White matter abnormalities in major depressive disorder with melancholic and atypical features: A diffusion tensor imaging study.

AIM: The DSM-IV recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes. METHODS: Subjects were 21 patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy and mean diffusivity value derived from DTI data on a voxel-by-voxel basis among the two diagnostic groups and healthy subjects. RESULTS: There were significant decreases of fractional anisotropy and increases of mean diffusivity in patients with MDD compared with healthy subjects in the corpus callosum, inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD. CONCLUSION: Our results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD.

Effect of L-theanine on sensorimotor gating in healthy human subjects.

AIM: l-Theanine (N-ethyl-l-glutamine) is an amino acid uniquely found in green tea. Growing evidence has suggested the possible effects of l-theanine on cognition. Previously, we found that l-theanine attenuates MK-801-induced deficit in prepulse inhibition (PPI) in mice. In this study, we examined the effect of l-theanine in increasing the PPI in healthy humans. METHODS: The subjects were 14 healthy adults who underwent PPI testing as a measure of sensorimotor gating 90 min after an oral intake of l-theanine (0, 200, 400, or 600 mg). PPI tests were done by examiners who were blind to the dose. RESULTS: The administration of 200 mg of l-theanine and that of 400 mg, but not 600 mg, significantly increased the % PPI compared to the baseline (0 mg). There was no significant relation between the dose of l-theanine and the startle magnitude or the habituation of startle response. The plasma concentrations of l-theanine correlated with the dose of l-theanine. CONCLUSION: The observed effect with 200-400 mg of l-theanine on PPI suggested that l-theanine at a particular dose range increases sensorimotor gating in humans.

Hypothalamic-pituitary-adrenal axis hyperactivity and brain differences in healthy women.

BACKGROUND: Previous studies have suggested that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis leads to brain changes. However, few studies have examined the whole brain configuration for an association with HPA axis activity. We examined the relationship between HPA axis activity and the whole brain configuration. METHODS: The subjects in this study were 34 healthy female volunteers. HPA axis activity was assessed by the dexamethasone/corticotropin-releasing hormone test. Structural volumes of the brain and diffusion tensor images were obtained, and correlations were evaluated voxel-wise. RESULTS: There was a significantly negative correlation between fractional anisotropy value and cortisol levels at 16:00 h (CL-2) in the anterior cingulum, left parahippocampus and right occipital region. There were significantly positive correlations between mean diffusivity value and CL-2 in the left hippocampus and bilateral parahippocampal regions. CONCLUSIONS: Our data suggest that reduced feedback of the HPA axis is associated with reduced neural connectivity throughout the brain, and such an association may be strong in the anterior cingulate, the hippocampus and the parahippocampal regions.

Discrimination between schizophrenia and major depressive disorder by magnetic resonance imaging of the female brain.

BACKGROUND: Although schizophrenia and major depressive disorder (MDD) differ on a variety of neuroanatomical measures, a diagnostic tool to discriminate these disorders has not yet been established. We tried to identify structural changes of the brain that best discriminate between schizophrenia and MDD on the basis of gray matter volume, ventricle volume, and diffusion tensor imaging (DTI). METHOD: The first exploration sample consisted of 25 female patients with schizophrenia and 25 females with MDD. Regional brain volumes and fractional anisotropy (FA) values were entered into a discriminant analysis. The second validation sample consisted of 18 female schizophrenia and 16 female MDD patients. RESULTS: The stepwise discriminant analysis resulted in correct classification rates of 0.80 in the schizophrenic group and 0.76 in MDD. In the second validation sample, the obtained model yielded correct classification rates of 0.72 in the schizophrenia group and 0.88 in the MDD group. CONCLUSION: Our results suggest that schizophrenia and MDD have differential structural changes in the examined brain regions and that the obtained discriminant score may be useful to discriminate the two disorders.

Differential diagnosis tool for parkinsonian syndrome using multiple structural brain measures.

Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and cerebellar subtype (MSA-C) from Parkinson's disease is difficult in the early stage of the disease. To identify the correlative pattern of brain changes for differentiating parkinsonian syndromes, we applied discriminant analysis techniques by magnetic resonance imaging (MRI). T1-weighted volume data and diffusion tensor images were obtained by MRI in eighteen patients with MSA-C, 12 patients with MSA-P, 21 patients with Parkinson's disease, and 21 healthy controls. They were evaluated using voxel-based morphometry and tract-based spatial statistics, respectively. Discriminant functions derived by step wise methods resulted in correct classification rates of 0.89. When differentiating these diseases with the use of three independent variables together, the correct classification rate was the same as that obtained with step wise methods. These findings support the view that each parkinsonian syndrome has structural deviations in multiple brain areas and that a combination of structural brain measures can help to distinguish parkinsonian syndromes.

Abnormalities of cerebral blood flow in multiple sclerosis: a pseudocontinuous arterial spin labeling MRI study.

Arterial spin labeling (ASL) is a noninvasive technique that can measure cerebral blood flow (CBF). To our knowledge, there is no study that examined regional CBF of multiple sclerosis (MS) patients by using this technique. The present study assessed the relationship between clinical presentations and functional imaging data in MS using pseudocontinuous arterial spin labeling (pCASL). Twenty-seven patients with MS and 24 healthy volunteers underwent magnetic resonance imaging and pCASL to assess CBF. Differences in CBF between the two groups and the relationships of CBF values with the T2-hyperintense volume were evaluated. Compared to the healthy volunteers, reduced CBF was found in the bilateral thalami and right frontal region of the MS patients. The volume of the T2-hyperintense lesion was negatively correlated with regional CBF in some areas, such as both thalami. Our results suggest that demyelinated lesions in MS mainly have a remote effect on the thalamus and that the measurement of CBF using ASL could be an objective marker for monitoring disease activity in MS.

