Abstract
To investigate whether aberrant interactions between brain structure and function present similarly or differently across probands with psychotic illnesses [schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar I disorder with psychosis (BP)] and whether these deficits are shared with their first-degree non-psychotic relatives. A total of 1199 subjects were assessed, including 220 SZ, 147 SAD, 180 psychotic BP, 150 first-degree relatives of SZ, 126 SAD relatives, 134 BP relatives, and 242 healthy controls (1). All subjects underwent structural MRI (sMRI) and resting-state functional MRI (rs-fMRI) scanning. Joint-independent component analysis (jICA) was used to fuse sMRI gray matter and rs-fMRI amplitude of low-frequency fluctuations data to identify the relationship between the two modalities. jICA revealed two significantly fused components. The association between functional brain alteration in a prefrontal–striatal–thalamic–cerebellar network and structural abnormalities in the default mode network was found to be common across psychotic diagnoses and correlated with cognitive function, social function, and schizo-bipolar scale scores. The fused alteration in the temporal lobe was unique to SZ and SAD. The above effects were not seen in any relative group (including those with cluster-A personality). Using a multivariate-fused approach involving two widely used imaging markers, we demonstrate both shared and distinct biological traits across the psychosis spectrum. Furthermore, our results suggest that the above traits are psychosis biomarkers rather than endophenotypes.
Highlights
Whether schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder are distinct illnesses or represent a continuum continues to be debated [2,3,4]
Our aims were to [1] detect whether aberrancies detected by fusing restingstate functional MRI (rs-fMRI) and structural MRI (sMRI) would be specific to SZ, SAD, or bipolar I disorder with psychosis (BP) or shared by these psychotic disorders relative to healthy controls; [2] investigate whether these abnormalities across two modalities would be shared by probands and their non-psychotic relatives, suggesting that they may represent endophenotypes across the psychosis dimension
It is possible to apply more advanced statistical techniques to define “cross-modal” brain relationships between disparate measures. We took this approach to detect common and unique abnormalities in a large psychosis sample by fusing two modalities using a Joint-independent component analysis (jICA) approach across the psychotic spectrum (SZ, SAD, and psychotic BP) and to investigate which of those are shared by their unaffected first-degree relatives, suggesting possible endophenotypes
Summary
Whether schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder are distinct illnesses or represent a continuum continues to be debated [2,3,4]. The above disorders are highly heritable [9, 10], and illness-related genes associated with the abnormalities in brain structure and function [11] may be present in their unaffected relatives. A recent restingstate functional MRI (rs-fMRI) study reported that SZ, SAD, and psychotic bipolar disorder share disruptions within the frontoparietal control network [7]. Both default mode network (DMN) and prefrontal–thalamic–cerebellar network connectivity have been reported to be abnormal in probands with SZ and bipolar disorder [15, 16] and between probands and relatives with SZ [17,18,19]. Examining abnormalities in structure and function together may help better characterize illness-related features and provide more information than each measure independently
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