Unique Brain Pattern May Predict Schizophrenia Conversion

George W. Citroner

November 15, 2018

A unique brain marker on fMRI may be associated with an increased likelihood of developing schizophrenia later in life. The findings may facilitate much earlier diagnosis of the disorder.

The study of more than 200 participants in China showed a threefold psychosis conversion rate for those who were deemed at clinically high risk (CHR) for schizophrenia and who displayed abnormal modular organization on baseline brain imaging.

"If we can map and understand the neurobiological processes that underlie the emergence of early symptoms and their progression into overt psychosis, this can help develop early intervention strategies and improve outcome," co–principal investigator Susan Whitfield-Gabrieli, PhD, visiting scientist at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology and psychology professor at Northeastern University College of Science, Boston, Massachusetts, told Medscape Medical News.

The study was published online November 8 in Molecular Psychiatry.

Disordered Thinking

Before experiencing a psychotic episode, characterized by sudden changes in behavior and loss of touch with reality, an individual may experience milder symptoms, such as disordered thinking, the researchers note.

Previous research has shown that approximately 20% to 30% of patients with a clinically high-risk profile develop overt psychosis within 1 to 2 years.

"There appear to be early clinical, cognitive, and brain markers that may help better predict which individuals will, and which will not, transition to psychosis," she said.

The current study included 251 participants who were recruited at the Shanghai Mental Health Center as part of the Shanghai at Risk for Psychosis program.

Prodromal/early symptoms were assessed using a validated Chinese version of the Structured Interview for Prodromal Symptoms. Participant total IQ was estimated using the Wechsler Abbreviated Scale of Intelligence.

Of these participants, who were between the ages of 13 and 34 years, 158 were identified as being at CHR because they showed early symptoms of schizophrenia. In addition, 93 participants who did not have any risk factors were also included.

The researchers used fMRI to measure a type of brain activity involving resting state networks.

These networks are brain regions that preferentially connect and communicate with each other when the brain is not involved in any particular cognitive task.

Distinct Pattern

Among the CHR patients, 23 experienced a psychotic episode and were diagnosed with schizophrenia 1 year after the first fMRI scans.

Those patients' scans, taken before diagnosis, showed a pattern of activity that was distinct from those of both the healthy control group and the at-risk participants who had not experienced psychosis.

The researchers state that this distinctive brain activity pattern may be an early indicator of the condition.

The CHR patients who were found to have an abnormal modular connectome organization, or map of neural connections, at baseline had a three times higher chance of developing psychosis than the CHR patients with typical connectome organization at baseline.

Results also showed that in most of the participants, the superior temporal gyrus (STG), which is involved in auditory processing, was highly connected to the regions involved in sensory perception and motor control.

By contrast, the STG was found to be more connected to limbic regions, which are involved in processing emotions, in the CHR patients who developed psychosis. The investigators note that this could help explain the auditory hallucinations typically experienced by patients with schizophrenia.

"Our findings have implications for understanding fMRI findings in schizophrenia," Whitfield-Gabrieli said. In addition, the finding of abnormalities in the modular organization of the brain in the early phase of schizophrenia "may potentially offer a mechanistic explanation for these abnormal functional connectivity patterns throughout the brain," she added.

"In terms of clinical implications, our findings that abnormal brain network organization at baseline is associated with a three times higher risk of developing psychosis in the subsequent year suggests that this brain marker may be useful in identifying individuals who are most at risk for psychosis and for whom early intervention would be most helpful," Whitfield-Gabrieli said.

Early Intervention May Be Key

Alex Dimitriu, MD, founder of Menlo Park Psychiatry and Sleep Medicine, California, told Medscape Medical News that he sees potential benefits to this approach.

"The hope is with better 'granularity' via either improved imaging or data analysis, we may be better able to predict early disease states and intervene. Earlier intervention may mitigate overall symptoms and illness burden for these patients," Dimitriu said.

The researchers are now investigating early interventions that may help fight the symptoms of schizophrenia, including cognitive-behavioral therapy (CBT) to correct harmful thought patterns and mindfulness meditation, which may help reduce STG activity.

"A lot of symptoms of schizophrenia can flare up with anxiety, stress, insomnia, and fatigue," noted Dimitriu.

"Any intervention which can lower our stress response, or firing of dopamine and norepinephrine, can be seen as being beneficial for someone predisposed to schizophrenia. CBT and mindfulness could certainly help by improving mood and stress tolerance," he said.

"As the authors describe, its still hard to tell if schizophrenia is a disorder of excessive connectivity vs excessive isolation of certain brain regions," Dimitriu added. "While the research is mixed, looking at the function and connectivity of the brain is certainly a future direction of brain research and of understanding the psychiatric and neurologic functions of the brain."

The research was funded by the National Institutes of Health and the Ministry of Science and Technology of China. The study authors have disclosed no relevant financial relationships.

Mol Psychiatry. Published online November 8, 2018. Abstract

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