Katsunori Takase

Diffusion tensor magnetic resonance imaging of disruption of regional white matter in schizophrenia.

Diffusion tensor imaging provides a new approach for quantifying anisotropic diffusion of white matter in vivo. We used this technique to investigate subtle disruption of regional white matter in schizophrenia. Twelve patients with schizophrenia were compared with 11 healthy controls. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. A significant fractional anisotropy (FA) reduction was found in all white matter regions bilaterally in schizophrenic patients. Higher FA of left frontal white matter correlated significantly with higher dosage of antipsychotic medication. These findings support the view that the pathological process is a distortion of the central nervous system myelination affecting the whole white matter. Our findings also show the effects of antipsychotics on the white matter in the left frontal region in schizophrenia.

Subtle Disruption of the Middle Cerebellar Peduncles in Patients with Schizophrenia

Diffusion tensor imaging (DTI) was used to investigate subtle disruption in the middle cerebellar peduncles in patients with schizophrenia. Fractional anisotropy (FA) was measured in 25 patients with schizophrenia and 21 healthy subjects using DTI. The FA of the right and left middle cerebellar peduncles was significantly lower in the schizophrenic patients compared to healthy subjects. FA in the left middle cerebellar peduncles was significantly correlated with the dosage of neuroleptics in patients with schizophrenia. There were no significant differences of mean diffusivity in the right and left middle cerebellar peduncles between patients with schizophrenia and healthy subjects. The findings of the study suggest that antipsychotics may improve the subtle disruption in the middle cerebellar peduncles in patients with schizophrenia.

Effects of Electroconvulsive Therapy on Frontal White Matter in Late-Life Depression: A Diffusion Tensor Imaging Study

This study was conducted to elucidate the effects of electroconvulsive therapy (ECT) on frontal white matter in late-life depressed patients. Diffusion tensor imaging was performed on 8 late-life depressed patients and 12 healthy age-matched controls. The patients were scanned before and after a course of ECT. Fractional anisotropy (FA) was determined in the frontal and temporal regions and the corpus callosum. A significant white matter FA reduction was found in widespread frontal and temporal brain regions in patients with depression before ECT treatment compared with controls. A significant increase in frontal white matter FA was seen following ECT treatment. A course of bilateral ECT ameliorated white matter integrity in frontal brain regions. This suggests a strong relationship with the antidepressant action of ECT.

Corpus Callosum in Patients with Obsessive-Compulsive Disorder: Diffusion-Tensor Imaging Study

PURPOSE To prospectively examine microstructural white matter abnormalities in the corpus callosum (CC) of patients with obsessive-compulsive disorder (OCD), as compared with control subjects, and to investigate the relationship between diffusion-tensor (DT) imaging measures of the CC region and clinical symptoms of OCD. MATERIALS AND METHODS Institutional review board approval was obtained, and each participant--or the participants parent(s)--provided written informed consent. Sixteen patients with OCD (seven male, nine female; mean age, 28.7 years +/- 9.8 [standard deviation]) and 16 matched healthy volunteers (control subjects) (seven male, nine female; mean age, 29.9 years +/- 9.0) were examined. Mean diffusivity and fractional anisotropy (FA) were measured in five subdivisions of the CC. The paired t test was performed to compare the mean diffusivity or the FA in CC regions between the patients with OCD and the control subjects. RESULTS There were no significant differences (rostrum, P = .15; genu, P = .88; rostral body, P = .12; isthmus, P = .77; splenium, P = .88) in mean diffusivity between the patients with OCD and the healthy volunteers. A significant reduction in FA was observed in the rostrum of the CC in patients with OCD compared with the rostral FA in the control subjects (P < .001). Higher FA in only the rostrum correlated significantly with lower Yale-Brown obsessive-compulsive scale score (r = -0.72, P = .002). CONCLUSION Study results support the widely held view that the orbital prefrontal region is involved in the pathophysiology of OCD and indicate that the orbitofrontal circuit influences symptom severity in patients with OCD.

Olanzapine Increases Grey and White Matter Volumes in the Caudate Nucleus of Patients with Schizophrenia

There are inconsistent reports regarding the caudate nucleus volume in patients with schizophrenia compared with healthy subjects. The reason for this is that neuroleptic medication may affect the volume of the caudate nucleus in schizophrenic patients. To clarify which antipsychotic medication changes the volume of the caudate nucleus in patients with schizophrenia, we measured the volumes of grey and white matter in the caudate nucleus of schizophrenic patients. Ten patients with schizophrenia were examined twice by magnetic resonance imaging (MRI) to measure the grey and white matter volumes in the caudate nucleus. After the first MRI examination, all the patients were treated with olanzapine. The clinical responses were evaluated by the positive and negative rating scale. When the symptoms improved, the patients were examined by a second MRI scan. Ten healthy control subjects also underwent MRI. The schizophrenic patients had reduced volumes of grey and white matter in the caudate nucleus compared to the healthy control subjects. The volumes of grey and white matter in the caudate nucleus of the schizophrenic patients increased after treatment with olanzapine. These findings suggest that treatment with olanzapine may increase the grey and white matter volumes in the caudate nucleus in patients with schizophrenia.

Cerebellar posterior superior vermis and cognitive cluster scores in drug-naive patients with first-episode schizophrenia.

