Survey of the relationship between internet addiction and social withdrawal (HIKIKOMORI) in Japan.

PURPOSE: The Internet was originally designed to facilitate communication and research activities.'However, there has been a dramatic increase in the use of the Internet in recent years for commerce, education, and entertainment, including video games. Internet addiction as.a phenomena has been described by researchers as excessive or compulsive use of computers that interferes with daily life. Hikikomori (social withdrawal) -has increasingly become a problem in Japan and has been hypothesized to be ,related to internet, addiction. Particularly amongst students, problematic internet use may be a major factor of social withdrawal. We conducted a survey of internet addiction. and social- withdrawal among college students and corhpany workers to examine this hypothesis. METHODS: Subjects were 63 university students and 56 company workers. To examine the relationship between internet addiction and social withdrawal, we administered the Internet Addiction Test (IAT) and the UCLA Loneliness Scale (ULS), a measure of social isolation, to all subjects. RESULTS: Students tended to score higher than workers on the IAT (Student u = 36.3, Worker u = 31.1, p<0.05). For students considered addictive internet users, we found a significant correlation between the ULS and the IAT (r=0.549,. p<0.05); suggesting that social isolation and internet addiction are associated with each other. Workers tended to score higher on the ULS than students (Worker p =40.4, Student u =37.5, p<0.05). For workers .who were not addictive internet users, we found a'mild, negative correlation between the ULS and the IAT (r=- 0.285, p<0.05), suggesting that use of the internet for workers was not a compensatory behavior. CONCLUSIONS: Based upon the IAT, we found that more students than workers reported problems with internet use. Based upon.the ULS, more workers reported feelings of loneliness than students. Workers' loneliness did not appear to be related to their use of the internet, but amongst students with internet addiction, loneliness appeared to be associated with internet use.

Influence of comorbid alcohol use disorder on treatment response of depressive patients.

Patients with major depressive disorder (MDD) frequently also have alcohol use disorder (AUD) and they are more likely to experience symptomatic recurrence and resist treatment. How the two disorders interrelate has not yet been fully examined in Japanese subjects. The treatment response of 47 MDD patients was followed for 12 weeks. Depressive symptoms were rated by the 17-item Hamilton Rating Scale for Depression (HAM-D) and those whose HAM-D score was less than 16 were excluded. The MDD patients were divided into a non-alcohol use disorder (NAUD) and an alcohol use disorder (AUD) group according to the Alcohol Use Disorder Identification Test (AUDIT). We applied a cutoff score of 12 in the AUDIT scale. After 8 weeks, HAM-D NAUD group scores were significantly lower compared with AUD patients. The NAUD group, 23 individuals, prescribed therapeutic doses of antidepressant (equivalent to more than 150 mg of imipramine per day) significantly improved their HAM-D scores but no improvement occurred in the AUD subjects. Correlation analysis in all subjects revealed a significant negative correlation between AUDIT score and improved HAM-D score at endpoint. Moreover, a significant negative correlation was found between total alcohol consumption during the study period and improvement of HAM-D score at endpoint in AUD patients. These results suggest that co-occurrence of MDD and AUD is associated with a lower response to antidepressant treatment and it may reflect an inhibitory effect of ethanol on antidepressants action in the brain.

[The Basic Act on Measures against Alcohol-related Health Harm and Role of General Psychiatrists--With focus on SBRIT and Deadly Triangle].

Japan has just enacted a national law for alcohol, that named "Basic Act on Measures Against Alcohol-related Health Harm". This article includes 5 topics; i) General psychiatrists have the roles and responsibilities in this law, ii) All psychiatrists need to know about alcohol-related health harm and alcohol-related problem, iii) Alcohol dependence is attributed to change of neurotransmitter in the brain, iv) Mood disorder is more likely to be complicated by alcohol dependence and/or hazardous drinking. Some of the patients with the above-mentioned complicated disease have alcohol-induced mood disorder, v) If the patient has alcohol-induced mood disorder, it will place priority on alcoholism treatment and will be important to quickly resolve with abstinence. Finally, the proposals are made as follows; i) Making a guideline, ii) Physicians skilled at SBIRT (Screening, Brief Intervention, and Referral to Treatment) should be qualified as a certifying physician, and having the qualification should allow reimbursing medical institutions for the alcohol related service provided.

Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons.

