Orbitofrontal sulcogyral morphology is a transdiagnostic indicator of brain dysfunction

Abstract

Atypical sulcogyral patterns in the orbitofrontal cortex (OFC) are associated with increased risk for schizophrenia, as well as with quantitative traits associated with schizophrenia, such as anhedonia. Here we conduct a cross-diagnostic comparison to assess whether atypical OFC sulcogyral patterns confer risk for multiple brain disorders. We examined structural images from 4 groups of adult participants (N = 189), including those diagnosed with schizophrenia (SZ; N = 49), bipolar disorder (BP; N = 46), attention deficit hyperactivity disorder (ADHD; N = 41), and controls (N = 53). OFC sulcogyral pattern types were determined based on the continuity of the medial and lateral orbitofrontal sulcus. Chi-square analysis was performed to compare the sulcogyral pattern frequency distributions between patient groups and controls. We find that both SZ and BP groups had atypical pattern distributions, with increased atypical pattern frequencies relative to controls in the left hemisphere, consistent with the overlapping clinical features and genetic etiology of these disorders (SZ: χ² = 17.6; p < 0.001; BP: χ² = 19.2, p < 0.001). The ADHD group distribution did not significantly differ from controls (χ² = 5.5; p = 0.06, NS.). Similar sulcogyral pattern frequencies across BP and SZ suggest that the sulcogyral phenotype may map more directly to a trait that is transdiagnostic. These results suggest that sulcogyral patterns present a novel morphological indicator for increased susceptibility to multiple psychiatric diagnoses.

Keywords: Attention deficit disorder; Bipolar disorder; Orbitofrontal cortex; Schizophrenia; Sulcogyral pattern.

Fig. 1

Examples of different H-sulcal pattern types. Type I on the far left is distinguished by its discontinuous Medial Orbital Sulcus (MOS) and continuous Lateral Orbital Sulcus (LOS). Type II in the middle is distinguished by its continuous MOS and LOS. Type III on the right is distinguished by a discontinuous MOS and discontinuous LOS. Red line indicates MOS. Blue line indicates LOS. Orange line indicates Transverse Orbital Sulcus (TOS). Green line indicates Intermediate Orbital Sulcus (IOS). Important note: We chose examples that had the same pattern type on the left and right hemispheres for clarity of illustration. However, it is more common for an individual to have different patterns on the left and right.

Fig. 2

Sulcal pattern distribution of the H-sulcal pattern in orbitofrontal cortex. Pattern frequencies plotted for each Type with diagnostic group clustered in columns. Note, frequencies of pattern type for each diagnosis group add up to a frequency of 1. Left-most column is control population. SZ, schizophrenia; BP, bipolar; ADHD, attention deficit hyperactivity disorder.