Objective: To explore grey-matter volume (GMV) differences between early-stage Huntington’s disease (HD) patients with and without significant irritability/aggression symptoms (IAs) and to assess it association with other clinical variables. To explore grey-matter volume (GMV) differences between early-stage HD patients with and without significant irritability/aggression symptoms (IAs) and to assess it association with other clinical variables.

Background: Irritability is a frequent neuropsychiatric feature of HD that ranges from bad temper to aggressive outbursts. Irritability and aggression have an enormous impact over patients and caregivers. However, irritability has been scarcely studied in HD and little is known on the neural mechanisms sub-serving its presentation.

Method: We rated the severity of IAs in 31 early HD participants using the Problem Behaviors Assessment for HD (PBA-s). The IAs score was computed as the mean severity score for the irritability and aggression PBA-s items, assuming an IAs score > 2 as clinically relevant. A voxel-wise group comparison was performed using age, UHDRS-TMS, severity of other PBA-s items and disease burden as covariates.

Results: Seventeen participants were classified as presenting “significant IAs”. In this group, higher obsessive/compulsive score was found (p=0.03). No other differences existed in sociodemographic and clinical variables. The IAs group showed lower GMV in the basal ganglia (bilateral caudate nucleus/putamen/pallidum), thalamus (pulvinar), medial orbital prefrontal cortex (BA 11), subgenual area (BA25), bilateral mid temporal gyrus and superior temporal pole. Lower GMV in the basal ganglia, thalamus, mid temporal gyrus and BA11 was associated with reduced semantic verbal fluency. Higher anxiety and suicidal ideation was associated with lower GMV in the thalamus and BA11 respectively. Lower GMV in BA11 was also associated with lower performance in the Stroop interference.

Conclusion: In HD, irritability and anger are subserved by GMV decreases in a set of fronto-temporal and basal ganglia structures that in general population are functionally associated with the expression of anger, social cognition, affect and decision making. These changes are not explained due to the influence of other clinical variables and correlate with poorer access to semantic knowledge, poorer inhibitory control, and with increased anxiety and suicidal ideation.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/grey-matter-volume-changes-underpinning-irritability-and-aggression-in-early-manifest-huntingtons-disease/