Epigenome information in mammalian brain cells reflects their developmental history, neuronal activity, and environmental exposures. Studying the epigenetic modifications present in neuronal cells is critical to a more complete understanding of the role of the genome in brain functions. We performed comprehensive DNA methylation analysis in neuronal and non-neuronal nuclei obtained from the human prefrontal cortex. Neuronal nuclei manifest qualitatively and quantitatively distinctive DNA methylation patterns, including relative global hypomethylation, differential enrichment of transcription-factor binding sites, and higher methylation of genes expressed in astrocytes. Non-neuronal nuclei showed indistinguishable DNA methylation patterns from bulk cortex and higher methylation of synaptic transmission-related genes compared with neuronal nuclei. We also found higher variation in DNA methylation in neuronal nuclei, suggesting that neuronal cells have more potential ability to change their epigenetic status in response to developmental and environmental conditions compared with non-neuronal cells in the central nervous system.

Stem cell therapy: a new approach to the treatment of refractory depression.

To better understand the relationship of repeated exposure to adversity during early development as a risk factor for refractory depression, we exposed pregnant female rats to ethanol and the resulting pups to corticosterone during adolescence. A stressful forced swim test was then used to induce depression-like behavior. The adolescent rat brains were examined for the possible therapeutic benefit of a combination of sertraline, an antidepressant, and neural stem cells (NSCs) complexed with atelocollagen in relation to the level of GABAergic interneuron and synaptic protein density in different brain regions. The combined exposures of prenatal and adolescent stress resulted in a reduction in parvalbumin (PV)-positive phenotype of GABAergic interneurons and reduced postsynaptic density protein 95 (PSD-95) levels in the anterior cingulate cortex, amygdala, and hippocampus. Treatments with sertraline and NSCs reversed the reductions in PV-positive cells and PSD-95 levels. Furthermore, the combined treatment of sertraline and NSCs resulted in reduced depressive-like behaviors. These experiments underscore a potentially important role for synaptic remodeling and GABAergic interneuron genesis in the treatment of refractory depression and highlight the therapeutic potential of stem cell and pharmacological combination treatments for refractory depression.

Plasticity-related gene 1 is important for survival of neurons derived from rat neural stem cells.

Plasticity-related gene 1 (Prg1) is a membrane-associated lipid phosphate phosphatase. In this study, we first investigated the role of Prg1 in the survival of neurons derived from rat neural stem cells (NSCs) using small interfering RNA (siRNA). Prg1 knock-down decreased the cell number. Interestingly, Prg1 knock-down increased genomic DNA fragmentation, suggesting the possible induction of apoptosis. Exogenously expressed Prg1 rescued the cells from death and restored the loss of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) activity induced with Prg1 siRNA. However, exogenously expressed mutated-Prg1 (the 253rd amino acid, histidine253, had been changed to alanine) did not rescue the cell death or restore the MTT activity. Histidine253 of Prg1 has been reported to be important for lipid phosphate phosphatase activity. These results suggest that Prg1 is important for survival of neurons through its dephosphorylation activity.

Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

[Reduction in alcohol consumption: therapeutic goal in alcohol dependence treatment].

