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Research on depression in Huntington鈥檚 Disease (HD) has focused largely on the role of biological and pathophysiological changes, while underlying psychosocial factors have remained less well studied. Yet, people who inherit the cytosine鈥揳denine鈥揼uanine (CAG) triplet repeats in the huntingtin gene (HD CAG) experience substantial stressors throughout the disease course, including the pre-symptomatic phase.¹

A study published in the Journal of Neurology begins to look more closely at the stress-depression relationship in HD, examining challenges unique to this population and their effect on patients with pre-manifest and early manifest disease (CAG repeat length 鈮� 36).¹

Researchers from Monash University in Australia recruited 57 adult participants; 33 did not yet meet a clinical diagnosis of HD based on motor symptoms, while 24 were in Stage I or II. All participants completed a depression questionnaire and reported how much stress they had experienced in the past month regarding 20 psychosocial domains. More than half of these patients had previously been diagnosed with major depressive disorder, and many were on a regimen of antidepressants. 

Worry for the future 

Several of the psychosocial domains studied were associated with depressive symptoms. The strongest link to depression was concern for the future: depression scores had significant independent associations with anxiety regarding the implications of an HD diagnosis (尾= .44, P=.001). Patients reported concern over the idea of worsening HD symptoms, losing their independence, and potentially passing HD expansion on to their children. 

Overall, the uncertainty associated with being an expansion carrier seems to create the chronic stress known to cause depression. Addressing these feelings, the authors note, may be an important aspect of psychological interventions in this setting.

Stress over sleep

Sleep disturbances were also associated with depressive symptoms in HD CAG expansion carriers, as seen in prior work. Depression scores had significant independent associations with stress related to sleep and psychological difficulties (尾=.28, P=.005). The authors theorize that sleep disturbances鈥攁long with other psychological symptoms like aggression and mood swings鈥攎ay be even more subjectively distressing to patients with HD than functional limitations such as motor and cognitive impairments, which were not strongly associated with depression. 

Interventions should be psychosocial 

While management of depression in HD is currently extrapolated from treatment guidelines for depression in neurologically healthy populations, this study highlights the potential of a more tailored approach. Because HD patients may be susceptible to depression from a pathophysiological standpoint, the challenges they face are often examined through a purely biomedical lens. However, the current findings suggest that interventions for depression in HD should be revised according to the unique psychosocial needs of this population. 

鈥淐onsidering the contributions of psychosocial factors to depression is essential when assessing HD patients, and when providing psychoeducation regarding depression to HD patients, their caregivers, and other members of the HD community,鈥� the authors advised. They also emphasize the importance of educating clinicians on the topic so they can better counsel their patients. 

Pre-manifest stress

This study also gives due attention to pre-symptomatic HD patients, who experience substantial stressors even before officially meeting the clinical criteria for diagnosis. In fact, the authors note that the incidence of depression peaks right before an HD diagnosis and in early disease. 

Interestingly, while the relationship between depression and stress regarding the future was stronger in participants with manifest disease, this domain was the only one that differed between groups. Such results suggest that pre-symptomatic patients are similarly affected by the stress of an HD diagnosis as patients with manifest disease. 

With this new data in hand, the authors call for further research that studies a greater number of stressors commonly associated with HD, in a more robust and diverse sample of patients.

Published: December 06, 2023