Dissimilarity in sulcal width patterns in the cortex can be used to identify patients with schizophrenia with extreme deficits in cognitive performance

Abstract

Schizophrenia is a biologically complex disorder with multiple regional deficits in cortical brain morphology. In addition, interindividual heterogeneity of cortical morphological metrics is larger in patients with schizophrenia when compared to healthy controls. Exploiting interindividual differences in severity of cortical morphological deficits in patients instead of focusing on group averages may aid in detecting biologically informed homogeneous subgroups. The Person-Based Similarity Index (PBSI) of brain morphology indexes an individual's morphometric similarity across numerous cortical regions amongst a sample of healthy subjects. We extended the PBSI such that it indexes morphometric similarity of an independent individual (e.g., a patient) with respect to healthy control subjects. By employing a normative modeling approach on longitudinal data, we determined an individual's degree of morphometric dissimilarity to the norm. We calculated the PBSI for sulcal width (PBSI-SW) in patients with schizophrenia and healthy control subjects (164 patients, 164 healthy controls; 656 MRI scans) and associated it with cognitive performance and cortical sulcation index. A subgroup of patients with markedly deviant PBSI-SW showed extreme deficits in cognitive performance and cortical sulcation. Progressive reduction of PBSI-SW in the schizophrenia group relative to healthy controls was driven by these deviating individuals. By explicitly leveraging interindividual differences in severity of PBSI-SW deficits, neuroimaging-driven subgrouping of patients is feasible. As such, our results pave the way for future applications of morphometric similarity indices for subtyping of clinical populations.

Personalized estimates of morphometric similarity in bipolar disorder and schizophrenia

“…Although the effect size of case-control differences was small, it raises the possibility that there may be a minority of patients with schizophrenia that differ significantly from others with the same diagnosis. This possibility is supported by Janssen and colleagues 47 who generated PBSI scores for cortical gyrification; most patients in their study had similar profiles to those of the healthy controls with the exception of a small subgroup that showed extreme deviance. Therefore, heterogeneity might be present in schizophrenia but may be limited to an "extreme" but a small subgroup that requires further study in larger samples.…”

“…A sample of 75 patients with schizophrenia and 87 healthy age-and sex-matched individuals (Table 1 and Supplementary Table 3) was provided by the Center of Biomedical Research Excellence (COBRE) (http://coins.trendscenter.org), which is an open-access collection of neuroimaging data in schizophrenia 52 . The diagnostic status of participants in the COBRE sample was ascertained according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) 53 using the Structured Clinical Interview for DSM-IV Axis I Disorders 47 . All participants were screened to exclude those with a history of neurological disorder, mental retardation, severe head trauma, substance abuse, or dependence within the last 12 months and MRI contraindications.…”