Neuropathological Similarities and Differences between Schizophrenia and Bipolar Disorder: A Flow Cytometric Postmortem Brain Study

Recent studies suggest that schizophrenia (SCH) and bipolar disorder (BPD) may share a similar etiopathology. However, their precise neuropathological natures have rarely been characterized in a comprehensive and quantitative fashion. We have recently developed a rapid, quantitative cell-counting method for frozen unfixed postmortem brains using a flow cytometer. In the present study, we not only counted stained nuclei, but also measured their sizes in the gray matter of frontopolar cortices (FPCs) and inferior temporal cortices (ITCs) from patients with SCH or BPD, as well as in that from normal controls. In terms of NeuN(+) neuronal nuclei size, particularly in the reduced densities of small NeuN(+) nuclei, we found abnormal distributions present in the ITC gray matter of both patient groups. These same abnormalities were also found in the FPCs of SCH patients, whereas in the FPCs of BPD patients, a reduction in oligodendrocyte lineage (olig2(+)) cells was much more common. Surprisingly, in the SCH FPC, normal left-greater-than-right asymmetry in neural nuclei densities was almost completely reversed. In the BPD FPC, this asymmetry, though not obvious, differed significantly from that in the SCH FPC. These findings indicate that while similar neuropathological abnormalities are shared by patients with SCH or BPD, differences also exist, mainly in the FPC, which may at least partially explain the differences observed in many aspects in these disorders

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

Classification of First-Episode Schizophrenia Patients and Healthy Subjects by Automated MRI Measures of Regional Brain Volume and Cortical Thickness

BACKGROUND: Although structural magnetic resonance imaging (MRI) studies have repeatedly demonstrated regional brain structural abnormalities in patients with schizophrenia, relatively few MRI-based studies have attempted to distinguish between patients with first-episode schizophrenia and healthy controls. METHOD: Three-dimensional MR images were acquired from 52 (29 males, 23 females) first-episode schizophrenia patients and 40 (22 males, 18 females) healthy subjects. Multiple brain measures (regional brain volume and cortical thickness) were calculated by a fully automated procedure and were used for group comparison and classification by linear discriminant function analysis. RESULTS: Schizophrenia patients showed gray matter volume reductions and cortical thinning in various brain regions predominantly in prefrontal and temporal cortices compared with controls. The classifiers obtained from 66 subjects of the first group successfully assigned 26 subjects of the second group with accuracy above 80%. CONCLUSION: Our results showed that combinations of automated brain measures successfully differentiated first-episode schizophrenia patients from healthy controls. Such neuroimaging approaches may provide objective biological information adjunct to clinical diagnosis of early schizophrenia

Mapping pathological changes in brain structure by combining T1- and T2-weighted MR imaging data

INTRODUCTION: A workflow based on the ratio between standardized T1-weighted (T1-w) and T2-weighted (T2-w) MR images has been proposed as a new tool to study brain structure. This approach was previously used to map structural properties in the healthy brain. Here, we evaluate whether the T1-w/T2-w approach can support the assessment of structural impairments in the diseased brain. We use schizophrenia data to demonstrate the potential clinical utility of the technique. METHODS: We analyzed T1-w and T2-w images of 36 schizophrenic patients and 35 age-matched controls. These were collected for the Function Biomedical Informatics Research Network (fBIRN) collaborative project, which had an IRB approval and followed the HIPAA guidelines. We computed T1-w/T2-w images for each individual and compared intensities in schizophrenic and control groups on a voxel-wise basis, as well as in regions of interest (ROIs). RESULTS: Our results revealed that the T1-w/T2-w image permits to discriminate brain regions showing group-level differences between patients and controls with greater accuracy than conventional T1-w and T2-w images. Both the ROIs and the voxel-wise analysis showed globally reduced gray and white matter values in patients compared to controls. Significantly reduced values were found in regions such as insula, primary auditory cortex, hippocampus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. CONCLUSION: Our findings were consistent with previous meta-analyses in schizophrenia corroborating the hypothesis of a potential “disconnection” syndrome in conjunction with structural alterations in local gray matter regions. Overall, our study suggested that the T1-w/T2-w technique permits to reliably map structural differences between the brains of patients and healthy individuals