Lower cortical thickness measures may indicate clinical high risk for psychosis

Widespread subtle, lower cortical thickness measures were associated with clinical high risk for psychosis, according to results of a working-group mega-analysis published in JAMA Psychiatry.

“The extent to which characteristic baseline (ie, when participants are initially ascertained and assessed at a first study visit) structural neuroimaging differences exist between those at [clinical high risk] who later develop a psychotic disorder compared with those who do not is debated,” Maria Jalbrzikowski, PhD, of the department of psychiatry at the University of Pittsburgh, and colleagues wrote. “Many studies failed to find baseline differences between these [two] groups, although a meta-analysis and multicenter study found lower prefrontal and temporal volumes or cortical thickness measured by MRI in individuals at [clinical high risk] who developed a psychotic disorder. High attrition rates in samples of individuals at [clinical high risk] coupled with low psychosis conversion rates often yielded insufficient power to detect between-group structural brain differences.”

The investigators established the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) Clinical High Risk for Psychosis Working Group, which conducted the current case-control study. They aimed to evaluate baseline structural neuroimaging differences between people at clinical high risk for psychosis and healthy controls, as well as between people at clinical high risk who later developed a psychotics disorder and those who did not. They pooled baseline T1-weighted MRI data from 31 international sites that participated in the ENIGMA Clinical High Risk for Psychosis Working Group, and they used the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes to evaluate clinical high-risk status. Further, they used harmonized protocol to process MRI scans and analyzed them within a mega-analysis and meta-analysis framework between January 2020 and October 2020. Regional cortical thickness, surface area and subcortical volumes measures extracted from T1-weighted MRI scans served as main outcomes and measures. Group and conversion status served as independent variables.

The researchers included 3,169 participants (women, 45.1%; mean age, 21.1 years), of whom 1,792 were at clinical high risk and 1,377 were healthy controls. They used longitudinal clinical information and identified. A total of 253 participants at clinical high risk later developed a psychotic disorder, 1,234 at clinical high risk did not develop a psychotic disorder and 305 at clinical high risk did not have follow-up data available.

Results showed those at clinical high risk had widespread lower cortical thickness measures, but not surface area or subcortical volume, compared with healthy controls. The researchers noted an association between psychosis conversion and lower cortical thickness measures in the fusiform, superior temporal and paracentral regions. Healthy controls had a stronger negative association between age and left fusiform cortical thickness measures and left paracentral cortical thickness measures compared with those at clinical high risk who later developed a psychotic disorder. Further, they noted effect sizes that represented lower cortical thickness associated with psychosis conversion resembled patterns of cortical thickness differences apparent in ENIGMA studies of schizophrenia and people with 22q11.2 microdeletion syndrome and psychotic disorder diagnosis.

“The specificity of these differences to [cortical thickness] — as well as age-associated deviations in regions sensitive to psychosis conversion — may point to abnormal development processes,” Jalbrzikowski and colleagues wrote. “These findings also point to age ranges (ie, early adolescence) when morphometric abnormalities in individuals at [clinical high risk] might be greatest.”