Hitoshi Miyaoka

THE PATIENT HEALTH QUESTIONNAIRE, JAPANESE VERSION : VALIDITY ACCORDING TO THE MINI-INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW-PLUS

To validate the Japanese version of the Patient Health Questionnaire against the Mini-International Neuropsychiatric Interview-Plus in Japan 131 patients in 4 primary care settings and 2 general hospital settings participated. These patients completed the Patient Health Questionnaire and returned it to their physician within 48 hr. Subsequently, the subjects underwent a diagnostic evaluation interview based on the Mini-International Neuropsychiatric Interview-Plus by an interviewer blind to the results of the Patient Health Questionnaire screening. The Patient Health Questionnaire diagnosis was characterized using kappa values between 0.70 and 1.0 for Somatoform Disorder, Major Depressive Disorder, Panic Disorder, Bulimia Nervosa, Alcohol Abuse/Dependence, and Premenstrual Disorder. Sensitivities, specificities, and negative predictive values were very good (between 0.84 and 1.0) for the first 4 diagnoses but not Alcohol Abuse/Dependence or Premenstrual Disorder, as were the Positive predictive values (between 0.78 and 1.0). Findings show very good concordance of the Japanese version of the Patient Health Questionnaire with the Japanese version of the Mini-International Neuropsychiatric Interview–Plus.

Amygdalic levels of dopamine and serotonin rise upon exposure to conditioned fear stress without elevation of glutamate

Conditioned fear is an artificial stress, induced by a stimulus, such as a tone, that does not elicit fear in nature. This fear response is acquired by experimental animals when tone is combined with an unconditioned stimulus, such as electrical foot shock. The amygdala is considered to be the area involved in acquisition, consolidation and recall of fear. A series of previous pharmacological studies showed antagonists of dopamine D1 and D2, glutamate N-methyl-D-asparatate and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors to prevent the acquisition of conditioned fear. However, little is known about the types of neurotransmitters released when conditioned fear is acquired and recalled. The present study was designed to continuously monitor changes in extracellular levels of glutamate, dopamine and serotonin in the amygdala, at the acquisition of conditioned fear on Day 1 and at fear recall in response to a tone as a conditioned stimulus on Day 2, using the in vivo microdialysis method. Glutamate was elevated only on Day 1, while dopamine and serotonin rose on both days. The periods of elevated dopamine and serotonin were longer on Day 1 than on Day 2. These results suggest that greater amounts of glutamate, dopamine and serotonin are necessary for acquisition than for recall of conditioned fear.

The experience of burnout among home caregivers of patients with dementia: relations to depression and quality of life.

Caregivers of patients with dementia often experience chronic and emotional strains, which may lead to emotional exhaustion and burnout. The objective of this study was to examine the relationships between burnout, depression, and quality of life in home caregivers of patients with dementia. The participants were 84 home caregivers (39 male; 45 female), and they were asked to complete three questionnaires: the Beck Depression Inventory Second Edition (BDI-II), the WHO Quality of Life 26 (WHO-QOL26), and the Pines Burnout Measure (BM). Results from a bivariate correlation showed that BM scores significantly correlated with the scores on BDI-II and WHO-QOL26. Results from ANOVA comparing the level of burnout with the scores on BDI-II and WHO-QOL26 revealed that there were differences between the burnout groups and the scores on BDI-II and WHO-QOL26. The higher levels of burnout were found to correspond to higher levels of depressive symptoms and lower QOL. These findings suggest that caregiver intervention to reduce burnout might benefit from strategies to reduce depression and increase QOL.

Depression and associated factors of informal caregivers versus professional caregivers of demented patients

Abstract  To examine the differences in depressive state and associated factors between informal and professional caregivers, a cross‐sectional study was carried out in 23 informal home‐based caregivers of demented patients, 24 professional caregivers working in the dementia ward of a psychiatric hospital, and 31 controls. Measurements included severity of dementia (Clinical Dementia Rating Scale, Mini Mental State Examination, MMSE) and levels of caregivers depression (Beck Depression Inventory; BDI), care burden (Zarit Caregiver Burden Interview; ZBI) and quality of life (World Health Organization–Quality of Life‐26, WHO‐QOL26). Informal caregivers had the highest BDI score and ZBI and the lowest QOL among the three studied groups. Regarding informal caregivers, there was a strong positive correlation between BDI and ZBI scores. The BDI and ZBI scores were significantly high when patients exhibited behavioral problems. The four WHO‐QOL categories (physical domain, psychological domain, social relationships and environment) had a strong negative correlation with BDI. Regression analysis demonstrated that the psychological domain points of WHO‐QOL, role strain factor of ZBI and MMSE score were significantly associated with BDI. Regarding professional caregivers, their BDI score had a strong negative correlation with the physical and psychological domains and environment categories of WHO‐QOL. Regression analysis demonstrated that their BDI score was significantly associated with the psychological domain and environment. It is thus very important to provide sufficient social care services and/or personal support to informal caregivers.

A Single Amino Acid Mutation in SNAP-25 Induces Anxiety-Related Behavior in Mouse

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC) phosphorylates Ser187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser187 of SNAP-25 with Ala using “knock-in” technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects.

