Toshihiko Hamada

Individual Trait Anxiety Levels Characterizing the Properties of Zen Meditation

Meditation is a specific consciousness state in which deep relaxation and increased internalized attention coexist. There have been various neurophysiological studies on meditation. However, the personal predispositions/traits that characterize the properties of meditation have not been adequately studied. We analyzed changes in neurophysiological parameters [EEG coherence and autonomic nervous activity using heart rate variability (HRV) as an index] during Zen meditation, and evaluated the results in association with trait anxiety (assessed by Spielberger’s State-Trait Anxiety Inventory) in 22 healthy adults who had not previously practiced any form of meditation. During meditation, in terms of mean values in all subjects, an increase in slow alpha interhemispheric EEG coherence in the frontal region, an increase in high-frequency (HF) power (as a parasympathetic index of HRV), and a decrease in the ratio of low-frequency to HF power (as a sympathetic index of HRV) were observed. Further evaluation of these changes in individuals showed a negative correlation between the percent change (with the control condition as the baseline) in slow alpha interhemispheric coherence reflecting internalized attention and the percent change in HF reflecting relaxation. The trait anxiety score was negatively correlated with the percent change in slow alpha interhemispheric coherence in the frontal region and was positively correlated with the percent change in HF. These results suggest that lower trait anxiety more readily induces meditation with a predominance of internalized attention, while higher trait anxiety more readily induces meditation with a predominance of relaxation.

Associations between trait anxiety, insulin resistance, and atherosclerosis in the elderly: A pilot cross-sectional study

Anxiety has been shown to be associated with cardiovascular disease. Atherosclerosis is responsible for the vast majority of cardiovascular events. Recent evidence is accumulating to show that insulin resistance (IR) plays a central role in determining the clinical manifestations of established atherosclerotic lesions. The current preliminary study aimed to investigate the associations between trait anxiety, IR, and atherosclerotic progression in healthy elderly subjects with normal fasting glucose and without metabolic syndrome. Thirty-five healthy elderly subjects (19 males and 16 females, mean age 64.5+/-4.7 years) were enrolled in this study. Trait anxiety was measured using a questionnaire corresponding to the trait anxiety scale taken from the State and Trait Anxiety Inventory. The homeostasis model assessment (HOMA-R) and plasma leptin-to-adiponectin ratio (L/A ratio), which are convenient IR indexes calculated from fasting blood sampling, were examined. As measurements of atherosclerotic progression, we performed two ultrasound methods, namely brachial artery flow-mediated dilation (FMD), an endothelial function assessment quantitatively reflecting the endothelium-dependent vasodilation responses following hyperemia, and measurement of carotid intima-media thickness (IMT). The severity of trait anxiety was positively associated with HOMA-R and L/A ratio, and negatively associated with the percent change of brachial artery FMD (%FMD). HOMA-R and L/A ratio were positively associated with carotid IMT, and L/A ratio was negatively associated with %FMD. These data showed the associations between trait anxiety, IR indexes and endothelial dysfunction or atherosclerotic progression. This pilot study, with a cross-sectional design, supports the promising role of IR for clarifying the pathophysiological mechanism by which anxiety contributes to an increasing risk of atherosclerosis.

Multifractal analysis of deep white matter microstructural changes on MRI in relation to early-stage atherosclerosis

