Common and distinct structural features of schizophrenia and bipolar disorder: The European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT) study

INTRODUCTION: Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology, their neural underpinnings are still under investigation. Here, structural Magnetic Resonance Imaging (MRI) data collected from a large sample of BD and SCZ patients and healthy controls (HC) were analyzed in terms of gray matter volume (GMV) using both voxel based morphometry (VBM) and a region of interest (ROI) approach. METHODS: The analysis was conducted on two datasets, Dataset1 (802 subjects: 243 SCZ, 176 BD, 383 HC) and Dataset2, a homogeneous subset of Dataset1 (301 subjects: 107 HC, 85 BD and 109 SCZ). General Linear Model analyses were performed 1) at the voxel-level in the whole brain (VBM study), 2) at the regional level in the anatomical regions emerged from the VBM study (ROI study). The GMV comparison across groups was integrated with the analysis of GMV correlates of different clinical dimensions. RESULTS: The VBM results of Dataset1 showed 1) in BD compared to HC, GMV deficits in right cingulate, superior temporal and calcarine cortices, 2) in SCZ compared to HC, GMV deficits in widespread cortical and subcortical areas, 3) in SCZ compared to BD, GMV deficits in insula and thalamus (p<0.05, cluster family wise error corrected). The regions showing GMV deficits in the BD group were mostly included in the SCZ ones. The ROI analyses confirmed the VBM results at the regional level in most of the clusters from the SCZ vs. HC comparison (p<0.05, Bonferroni corrected). The VBM and ROI analyses of Dataset2 provided further evidence for the enhanced GMV deficits characterizing SCZ. Based on the clinical-neuroanatomical analyses, we cannot exclude possible confounding effects due to 1) age of onset and medication in BD patients, 2) symptoms severity in SCZ patients. CONCLUSION: Our study reported both shared and specific neuroanatomical characteristics between the two disorders, suggesting more severe and generalized GMV deficits in SCZ, with a specific role for insula and thalamus.Funding: PB was partially funded by grants from the Ministry of Health (RF-2011-02352308). Grant support of EM was provided by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602450 (IMAGEMEND Project). Part of the present study was conducted at the Hospital Universitario MarqueÂs de Valdecilla, University of Cantabria (Santander, Spain), under the following grant support: Carlos III Health Institute PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005- Orden sco/3246/2004, SENY Fundacio Research Grant CI 2005-0308007 and FundacioÂn MarqueÂs de Valdecilla API07/011. We wish to acknowledge IDIVAL Neuroimaging Unit for imaging acquirement and analysis. Part of the study was conducted at the Ospedale San Raffaele, Milano, supported by the European Union EU-FP7-HEALTH-F2-2008-222963 “MOODINFLAME” and by the Italian Ministry of Health RF-2011-02350980 projects. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Reduced Gray to White Matter Tissue Intensity Contrast in Schizophrenia

BACKGROUND: While numerous structural magnetic resonance imaging (MRI) studies revealed changes of brain volume or density, cortical thickness and fibre integrity in schizophrenia, the effect of tissue alterations on the contrast properties of neural structures has so far remained mostly unexplored. METHODS: Whole brain high-resolution MRI at 3 Tesla was used to investigate tissue contrast and cortical thickness in patients with schizophrenia and healthy controls. RESULTS: Patients showed significantly decreased gray to white matter contrast in large portions throughout the cortical mantle with preponderance in inferior, middle, superior and medial temporal areas as well as in lateral and medial frontal regions. The extent of these intensity contrast changes exceeded the extent of cortical thinning. Further, contrast changes remained significant after controlling for cortical thickness measurements. CONCLUSIONS: Our findings clearly emphasize the presence of schizophrenia related brain tissue changes that alter the imaging properties of brain structures. Intensity contrast measurements might not only serve as a highly sensitive metric but also as a potential indicator of a distinct pathological process that might be independent from volume or thickness alterations

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Sexual Regional Dimorphism of Post-Adolescent and Middle Age Brain Maturation. A Multi-center 3T MRI Study

Sex-related differences are tied into neurodevelopmental and lifespan processes, beginning early in the perinatal and developmental phases and continue into adulthood. The present study was designed to investigate sexual dimorphism of changes in gray matter (GM) volume in post-adolescence, with a focus on early and middle-adulthood using a structural magnetic resonance imaging (MRI) dataset of healthy controls from the European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT). Three hundred and seventy three subjects underwent a 3.0 T MRI session across four European Centers. Age by sex effects on GM volumes were investigated using voxel-based morphometry (VBM) and the Automated Anatomical Labeling atlas regions (ROI). Females and males showed overlapping and non-overlapping patterns of GM volume changes during aging. Overlapping age-related changes emerged in bilateral frontal and temporal cortices, insula and thalamus. Both VBM and ROI analyses revealed non-overlapping changes in multiple regions, including cerebellum and vermis, bilateral mid frontal, mid occipital cortices, left inferior temporal and precentral gyri. These findings highlight the importance of accounting for sex differences in cross-sectional analyses, not only in the study of normative changes, but particularly in the context of psychiatric and neurologic disorders, wherein sex effects may be confounded with disease-related changes

Decreased bilateral thalamic gray matter volume in first-episode schizophrenia with prominent hallucinatory symptoms: A volumetric MRI study

Studies comparing gray matter (GM) volume of schizophrenic patients with or without auditory verbal hallucinations (AVHs) to that of normal controls remain controversial. This project aims to investigate changes of GM volumes of drug-naïve schizophrenic patients with and without AVHs. Eighteen first episode schizophrenic (FES) patients with AVHs, 18 FES patients without AVHs, and 18 healthy controls were scanned using structural MRI. Voxel-based morphometry (VBM) analysis was conducted to investigate changes of GM volume among the three groups. Patients with and without AVHs exhibited reduced GM volumes relative to normal controls in the left superior temporal gyrus, frontal regions, cerebellum and caudate. Further analysis of the GM of subcortical structures found that patients with AVHs had reduced thalamic volume than healthy controls. No significant difference was found between patients with and without AVHs. Significant correlation was found between the total scores of the Positive and Negative Syndrome Scale and bilateral thalamic volume. ROC analysis of thalamic volumes of the patients with AVHs and normal controls showed that the area under the curve was 0.698 (P = 0.043). The decreased thalamic volumes might serve as a biomarker for discriminating FES AVHs patients from normals