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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. Copyright © 2013 John Wiley & Sons, Ltd.

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. Copyright © 2013 John Wiley & Sons, Ltd.

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. Copyright © 2011 John Wiley & Sons, Ltd.

Aim: The Social Adaptation Self-evaluation Scale (SASS) was developed to assess the social impairment caused by depression. The purposes of this study were to develop a Japanese version of the SASS (SASS-J) and to evaluate its reliability and validity. Methods: The SASS-J and the 21-item Beck Depression Inventory (BDI) were administered to 322 participants (95 working patients who were working while under treatment for depression, 99 non-working patients who were absent from their work due to depression, and 128 healthy controls). The healthy controls underwent both questionnaires twice, at baseline and 2 weeks later, in order to assess test–retest reliability. Results: Cronbach's alpha was 0.81. Significance correlations were found between SASS-J scores at baseline and 2 weeks later in healthy controls (R = 0.845, P

Background Depression is a risk factor for coronary heart disease. Nitric oxide (NO) plays an important role in both coronary heart disease and depression. Methods Fifty-one inpatients and outpatients who met the Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition criteria for major depressive disorder (MDD) in the university hospital of the University of Occupational and Environmental Health and 58 age-matched and sex-matched healthy controls enrolled in this study. We investigated the association between the three polymorphisms of the endothelial nitric oxide synthase (eNOS) gene (single-nucleotide polymorphism (SNP); rs2070744, rs1799983, variable number tandem repeat (VNTR) in intron 4) and scores on the Hamilton Rating Scale for Depression, plasma metabolites of NO (NOx) or ankle brachial index in patients with MDD and healthy controls. Results We did not find significant differences in the genotype distributions between patients with MDD and healthy volunteers. No associations were observed between any of the polymorphisms of the eNOS gene and the Hamilton Rating Scale for Depression or ankle brachial index in patients with MDD. However, plasma NOx level was significantly associated with a polymorphism of the eNOS gene (rs207044 and variable number tandem repeat in intron 4). Conclusion These results suggest that the direct association was not observed between the polymorphisms of the eNOS gene and the pathogenesis of depression. Copyright © 2011 John Wiley & Sons, Ltd.

Background Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems. Recent studies have suggested that BDNF plays a role in the pathogenesis of psychiatric symptoms in patients with systemic lupus erythematosus (SLE). Objectives We hypothesized that the polymorphism of BDNF Val66Met is associated with the emergence of psychiatric symptoms (PS) and serum BDNF levels in SLE patients. To examine the hypothesis, we compared the BDNF Val66Met polymorphism and serum BDNF levels in patients with SLE with or without PS. Methods Psychiatric symptoms were assessed in 54 patients with SLE. PS were evaluated using the Brief Psychiatric Rating Scale. Genotyping was carried out using a 54-nuclease assay. Serum BDNF levels were measured by using enzyme-linked immunosorbent assay. Results The presence of the Met allele was not significantly associated with the presence of PS or with serum BDNF levels in patients with SLE. Conclusion Our data do not support the common variant Val66Met of the BDNF gene as an etiologic factor in the various forms of PS and serum BDNF levels in SLE. Copyright © 2011 John Wiley & Sons, Ltd.

In the present study, we investigated the serum BDNF levels and plasma IL-6 levels in patients with dysthymic disorder, major depressive disorder and control subjects. Eighteen patients who met the DSM-IV criteria (American Psychiatric Association, 1994) for dysthymic disorder (male/female: 5/13; age: 36 ± 9 year) and 20 patients (male/female: 7/13; age: 38 ± 10 year) who met the criteria for major depressive disorder were enrolled. The serum BDNF levels in patients with dysthymic and major depressive disorder were significantly lower than those in the control subjects. However, no difference was found between the dysthymic group and major depression group. The plasma IL-6 levels in the dysthymic group and major depression group were significantly higher than those in the control group. No difference was observed in the plasma IL-6 levels between the dysthymic group and major depression group. These results suggest that the pathophysiology of dysthymic disorder and major depression might be similar in terms of the blood levels of BDNF and IL-6. Copyright © 2011 John Wiley & Sons, Ltd.

