Does subjective sleep quality improve by a walking intervention? A real-world study in a Japanese workplace.

OBJECTIVES: The purpose of this study was to evaluate the impact of a 4-week walking intervention on subjective sleep quality. DESIGN: A prospective open-label study. PARTICIPANTS: A total of 490 healthy workers were included in the study. The 490 participants were divided into a group of 214 participants with exercise habits (exercising group, EG) and a group of 276 participants without exercise habits (non-EG). INTERVENTIONS: A walking intervention with a target of walking 10 000 steps daily for 4 weeks. OUTCOME MEASURES: The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered twice (before the start and after the end of the study). RESULTS: Overall, the walking intervention improved the participants' PSQI global score, sleep latency (minutes), sleep duration (hours), perceived sleep quality factor and daily disturbance factor. Among the EG participants, the walking intervention significantly improved the PSQI global score and perceived sleep quality. Among the non-EG participants, the walking intervention significantly improved the PSQI global score, sleep latency, sleep duration and perceived sleep quality. CONCLUSIONS: A walking intervention might reduce the sleep latency and increase total sleep duration in working persons without exercise habits.

[Niacin deficiency and cutaneous immunity].

Niacin, also known as vitamin B3, is required for the synthesis of coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Niacin binds with G protein-coupled receptor (GPR) 109A on cutaneous Langerhans cells and causes vasodilation with flushing in head and neck area. Niacin deficiency due to excessive alcohol consumption, certain drugs or inadequate uptake in diet causes pellagra, a photosensitivity dermatitis. Recently several studies have revealed the mechanism of photosensitivity in niacin deficiency, which may pave a way for new therapeutic approaches. The expression level of prostaglandin E synthase (PTGES) is up-regulated in the skin of both pellagra patients and niacin deficient pellagra mouse models. In addition, pellagra is mediated through prostaglandin E2-EP4 (PGE2-EP4) signaling via reactive oxygen species (ROS) production in keratinocytes. In this article, we have reviewed the role of niacin in immunity and the mechanism of niacin deficiency-induced photosensitivity.

Serum proBDNF/BDNF and response to fluvoxamine in drug-naïve first-episode major depressive disorder patients.

BACKGROUND: We investigated the association between serum proBDNF, a precursor of brain-derived neurotrophic factor (BDNF), and response to fluvoxamine in patients with major depressive disorder (MDD) using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR): physically healthy and free of current alcohol or drug abuse, comorbid anxiety, or personality disorders. METHODS: Fifty-one patients with MDD (M/F, 19:32; age, 38 ± 19 years) and 51 healthy controls (M/F, 22:29; age, 34 ± 17 years) were studied using DSM-IV-TR: physically healthy and free of current alcohol or drug abuse, comorbid anxiety, or personality disorders. Serum levels of proBDNF and MDNF were measured by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum mature BDNF levels in the MDD patients were significantly lower than those in the healthy controls (t = 3.046, p = 0.0018). On the other hand, no difference was found in serum proBDNF between the MDD patients and the healthy controls (t = -0.979, p = 0.833). A trend of negative correlation was found between baseline serum BDNF and baseline scores of the 17 items of the Hamilton Rating Scale for Depression (HAMD17) (r = -0.183, p = 0.071). No correlation was however found between HAMD17 scores and proBDNF at baseline (r = 0.092, p = 0.421). Furthermore, no correlation was observed between baseline HAMD17 scores and baseline proBDNF/BDNF (r = -0.130, p = 0.190). No changes were observed in serum levels of proBDNF and BDNF during the treatment periods. CONCLUSIONS: These results suggest that there is no association between serum proBDNF/BDNF and fluvoxamine response in MDD patients at least within 4 weeks of the treatment.

Comparison of lithium, aripiprazole and olanzapine as augmentation to paroxetine for inpatients with major depressive disorder.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatments for major depressive disorders (MDD). It has been reported, however, that 30-40% of patients with MDD who received SSRIs failed to respond to treatment. Use of lithium (Li) to augment SSRIs seems to be the most common strategy in such cases. It was recently demonstrated that atypical antipsychotics are effective augmentation agents in MDD. Here, we present a randomized controlled study that compared augmentation with Li, olanzapine (OLA) or aripiprazole (ARI) in paroxetine-refractory patients with MDD. METHODS: Participants were 30 patients who met Diagnostic and Statistical Manual of Mental Disorders IV criteria for MDD and refractory to paroxetine treatment. Treatment with Li, OLA or ARI was added to paroxetine in a randomized protocol for 4 weeks. We defined the patients whose scores on the Hamilton Rating Scale for Depression decreased 50% or more as responders. RESULTS: Two patients dropped out because of adverse effects. Response rates to Li, OLA or ARI augmentation were 4/10 (40%), 3/10 (30%) and 4/10 (40%), respectively. In addition, Li, OLA and ARI did not influence plasma paroxetine concentrations. CONCLUSIONS: We concluded that OLA or ARI could be used as alternatives to Li as options for patients who do not respond to paroxetine treatment.

COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study.

We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and white matter changes in patients with major depressive disorder (MDD) and healthy subjects using diffusion tensor imaging (DTI). We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years) and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years). Using DTI analysis with a tract-based spatial statistics (TBSS) approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects). In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05). No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association between the COMT gene Val158Met and the white matter abnormalities found in the temporal lobe of patients with MDD.

Duloxetine, a Selective Noradrenaline Reuptake Inhibitor, Increased Plasma Levels of 3-Methoxy-4-hydroxyphenylglycol but Not Homovanillic Acid in Patients with Major Depressive Disorder.

OBJECTIVE: We investigated the effects of duloxetine on the plasma levels of catecholamine metabolites and serum brain-derived neurotrophic factor (BDNF) in 64 patients with major depressive disorder (MDD). METHODS: Major depressive episode was diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) according to the DSM-IV text revision (DSM-IV-TR) criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17). Blood sampling and clinical evaluation were performed on days 0, 28, and 56. RESULTS: Duloxetine treatment for 8 weeks significantly increased the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels but not the homovanillic acid (HVA) levels in responders with MDD. CONCLUSION: These results imply that noradrenaline plays an important role in alleviating depressive symptoms.

Abnormal white matter integrity in the corpus callosum among smokers: tract-based spatial statistics.

In the present study, we aimed to investigate the difference in white matter between smokers and nonsmokers. In addition, we examined relationships between white matter integrity and nicotine dependence parameters in smoking subjects. Nineteen male smokers were enrolled in this study. Eighteen age-matched non-smokers with no current or past psychiatric history were included as controls. Diffusion tensor imaging scans were performed, and the analysis was conducted using a tract-based special statistics approach. Compared with nonsmokers, smokers exhibited a significant decrease in fractional anisotropy (FA) throughout the whole corpus callosum. There were no significant differences in radial diffusivity or axial diffusivity between the two groups. There was a significant negative correlation between FA in the whole corpus callosum and the amount of tobacco use (cigarettes/day; R = - 0.580, p = 0.023). These results suggest that the corpus callosum may be one of the key areas influenced by chronic smoking.

Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production.

Pellagra is a photosensitivity syndrome characterized by three "D's": diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE2 production via induction of ROS formation.

Plasma levels of interleukin-6 and selective serotonin reuptake inhibitor response in patients with major depressive disorder.

OBJECTIVE: We investigated the plasma levels of interleukin (IL)-6 and 5-HTT polymorphisms in patients with major depressive disorder (MDD). This is the first report, to our knowledge, of an investigation into the association between 5-HTT gene polymorphism, plasma IL-6 levels, and responses to selective serotonin reuptake inhibitors (SSRIs) in Japanese patients with MDD. METHOD: One-hundred and eighteen patients (51 male, 67 female) who met the DSM-IV criteria for MDD were enrolled. Their ages ranged from 24 to 78 (mean ± SD = 44 ± 12) years. The patients were treated with SSRIs (paroxetine in 66 cases, sertraline in 42 cases) for 8 weeks. RESULTS: The plasma levels of IL-6 were significantly higher in the SSRI responders than in the nonresponders (p = 0.0328), and the changes in plasma IL-6 levels correlated significantly with the changes in severity of depressive state (p = .0.007). No difference was found in baseline and the changes in plasma IL-6 levels between the patients with a 5-HTT gene (5-HTTLPR) L-carrier and those with S/S. CONCLUSION: These results suggest that the plasma levels of IL-6 reflect the severity of MDD and that plasma IL-6 levels might be another biological-state marker for the depressive state. In addition, the 5-HTTLPR polymorphism might be independent of plasma IL-6 levels.

Follow-up Study on Electroconvulsive Therapy in Treatment-resistant Depressed Patients after Remission: A Chart Review.

