Neural substrates of psychiatric symptoms in patients with Huntington's disease

INTRODUCTION: Numerous studies in Huntington’s disease (HD) have shown striatum as the major site of neuronal loss, but recently the presence of neurodegeneration in other regions of the brain is gaining attention. In our study, we used voxel-based morphometry and diffusion tensor imaging to identify other areas in the brain that are involved in the disease. METHODS: The present study is a prospective study conducted in the Departments of Neurology, Psychiatry, and Neuroimaging and Interventional Radiology (NIIR), NIMHANS, Bengaluru. The study included 20 genetically confirmed HD patients and 20 healthy controls. Magnetic resonance imaging was performed on a 3-Tesla Philips Achieva scanner with a 32-channel head coil with the acquisition of whole-brain T1-weighted and DTI. RESULTS: The patients (41.25 ± 10.04 years) and controls (38.27 ± 11.29 years) were age-matched (P = 0.38), and the mean age at the onset of the symptoms of the disease was 37.53 ± 10.11 years, and the expanded CAG repeat allele was 45.95 ± 7.27 (range 40–73) repeats. All patients had psychiatric symptoms at presentation such as anger outbursts, irritability, abusive behavior, apathy, low mood, crying spells, delusions, lack of initiation, and obsessive–compulsive disorder. Compared with controls, HD patients had significant atrophy of bilateral caudate nuclei, right globus pallidus, left culmen, right precuneus, hypothalamus, and right superior temporal gyrus. Fractional anisotropy was increased in bilateral cerebral white matter and thalamus with the reduction in mean diffusivity. CONCLUSIONS: In addition to atrophy of caudate, atrophy was also observed in globus pallidus, thalamus, hypothalamus and right superior temporal gyrus. This may explain the neuropsychiatric and cognitive symptoms observed in these patients.