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Background Negative symptoms can be seen to represent a continuum from subclinical manifestations in the general population to severe symptoms in schizophrenia. Neuroanatomical studies show evidence of fronto-striatal structural abnormalities linked to negative symptoms in patients with schizophrenia (Walton et al. 2018). However, it remains an open question whether these structural associations are also observed in ostensibly healthy individuals reporting subclinical negative symptoms. The present study used structural T1-weighted brain imaging data from the ENIGMA Schizotypy Working Group to investigate the relationship between subclinical negative symptoms and fronto-striatal structural measures. Methods We included 2,235 healthy unmedicated individuals with varying levels of schizotypy from 17 centers around the world. The complete sample had a weighted mean (range) age of 29.2 (15.9–39.6) and 59.4% (51–100) were male. Subclinical negative symptoms were assessed at each site separately using factor scores from self-report schizotypy questionnaires (i.e., the Community Assessment of Psychic Experiences, the Oxford-Liverpool Inventory of Feelings and Experiences, or the Schizotypal Personality Questionnaire). Based on prior studies in schizophrenia, we obtained cortical thickness from 22 frontal regions-of-interest (ROIs) and subcortical volumes from 6 striatal ROIs using FreeSurfer. We performed meta-analyses of effect sizes (standardized regression coefficients) from a model predicting mean cortical thickness by subclinical negative symptom scores, adjusting for age, sex, and site. The same analysis was repeated for subcortical volumes including intracranial volume as additional covariate. Results Meta-analyses revealed significant positive associations between subclinical negative symptoms and cortical thickness of the left frontal pole (βstd=0.091; pFDR=0.009), right medial orbitofrontal cortex (βstd=0.083; pFDR=0.009) and right anterior cingulate cortex (βstd=0.07; pFDR=0.011). Discussion Using a large sample of healthy unmedicated individuals with varying levels of schizotypal personality traits, this ENIGMA meta-analysis showed that subclinical negative symptoms are associated with thicker prefrontal cortex. The present data are contrary to previous findings in schizophrenia, which demonstrates a relationship between negative symptoms and lower prefrontal cortical thickness (Walton et al. 2018). These divergent neural correlates suggest that thicker cortex could be a potential compensatory mechanism preventing individuals with schizotypy from the clinical manifestation of severe negative symptoms. Alternatively, greater prefrontal cortical thickness could also be associated with pathological processes along the negative symptom continuum prior to clinical manifestation.

T162. THICKER PREFRONTAL CORTEX IS ASSOCIATED WITH SUBCLINICAL NEGATIVE SYMPTOMS IN SCHIZOTYPY - AN ENIGMA CONSORTIUM META-ANALYSIS