Marker of brain dysfunction tied to unawareness of illness in psychotic patients

By John Murphy, MDLinx
Published January 13, 2016

Key Takeaways

If people with schizophrenia or other psychotic disorders refuse to believe they are ill, they’re likely to resist treatment. Awareness of illness—termed “insight”—is a serious problem in the treatment of psychotic patients. A new study has now shown that low levels of a marker of brain cell dysfunction are associated with impaired insight, according to research presented September 1, 2015 at the European College of Neuropsychopharmacology Congress in Amsterdam.

Prior research indicated that the prefrontal cortex may be associated with poor insight. Numerous studies have also found reduced levels of the neurometabolite N-acetylaspartate (NAA) in the prefrontal cortex of patients with psychotic disorders. Reduced NAA appears to signify impaired functioning, damage, or loss of brain cells.

In this study, which aimed to test NAA levels against insight, researchers from the University of Groningen in the Netherlands recruited 80 patients with psychotic disorders. They evaluated their levels of insight using standard questionnaires (Birchwood Insight Scale, and one item of the Positive and Negative Syndrome Scale), and then used proton magnetic resonance spectroscopy to measure the concentrations of various neurometabolites in the dorsolateral prefrontal cortex.

The researchers found that patients with poorer insight had significantly lower levels of NAA in the prefrontal cortex. Levels of other neurometabolites in the prefrontal cortex showed no significant relation to insight.

“NAA is seen as a marker for brain cell density and viability. What we found is a specific association between decreased NAA concentrations and impaired insight,” said presenting author Daouia Larabi, a PhD candidate at the University of Groningen. “Basically, the lower the levels of NAA in the  prefrontal cortex, the worse patient’s insight is.” The presenters noted that this was a correlational study, so they can’t confirm a causal effect.

“People with poor insight tend to drop out of treatment, have poorer functioning in general, and have worse prognosis. If you are convinced that you are not ill, you won’t want to be treated,” Ms. Larabi said. “We hope our findings will help in a better understanding of the neurobiology of impaired insight. This may help in the development of new treatment options such that insight, and consequently patients’ likely course of their condition, can be improved.”

This research may one day extend beyond patients with psychosis and, with further studies, perhaps shed light on neurological conditions. “In dementia, including Alzheimer’s, lack of insight can also be a significant problem,” said co-author André Aleman, PhD, Professor of Cognitive Neuropsychiatry at the University of Groningen. “I am not aware of any studies as yet that address neurometabolites (as measured with MRS) in dementia in relationship to insight. However, I would think that the neural correlates could be very similar to schizophrenia.”

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