Multivariate patterns of gray matter volume in thalamic nuclei are associated with positive schizotypy in healthy individuals

Background: Previous models suggest biological and behavioral continua among healthy individuals (HC), at-risk condition, and full-blown schizophrenia (SCZ). Part of these continua may be captured by schizotypy, which shares subclinical traits and biological phenotypes with SCZ, including thalamic structural abnormalities. In this regard, previous findings have suggested that multivariate volumetric patterns of individual thalamic nuclei discriminate HC from SCZ. These results were obtained using machine learning, which allows case-control classification at the single-subject level. However, machine learning accuracy is usually unsatisfactory possibly due to phenotype heterogeneity. Indeed, a source of misclassification may be related to thalamic structural characteristics of those HC with high schizotypy, which may resemble structural abnormalities of SCZ. We hypothesized that thalamic structural heterogeneity is related to schizotypy, such that high schizotypal burden would implicate misclassification of those HC whose thalamic patterns resemble SCZ abnormalities.

Methods: Following a previous report, we used Random Forests to predict diagnosis in a case-control sample (SCZ = 131, HC = 255) based on thalamic nuclei gray matter volumes estimates. Then, we investigated whether the likelihood to be classified as SCZ (π-SCZ) was associated with schizotypy in 174 HC, evaluated with the Schizotypal Personality Questionnaire.

Results: Prediction accuracy was 72.5%. Misclassified HC had higher positive schizotypy scores, which were correlated with π-SCZ. Results were specific to thalamic rather than whole-brain structural features.

Conclusions: These findings strengthen the relevance of thalamic structural abnormalities to SCZ and suggest that multivariate thalamic patterns are correlates of the continuum between schizotypy in HC and the full-blown disease.