OBJECTIVE: Electroconvulsive therapy (ECT) has proven to be effective in treatment-resistant depression (TRD). In recent reports, 70% to 90% of patients with TRD responded to ECT. However, post-ECT relapse is a significant problem. There are no studies investigating risk factors associated with reintroducing ECT in depressive patients after remission previously achieved with former ECT. The aim of the present study is to examine such risk factors using a sample of TRD patients. METHODS: We conducted a chart review to examine patient outcomes and adverse events over short- and long-term periods. Forty-two patients met the criteria for major depressive disorder. RESULTS: The response rate was 85.7% (36/42). There were no significant differences in the baseline characteristics of patients exhibiting remission, response or non-response. The rate of adverse events was 21.4% (9/42). Among 34 patients who were available for follow-up, 18 patients relapsed (relapse rate, 52.9%), and 6 patients were reintroduced to ECT. The patients' age and age of onset were significantly higher in the re-ECT group than non re-ECT group. CONCLUSION: Our results suggest that older age and older age of onset might be considered for requirement of re-ECT after remission previously achieved with former ECT.

Current smoking rate in patients with psychiatric disorders in Japan: questionnaire survey.

The association between smoking and psychiatric disorders (PD) has been known for many years. Support for smoking cessation among patients with PD is provided in advanced nations, but there is a little support for smoking cessation among patients with PD in Japan, where few studies have investigated the smoking rate. The aim of the present study is to determine the smoking rate and smoking habits of Japanese patients with PD. The subjects included outpatients who visited the outpatient psychiatric clinic at a University hospital between January and March of 2011. They answered a questionnaire consisting of questions about their sociodemographic background and smoking habits. In an analysis of 733 subjects, the overall smoking rate was 25.1%. The smoking rates among the patients with schizophrenia and depression were 17.3% and 23.9%, respectively, and these rates were lower than the results of previous studies. Among the current smokers, 43.4% had experienced smoking cessation, and only 26.1% were not interested in smoking cessation. Of the current smokers, 37.5% spent between US$128.88 and US$257 per month on cigarettes.

The effects of a walking intervention on depressive feelings and social adaptation in healthy workers.

The effects of walking on mental health problems among healthy Japanese workers are not fully understood. In the present study, we investigated the effects of a four-week walking program on the psychological functioning of a nonclinical sample of healthy workers in Japan.A total of 606 healthy subjects were enrolled in the study and were evaluated by the Zung Self-rating Depression Scale (SDS) and the Social Adaptation Self-evaluation Scale (SASS) both before and after the walking program.The subjects were divided into an exercising group and a non-exercising group.There were significant differences in the SDS and SASS scores between the exercising and the non-exercising groups.Following the walking program, the non-exercising group's SDS scores decreased and their SASS scores increased compared to before the walking program.In contrast, the SDS and SASS scores of the exercising group did not change.These results suggest that subjects who exercise regularly experience fewer depressive feelings and exhibit better social adaptation in the workplace than those who do not exercise.The walking program improved depressive feelings and social adaptation in the non-exercising group.

Plasma catecholamine metabolite levels and the activities of psychiatric symptoms in systemic lupus erythematosus.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is accompanied by neurological or psychiatric symptoms that can be severe. We hypothesized plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels were the biological marker that reflected the severity of the NPSLE psychiatric symptoms, and we examined MHPG and HVA levels in systemic lupus erythematosus (SLE) patients. METHODS: The participants were 42 healthy volunteers and 41 SLE patients. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms (NP group), NPSLE without psychiatric symptoms (NN group), and SLE without neuropsychiatric symptoms (S group). All blood samples were drawn before (T0) and after 4 weeks of treatment (T4) in all SLE patients, and once in the healthy volunteers. Plasma levels of MHPG and HVA were analyzed using high-performance liquid chromatography. RESULTS: Plasma MHPG levels at T0 were significantly increased in the SLE compared to those in healthy volunteers. The NN group had the greatest increase compared with other SLE patient groups. There were no significant differences in plasma HVA levels at T0 between the four groups, and there was also no difference in MHPG and HVA plasma levels between T0 and T4. CONCLUSION: Hyperactivity of noradrenergic neurons and/or sympathetic nerves might be involved in SLE pathophysiology.

Erythema annulare centrifugum associated with herpes zoster.