Multifractal analysis based on generalized concepts of fractals has been applied to evaluate biological tissues composed of complex structures. This type of analysis can provide a precise quantitative description of a broad range of heterogeneous phenomena. Previously, we applied multifractal analysis to describe heterogeneity in white matter signal fluctuation on T2-weighted MR images as a new method of texture analysis and established Deltaalpha as the most suitable index for evaluating white matter structural complexity (Takahashi et al. J. Neurol. Sci., 2004; 225: 33-37). Considerable evidence suggests that pathophysiological processes occurring in deep white matter regions may be partly responsible for cognitive deterioration and dementia in elderly subjects. We carried out a multifractal analysis in a group of 36 healthy elderly subjects who showed no evidence of atherosclerotic risk factors to examine the microstructural changes of the deep white matter on T2-weighted MR images. We also performed conventional texture analysis, i.e., determined the standard deviation of signal intensity divided by mean signal intensity (SD/MSI) for comparison with multifractal analysis. Next, we examined the association between the findings of these two types of texture analysis and the ultrasonographically measured intima-media thickness (IMT) of the carotid arteries, a reliable indicator of early carotid atherosclerosis. The severity of carotid IMT was positively associated with Deltaalpha in the deep white matter region. In addition, this association remained significant after excluding 12 subjects with visually detectable deep white matter hyperintensities on MR images. However, there was no significant association between the severity of carotid IMT and SD/MSI. These results indicate the potential usefulness of applying multifractal analysis to conventional MR images as a new approach to detect the microstructural changes of apparently normal white matter during the early stages of atherosclerosis.

Association between trait anxiety and endothelial function observed in elderly males but not in young males.

BACKGROUND AND OBJECTIVES Endothelial function plays a key role in determining the clinical manifestations of atherosclerosis. Recent reports have shown that healthy elderly subjects with higher trait anxiety tend to have heightened risks of atherosclerotic lesions and cardiovascular disease. The present study was intended to examine whether an association exists between trait anxiety and endothelial function in healthy young and elderly subjects. METHODS This study examined 26 young male and 30 elderly male subjects using brachial artery flow-mediated dilation (FMD) - a non-invasive ultrasound method - to evaluate endothelial function by measuring the dilation responses of vascular smooth muscle to the nitric oxide produced by endothelial cells following hyperemia. RESULTS A significant negative correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and the percentage change of FMD (%FMD) in the elderly subjects, but not in the young subjects. The elderly subjects showed significantly lower %FMD than the young subjects. CONCLUSION These results suggest the possibility that trait anxiety is a predisposing risk factor for cardiovascular damage that might, over a long period, induce atherosclerotic lesions.

Mitral valve prolapse and autonomic function in panic disorder.

We investigated the significance of mitral valve prolapse (MVP) and autonomic function in 121 patients diagnosed with panic disorder (PD). The incidence of MVP was higher in these patients (32.2%) than in the healthy controls (16.7%), but the difference was not significant. In the group with PD accompanied by depression, the MVP rate was 58.1%, significantly higher than the value of 25.7% observed in the PD patients without depression. The severity of MVP was mild; nearly all of the cases were silent, without cardiac murmur, and there was no problem with the left ventricular function. The coefficient of variation for R‐R intervals on electrocardiograms (CV R‐R) was smaller in patients with PD than in healthy controls. The CV R‐R of PD patients was significantly lower in the group with MVP than in the group without MVP, suggesting a strong association with the parasympathetic nervous system. Since the CV R‐R tended to decrease in the presence of depression, involvement of the parasympathetic nervous system was inferred.

The clinical significance of abnormal diurnal blood pressure variation in healthy late middle-aged and older adults

Objective. A fall in nocturnal blood pressure (BP) is generally observed in normotensive subjects as well as in those with mild to moderate essential hypertension, regardless of the level of daytime BP. Among elderly hypertensive subjects, extreme‐dippers with a marked nocturnal fall in BP as well as non‐dippers with nocturnal fall absence are at increased risk for cardiovascular and cerebrovascular complications. However, the relationship between these abnormal diurnal BP variation patterns in normotensive elderly subjects has not been investigated. Methods. We classified 45 healthy late middle‐aged and older adults into three groups according to the nocturnal systolic BP fall pattern examined by 24‐h ambulatory BP monitoring (dipper, non‐dipper and extreme‐dipper), and compared the parameters of initial atherosclerosis, endothelial function and autonomic function. As a parameter of atherosclerotic factors, the intima‐media thickness (IMT) of the carotid artery was examined, and as a parameter of endothelial function, brachial artery endothelium‐dependent flow‐mediated dilation (FMD) was ultrasonographyically measured. Autonomic function was assessed by power spectral analysis of heart rate variability (HRV). Results. No difference was observed in the severity of IMT between the three groups. The percent change of FMD in subjects in the extreme‐dipper group was significantly lower than that of subjects in the dipper group, indicating that extreme‐dippers in healthy elderly subjects may be associated with endothelial dysfunction. Also, HRV due to sympathetic modulation of subjects in the extreme‐dipper group was significantly higher than that of subjects in the dipper and non‐dipper groups, suggesting the activation of sympathetic tone. Conclusion. In healthy elderly subjects, the extreme‐dipper type may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than the dipper type.