Mean per capita consumption of alcohol for Japanese adults has been gradually decreasing for more than15 years, while it still remains at a high level. It is pointed out that those who consume alcoholic beverages become more diversified and that the proportion of male drinkers tends to gradually decrease. On the other hand, it is estimated that the proportion of female drinkers, especially, young generation, remarkably increases. The existing cross-sectional and longitudinal studies suggest that alcohol consumption causes a variety of health- and social-related problems with accelerating increase over the past few decades except for some exceptions. The results from a patient survey show that the number of patients with alcohol dependence who receive medical treatment tends to increase. However, the percentage of patients who receive medical care is estimated to be only 5% of total number of patients with the disease, which means that there exist many untreated patients or potential patients who undergo treatment for complications only. Treatment for alcohol dependence can be divided into psychosocial and pharmacological treatment. The former is a mainstream of the treatment. Although medications available in Japanese clinical practice are limited to so called anti-alcoholic drugs, disulfiram and cyanamide, pharmacological treatment is expected to become more accessible because many potential patients can benefit from pharmacotherapy. Treatment outcomes for alcohol dependence are not necessarily high in Japan as shown by the fact that abstinence rate 1 - 3 years after treatment is 7% - 30%, while mortality rate is extremely high. However, not a few individuals are able to maintain a reduced alcohol consumption, and some are able to do so for a long period of time. It is shown that many risks of health-related problems including cancer, hypertension and intra cerebral haemorrhage and social-related problems including suicide increase with the increasing alcohol consumption in a dose-dependent manner. A certain types of disease including ischemic heart disease and cerebral infarction are indicated to have a J-shaped relationship with alcohol consumption. On the other hand, once alcohol consumption exceeds a certain level, the risks increase with the amount of alcohol consumed. Thus, reduction in alcohol consumption can lead to decrease in a large number of health-related and social-related problems in general population. Many studies indicate that reduction in alcohol consumption in patients with alcohol dependence can also lead to the improvement of these problems. In recent years, in Japan, there have been some discussions as to whether "harm reduction" approaches that target reduction in alcohol consumption are needed and the approaches should be aggressively introduced into clinical practice, stimulated by requests from clinicians, the established efficacy of novel therapeutic approaches on reduction in alcohol consumption and trend of various countries. The results from a survey on therapeutic goals in alcohol dependence treatment show that many experts in alcohol dependence answered that they could accept reduction in alcohol consumption (controlled drinking) as a stepwise/interim treatment goal for guiding abstinence if the patient rejects abstinence as a therapeutic goal. Regarding effective medications for reduction in alcohol consumption, most experts answered that they found the medications clinical significant and that they would use them for controlled drinking or abstinence form alcohol when available. In Japan, available drugs for alcohol dependence are extremely limited. Comments in the column for unreserved opinions on the survey questionnaire reveals that many experts hope novel agents will be developed to improve the current treatment as much as possible.

[Treatment response of depressive patients with comorbid problem drink].

In this study, we investigated the impact of Problem Drink on depression. Forty participants with depression were divided into 2 groups: non-Problem Drinker (NPD) group (n = 22) and Problem Drinker (PD) group (n = 18) according to Alcohol Use Disorder Identification Test (AUDIT) score (NPD < 12, PD > or = 12). Depression was assessed by the Mini-International Neuropsychiatric Interview. The effect of medication on depressive symptoms was monitored over 12 weeks using the Hamilton Rating Scale for Depression (HAM-D). Significant improvement in HAM-D score was observed at 2 weeks in NPD patients but not until 4 weeks in PD patients. Total HAM-D scores were lower in NPD than in PD patients at the end of the treatment period. Therapeutic doses (dose of antidepressant used was equivalent to greater than 75 mg of imipramine) of antidepressants resulted in significant improvement in HAM-D scores at 2 weeks in NPD patients, but not until 8 weeks in PD patients and brought lower HAM-D scores in NPD than in PD patients at the end of the treatment period. The AUDIT score and total alcohol consumption during the study period were negatively correlated to the improvement in HAM-D score. In NPD patients, the level of education of patients in remission was higher than those by patients not in remission. In contrast, level of education of patients in remission were similar to those in PD patients not in remission. The above results suggest that co-occurrence of alcohol use disorders with depression is associated with a lower response to antidepressants which may reflect not only the result of biological alterations in the brain by chronic ethanol ingestion but also an inhibitory effect of ethanol on antidepressant action in the brain. Drinking-related cognitive dysfunction may also relate to the decreased response to treatment in the depressed patients with comorbid Problem Drinker.

[A survey of alcoholics and their families on controlled drinking as a treatment goal: discussions on new treatment approaches].

INTRODUCTION: To encourage persons with alcoholism to seek treatment or to overcome denial is an important issue to be addressed in the treatment of alcoholism. Recognizing one's own addiction might be the first step in overcoming alcohol abuse. Abstaining from alcohol consumption was found to be the only effective treatment in Japan. Efforts are in place to introduce abstinence therapy as a first step towards overcoming denial. Abstinence therapy is very popular worldwide: however, many people oppose its introduction in Japan. Concern about relapse is the main reason for this apprehension. Therefore, we conducted a survey to assess awareness of sobriety treatment among persons with alcoholism and their families. METHODS: Subjects were 109 patients with a diagnosis of alcohol dependence and their families who attended family therapy. To examine the consideration of alcoholics and their families for sobriety treatment, we administered a questionnaire that measured awareness of sobriety treatment. RESULTS: Based on the results of the survey, 24% of workshop participants and 25% of hospital patients were admitted for sobriety treatment. According to the sobriety treatment, 41% of patients and 53% of family members realized the need "not to drink too much" (patients who have control over their drinking limit), while 67% of patients and 53% of family members acknowledged "not to pull out the healthy problem." For sobriety treatment, the patients' families tended to focus on the "patient's attitude toward sobriety," "social status," and "extent of mental dependence." The results of "liver dysfunction," "history of alcohol abuse," "treatment history," and "extent of mental dependence" are considered important in the decision to initiate sobriety treatment. CONCLUSIONS: Attitude toward sobriety, abstinence of patients, and social stability were found to be important factors in the choice of treatment focus. Further investigation is needed for the successful introduction of new treatment methods.