Multimodal image analysis of sensorimotor gating in healthy women.

Prepulse inhibition (PPI) deficits have been reported in individuals with schizophrenia and other psychiatric disorders with dysfunction of the cortico-striato-pallido-thalamic circuit. The purpose of this study was to investigate the structural neural correlates of PPI by using magnetic resonance imaging (MRI) metrics. The subjects were 53 healthy women (mean age; 40.7±11.3 years). We examined the possible relationships between PPI and diffusion tensor imaging (DTI) metrics to estimate white matter integrity and gray matter volume analyzed using the DARTEL (diffeomorphic anatomical registration through exponentiated lie) algebra method. There were significant correlations between DTI metrics and PPI in the parahippocampal region, the anterior limb of the internal capsule, the ventral tegmental area, the thalamus and anterior thalamic radiations, the left prefrontal region, the callosal commissural fiber, and various white matter regions. There were also positive correlations between PPI and gray matter volume in the bilateral parietal gyri and the left inferior prefrontal gyrus at a trend level. The present study revealed evidence of a relationship between PPI and the integrity of white matter. This result was compatible with the previous suggestion that PPI would be modulated by the cortico-striato-thalamic-pallido-pontine circuit.

Discrimination of female schizophrenia patients from healthy women using multiple structural brain measures obtained with voxel-based morphometry.

AIM: Although schizophrenia and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between the two groups are low. To identify the correlative pattern of brain changes that best discriminate schizophrenia patients from healthy subjects, discriminant analysis techniques using voxel-based morphometry were applied. METHODS: The first analysis was conducted to obtain a statistical model that classified 105 female healthy subjects and 38 female schizophrenia patients. First, the differences in gray matter and cerebrospinal fluid volume between the patients and healthy subjects were evaluated using optimized voxel-based morphometry. Then, a discriminant analysis reflecting the results of this evaluation was adopted. The second analysis was performed to prospectively validate the statistical model by successfully classifying a new group that consisted of 23 female healthy subjects and 23 female schizophrenia patients. RESULTS: The use of these variables resulted in correct classification rates of 0.72 in the control subjects and 0.76 in the schizophrenia patients. In the second validation analysis using these variables, correct classification rates of 0.70 in the control subjects and 0.74 in the schizophrenia patients were achieved. CONCLUSION: Schizophrenia patients have structural deviations in multiple brain areas, and a combination of structural brain measures can distinguish between patients and controls.

Neuroimaging study in subjects at high risk of psychosis revealed by the Rorschach test and first-episode schizophrenia.

OBJECTIVE: There is increasing evidence of neuroanatomical pathology in schizophrenia, but it is unclear whether changes exist prior to disease onset. This study aimed to examine whether changes exist prior to disease onset, especially in the temporal lobes. METHODS: T1-weighted and diffusion tensor magnetic resonance imaging were performed on 9 first-episode schizophrenia patients, 10 patients who were at high risk of schizophrenia and 10 healthy controls. Voxel-based analysis using the normalised images of cortical volume data was examined, and the fractional anisotropy value at three component fibres of the temporal lobes, inferior longitudinal fasciculus, superior longitudinal fasciculus (SLF) and cingulum hippocampal part was compared among the three groups. RESULTS: There were statistically significant volume differences at the bilateral temporal lobe between the healthy subjects and high-risk group. Between the schizophrenic group and healthy subjects, statistically significant volume differences were detected at the bilateral temporal lobes and anterior cingulate cortex. The fractional anisotropy values of the SLF in the schizophrenic and high-risk groups were significantly lower than in the healthy subjects. CONCLUSION: Our findings indicate that some brain alterations may progress in patients at psychosis pre-onset, possibly because of disrupted developmental mechanisms, and these pathological changes may be predictive of functional outcome.

Progressive brain changes in schizophrenia: a 1-year follow-up study of diffusion tensor imaging.

OBJECTIVE: Recent cross-sectional studies suggest that brain changes in schizophrenia are progressive during the course of the disorder. However, it remains unknown whether this is a global process or whether some brain areas are affected to a greater degree. The aim of this study was to examine the longitudinal brain changes in patients with chronic older schizophrenia by magnetic resonance imaging (MRI). METHODS: Three-dimensional (3D) T1-weighted and diffusion tensor (DT) MRI were performed twice on each of 16 chronic older schizophrenia patients (mean age = 58.1 ± 6.7 years ) with an interval of 1 year between imaging sessions. To clarify the longitudinal morphological and white matter changes, volume data and normalised diffusion tensor imaging (DTI) metrics were compared between the first and follow-up studies using a paired t-test. RESULTS: Focal cortical volume loss was observed in the left prefrontal lobe and anterior cingulate on volumetric study. In addition, DTI metrics changed significantly at the bilateral posterior superior temporal lobes, left insula, genu of the corpus callosum and anterior cingulate. CONCLUSION: There are ongoing changes in the brains of schizophrenic patients during the course of the illness. Discrepancies between volume data and DTI metrics may indicate that the pattern of progressive brain changes varies according to brain region.