Yuki Oe

Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain

Transcranical direct current stimulation (tDCS) is a treatment known to ameliorate various neurological conditions and enhance memory and cognition in humans. tDCS has gained traction for its potential therapeutic value; however, little is known about its mechanism of action. Using a transgenic mouse expressing G-CaMP7 in astrocytes and a subpopulation of excitatory neurons, we find that tDCS induces large-amplitude astrocytic Ca2+ surges across the entire cortex with no obvious changes in the local field potential. Moreover, sensory evoked cortical responses are enhanced after tDCS. These enhancements are dependent on the alpha-1 adrenergic receptor and are not observed in IP3R2 (inositol trisphosphate receptor type 2) knockout mice, in which astrocytic Ca2+ surges are absent. Together, we propose that tDCS changes the metaplasticity of the cortex through astrocytic Ca2+/IP3 signalling.

Cerebral Blood Flow Modulation by Basal Forebrain or Whisker Stimulation Can Occur Independently of Large Cytosolic Ca2+ Signaling in Astrocytes

We report that a brief electrical stimulation of the nucleus basalis of Meynert (NBM), the primary source of cholinergic projection to the cerebral cortex, induces a biphasic cerebral cortical blood flow (CBF) response in the somatosensory cortex of C57BL/6J mice. This CBF response, measured by laser Doppler flowmetry, was attenuated by the muscarinic type acetylcholine receptor antagonist atropine, suggesting a possible involvement of astrocytes in this type of CBF modulation. However, we find that IP3R2 knockout mice, which lack cytosolic Ca2+ surges in astrocytes, show similar CBF changes. Moreover, whisker stimulation resulted in similar degrees of CBF increase in IP3R2 knockout mice and the background strain C57BL/6J. Our results show that neural activity-driven CBF modulation could occur without large cytosolic increases of Ca2+ in astrocytes.

Glycogen distribution in the microwave-fixed mouse brain reveals heterogeneous astrocytic patterns.

In the brain, glycogen metabolism has been implied in synaptic plasticity and learning, yet the distribution of this molecule has not been fully described. We investigated cerebral glycogen of the mouse by immunohistochemistry (IHC) using two monoclonal antibodies that have different affinities depending on the glycogen size. The use of focused microwave irradiation yielded well‐defined glycogen immunoreactive signals compared with the conventional periodic acid‐Schiff method. The IHC signals displayed a punctate distribution localized predominantly in astrocytic processes. Glycogen immunoreactivity (IR) was high in the hippocampus, striatum, cortex, and cerebellar molecular layer, whereas it was low in the white matter and most of the subcortical structures. Additionally, glycogen distribution in the hippocampal CA3‐CA1 and striatum had a ‘patchy’ appearance with glycogen‐rich and glycogen‐poor astrocytes appearing in alternation. The glycogen patches were more evident with large‐molecule glycogen in young adult mice but they were hardly observable in aged mice (1–2 years old). Our results reveal brain region‐dependent glycogen accumulation and possibly metabolic heterogeneity of astrocytes. GLIA 2016;64:1532–1545

A mindfulness-based stress management program and treatment with omega-3 fatty acids to maintain a healthy mental state in hospital nurses (Happy Nurse Project): study protocol for a randomized controlled trial

