Sound processing, behaviors linked in women with fragile X premutations

Finding suggest a 'spectrum' of characteristics among subgroups of carriers

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Lightning shoots out of a cloud-like brain.

How the brain processes sound varies across three neuropsychiatric feature-based subgroups of women who carry so-called premutations in FMR1, the gene associated with fragile X syndrome, a pilot study showed.

“Our findings suggest a spectrum of sensory processing characteristics present in subgroups of premutation carriers that have been previously understudied due to lack of overall group differences,” the researchers wrote, noting their results validated the subgroups by showing links between disruptions in brain pathways and behavioral characteristics that may help identify therapies for premutation carriers.

The study, “Neuropsychiatric feature-based subgrouping reveals neural sensory processing spectrum in female FMR1 premutation carriers: A pilot study,” was published in Frontiers in Integrative Neuroscience.

The FMR1 gene encodes FMRP, a protein that regulates the production of proteins that support nerve cell communication. This gene has up to about 40 repeats of three nucleotides, or DNA’s building blocks — CGG, with the C standing for cytosine and G for guanine.

The abnormal presence of 55 to 200 CGG repeats is classified as a premutation. More than 200 is called a full mutation and leads to severe FMRP deficit and fragile X.

While those with the premutation don’t show full fragile X symptoms, they can have anxiety, depression, cognitive impairment, and behavioral challenges. Women with the premutation “may experience impaired executive function and social processing difficulties in addition to increased neuropsychiatric risk,” the researchers wrote. The types and severity of symptoms vary in premutation carriers, in general.

In a previous study, researchers in the U.S. identified three distinct subgroups among women with FMR1 premutations based on their emotional, cognitive, and behavioral features.

The first subgroup (cluster 1) had more psychiatric features, including increased depression and anxiety, but relatively normal resting electroencephalogram (EEG) results. An EEG measures electrical brain wave activity using small electrodes attached to the scalp. Cluster 2 showed increased executive dysfunction, or an inability to manage thoughts, emotions, and actions, and altered EEG findings similar to fragile X patients. Cluster 3 was relatively unaffected by cognitive or psychiatric symptoms.

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Assessing sensory processing in fragile X premutations

The same researchers investigated whether sensory processing, as measured with EEG, differed across these three subgroups.

Abnormal sensory processing is a common sign of fragile X, mostly presenting as hypersensitivity to bright lights, sounds, and smells. Few studies have examined sensory processing with premutations, however.

A total of 33 women, ages 19-78, with the FMR1 premutation were included in the study. Among them, 11 had been taking antidepressant medications, but none had a history of seizures nor used anti-seizure therapies, which could interfere with EEG readings.

Participants underwent EEG while listening passively to bursts of static-like white noise through headphones while watching a silent movie.

Eight women with more CGG repeats, anxiety, and depression were classified cluster 1. They showed reduced sound sensitivity, similar to those with other psychiatric disorders, but different from fragile X patients.

The 10 women placed into cluster 2, having fewer CGG repeats and greater executive function problems, showed an inability for their brain waves to synchronize and follow the timing of the sound.

These findings were consistent with EEG readings from fragile X patients. This group also showed more sensory sensitivity than the other two subgroups, “suggesting heightened sensory detection,” the researchers wrote.

The remaining 11 women, with similar CGG repeat numbers to cluster 2 and largely unaffected by cognitive or psychiatric symptoms, were placed in the third cluster. They showed the most normal EEG findings in response to sound bursts.

“Resting EEG differences in this subgroup may represent compensatory responses that reduce risk for psychiatric, executive function, and sensory processing deficits,” the researchers wrote. “We find differences notable by cluster membership supporting initial cluster characterizations and conclusions that [variable] symptom presentations reflect underlying spectrum characteristics forming unique subgroupings.”

The researchers said their results “further validate the pre-defined clinical subgroups by supporting links between disturbances in well-defined neural pathways and behavioral alterations” that might help identify the mechanisms underlying risk factors with the FMR1 premutation and their different therapeutic needs.