Local Gyrification Index in Probands with Psychotic Disorders and Their First-Degree Relatives

Background: Psychotic disorders are characterized by aberrant neural connectivity. Alterations in gyrification, the pattern and degree of cortical folding, may be related to the early development of connectivity. Past gyrification studies have relatively small sample sizes, yield mixed results for schizophrenia, and are scant for psychotic bipolar and schizoaffective (SZA) disorders and for relatives of these conditions. Here, we examine gyrification in psychotic disorder patients and their first-degree relatives as a possible endophenotype. Methods: Regional local gyrification index (LGI) values, as measured by FreeSurfer software, were compared between 243 control subjects, 388 psychotic disorder probands, and 300 of their first-degree relatives. For patients, LGI values were examined grouped across psychotic diagnoses and then separately for schizophrenia, SZA, and bipolar disorder. Familiality (heritability) values and correlations with clinical measures were also calculated for regional LGI values. Results: Probands exhibited significant hypogyria compared with control subjects in three brain regions and relatives with Axis II cluster A disorders showed nearly significant hypogyria in these same regions. Local gyrification index values in these locations were significantly heritable and uncorrelated with any clinical measure. Observations of significant hypogyria were most widespread in SZA. Conclusions: Psychotic disorders appear to be characterized by significant regionally localized hypogyria, particularly in cingulate cortex. This abnormality may be a structural endophenotype marking risk for psychotic illness and it may help elucidate etiological underpinnings of psychotic disorders.