Frontal Intermittent Delta Activity in Schizophrenic Patients Receiving Antipsychotic Drugs

FIRDA was found in 14 EEGs recorded from 338 schizophrenic patients receiving antipsychotic drugs, although they showed no FIRDA in the baseline EEG. The daily dose of antipsychotic drugs when FIRDA was found was larger than when FIRDA disappeared. FIRDA was assumed to be induced by relatively high doses of antipsychotic drugs. Thus, the effect of antipsychotic drugs should be added to the list of differential diagnoses associated with FIRDA. FIRDA did not correlate with the baseline psychopathology of schizophrenic patients. Patients without FIRDA tended to respond poorly to antipsychotic drugs in terms of negative symptoms. Improvement of positive symptoms in FIRDA patients was not as remarkable as in patients without FIRDA.

Abnormal Nocturnal Blood Pressure Fall in Senile-Onset Depression with Subcortical Silent Cerebral Infarction

Recent studies have shown that the complication rate of silent cerebral infarction (SCI) in patients with geriatric depression increases with the age at the onset of depression. This study investigated the cardiovascular factors involved in the development of SCI in geriatric depression. Thirty-six patients with geriatric depression were classified according to the age at onset into 16 who developed depression at the age of <50 years (early-onset group) and 20 who developed depression at the age of ≧50 years (late-onset group). The incidence of SCI assessed by subcortical hyperintensity on MRI images, office blood pressure (BP), nocturnal systolic BP fall pattern examined by 24-hour ambulatory BP monitoring, and the severity of carotid atherosclerosis examined by B-mode ultrasonography were compared between the two groups. Furthermore, the association between the presence or absence of SCI and the nocturnal systolic BP fall pattern or the severity of carotid atherosclerosis was evaluated. The SCI complication rate was higher in the late-onset group (55.0%) than in the early-onset group (18.7%). The office BP and mean 24-hour BP did not differ significantly between the two groups. Abnormal nocturnal systolic BP fall patterns were observed in 85.0% (nondipper type showing a fall of <10% in 60.0%, extreme-dipper type showing a fall of ≧20% in 25.0%) in the late-onset group, which was significantly higher than the incidence in the early-onset group (18.7%). No significant difference was observed in any parameter of carotid atherosclerosis between the two groups. In addition, the patients with SCI more frequently showed abnormal nocturnal systolic BP fall patterns than those without SCI. These results suggest that abnormal nocturnal BP fall patterns appear to be involved in the development of SCI in senile-onset depression.

White coat phenomenon, anxiety and endothelial function in healthy normotensive elderly subjects.

Objective. The white coat phenomenon (WCP) is a blood pressure (BP) elevation specifically observed in the clinical setting. Though WCP has been suggested to associate with emotional responses such as anxiety or with cardiovascular complications, its pathogenesis and clinical significance are unclear. We studied the possible association between WCP and anxiety or vascular function in normotensive elderly subjects without major cardiovascular risk factors. Methods. As a parameter of anxiety, the State and Trait Anxiety Inventory (STAI) was used. WCP was evaluated by calculating the difference between the clinic BP and mean daytime ambulatory BP. As parameters of vascular function, brachial artery endothelium‐dependent flow‐mediated dilation (FMD) and the endothelium‐independent dilation response to sublingual glyceryl trinitrate (GTN) were measured using high‐resolution ultrasound. Results. Using confounding factors as covariates, no association was observed between WCP and the STAI‐trait or STAI‐state score. There was a significant negative association between WCP and the percent change of FMD but no association between WCP and the percent change of GTN. Conclusion. WCP in the healthy normotensive elderly subjects may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than anxiety.