[Lessons from addiction psychiatry].

In this paper, I would like to share my experience of helping to establish treatment systems for alcohol dependence in hospital and community settings during the period of relatively inadequate alcohol-dependence care in the 1970s. In the hospital-based treatment system, it was important to ensure that information on the patient's condition and course of treatment was shared with colleagues. It was also important to nurture the patient's compliance with treatment decisions, and involve family members in the treatment process. To promote the rehabilitation of the patient back into the community, it was vital to develop a network of staff in relevant hospitals, clinics, health centers, and welfare offices. Self-help groups also played an important role in rehabilitation. The systems we developed for the treatment of alcoholics offer many instructive lessons for the care of patients with other psychiatric disorders. Alcohol dependence and depression share many common symptoms and biological mechanisms. In consequence, studies on the biological basis of alcohol dependence can provide insights into biological mechanisms underlying other psychiatric disorders.

Rhotekin modulates differentiation of cultured neural stem cells to neurons.

Rhotekin is a downstream signal of Rho and is expressed in the central nervous system. However, the physiological role of rhotekin in the development of neural stem cells (NSCs) into neurons is unknown. In this study, we knocked down the expression of rhotekin protein with small interfering RNA (siRNA) in the NSCs and in neural differentiated cells and measured cell proliferation, differentiation, neurite length, and survival. By using immunocytochemistry and Western blot, the production of rhotekin was observed in NSCs and neuronal cells. Furthermore, rhotekin production was increased in accordance with neural differentiation. Rhotekin knock-down reduced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) activity and increased the cell death 72 hr after transfection in neurons. On the other hand, in NSCs, rhotekin knock-down increased MTT activity and the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells. In the present study, we demonstrated that rhotekin is required for maintenance and survival of neurons and positively regulates differentiation and neurite outgrowth. Moreover, we found that rhotekin is produced in NSCs and that the role of rhotekin is to regulate cell proliferation negatively. In conclusion, these results suggest that rhotekin is one of the key molecules in the differentiation of NSCs into neurons.

Hikikomori as a possible clinical term in psychiatry: a questionnaire survey.

BACKGROUND: The word hikikomori, the abnormal avoidance of social contact, has become increasingly well-known. However, a definition of this phenomenon has not been discussed thoroughly. The aim of this study is to gain a better understanding of the perception of hikikomori amongst health-related students and professionals and to explore possible psychiatric conditions underlying hikikomori. METHODS: A total of 1,038 subjects were requested to complete a questionnaire regarding hikikomori phenomenon. RESULTS: While some differences in the perception of hikikomori do exist, all subjects tended to disagree with the statement, "hikikomori is NOT a disorder". Regarding the underlying psychiatric disorders of hikikomori, approximately 30% of psychiatrists chose schizophrenia as the most applicable ICD-10 diagnosis for hikikomori, whereas 50% of pediatricians chose neurotic or stress-related disorders. CONCLUSIONS: An argument still exists regarding the relationship between hikikomori and psychiatric disorders. We propose that the term hikikomori could be used to describe severe social withdrawal in the setting of a number of psychiatric disorders.

[Recommendation for revision of the General Principles of Suicide Prevention Policy].

Since the promulgation of the Basic Act for Suicide Prevention, suicide prevention in Japan has developed rapidly. In order to further reinforce such activities, it is necessary to balance universal, selective, and indicated prevention. For the revision of the General Principles of Suicide Prevention Policy, the Center for Suicide Prevention announced this recommendation with 29 societies. We hope that it will promote suicide prevention in Japan and lead to expansion of the suicide prevention network by academic organizations, NGOs, as well as local and central government.

