Early psychosis has been linked to reduced brain gray matter volume

Researchers from five countries analyzed magnetic resonance imaging scans of patients with early psychosis and found that this condition is associated with a widespread decrease in gray matter volume in the cerebral cortex of the large cerebral hemispheres. As reported in the journal Molecular Psychiatry, this volume also depended on the age of onset and the dose of chlorpromazine taken. The volume of white matter changed to a lesser extent.

Early psychosis, or early-onset psychosis, refers to psychoses in children younger than 18 years of age. They are often caused by an early form of schizophrenia, affective and nonaffective psychotic disorders. Because these psychoses occur during a critical period of nervous system development, they are associated with unfavorable long-term outcomes, including more severe and prolonged symptoms and poor response to treatment. A long-term study found that 60 percent of patients with early psychosis develop severe psychiatric disorders during a 40-year follow-up.

However, because of the low prevalence of early psychosis (no more than one percent), there are few studies examining organic brain changes in this condition. The ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis initiative) working group is trying to address this problem by pooling samples from research groups around the world. It has previously shown that early psychosis is associated with significantly lower intracranial volume and hippocampal volume.

Now, this team of scientists from five countries, led by Shuqing Si of King's College London, has developed a standardized method for calculating the volumes of brain structures from magnetic resonance imaging (MRI) scans, so that scientists from different countries can bring their measurements into a single format that is convenient for final analysis. The study sample included 482 people with early psychosis and 469 healthy control participants. All patients in the study group were diagnosed with psychosis before the age of 18 and were between 14 and 26 years old at the time of the survey, with a cumulative mean age at the time of the survey of 17.1 and age of onset of 15.3.

Regional and global case-control analyses showed that patients with early psychosis had significantly lower gray matter volume in all brain lobes (p = 0.0006) with a peak effect in the middle cingulate gyrus (p = 0.001). The large cluster also included the temporal, frontal and postcentral gyrus. As for the white matter, its volume was marginally reduced on both sides only in the inferior longitudinal fasciculus.

Older age of first psychosis was associated with smaller gray matter volume in the cerebellum, left inferior parietal gyrus, and thalamus and smaller white matter volume in the middle legs of the cerebellum. In addition, a higher equivalent dose of chlorpromazine (a baseline antipsychotic) taken was associated with reduced gray matter volume. Notably, longer disease duration was associated with higher volumes of the right precentral and spindle gyrus, and a higher IQ score was associated with greater temporal area volume. Additional statistical meta-analyses confirmed the associations found.

This study suggests that organic brain changes exist in patients with early psychosis. Further research should characterize the relationship between these observations and answer the question of the underlying cause of these abnormalities.