Psychiatry has been strongly influenced by culture, society, history and the prevailing public needs of the particular country.1–3 Accordingly, psychiatric training systems differ from country to country, which might be a mirror of the particular country's current situation and its future prospects toward mental health.4 A well-balanced view toward psychiatry, which is often described as a ‘biopsychosocial model of psychiatry’, has been proclaimed as ideal. However, recent increasing demand for biological factors of psychiatry presents a potential gap between expected and actually acquired skills in terms of psychosocial factors, leading younger psychiatrists to fall between mind–brain (or mind–body) dichotomy.5–8 How do young psychiatrists (in this article, ‘young psychiatrists’ are defined as psychiatric residents, trainees, and certified psychiatrists with clinical experience of 10 years or fewer) see themselves from biopsychosocial perspectives? Do they define themselves as doctors of the ‘brain’, doctors of the ‘mind’, or doctors who address sociocultural issues? The answer may be influenced by multiple factors, including their original motivation to become psychiatrists, their domains of interests, and the level of acquired skills and education/training undertaken. Facing recent sociocultural changes, such as aging society and high suicide rate, Japan implemented a new system of postgraduate medical education (PGME) in 2004. Until that time, psychiatric residents would start their psychiatric training immediately after graduating from medical school, join a specific clinical department of psychiatry in medical universities, known as ikyoku,9 and rotate through psychiatric hospitals.9–11 Therefore, under the pre-2004 PGME system, psychiatrists used to devote most of their time to psychiatry11 and have very little experience with medical approaches epitomized by evidence-based medicine and the systematic problem–solution approach. Since 2004, a two-year general residency has been required of medical graduates,12–14 in order to improve basic clinical skills of all medical doctors in primary care settings.15 In this new PGME system, first-year residents rotate in internal medicine, surgery, emergency medicine and anesthesiology, and second-year residents rotate in pediatrics, community medicine, obstetrics/gynecology and psychiatry for at least one month each. Thereafter, residents start their specialty training, including psychiatry, for up to 4 years.9 The balance among biological, psychological and sociocultural orientations may have been influenced by the implementation of the new PGME system. We hypothesized that psychiatrists trained in the new PGME system might lay more emphasis on biological factors because of their two-year rotation in medicine. Thus, the present study aimed to explore the balance among biological, psychological and sociocultural factors in young psychiatrists' attitudes – namely, to explore whether young psychiatrists consider themselves doctors of ‘brain’, doctors of ‘mind’, or doctors who address sociocultural issues. Changes in their attitudes before and after implementation of the new PGME system, as well as possible contributing factors, were also explored. The same questionnaire was distributed to both psychiatrists in and out of Japan, in order to highlight their differences.

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat both anxiety disorders and depressive disorders. However, nonadherence to SSRIs is a major issue in recurrence. In the present study, we investigated paroxetine adherence in depressed patients by monitoring the plasma paroxetine concentrations between patients with rapid and those with a late response to paroxetine treatment. Twenty inpatients in our university hospital, who met the DSM-IV-TR diagnosis of major depressive disorder in a single episode, were enrolled in the study. Twelve patients (M/F: 7/13, age: 37.4 +/- 10.4 years) were treated with paroxetine (40 mg/day), and all achieved remission (HAMD < or = 7) within at least 12 weeks. We divided the patients into two groups, an early-remission group (HAMD < or = 7 within 4 weeks) and a late-remission group (HAMD < or = 7 within 8-12 weeks). Their dosages of paroxetine were constant because of no emerging adverse effects. Blood samples were obtained on the day the subjects were discharged (B) and 12 weeks after discharge. The paroxetine concentrations in the early-remission group were significantly decreased 12 weeks after discharge, and no difference was found between the early- and late-remission groups. These results suggest that adherence to paroxetine was independent of the duration of the depressive state suffered by the patients. Clinicians always take their cautions for the adherence to paroxetine regardless of the clinical time courses the patients recovering from their depressive symptoms.