[Promising therapy of neural stem cell transplantation for FASD model--neural network reconstruction and behavior recovery].

OBJECTIVES: It has been elucidated that psychiatric disorders are associated with impairment of the brain neural network. Reduction in brain size and hypoplasia of the basal ganglia and corpus callosum have been reported in Fetal Alcohol Spectrum Disorder (FASD). It is believed that the formation of the neural network is influenced by alcohol exposure during the fetal period. Additionally, it is well known that the functional expression of CNS consequences of prenatal alcohol exposure includes cognitive and attentional processes, as well as social behavioral problems. It has also been reported that abnormal 5-HT neuron development can be reversed by treatment with a 5-HT1A agonist in a prenatal alcohol exposure model. However, these treatments are prophylactic. Without early intervention, the consequences of FASD are permanent. Recently, emerging evidence suggest that many clinical symptoms observed in psychiatric disease are likely related to neural network disruptions including neurogenesis dysfunction. Neural stem cell (NSC) transplantation has been investigated in areas such as brain injury, stroke and neurodegenerative diseases and may be a way to reverse neurogenesis dysfunction. In the present work, we evaluated the usefulness of intravenous transplantation of NSCs in the FASD model rat focusing on the possibility of regenerative therapy, particularly regarding behavioral abnormalities, for FASD rats. RESULTS: Abnormal behaviors FASD model rats suggest that reduced social activity , and cognitive dysfunction are major symptoms in FASD patients. Intravenous NSC transplantation appeared to partially correct these behavioral abnormalities in FASD model rats. In the Amygdala areas intravenous NSC transplantation appears to have partially regaenerates expression of PSD95 in FASD model rats. CONCLUSIONS: The results suggest that intravenous NSC transplantation may be an advanced approach to recover neural network damage and CNS dysfunction in FASD and possibly other psychiatric disorders.

[Gender dysphoria in pervasive developmental disorders].

Pervasive developmental disorders (PDD) are characterized by two essential symptoms: impairment in social interaction, and restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. PDD include autistic disorder, Asperger's disorder, and PDD-Not Otherwise Specified (PDD-NOS). These three disorders are sometimes termed autism spectrum disorders. A recent epidemiological survey demonstrated that the rate of PDD may be almost 1% and that many PDD cases might not be diagnosed properly in childhood. Erik Erikson described eight stages of psychosocial development through which a normally developing human should pass from infancy to adulthood. In the theory, an adolescent shows 'Identity vs. Role Confusion'. It has been reported that individuals with PDD often have identity crises which sometimes include gender dysphoria. This phenomenon might be related to the so-called identity diffusion in youth. When they reach their young youth, it has been said that subjects with PDD realize their uniqueness and differences compared to others, and, as a result, they may develop confusion of identity which could be exhibited as gender identity disorder. A recent study demonstrated that, amongst 204 children and adolescents who visited a GID clinic in the Netherlands, 7.8% were diagnosed with autism spectrum disorders after a careful diagnostic procedure by a multi-disciplinary team. Taken together, PDD and GID seem closely related to each other. In this paper, we present four PDD cases with gender dysphoria and related symptoms: 1) a girl with PDD who repeatedly asserted gender identity disorder (GID) symptoms in response to social isolation at school, 2) a junior high school boy with PDD and transvestism, 3) a boy diagnosed with Asperger's disorder who developed a disturbance of sexual orientation, and 4) a boy with Asperger's disorder and comorbid childhood GID. Many of the clinical symptoms related to gender dysphoria might be explained by the cognitive characteristics and psychopathology of PDD. The Japanese Society of Psychiatry and Neurology published guidelines for the assessment and treatment of GID in 1997, and revised them in 2006. As a result, GID has become well known as a clinical entity in Japan, and there have been an increasing number of Japanese patients complaining of gender dysphoria. It is important to consider an underlying diagnosis of PDD when encountering patients with gender dysphoria.

Investigation of annexin A5 as a biomarker for Alzheimer's disease using neuronal cell culture and mouse model.

Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (Abeta). Abeta, a proteolytic product of amyloid precursor proteins (APP), has a toxic effect on neuronal cells, which involves perturbation of their Ca(2+) homeostasis. This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without Abeta and isolated a Ca(2+)-dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with Abeta. We focused on annexin A5, among these proteins, because it binds both Ca(2+) and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group (P < 0.0001 in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD.

