Psychiatric symptoms predate motor onset in Huntington’s disease

By Lucy Piper, Senior medwireNews Reporter

Prodromal psychiatric symptoms may be more common in patients with Huntington’s disease than previously thought and worsen as the condition progresses, longitudinal study findings show.

The study researchers report that 1007 patients carrying the Huntington’s disease mutation but without motor symptoms gave significantly higher ratings on eight of the 12 psychiatric measures on the Symptom Checklist–90–Revised at baseline than did 298 individuals without the condition. And ratings on these measures increased significantly more over time in the individuals with Huntington’s disease than in those without the disease.

“The present study […] provides confidence that the psychiatric symptoms seen in Huntington’s disease progress with disease severity and thus are likely secondary to the neurodegenerative disease process”, the researchers comment in The American Journal of Psychiatry.

The psychiatric measures showing significant and increasing differences included positive symptoms, obsessive–compulsive symptoms, interpersonal sensitivity, depression, hostility and phobic anxiety. Anxiety, paranoid ideation and psychoticism showed baseline differences between patients and controls but did not worsen over time.

When the researchers grouped the patients according to probability of imminent progression to a motor diagnosis, based on CAG-age product score, the 356 and 371 Huntington’s disease patients with medium (7.6–12.8 years) and high (<7.6 years) probability, respectively, had significantly higher scores for 11 of 12 psychiatric measures at baseline compared with controls. For the 280 patients with low probability (>12.8 years), significant differences were seen in only nine measures compared with in controls.

“Since mental health professionals may see prodromal Huntington’s disease in clinical practice a decade before movement disorder specialists do, an earlier diagnosis may be prudent for many individuals”, Jane Paulsen (University of Iowa, Iowa City, USA) and fellow PREDICT-HD investigators comment.

However, they note that the source of measurement significantly affected the findings. In addition to asking Huntington’s disease patients to rate their own psychiatric symptoms, the team also asked 1235 of their companions, predominantly a spouse or partner, to do so.

At baseline, significant differences between companion ratings of the patients and the ratings of controls were seen for 11 of 12 psychiatric measures for patients with medium and high probabilities of progression to motor onset, compared with just one measure for patients with low probability.

According to patient ratings, only seven of 12 psychiatric measures showed significant change over time compared with controls and only among those with imminent motor onset. But according to companions, there was significant worsening for 11 of 12 symptoms for patients with a high probability of an imminent motor diagnosis, six symptoms in those with a medium probability and two symptoms in those a long way from motor onset.

The findings indicate a reduced awareness in prodromal Huntington’s disease patients, says the team.

“In participants closer to estimated motor onset, the companion ratings appear to be more valid, whereas in gene-mutation carriers who are farthest from estimated motor onset, self-reported psychiatric symptoms may be more appropriate”, the researchers suggest.

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