Mahito Kimura

Assessment of the Dexamethasone/CRH Test as a State-Dependent Marker for Hypothalamic-Pituitary-Adrenal (HPA) Axis Abnormalities in Major Depressive Episode: A Multicenter Study

There is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in depression. Growing evidence has suggested that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA axis abnormalities. We organized a multicenter study to assess the DEX/CRH test as a state-dependent marker for major depressive episode in the Japanese population. We conducted the DEX/CRH test in 61 inpatients with major depressive episode (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)) and 57 healthy subjects. In all, 35 patients were repeatedly assessed with the DEX/CRH test on admission and before discharge. The possible relationships between clinical variables and the DEX/CRH test were also examined. Significantly enhanced pituitary–adrenocortical responses to the DEX/CRH test were observed in patients on admission compared with controls. Such abnormalities in patients were significantly reduced after treatment, particularly in those who underwent electroconvulsive therapy (ECT) in addition to pharmacotherapy. Age and female gender were associated with enhanced hormonal responses to the DEX/CRH test. Severity of depression correlated with DEX/CRH test results, although this was explained, at least in part, by a positive correlation between age and severity in our patients. Medication per se was unrelated to DEX/CRH test results. These results suggest that the DEX/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities in major depressive episode during treatment. Restoration from HPA axis abnormalities occurred with clinical responses to treatment, particularly in depressed patients who underwent ECT.

Effects of propofol anesthesia on cognitive recovery of patients undergoing electroconvulsive therapy

The effects of different doses of propofol on post‐electroconvulsive therapy (ECT) cognitive recovery were evaluated together with the effects on seizure duration and hemodynamic changes during ECT in 15 depressive patients. Propofol attenuated the increase in arterial blood pressure and heart rate in a dose‐dependent manner compared with thiamylal. Propofol showed a clinically significant anticonvulsant effect during ECT in a dose‐dependent manner. There were no significant differences among the four different induction groups in the mean recovery time from anesthesia, however, a low dose of propofol suppressed the early recovery of cognitive function. For early cognitive recovery after ECT, a deep anesthetic level is necessary when the traditional ECT apparatus is used which produces sine curve wave stimuli.

Landiolol attenuates acute hemodynamic responses but does not reduce seizure duration during maintenance electroconvulsive therapy

Abstract  Maintenance electroconvulsive therapy (mECT) is an outpatient procedure that requires further consideration in terms of management of ambulatory anesthesia. Although many adjunctive drugs for stabilizing hemodynamic changes during ECT have been reported, side‐effects of these drugs may delay recovery and discharge from hospital. The effects of landiolol, a novel ultra‐short‐acting β‐adrenergic blocker, have been measured on seizure duration, hemodynamic changes, recovery from anesthesia, and cognitive function during mECT under propofol anesthesia. A total of 10 patients with depression in the remission phase, were studied in a randomized, double‐blind, placebo‐controlled, crossover manner. Administration of 0.1 mg/kg of landiolol immediately before anesthesia significantly blunted the increase in heart rate and blood pressure during convulsions compared with placebo; landiolol was not associated with excessive hypotension or bradycardia. Landiolol did not affect seizure duration, recovery from anesthesia, or cognitive function before or after ECT. These results suggest that landiolol can be used effectively and safely during mECT.

Comparison of regional gray matter volume abnormalities in Alzheimer׳s disease and late life depression with hippocampal atrophy using VSRAD analysis: A voxel-based morphometry study

Previous voxel-based morphometry (VBM) studies revealed that hippocampal volume loss in patients with late life depression (LLD) is associated with cognitive impairment and a higher risk for dementia. However, LLD patients can experience hippocampal atrophy without cognitive impairment. Thus, while LLD and AD can show comparable hippocampal atrophy, they may encompass different neuropathological changes. Using VBM, we therefore investigated differences in regional gray matter changes in 17 late-onset LLD patients and 21 AD patients (without a history of LLD) who exhibited comparably severe atrophy of the entorhinal cortex and the parahippocampal gyrus on MRI scans for voxel-based specific regional analysis system for AD (VSRAD). Relative to the VSRAD database for healthy individuals, significant atrophy was observed in mesial temporal lobe structures and the anterior cingulate cortex in both groups. Atrophy of the posterior cingulate cortex and precuneus was observed only in the AD group. Comparisons of gray matter volume by multivariate analysis of variance revealed significantly reduced volume of the right middle and inferior temporal gyrus, uncus, posterior cingulate cortex, and precuneus in the AD group only, suggesting impairment of different networks in AD and LLD. Indeed, structural changes in the posterior part of the default-mode network are believed to be associated with cognitive impairments specific to AD.

Glial cell line-derived neurotrophic factor-mediated enhancement of noradrenergic descending inhibition in the locus coeruleus exerts prolonged analgesia in neuropathic pain

The locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line‐derived neurotrophic factor (GDNF), a well‐established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC.

