Associating Psychotic Symptoms with Altered Brain Anatomy in Psychotic Disorders Using Multidimensional Item Response Theory Models

Abstract

Reduced cortical thickness has been demonstrated in psychotic disorders, but its relationship to clinical symptoms has not been established. We aimed to identify the regions throughout neocortex where clinical psychosis manifestations correlate with cortical thickness. Rather than perform a traditional correlation analysis using total scores on psychiatric rating scales, we applied multidimensional item response theory to identify a profile of psychotic symptoms that was related to a region where cortical thickness was reduced. This analysis was performed using a large population of probands with psychotic disorders (N = 865), their family members (N = 678) and healthy volunteers (N = 347), from the 5-site Bipolar-Schizophrenia Network for Intermediate Phenotypes. Regional cortical thickness from structural magnetic resonance scans was measured using FreeSurfer; individual symptoms were rated using the Positive and Negative Syndrome Scale, Montgomery-Asberg Depression Rating Scale, and Young Mania Rating Scale. A cluster of cortical regions whose thickness was inversely related to severity of psychosis symptoms was identified. The regions turned out to be located contiguously in a large region of heteromodal association cortex including temporal, parietal and frontal lobe regions, suggesting a cluster of contiguous neocortical regions important to psychosis expression. When we tested the relationship between reduced cortical surface area and high psychotic symptoms we found no linked regions describing a related cortical set.

Factor analysis of lifetime psychopathology and its brain morphometric and genetic correlates in a transdiagnostic sample

“…When comparing our results to previous dimensional studies, a recent study also identified subcortical volume reductions associated with hallucinations as well as delusions [ 69 ], but reductions of superior temporal areas have also been well established in SSD [ 1 , 3 , 70 , 71 ]. The present findings are also in line with a recent investigation where psychotic symptoms were negatively correlated with CT in a large sample of SSD patients, relatives and healthy controls [ 72 ]. Consistent with previous studies in SSD, we found cortical thinning in the bilateral STG to be correlated with the PHS factor [ 73 ], indicating this brain structure to be a core feature of positive symptomatology.…”

The social vulnerability metric (SVM) as a new tool for public health

“…This relaxes the assumption of an interval scale of measurement such that every additional unit/interval increase of the SVM score does not have to reflect a uniform magnitude of increased/decreased social vulnerability. While many of the SDoH variables are measured on a continuous scale, we transformed them to quintiles for analysis and scoring, similar to previous methods applying the bifactor model to a mix of clinical and biological variables 19 . The scores for the primary dimension of SDoH are Bayes expected a posteriori (EAP) estimates that are expressed on an underlying unit normal (N(0,1)) scale and can be transformed to percentiles using an inverse normal transformation.…”

“…While many of the SDoH variables are measured on a continuous scale, we transformed them to quintiles for analysis and scoring, similar to previous methods applying the bifactor model to a mix of clinical and biological variables. 19 The scores for the primary dimension of SDoH are Bayes expected a posteriori (EAP) estimates that are expressed on an underlying unit normal (N(0,1)) scale and can be transformed to percentiles using an inverse normal transformation. We computed the empirical reliability of the test as the ratio of the empirical variance of the test (expected value = 1.0, true score variance) to the total variance, or the empirical variance plus the posterior variance of the estimator (error variance).…”

Biotyping in psychosis: using multiple computational approaches with one data set

“…Ours is an alternative statistical approach to look at the relationship between psychotic symptoms and regional cortical thickness, using MIRT. The MIRT approach examined both symptomatic (psychosis) and biological (cortical thickness) domains simultaneously while maintaining item-level symptom ratings and regional cortical thickness measures as inputs to the model, simultaneously, aiming to enhance precision in characterizing the relationship [36].…”