Erythema annulare centrifugum (EAC) presents as erythematous or urticarial papules, each with an annular shape, that exhibit peripheral extension. Internal malignancies are occasionally associated with EAC, and infectious diseases, including fungal, bacterial or viral infections, have also been regarded as possible causes of EAC. A 35-year-old man had a 1-week history of a painful vesicular eruption over the trunk corresponding to dermatomes Th8-10. Concomitantly, he developed several annular eruptions over the trunk. We diagnosed the former lesions as herpes zoster and the latter as EAC associated with herpes zoster. Although DNA was extracted from the EAC region, no varicella-zoster virus DNA was detected. We consider that this is Wolf's isotopic response, which is caused by an alteration of the local immunity due to viral infection. An etiologic relationship between EAC and herpes zoster is strongly suggested by the present case and by our review.

Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in Japanese patients with major depressive disorder (MDD).

OBJECT: We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients. METHODS: Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively. RESULTS: Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels. CONCLUSION: Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.

Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder.

OBJECTIVE: Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression. SUBJECTS AND METHODS: Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean±SD=39±12) years. Patients were prescribed paroxetine (n=11) or sertraline (n=13) for 4weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4weeks. RESULTS: Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group. CONCLUSION: Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.

Six-month treatment with atypical antipsychotic drugs decreased frontal-lobe levels of glutamate plus glutamine in early-stage first-episode schizophrenia.

OBJECTIVE: To study the effects of treatment with atypical antipsychotic drugs on brain levels of glutamate plus glutamine in early-stage first-episode schizophrenia. PARTICIPANTS: Sixteen patients (eight males, eight females; aged 30 ± 11 years) completed the study. METHODS: We used administered 6 months of atypical antipsychotic drugs and used proton magnetic resonance spectroscopy to evaluate the results. RESULTS: We found that the administration of atypical antipsychotic drugs for 6 months decreased the glutamate plus glutamine/creatine ratio in the frontal lobe. These results suggest that the administration of atypical antipsychotic drugs for at least 6 months decreased glutamatergic neurotransmissions in the frontal lobe in early-stage first-episode schizophrenia, but there was no difference in frontal-lobe levels between patients and control subjects before administration. CONCLUSION: Taking these findings into account, the glutamatergic and GABAergic neurons are implicated in early-stage first-episode schizophrenia, but in complex ways.

The cognitive profile of aripiprazole differs from that of other atypical antipsychotics in schizophrenia patients.

We investigated the effects of the atypical antipsychotics risperidone, olanzapine, and aripiprazole on the cognitive functions of Japanese patients with schizophrenia with respect to dosage amounts and dosing schedules. We performed a cross-sectional survey using the Brief Assessment of Cognition in Schizophrenia - Japanese Language Version (BACS-J) to evaluate the neurocognitive functions of 101 schizophrenic patients who took the same dose of one of the three aforementioned antipsychotics for at least 3 months. The BACS-J composite score correlated negatively with the prescribed dosages of risperidone and olanzapine. In contrast, we did not find a correlation between the BACS-J composite score and the prescribed dosage of aripiprazole. Moreover, the primary scores for verbal learning, motor function, and attention and processing speed were significantly lower among the patients who were taking the prescribed dosage of risperidone. The scores for verbal learning and motor function were also significantly lower when correlated with the prescribed dosage of olanzapine. We did not find a correlation between any of the primary scores on the BACS-J and the prescribed dosage of aripiprazole. In fact, the results suggest there is no linear relationship between the dose of aripiprazole and cognitive impairment, which may be due to its unique pharmacological profile.

Aripiprazole altered plasma levels of brain-derived neurotrophic factor and catecholamine metabolites in first-episode untreated Japanese schizophrenia patients.

OBJECTIVE: We investigated the effects of aripiprazole on plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in first-episode untreated schizophrenia patients. METHODS: The subjects were 50 Japanese first-episode untreated schizophrenia patients who met the Diagnostic and Statistical Manual of Mental Disorders Text Revision criteria and were treated with aripiprazole monotherapy. Twenty-nine were males, and 21 were females. The age ranged from 21 to 42 years (mean ± SD; 30.8 ± 5.3 years). Plasma BDNF and catecholamine metabolites were measured by ELISA and HPLC, respectively. Psychiatric symptoms were evaluated using by Positive and Negative Syndrome Scale. RESULTS: Treatment with aripiprazole for 8 weeks significantly increased plasma BDNF levels. It also changed plasma levels of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. A negative correlation was also observed between duration of psychosis and plasma BDNF levels. No correlation was observed however between plasma BDNF levels and the dose of aripiprazole. CONCLUSIONS: To the best of our knowledge, this is the first report showing that aripiprazole increases plasma BDNF levels in first-episode untreated schizophrenia patients. Furthermore, the BDNF Val66Met polymorphism was independent of the response to aripiprazole.