BackgroundIt is reported that nursing is one of the most vulnerable jobs for developing depression. While they may not be clinically diagnosed as depressed, nurses often suffer from depression and anxiety symptoms, which can lead to a low level of patient care. However, there is no rigorous evidence base for determining an effective prevention strategy for these symptoms in nurses. After reviewing previous literature, we chose a strategy of treatment with omega-3 fatty acids and a mindfulness-based stress management program for this purpose. We aim to explore the effectiveness of these intervention options for junior nurses working in hospital wards in Japan.Methods/DesignA factorial-design multi-center randomized trial is currently being conducted. A total of 120 nurses without a managerial position, who work for general hospitals and gave informed consent, have been randomly allocated to a stress management program or psychoeducation using a leaflet, and to omega-3 fatty acids or identical placebo pills. The stress management program has been developed according to mindfulness cognitive therapy and consists of four 30-minute individual sessions conducted using a detailed manual. These sessions are conducted by nurses with a managerial position. Participants allocated to the omega-3 fatty acid groups are provided with 1,200 mg/day of eicosapentaenoic acid and 600 mg/day of docosahexaenoic acid for 90 days.The primary outcome is the change in the total score of the Hospital Anxiety and Depression Scale (HADS), determined by a blinded rater via the telephone at week 26. Secondary outcomes include the change in HADS score at 13 and 52 weeks; presence of a major depressive episode; severity of depression, anxiety, insomnia, burnout, and presenteeism; utility scores and adverse events at 13, 26 and 52 weeks.DiscussionAn effective preventive intervention may not only lead to the maintenance of a healthy mental state in nurses, but also to better quality of care for inpatients. This paper outlines the background and methods of a randomized trial that evaluates the possible additive value of omega-3 fatty acids and a mindfulness-based stress management program for reducing depression in nurses.Trial registrationClinicaltrials.gov: NCT02151162 (registered on 27 May 2014).

Validity and clinical interpretability of Overall Anxiety Severity And Impairment Scale (OASIS).

BACKGROUND The Overall Anxiety Severity and Impairment Scale is a brief generic measure for anxiety that encompasses frequency and intensity as well as behavioral and functional aspects of anxiety. This study was conducted to elucidate aspects of reliability, validity, and interpretability, such as equivalence of factor loadings across non-clinical and clinical populations, convergence and discriminance of related variables, and performance of detecting diagnostic and medical status of anxiety disorders. METHODS Non-clinical and clinical Japanese populations were taken from a panelist pool registered with an internet survey company (total n=2830; 619 panic disorder, 576 for social anxiety disorder, 645 for obsessive-compulsive disorder, a 619 for major depressive disorder, and 371 for non-disorder panelists). Conventional measures of anxiety, depression, mental health and measures for discriminant validity were administered in addition to OASIS. RESULTS Exploratory and confirmatory factor analyses indicated good fit to data for the one-factor model of OASIS. Multi-group confirmatory factor analysis showed the equivalence of the factor loadings between those of non-clinical and clinical subsamples. The OASIS reliability was confirmed by internal consistency and test-retest coefficients. Receiver operating characteristic curve analyses showed that OASIS and conventional anxiety measures have fair performance for detecting diagnostic and medical status as anxiety disorders. LIMITATIONS Participants were limited to a Japanese population of people who had registered themselves at an internet survey company. CONCLUSIONS Along with useful information to interpret OASIS, the results suggest the reliability and validity of OASIS in Japanese populations. These results also suggest cross-cultural validity.

Assessing Depression Related Severity and Functional Impairment: The Overall Depression Severity and Impairment Scale (ODSIS)

Background The Overall Depression Severity and Impairment Scale (ODSIS) is a brief, five-item measure for assessing the frequency and intensity of depressive symptoms, as well as functional impairments in pleasurable activities, work or school, and interpersonal relationships due to depression. Although this scale is expected to be useful in various psychiatric and mental health settings, the reliability, validity, and interpretability have not yet been fully examined. This study was designed to examine the reliability, factorial, convergent, and discriminant validity of a Japanese version of the ODSIS, as well as its ability to distinguish between individuals with and without a major depressive disorder diagnosis. Methods From a pool of registrants at an internet survey company, 2830 non-clinical and clinical participants were selected randomly (619 with major depressive disorder, 619 with panic disorder, 576 with social anxiety disorder, 645 with obsessive–compulsive disorder, and 371 non-clinical panelists). Participants were asked to respond to the ODSIS and conventional measures of depression, functional impairment, anxiety, neuroticism, satisfaction with life, and emotion regulation. Results Exploratory and confirmatory factor analysis of three split subsamples indicated the unidimensional factor structure of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor loadings between non-clinical and clinical subsamples. The ODSIS also showed excellent internal consistency and test–retest intraclass correlation coefficients. Convergence and discriminance of the ODSIS with various measures were in line with our expectations. Receiver operating characteristic curve analyses showed that the ODSIS was able to detect a major depressive syndrome accurately. Conclusions This study supports the reliability and validity of ODSIS in a non-western population, which can be interpreted as demonstrating cross-cultural validity.

