p<0.01), repetitive behaviours (rs=−0.326, p<0.01) and mPBA (rs=−0.265, p<0.05), but not the affect or anger scores. Significant differences between cases and controls and significant correlations with TFC scores were also found with the Apathy subscale of the Frontal Systems Behaviour Scale (FrSBe) and the Apathy Evaluation Scale (AES), but not with PRO measures of anxiety, depression or irritability. Conclusions This preliminary analysis confirms that apathy and perseveration correlate with disease stage, while disorders of mood (depression and anxiety) and irritability are more variable over time, and from person to person. This may reflect the complex aetiology of affective symptoms, involving psychological variables and variation in genetic susceptibility as well as HD. Symptomatic treatment with antidepressants may also mask any relationship with disease progression.