A fundamental bias in calculating dimensions from finite data sets

Abstract One bias inherent in calculating dimension for limited time-series data is investigated. The bias is derived from the fluctuation of the distribution of measures in the phase space and distorts the scaling with respect to each reference point to be concave up or down. These distortions are pronounced for the experimental data whose number of points is not sufficient and whose scaling region is restricted to a relatively small interval. It is possible that the Grassberger–Procaccia algorithm and all its modified ones are affected by the bias. We evaluate the distortion quantitatively and show the procedure required for the correction of the bias taking the case of an electroencephalogram (EEG).

Oral cenesthopathy examined by Rorschach test

Abstract  Experience of abnormal pains and unusual sensations in the mouth without a somatic base, for example abnormal mucus secretion, pulling sensation on the jaw or teeth, or a vibrating sensation, is termed ‘oral cenesthopathy’. Psychological factors were investigated in terms of cognitive functions and personality tendencies, using Rorschach test in 28 patients with this condition (three men and 25 women). In oral cenesthopathy patients (i) the processing of new information is inefficient; (ii) the necessary resources for social adaptation are lacking, emotional control is inadequate, and uncomfortable emotions are expressed less; and (iii) with regard to interpersonal interaction, less interest is shown in others, trust in others is diminished, and they tend to have a higher Coping Deficit Index.

Two cases of emotional disorder after middle cerebral artery infarction showing distinct responses to antidepressant treatment

Many emotional disturbances such as post-stroke depression (PSD) and emotional incontinence (EI) commonly occur following cerebrovascular events. The efficacy of antidepressants for these conditions has been established but their comorbid treatment has not been well characterized. In the current study, the authors describe two cases of post-stroke emotional dysregulation; one case with EI; and the other with EI complicated by PSD. The authors describe their differential responses to treatment. Case 1 developed EI after an infarct due to occlusion of the penetrating branches of the left middle cerebral artery (MCA). Case 2 developed both PSD and EI after right MCA stem occlusion. Both patients were initially treated with the selective serotonin reuptake inhibitor (SSRI) paroxetine. Case 1 reacted promptly to SSRI treatment. However, Case 2 had only a partial response to paroxetine, even after many months of treatment. Adjunctive therapy with low-dose aripiprazole was eventually added, resulting in complete improvement of both EI and PSD after 2 additional months of treatment. Thus, Case 2 required a different treatment strategy than Case 1. These findings suggest that aripiprazole adjunctive therapy could be effective for some complex post-stroke emotional disorders.

Changes in regional cerebral blood flow on recovery from depression—comparison of vascular depression and non-vascular depression

Abstract Cerebrovascular or vascular change is frequent in elderly patients with depression. The concept of vascular depression (VD) has been a topic of interest in neuropsychiatry. During the last decade, functional neuroimaging studies have reported that recovery from depression was associated with increased regional cerebral blood flow (rCBF) in specific regions. However, the majority of studies have been confined to depression without cerebrovascular changes. Therefore, this study was undertaken to examine changes in rCBF on recovery from vascular depression. We measured rCBF in nine patients with ‘vascular depression’ and 11 patients with ‘non-vascular depression’ using 123I-IMP single photon emission computed tomography (SPECT) during illness and after recovery. The results showed that VD has significantly lower mean rCBF than non-VD during both depressed and remitted state, localized to the left anterior frontal region. This suggested that persisting left frontal hypoperfusion may lead to longer duration or higher frequency of relapse. Both VD and non-VD showed significantly higher mean rCBF in remitted state than in depressed state, especially left anterior temporal rCBF correlated with recovery from depression. This suggested that left temporal activity might be a state or episode-dependent marker for both VD and non-VD

Acute Poststroke Depression Is Associated with Thalamic Lesions and Clinical Outcomes: A Case–Control Study

BACKGROUND We investigated the role of acute-phase stroke lesions and patient characteristics in poststroke depression (PSD) and its effect on the clinical outcome. PATIENTS AND METHODS Five and 30 days after admission, 175 patients self-reported their depressive symptoms on the Patient Health Questionnaire-9. We compared the clinical characteristics and outcomes in patients with (n = 41) and without PSD (n = 134). Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS); the modified Rankin Scale (mRS) was used to determine the functional outcome. RESULTS There was no significant difference between patients with and without PSD in the age, gender ratio, lesion side, and the history of hypertension, diabetes mellitus, alcohol and tobacco use, and previous stroke. Thalamic lesions were significantly associated with PSD (P = .03), although there was no significant difference in both the NIHSS score and the final mRS score of patients with thalamic lesions. Backward stepwise logistic regression analysis showed that a higher NIHSS score and thalamic lesions were independent predictors of PSD. Total hospitalization was significantly longer in patients with PSD. At the time of admission, the NIHSS score was significantly higher in patients who developed moderate to severe PSD than in those with mild PSD or without PSD. CONCLUSIONS PSD in the acute phase was associated with thalamic lesions and severe stroke. Hospitalization was significantly longer in patients with PSD and their functional disability was more severe, suggesting that PSD played a role in the unsatisfactory results of poststroke rehabilitation.