麻豆传媒

A top cause of death in Huntington's disease, an incurable, progressive illness with devastating physical, mental, and emotional symptoms, is suicide.

Studies have attributed up to 10% of deaths in Huntington's disease to suicide compared with about 1% in the general population. A recent from England showed a 9.2-fold higher risk of death from suicide in Huntington's disease compared with the general population, with a 54-fold higher risk for those younger than 45.

And, "a rough rule of thumb is there's a base rate of 25% incidence of suicidal ideation at any given point within the [Huntington's disease] population," noted Ciaran Considine, PhD, a clinical neuropsychologist at Vanderbilt University Medical Center in Nashville, Tennessee. "So there's an enormous amount of elevated risk, of both the suffering of persisting or recurring ideation about ending one's own life, or the actual completion of that."

Another study of found a roughly fourfold elevated risk of completed suicides compared with the general U.S. population (72 vs 21 per 100,000).

However, the situation isn't hopeless, as risk may be reduced with close attention to patients and their families, said Considine.

"The family system is something that we try to integrate into our clinic care and into research opportunities, and to not just isolate this as a disease that arises later in life in one person, but to recognize its profound implications up and down the family tree and in the family structure," he told 麻豆传媒.

For example, Considine pointed to children watching a parent develop symptoms, typically at age 30 to 50, and go through diagnosis and the disease process and facing the stress of becoming a caregiver. These experiences may contribute to their higher risk for suicide ideation later themselves, as each child of a person with Huntington's disease faces a 50-50 chance of inheriting the disease.

Fostering connections with these individuals before they may even know their own genetic carrier status "is how we try to combat this in part," Considine said. "Softly open the door instead of bashing them over the head with risk assessments and numbers."

Risk Factors

There are three general pathways to this risk, Considine noted, although "the complexity of psychiatric conditions like depression or suicidality mean it's sometimes difficult to understand if these are representing an early manifestation of Huntington's pathology and those brain regions affecting mood, or if it's a reaction to the environment and stressors, or both."

Cognitive and psychiatric-behavioral symptoms can frequently begin years or even decades prior to the motor symptoms, including anxiety, depression, agitation, and sometimes aggression.

Not only is there to increasing difficulty at work, seeing symptom progression, and changing roles in the family, but there are also changes in the brain with the disease that lead both to anxiety and trouble dealing with anxiety, notes the Huntington's Disease Society of America.

The cognitive decline in Huntington's hits executive function early, impairing that regulation of the "internal monologue" and perhaps mood regulation as well, Considine explained. "So we see a phenomenon where sometimes individuals will be perseverative, which is an executive dysfunction. They get stuck doing the same compulsive acts over and over again or thinking about the same things over and over again."

Some studies suggest on the idea of suicide in individuals with Huntington's disease among those who complete it.

Loss of functions, like driving, due to motor symptoms can exacerbate the problem by creating a sense of .

Notably, there appear to be two periods of especial risk for suicidal ideation.

A of some 4,000 Huntington Study Group database patients showed that suicidal ideation doubled to 19.8% in those considered at risk who had soft neurological signs of the disease and to 23.5% in those with possible Huntington's disease -- immediately before receiving a formal diagnosis. Then after diagnosis, prevalence of suicidal ideation spiked back up to 21.6% in stage II of the disease, "when independence diminishes."

The researchers concluded that "it is critical for health care providers to be aware of periods during which patients may be at an increased risk."

The slight dip in risk between diagnosis and stage II disease may reflect "a sense of some relief about knowing what's going on" along with a "surge of support" from the healthcare team and family members, Considine pointed out.

In stage II, individuals are suffering more severe cognitive and psychiatric symptoms and functional decline, but "they still have the preserved capacity to arrange and enact suicidal acts," he said. "So that's kind of a worst of all the circumstances."

Beyond stage II disease, as is seen in many neurodegenerative diseases, anosognosia "may be actually, ironically, a protective factor as the patients become less distressed about their circumstance," Considine added.

Addressing the Risk

Knowing that the time around diagnosis is a particularly risky period, "psychoeducation about the disease, the treatments available, the research that's going on, the support networks that exist, might be methods to blunt some of that triggering effect," Considine suggested.

Recognizing early signs of more profound psychiatric distress or cognitive impairment as being likely Huntington's disease related could reduce frustration and open up doors for treatment and support, he added.

The Huntington's Study Group Neuropsychiatry Working group, of which Considine is co-chair, has endorsed the of a Movement Disorder Society task force in 2019 calling for diagnostic criteria to go beyond just motor symptoms to include cognitive change as "sufficient, because it is atypical to happen so early."

The European Huntington's Disease Network is developing a Huntington's disease-specific scale toward that end.

"We're working toward ways to engage in diagnosis of Huntington's disease and not to gatekeep resources so late," Considine said. It also might reduce the frustration and worry that accompanies the high-risk period before diagnosis based on motor symptoms, when the cognitive and psychiatric symptoms may already have been ongoing for some time, he added.

Once patients are connected with treatment for depression, anxiety, and other neuropsychiatric symptoms, conventional psychiatric approaches with antidepressants and antipsychotics are typical, as is psychotherapy. Some individuals also try off-label medications like or experiments with electroconvulsive therapy, for example.

While not yet in sight, "the true silver bullet is trying to find a medication that can interrupt the aggregation of this mutant Huntington's protein, either prevent it or aid its clearance," Considine noted. "I'm optimistic in my lifetime it will happen."

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