Meta-analysis of gray matter anomalies in schizophrenia: application of anatomic likelihood estimation and network analysis

Abstract

Background: Although structural neuroimaging methods have been widely used to study brain morphology in schizophrenia, synthesizing this literature has been difficult. With the increasing popularity of voxel-based morphometric (VBM) methods in which group differences are reported in standardized coordinates, it is possible to apply powerful meta-analytic techniques initially designed for functional neuroimaging. In this study, we performed a voxelwise, coordinate-based meta-analysis to better conceptualize the neuroanatomic correlates of schizophrenia.

Methods: Thirty-one peer-reviewed articles, with a total of 1195 patients with schizophrenia contrasted with 1262 healthy volunteers, were included in the meta-analysis. Coordinates from each article were used to create a statistical map that estimated the likelihood of between-group gray matter density differences at every brain voxel. These results were subsequently entered into a network analysis.

Results: Patients had reduced gray matter density relative to control subjects in a distributed network of regions, including bilateral insular cortex, anterior cingulate, left parahippocampal gyrus, left middle frontal gyrus, postcentral gyrus, and thalamus. Network analysis grouped these regions into four distinct networks that potentially represent different pathologic processes. Patients had increased gray matter density in striatal regions.

Conclusions: This study expands on previous meta-analyses of the neuroanatomy of schizophrenia by elucidating a series of brain networks disrupted by the illness. Because it is possible that these networks are influenced by independent etiologic factors, this work should foster more detailed neural models of the illness and focus research designed to discover the mechanisms of gray matter reduction in schizophrenia.

Figure 1

Results from an ALE meta analysis of 31 VBM studies investigating gray matter density changes in schizophrenia. Hot colors represent areas of gray matter density decrease in patients with schizophrenia relative to healthy comparison subjects. Cold or blue colors represent areas of increased gray matter density in patients with schizophrenia relative to comparison subjects.

Figure 2

Three regions of anterior cingulate gyrus were found to have lower gray matter density in schizophrenia: dorsal, ventral and subgenual. These regions include both the cognitive and affective regions of cingulate (33).

Figure 3

Fractional similarity network analysis parsed regions of gray matter density reduction in schizophrenia into four distinct subnets: bilateral insular cortex, left parahippocampal and left post central gyri (red); left middle frontal gyrus and ventral anterior cingulate (green); thalamus and dorsal anterior cingulate (blue); and subgenual cingulate (yellow). Part (A) represents two-dimensional views of these subnets while (B) displays a three-dimensional rendering of these network components.