Previously, we performed an MRI study that revealed smaller volumes of the subregions of the cerebellar vermis in men and women with chronic schizophrenia. An issue that arose from that study was whether similar structural changes in the cerebellum are found in patients with first-episode schizophrenia. In the present study, MRI scans were acquired from 14 drug-naive patients with first-episode schizophrenia and 16 healthy subjects, and used to measure the volumes of their cerebellar subregions. Positive symptom, negative symptom and cognitive cluster scores were attained using the Positive and Negative Syndrome Scale. Patients with first-episode schizophrenia had reduced volumes of the anterior vermis and posterior superior vermis compared with healthy subjects. We confirmed that there was a volume reduction of the cerebellar vermis in drug-naive patients with first-episode schizophrenia. Smaller volumes of the posterior superior vermis were associated with worse cognitive cluster scores in patients with first-episode schizophrenia.

Reduced white matter volume of the caudate nucleus in patients with schizophrenia.

To examine volumetric abnormality, the caudate nucleus was measured in patients with schizophrenia and healthy subjects using magnetic resonance imaging. The absolute and relative volumes of white matter in the caudate nucleus were found to be significantly smaller in patients with schizophrenia compared to those in healthy subjects. There were significant correlations between dosages of neuroleptics during the previous year and absolute gray matter volumes of the caudate nucleus as well as relative white matter volumes in patients with schizophrenia. These findings suggest that reduced white matter volume of the caudate nucleus may be a factor affecting the abnormal connectivity of the corticostriatal loop, and that neuroleptic medication would be related to white matter alteration in patients with schizophrenia. Our result replicates a previous study reporting that there is a lack of negative correlation between age and caudate nucleus volume. We also suggest that the disease process of schizophrenia might interfere with normal aging.

Inter- and intraoperator reliability of brain tissue measures using magnetic resonance imaging

Abstract.Grey matter, white matter and cerebrospinal volume in the human brain were measured using magnetic resonance image analysis software BRAINS. Ten volunteers were scanned in the MR sequence (3D-SPGR; 1.5-mm slice thickness and T2 images; 3mm slice thickness). Two operators obtained ten volume measures of grey matter,white matter and cerebrospinal fluid (CSF) in the intracranial box, frontal box, temporal box, parietal box and occipital box. The same data set of ten scans was segmented and the volumes measured on a second occasion by one operator using the same procedure. The interoperator and intraoperator reliabilities for measures of the three brain tissues were very good, with reliability coefficients (intraclass correlation coefficients) ranging between 0.971 and 0.999. The segmentation and measurement are useful for volumetric studies in the human brain using BRAINS.

A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein.

A new strategy for organ allografts that does not require recourse to immunosuppressants is established in mice. The strategy includes sublethal (7 Gy) irradiation followed by the injection of donor bone marrow cells (BMCs) via the portal vein (P.V.) and organ allografts 1 day after irradiation. Irradiation doses (≤7 Gy) are found to allow the recipients to survive without the need to reconstitute the BMCs, as the recipient hematolymphoid cells can gradually recover. One hundred percent of recipients irradiated with 7 Gy followed by either P.V. or i.v. injection of donor BMCs accept organ allografts (the skin, pancreas, and adrenal glands) for more than 1 year. However, organ allograft survival rates decrease when irradiation doses are reduced; the skin graft survival rate of mice treated with 6.5 Gy and P.V. injection of BMCs is 79%, whereas that of mice treated with 6.5 Gy and i.v. injection is 50%, indicating that the P.V. injection of BMCs induces persistent tolerance more effectively than the i.v. injection. H-2 typing reveals that almost all the hematolymphoid cells (>98%) in the peripheral blood and hematolymphoid organs are donor-derived even 1 year after the treatment (7 Gy and P.V.). The T cells are tolerant to both donor-type and host-type MHC determinants. The major mechanism underlying the persistent tolerance induced by this strategy seems to be because of clonal deletion. This simple and safe strategy would be of great advantage for human organ transplantation.

Age-related changes of cornu ammonis 1 pyramidal neurons in gerbil transient ischemia

This study reports that postischemic apoptotic cell death of the hippocampal cornu ammonis (CA) 1 neurons is delayed in aged gerbils. Age‐related changes in the process of CA1 neuronal death following transient ischemia was studied. Two groups of Mongolian gerbils were used in this study, which compared adult (4‐month‐old) and aged (24‐month‐old) animals by hematoxylin–eosin stain, in situ nick‐end labeling (TUNEL method) and electron microscopy. In the process of neuronal death, neuronal loss of the aged group was histologically less severe than that of the adult group. TUNEL‐positive cells were found on days 3–5 after ischemia in the adult group, while they were still found on day 7 in the aged group. The apoptotic process of the aged group was delayed compared to the adult group. Furthermore, lipofuscin was ultrastructurally observed inside the apoptotic body 5 days after ischemia in CA1 pyramidal neurons of the aged group. It is likely that colocalization of lysosomal enzyme cathepsin D with lipofuscin might be associated with the age‐related alteration of lysosomal system in the neurons. Altogether these data suggest that age‐related lysosomal changes might affect the apoptotic cascade process in postischernic CA1 neurons.