cognitive behavioral therapy for depression in Japanese Parkinson's disease patients: a pilot study

Objectives This study evaluated the feasibility of cognitive behavioral therapy (CBT) for Japanese Parkinson’s disease (PD) patients with depression. To increase cultural acceptability, we developed the CBT program using manga, a type of Japanese comic novel. Methods Participants included 19 non-demented PD patients who had depressive symptoms (GRID-Hamilton Rating Scale for Depression score ≥8). A CBT program comprising six sessions was individually administered. We evaluated the feasibility and safety of the CBT program in terms of the dropout rate and occurrence of adverse events. The primary outcome was depressive symptom reduction in the GRID-Hamilton Rating Scale for Depression upon completion of CBT. Secondary outcomes included changes in the self-report measures of depression (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale-Depression), anxiety (Hospital Anxiety and Depression Scale-Anxiety, State and Trait Anxiety Inventory, Overall Anxiety Severity and Impairment Scale), functional impairment, and quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey). Results Of the 19 participants (mean age =63.8 years, standard deviation [SD] =9.9 years; mean Hohen–Yahr score =1.7, SD =0.8), one patient (5%) withdrew. No severe adverse event was observed. The patients reported significant improvements in depression (Hedges’ g =−1.02, 95% confidence interval =−1.62 to −0.39). The effects were maintained over a 3-month follow-up period. Most of the secondary outcome measurements showed a small-to-moderate but nonsignificant effect size from baseline to post-intervention. Conclusion This study provides preliminary evidence that CBT is feasible among Japanese PD patients with depression. Similar approaches may be effective for people with PD from other cultural backgrounds. The results warrant replication in a randomized controlled trial.

Cognitive behavioral therapy for irritable bowel syndrome

Irritable bowel syndrome (IBS) is the disease in which abdominal pain and related bowel movements such as diarrhea and constipation persist. IBS is classified in chronic primary pain as well as fibromyalgia and non–specific low back pain. Psychological intervention is important in the treatment of refractory IBS. In particular, cognitive behavioral therapy (CBT) which is a kind of psychotherapy has attracted attention recently. We have developed a Japanese version of the cognitive behavioral therapy protocol for IBS which called CBT–IE and have been practicing on IBS patients. When conducting CBT for patients with chronic pain, including IBS, it is important not to target the disappearance of symptoms, but to aim for improving the quality of life.

Reliability and validity of the Japanese version of the Emotion Regulation Skills Questionnaire

BACKGROUND The Emotion Regulation Skills Questionnaire (ERSQ) comprehensively assesses nine aspects of emotion regulation skills: awareness, clarity, sensation, understanding, compassionate self-support, modification, acceptance, tolerance, and readiness to confront. However, it is unknown about the levels of emotion regulation skills in various mental disorders, and its cross-cultural validity. We developed a Japanese version of the ERSQ, then examined its validity and reliability in clinical and non-clinical populations. METHODS In an Internet-based survey, 2684 participants (406 with MDD, 198 with PD, 116 with SAD, 66 with OCD, 636 with comorbid MDD and ≥1 anxiety disorder, and 99 with comorbid anxiety disorders; 1163 non-clinical sample) answered the ERSQ, diagnostic status, and measures of mindfulness, emotion regulation, behavioral activation, psychological distress, and life satisfaction. RESULTS Confirmatory factor analysis (CFA) replicated the theoretical nine-factor structure of the original ERSQ. Higher-order factor analysis model assuming two second-order factors and nine first-order factors also showed adequate fit to the data, suggesting the factorial validity of the scale. Analyses of multi-group CFA indicated the equivalence of factor loadings across clinical and non-clinical subsamples. The levels of internal consistency and time stability were sufficient. Convergent validity of the scale was also confirmed for most of external criteria. Character on the emotion regulation skills for each diagnostic group was depicted. LIMITATIONS Internet survey of samples with limited disorders, with self-reported diagnoses, may limit generalizability. CONCLUSIONS The Japanese version of the ERSQ showed adequate reliability and validity.