Longitudinal Psychiatric Symptoms in Prodromal Huntington’s Disease: A Decade of Data

Abstract

Objective Psychiatric symptoms are a significant aspect of Huntington disease (HD), an inherited neurodegenerative illness. The presentation of these symptoms is highly variable in patients, and their course does not fully correlate with motor or cognitive disease progression. We sought to better understand the development and longitudinal course of psychiatric manifestations in patients who carry the HD mutation starting from the prodromal period prior to motor diagnosis. Method Longitudinal measures for up to 10 years of psychiatric symptoms from the Symptom Checklist-90-Revised were obtained from 1305 participants (1007 carrying the HD mutation) and 1235 companions enrolled in the Neurobiological Predictors of Huntington’s Disease (PREDICT-HD) study. Participants with the HD mutation were stratified into three groups according to probability of motor diagnosis within five years. Using linear mixed effects regression models, differences in psychiatric symptoms at baseline and over time between HD mutation positive groups and controls were compared as well as between HD mutation participants and their companions. Results 19 of 24 psychiatric measures showed significant increases at baseline and longitudinally in HD mutation carrying individuals or their companions versus controls. The differences were greatest when comparing symptom reports from companions (versus self-report), especially in participants who were closest to motor diagnosis. Conclusions Results indicate psychiatric manifestations develop more often than previously thought in the HD prodrome. Symptoms also increase with progression of disease severity. Companions of HD mutation carriers also report greater psychiatric symptoms over time compared to affected individuals, consistent with decreasing awareness.

Huntington's Disease: Premotor Phase

“…Paranoid ideation and somatization are not characteristic of HD [8]. These results are consistent with other literature [9,10,11,12]. …”

“…Previous research has suggested that there is no relation between them [1]. More recently, some longitudinal studies showed progression of the majority of the psychiatric symptoms closer to the date of onset [9,13], although this relation with progression was only found for apathy in some other large studies [12,14,15]. While the first couple of articles used the SCL-90R as an assessment tool, the latest studies all used a Problem Behaviour Assessment (which includes depressed mood, suicidal ideation, anxiety, irritability, angry or aggressive behavior, lack of initiative, perseverative thinking or behavior, obsessive compulsive behaviors, delusion and paranoid thinking, hallucinations, and disoriented behavior during the last month).…”

“…In this study there is evidence of significant differences between prodromal HD patients and controls in 19 (out of 24) variables, both at baseline and longitudinally, and 3 (of the remaining 5) only showed differences at baseline (not showing progression over time). This progression is likely due to the neurodegenerative process of HD [9]. …”

“…Beglinger et al [3] studied the obsessive-compulsive symptoms in the premotor phase more comprehensively, as the evaluation of previous studies was limited to a handful of items on a subscale of the SCL-90-R [9,13]. They assessed 300 pre-HD (near to onset, midway to onset, and far from onset) and 108 non-gene-expanding controls from the PREDICT-HD study.…”

Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes

“…HD is an auto-somal dominant inherited disorder caused by an expansion of the trinucleotide repeat cytosine-adenine-guanine (CAG). Individuals with pmHD do not yet exhibit the motor symptoms including chorea, but can exhibit cognitive or psychiatric changes (Epping et al, 2015; Paulsen et al, 2013), including working memory impairments (You et al, 2014). Caudate volume loss is present more than a decade before HD diagnosis and contributes robustly to cognitive impairment, whereas hippocampal volumes are relatively preserved and do not predict cognitive impairment (Aylward et al, 2013, 2004).…”