Schizophrenic patients demonstrate a variety of cognitive deficits, including attention, executive functions, and working memory, even in the early stage of disease. In the present study, we examined the association between blood levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), or brain-derived neurotrophic factor (BDNF) and scores on the Wisconsin Card Sorting Test (WCST) in patients with early-stage schizophrenia. We also investigated the association between frontal GABA levels using 1H-magnetic resonance spectroscopy (MRS) at 3T and scores on the WCST in the same patients. Blood levels of BDNF and catecholamine metabolites and brain GABA levels using 1H-MRS were measured in 18 schizophrenic patients (nine males, nine females; age range 13-52 year). A significantly positive correlation was observed between plasma MHPG levels and %PEM (rho = -0.686, p = 0.0047). A trend toward negative correlation was found between frontal lobe GABA levels and the per cent of preservation error (%PEM) in the early stage of schizophrenia (rho = -0.420, p = 0.0836). These results suggest that noradrenergic neurons might be involved in neuropsychological functions in early-stage of schizophrenia.

Alcohol dependence is often comorbid with depression. The purpose of the present study was to compare serum brain-derived neurotrophic factor (BDNF) levels between depressive patients with and without alcohol dependence. Our subjects were 16 inpatients (M/F: 13/3, age: 48 +/- 8 years) at our university hospital who met the DSM-IV-TR criteria for both major depressive disorder and alcohol dependence and whose Hamilton Rating Scale for Depression (HAM-D) scores were at least 15. Twenty sex- and age-matched depressive patients and 20 healthy subjects were also examined. Serum BDNF levels in the depressive patients with (9.0 +/- 4.3 ng/ml) and without (9.8 +/- 5.2 ng/ml) alcohol dependence were significantly lower than those in the healthy subjects (21.1 +/- 7.0 ng/ml); however, no significant difference was found in the serum BDNF levels of depressive patients with and without alcohol dependence. Eight of the 16 (50%) depressive patients suffering from both depression and alcohol dependence responded to 8 weeks of treatment with antidepressant drugs which significantly increased their serum BDNF levels. These results suggest that the serum BDNF level is a useful biological marker for depression in patients with alcohol dependence.

In the present study, we examined the efficacy of risperidone addition on sertraline-resistant depressed patients and the effects of risperidone on the metabolism of sertraline. Ten patients (M/F: 4/6, age: 54 +/- 10 years) met the DSM-IV criteria for major depressive disorder enrolled the study. Hamilton Dating Scale for Depression (HAM-D) scores (mean +/- SD) in all 10 patients significantly decreased from 19 +/- 4 (before risperidone addition) to 11 +/- 3 (4 weeks after risperidone addition). Plasma levels of sertraline and desmethylsertraline did not change after risperidone addition. Serum BDNF levels in responders to risperidone addition were changed from 8.1 +/- 2.7 ng/ml (before risperidone addition) to 11.5 +/- 0.9 ng/ml (4 weeks after risperidone addition); in contrast, those in nonresponders changed from 7.8 +/- 2.2 ng/ml (before risperidone addition) to 7.9 +/- 2.4 ng/ml (4 weeks after risperidone addition). These results suggest that the addition of risperidone to sertraline is effective and well tolerated for sertraline-resistant depressive patients, which is accompanied with the increase in serum BDNF levels in responders to the risperidone addition, and the addition of risperidone to sertraline does not seem to influence sertraline metabolism.

Excessive cigarette smoking and caffeine intake are often seen in schizophrenic patients being treated with antipsychotic drugs, particularly typical antipsychotic drugs. Using nicotine and caffeine sometimes influences psychotic symptoms in these patients. Clozapine is the only antipsychotic drug reported to reduce the amount of cigarette smoking, however, still remains controversial of its efficacy. In the present study, we examined the effect of acute risperidone treatment on the amount of cigarette smoking and plasma levels of cotinine and caffeine in schizophrenic patients. Treatment with risperidone for 4 weeks did not increase daily cigarette consumption or plasma levels of cotinine and caffeine. The results suggest that acute risperidone treatment does not promote the intake of nicotine and caffeine at least by 4 weeks in schizophrenic patients.