Phase I study of YM155, a novel survivin suppressant, in patients with advanced solid tumors.

PURPOSE: YM155, a novel molecular targeted agent, suppresses survivin, a member of the inhibitor of apoptosis protein family that is overexpressed in many tumor types. The aim of this study was to determine the maximum tolerated dose (MTD) and to assess the safety, pharmacokinetics, and antitumor activity of YM155 in patients with advanced refractory solid tumors. EXPERIMENTAL DESIGN: Patients with advanced refractory solid tumors were treated with escalating doses of YM155 administered by continuous i.v. infusion for 168 hours in 21-day cycles. RESULTS: Of the 34 patients enrolled, 33 (median age, 59 years) received at least 1 dose of YM155 (range, 1-19 cycles). The dose levels studied were 1.8, 3.6, 4.8, 6.0, 8.0, and 10.6 mg/m(2)/d. The MTD was determined to be 8.0 mg/m(2)/d, based on a dose-limiting toxicity of increased blood creatinine observed in 2 patients receiving 10.6 mg/m(2)/d. The most common adverse reactions judged to be related to YM155 were urine microalbumin present; fever; injection-site phlebitis; fatigue; and decreased hemoglobin/anemia, blood albumin, and lymphocyte count. The pharmacokinetic profile was almost linear over the dosing range and was similar between cycles 1 and 2. Urinary excretion of YM155 showed no definite difference among doses. Stable disease was achieved in nine patients. CONCLUSIONS: YM155 was safely administered to patients with advanced refractory solid tumors by 168-hour continuous i.v. infusion in 21-day cycles. The MTD was determined to be 8.0 mg/m(2)/d. The safety profile, plasma concentrations achieved, and antitumor activity observed merit further studies with this survivin suppressant, alone and in combination regimens.

Attitudes of early-career psychiatrists in Japan toward child and adolescent psychiatry and their career decision.

The aim of the present study was to carry out a national survey to understand the attitude of early-career psychiatrists toward child and adolescent psychiatry (CAP). The subjects were 348 early-career psychiatrists. A questionnaire was sent to the subjects and returned anonymously. A total of 234 subjects (67.2%) responded. Ten out of 115 psychiatrists (8.9%) in their first-third year of experience, and 18 of 119 psychiatrists (15.1%) in their fourth-10th year answered that they had interest in CAP. Psychiatry rotations with adequate CAP cases may be necessary to attract early-career psychiatrists to CAP.

Low serum BDNF and food intake regulation: a possible new explanation of the pathophysiology of eating disorders.

BACKGROUND: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behavior, and poorly balanced diets lead to a decrease in blood BDNF levels. However, studies regarding BDNF blood levels in eating disorders (ED) have yielded inconsistent results. We measured serum concentrations of BDNF and assessed behavior and cognition related to eating in ED patients and control subjects. METHODS: Forty female drug-free patients [19 with anorexia nervosa (AN), 21 with bulimia nervosa (BN)], who did not meet the diagnostic criteria for depressive disorder, and 24 age-matched normal control subjects were enrolled in the current study. We evaluated eating-related psychopathology and depressive symptoms using the Eating Disorder Inventory-2 (EDI-2), Eating Attitude Test-26 (EAT-26) and the Hamilton Depression Rating Scale (HDRS), and measured serum BDNF levels by an enzyme-linked immunosorbent assay. RESULTS: Compared to normal controls, serum levels of BDNF were significantly reduced in AN, but not in BN. There was a significant positive correlation between serum BDNF levels and BMI in both AN patients (r=.649, p=.003) and BN patients (r=.626, p=.002). However, no correlation between serum BDNF levels and BMI was detected in the controls. Furthermore, there was a significant negative correlation between serum BDNF levels and the oral control subscale scores of EAT in both AN patients (r=-.506, p=.027) and BN patients (r=-.511, p=.018); whereas, no correlation was detected in normal controls. CONCLUSION: Our study demonstrated that individuals showing more extreme food intake regulation were those with lower serum BDNF levels. This finding is contrary to that in mice where mice with reduced BDNF levels showed aberrant eating behavior. This result suggests that BDNF is no longer functioning appropriately in ED patients, which could be an important factor in the pathophysiological of ED.