Psychiatric and Behavioral Problems in Huntington’s Often Ignored in Research, Review Finds

Psychiatric and Behavioral Problems in Huntington’s Often Ignored in Research, Review Finds

A recent review summarizes the scientific literature on behavioral and psychiatric symptoms of Huntington’s disease, noting that plenty of research is still needed to better understand and treat such symptoms, which traditionally have taken second stage to the disease’s movement problems.

The review, “Changes in mental state and behaviour in Huntington’s disease,” published in the journal The Lancet Psychiatry, noted that behavioral and psychiatric symptoms are often the most burdensome for patients and their families, and highlighted research initiatives needed for a fuller understanding of the complex condition that is Huntington’s.

Researchers at the BSMHFT National Centre for Mental Health in Birmingham, U.K., underscored that assessing psychiatric problems in Huntington’s disease can be difficult as the symptoms do not always fit diagnostic criteria. Also, some symptoms may not be evident to the patients themselves, but can be very stressful for family and caretakers.

Anxiety and Depression

Anxiety and depression are more common in people with Huntington’s disease compared to the general population. There is no difference between the sexes in the prevalence of these conditions among Huntington’s patients. In contrast, in the general population, both anxiety and depression are more common in women.

No randomized controlled trials have been performed investigating treatments for anxiety and depression in Huntington’s, but smaller studies show that patients often respond to medical, as well as behavioral, treatment.

Suicide

Suicide can be common in the Huntington’s population, and a study found that thoughts of suicide might have a comforting, rather than distressing, purpose in such patients, since they can help individuals to maintain a feeling of control over their disease.

But the quality of life for caregivers is also affected by such suicidal tendencies, and the review noted the need to include screening for suicide ideation in routine assessments.

Perseverative behavior is a common problem in Huntington’s patients, but according to the review it differs from obsessive compulsive disorder, which might seem similar. People with Huntington’s do not always have insight into their repetitive behavior and do not try to control it, while people with obsessive compulsive disorder do.

Disinhibition

Disinhibition can be one of the most troublesome symptoms in Huntington’s disease, particularly for the family and caregivers. Milder symptoms can include speaking out of turn, embarrassing remarks, and childish behavior.  More socially compromising behaviors, such as inappropriate sexual remarks, hypersexual behavior or exhibitionism can be particularly troubling.

Studies also show that disinhibition is closely linked to delusions, irritability, and agitation, suggesting that the symptoms may be on a spectrum of more classical psychotic symptoms, also commonly seen in Huntington’s.

The problems may also be more severe in younger Huntingtin gene carriers. The reviewers noted that disinhibition can be treated both with behavioral interventions and with selective serotonin reuptake inhibitors (SSRIs). Drugs used for behavioral problems in frontotemporal dementia might also be valuable.

Irritability

Irritability is also very common in Huntington’s, and usually increases in the early disease stages. It tends to level out as the disease gets more severe. Studies show that irritability is linked to aggression and impulsivity.

Most experts recommend that SSRIs or other antidepressants be used to manage irritability when a patient also suffers anxiety, depression, or perseverative behaviors. If irritability is linked to aggression, hypersexuality, or impulsivity, antipsychotic medicines may be a better option.

Apathy

In contrast to most behavioral problems in Huntington’s, apathy, affecting up to 76 percent of patients, may be linked to disease progression. Studies report that it can severely reduce quality of life in patients. Despite that, no clinical trials have explored drugs targeting this symptom, and no drugs are approved for the condition.

Psychosis

Psychotic symptoms are not more common in Huntington’s compared to the general population. As with other behavioral and psychiatric problems, not much research has explored antipsychotic medicine among Huntington’s patients. Small studies have suggested that risperidone, aripiprazole, and olanzapine can be effective.

The review noted that the relatively lower rates of psychosis in Huntington’s disease, compared to other types of psychiatric symptoms, may be caused by the use of drugs blocking dopamine to treat motor problems in Huntington’s.

Social Cognition

One particularly troubling symptom in Huntington’s disease is the inability to understand emotions in others. More recent studies have shown that the difficulties likely extend to the inability to reason about mental states, such as beliefs and emotions.

Some studies have linked the deterioration of social cognition to movement problems, and so it is possible that social cognition could follow disease progression. There are, however, no studies following patients over time that could confirm this.

In addition, Huntington’s patients may have problems in reflecting on and describing their own emotions, a condition called alexithymia.

Future Directions

The review underscored that scientists need to refine the ability to measure changes in mental state and behavior in Huntington’s disease to enable clinical trials.

Researchers also need to focus attention on the symptoms that are the most troubling and impairing for patients and their families. For this, doctors and researchers need to develop their language to integrate the mental, behavioral, cognitive, emotional, social, and motor facets of Huntington’s disease.

More specifically, longitudinal studies of behavioral and psychiatric changes are badly needed, as are assessments of appropriate psychiatric rating scales to measure meaningful change in clinical trials.

Another point that would aid the development of treatments would be to identify brain changes linked to cognitive problems.  Genome-wide association studies looking at specific behavioral problems could also identify treatment targets.

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Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.

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