Enhancement of delayed release of dopamine in the amygdala induced by conditioned fear stress in methamphetamine-sensitized rats

Behavior during conditioned fear stress, a form of psychological stress, and the release of dopamine in the amygdala were measured over time using methamphetamine-sensitized rats, which are considered to be a model of hypersensitivity and vulnerability to emotional stress associated with stimulant-induced psychosis and schizophrenia. Dopamine release in the amygdala showed a delayed increase following completion of freezing behavior induced by conditioned fear stress regardless of the presence or absence of methamphetamine-sensitization. Since methamphetamine treatment did not lower the basal level of dopamine in the amygdala, under the conditions of this study, methamphetamine was presumed not to show neurotoxicity. On the other hand, basal dopamine levels after 15 h of repeated electric foot shock were about 40% lower than those in the control group (p<0.0002). In addition, dopamine release following conditioned fear stress in animals repeatedly treated with methamphetamine increased significantly from 40 to 100 min after conditioned fear stress while the duration of freezing behavior or latency of the appearance of grooming were not different from those in the control group. The above results suggested that delayed dopamine release in the amygdala is a phenomenon strongly associated with the emotional context of conditioned fear stress, and hypersensitivity and vulnerability to stress are at least partially involved with the overreaction to stress.

The differential ACTH responses to combined dexamethasone/CRH administration in major depressive and dysthymic disorders.

In a preliminary study, we performed the combined dexamethasone/CRH test on patients with major depressive and dysthymic disorders as well as healthy controls. The ACTH response was significantly enhanced in the major depression group compared to the control group and tended to be heightened compared to the dysthymia group. The cortisol response was not significantly different among the three groups. We assume that major depression and dysthymia are neuroendocrinologically distinct disorders, although whether the difference is quantitative or qualitative remains to be examined.

Subjective experiences of family caregivers of patients with dementia as predictive factors of quality of life.

Background:  The aim of the present study was to investigate predictive factors of quality of life (QOL) in home caregivers of patients with dementia.

Predictors of Psychological Distress After Diagnosis in Breast Cancer Patients and Patients with Benign Breast Problems

OBJECTIVE The objective of this study was to determine how age and psychological characteristics assessed prior to diagnosis could predict psychological distress in outpatients immediately after disclosure of their diagnosis. METHODS This is a longitudinal and prospective study, and participants were breast cancer patients and patients with benign breast problems (BBP). Patients were asked to complete questionnaires to determine levels of the following: trait anxiety (State-Trait Anxiety Inventory), negative emotional suppression (Courtauld Emotional Control Scale), life stress events (Life Experiences Survey), and psychological distress (Profile of Mood Status) prior to diagnosis. They were asked to complete a questionnaire measuring psychological distress after being told their diagnosis. We analyzed a total of 38 women diagnosed with breast cancer and 95 women diagnosed with a BBP. RESULTS A two-way analysis of variance (prior to, after diagnosis × cancer, benign) showed that psychological distress after diagnosis among breast cancer patients was significantly higher than in patients with a BBP. The multiple regression model accounted for a significant amount of variance in the breast cancer group (model adjusted R(2) = 0.545, p < 0.001), and only trait anxiety was statistically significant (β = 0.778, p < 0.001). In the BBP group, the multiple regression analysis yielded a significant result (model adjusted R(2) = 0.462, p < 0.001), with trait anxiety and negative life changes as statistically significant factors (β = 0.449 and 0.324 respectively; p < 0.01). CONCLUSIONS In both groups, trait anxiety assessed prior to diagnosis was the significant predictor of psychological distress after diagnosis, and might have prospects as a screening method for psychologically vulnerable women.

Moderate hyperventilation prolongs electroencephalogram seizure duration of the first electroconvulsive therapy.

Although it is controversial that seizure duration can influence the efficacy of electroconvulsive therapy (ECT), a missed or brief seizure is considered less effective ECT. Of the background in the practice of ECT, hyperventilation may augment the seizure duration. To elucidate these hypotheses, we performed double-blind randomized controlled trial for 19 patients. They were divided into 2 groups, according to the end-tidal pressure of carbon dioxide (ETCO2): The moderate hyperventilation group with ETCO2 of 30 mm Hg and the normal ventilation group with ETCO2 of 40 mm Hg. ECT was performed under general anesthesia with propofol and suxamethonium. During ECT electroencephalogram (EEG) and electromyogram were recorded. The Global Assessment of Functioning scores were also analyzed before and after 6 sequential ECT. The moderate hyperventilation group showed a significant increase in EEG seizure duration in the first treatment compared with the normal ventilation group (P < 0.05). However, EEG seizure duration in the subsequent treatments and electromyogram seizure duration in all the treatments did not differ between 2 groups. The moderate hyperventilation did not prevent the increase in seizure threshold or shortening of seizure duration. No complications or sever adverse effects were observed after ECT in any of the 6 treatments. The Global Assessment of Functioning scores were not significantly changed with moderate hyperventilation. We conclude that moderate hyperventilation is safe and may be useful for seizure augmentation before the restimulation with higher intensities.