Characterization of depression in prodromal Huntington disease in the neurobiological predictors of HD (PREDICT-HD) study

Abstract

Depression causes significant morbidity and mortality, and this also occurs in Huntington Disease (HD), an inherited neurodegenerative illness with motor, cognitive, and psychiatric symptoms. The presentation of depression in this population remains poorly understood, particularly in the prodromal period before development of significant motor symptoms. In this study, we assessed depressive symptoms in a sample of 803 individuals with the HD mutation in the prodromal stage and 223 mutation-negative participants at the time of entry in the Neurobiological Predictors of HD (PREDICT-HD) study. Clinical and biological HD variables potentially related to severity of depression were analyzed. A factor analysis was conducted to characterize the symptom domains of depression in a subset (n=168) with clinically significant depressive symptoms. Depressive symptoms were found to be more prevalent in HD mutation carriers but did not increase with proximity to HD diagnosis and were not associated with length of the HD mutation. Increased depressive symptoms were significantly associated with female gender, self-report of past history of depression, and a slight decrease in functioning, but not with time since genetic testing. The factor analysis identified symptom domains similar to prior studies in other populations. These results show that individuals with the HD mutation are at increased risk to develop depressive symptoms at any time during the HD prodrome. The clinical presentation appears to be similar to other populations. Severity and progression are not related to the HD mutation.

Disease stage, but not sex, predicts depression and psychological distress in Huntington's disease: A European population study

“…Due to the familial nature of the disease, HD mutation carriers may also be at a higher risk for depression and anxiety from having to deal with challenges, perhaps from an early age, such as witnessing family members with, or dying from, the disease; caregiving duties for family members; decisions around reproductive choices; and concerns about informing others of genetic risk. Despite these additional stresses potentially increasing vulnerability to anxiety and depression, and the deleterious effects that mood difficulties have on morbidity and mortality in HD [8], evidence suggests anxiety and depression are under-treated in HD [9]. Therefore, understanding risk factors for anxiety and depression in HD is vital for adequate detection, treatment and, ideally, prevention.…”

Behavioral phenotyping of minipigs transgenic for the Huntington gene

“…Thus, several of the motor tests introduced relate to motor symptoms assessed as part of the Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS), the gold standard for clinical motor assessment in human HD (Huntington Study Group, 1996;Reilmann et al, 2009). Similarly deficits in cognitive (Bonner-Jackson et al, 2013;e.g., Paulsen, 2011;Stout et al, 2012) and behavioral domains (e.g., Craufurd et al, 2001;Epping et al, 2013;Fisher et al, 2014) were included in the battery as described above, for instance the "Discrimination Test" and the "Dominance Test".…”

Huntington's Disease: Looking Beyond the Movement Disorder

“…Per Epping et al, clinically significant depression (Beck Depression Inventory score >13) is noted in 20-30% of gene-expanded individuals, which is slightly more frequent than in controls [32] . Depressive symptoms can occur at any time during prodromal HD and are not associated with proximity to genetic testing or the expected time to diagnosis [32] .…”

“…Depressive symptoms can occur at any time during prodromal HD and are not associated with proximity to genetic testing or the expected time to diagnosis [32] . Not surprisingly, geneexpanded females have a higher frequency of depression when compared with similar males, and the severity of symptoms contributes to increased cognitive impairment, perceived stress, and negative life experience [32][33][34] . Whereas unipolar depression is relatively common in HD, bipolarity is infrequently seen [7] .…”