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.

[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.

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.

Characteristics of attempted suicide by patients with schizophrenia compared with those with mood disorders: a case-controlled study in northern Japan.

Recent reports suggest a lifetime suicide risk for schizophrenia patients of approximately 5%. This figure is significantly higher than the general population suicide risk consequently, detection of those at risk is clinically important. This study was undertaken to define the characteristics of suicide attempts by schizophrenia patients compared with attempts by patients with mood disorders. All patients were diagnosed using the ICD-10 criteria. The study population comprised 65 patients with F2 disorders (schizophrenia, schizotypal and delusional disorders), i.e., "the F2 group", and 94 patients with F3 disorders (mood disorders), i.e., "the F3 group", who presented in the clinical setting of consultation-liaison psychiatry. The F2 group had a significantly younger mean age and significantly higher ratios of 'past/present psychiatric treatment' and 'more than 3 months interruption of psychiatric treatment'. In contrast, the ratios of 'physical disorder comorbidity', 'alcohol intake at suicide attempt' and 'suicide note left behind' were significantly higher in the F3 group. The F2 group attempted suicide by significantly more serious methods. Furthermore, 'hallucination-delusion' was the most prevalent motive in the F2 group and was the only factor that showed a significant association with the seriousness of the method of suicide attempt (OR = 3.36, 95% CI: 1.05-11.33).

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.

Consensus paper of the WFSBP task force on biological markers: biological markers for alcoholism.

OBJECTIVES: This article presents an overview of the current literature on biological markers for alcoholism, including markers associated with the pharmacological effects of alcohol and markers related to the clinical course and treatment of alcohol-related problems. Many of these studies are well known, while other studies cited are new and still being evaluated. METHODS: In this paper we first describe known biomarkers of alcohol-related disorders, review their features and the problems involved in their use. We then consider future developments on biomarkers and their possible impact on the field. RESULTS: More recent findings cited include the work on type 7 adenylcyclase (AC) polymorphism and its lower expression levels in female alcoholics. Neuroimaging studies involving biomarkers have also reported brain volume reductions of gray and white matter, including amygdala and subcortical regions in alcoholic patients, while a high association between the copy number variations (CNVs) in 6q14.1/5q13.2 and alcohol dependence has more recently been identified in genetic studies. CONCLUSIONS: In addition to their possible importance for diagnosis, biomarkers may have utility for predicting prognosis, progression of the disorder, the development of new treatments, and monitoring treatment effects. Although such findings should be verified in independent studies, the search for new biomarkers is continuing. Several potential candidate biomarkers have been found recently in blood, imaging, and genetic studies with encouraging results.

[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.

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.

WITHDRAWN: Neuronal cell-type specific DNA methylation patterns of the Cacna1cgene.

The Publisher regrets that this article is an accidental duplication of an articlethat has already been published, http://dx.doi.org/10.1016/j.ijdevneu.2012.11.007. The duplicate article has therefore been withdrawn.

[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.

[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.

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.

Evaluation of annexin A5 as a biomarker for Alzheimer's disease and dementia with lewy bodies.

BACKGROUND: Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (Aß42). Using a cell culture model we previously identified annexin A5, a Ca(2+), and phospholipid binding protein, as an AD biomarker. Plasma level of annexin A5 was significantly higher in AD patients compared to that in a control group. On the other hand, AD has been identified to share a number of clinical and pathological features with Dementia with Lewy bodies (DLB). The present study was done to examine whether or not plasma annexin A5 is a specific marker for AD, when being compared with the levels of DLB patients. As Apolipoprotein E (ApoE) gene subtype ε4 (ApoE-ε4) has been noticed as the probable genetic factor for AD, we also examined and compared ApoE genotype in both AD and DLB. METHODS: Blood samples were obtained from 150 patients with AD (aged 77.6 ± 6.5 years), 50 patients of DLB (79.4 ± 5.0) and 279 community-dwelling healthy elderly individuals of comparable age and sex (75.6 ± 8.1). All AD patients met NINCDS-ADRDA criteria and all DLB patients were diagnosed as probable DLB according to the latest consensus diagnostic criteria. Quantification was done using the Chemiluminescent Enzyme Immunoassay (CLEIA) Technique (SphereLight assay) using the monoclonal antibodies against annexin A5. DNA genotyping of ApoE was performed by distinguishing unique combinations of Hha1 fragments of PCR-amplified genomic DNA products. RESULTS: The plasma level of annexin A5 was significantly higher in AD patients than in the healthy individuals (control) (P < 0.0001). The plasma annexin A5 level was also significantly higher in DLB patients than in the control group (P < 0.0001). From the ROC curves with plasma annexin A5 concentrations, the mean areas under the curve were 0.863 and 0.838 for the AD/control and DLB/control, respectively. The rate of ApoE4 carrier status and the frequency of the ε4 allele were significantly higher in AD or DLB than in control and there was no significant difference between AD and DLB. CONCLUSIONS: These results suggest that both annexin A5 and ApoE4 are common markers for AD and DLB.

[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.

Neuronal cell-type specific DNA methylation patterns of the Cacna1c gene.

Gene expression of the alpha-1 subunit of the L-type voltage-gated calcium channel, CACNA1C, is known to be complexly regulated. Because CACNA1C is not only a crucial gene in normal brain function but also a promising candidate risk gene for psychiatric disorders such as bipolar disorder and schizophrenia, elucidating the molecular basis of transcriptional regulatory mechanism will be critically important. Here we examined DNA methylation status of CpG islands and a CpG island shore on mouse Cacna1c in neuronal and non-neuronal nuclei, which were separated with a fluorescent activated cell sorting technique. We found that neurons and non-neurons showed differential DNA methylation profile on a CpG island shore. This difference was evolutionarily conserved in human neuronal and non-neuronal nuclei in the prefrontal cortex, suggesting that DNA methylation status on the CpG island shore of Cacna1c may have an important role in transcript regulation.

The study of cognitive characteristics in Asperger's disorder by using a modified Prisoner's Dilemma game with a variable payoff matrix.

Individuals with Asperger's Disorder (ASP) have difficulties in social reciprocity and in providing appropriate cooperative behavior. The Prisoner's Dilemma (PD) is a well-known model in game theory that illustrates the paradoxical disposition of interaction between two individuals with opposing interests, and may be a useful tool in the diagnosis of ASP in early childhood. In this study, we investigated the cognitive characteristics of ASP by using a modified PD game. The subjects were 29 individuals with ASP and 28 age- and IQ-matched controls. In the PD game, each of two players has two cards: card 1 represents cooperation and card 2 betrayal. The score each player obtains is decided according to a 2 x 2 payoff matrix and depends on the combination of their selections. The P-score ("P" for punishment) is defined as the score that is given when they both select betrayal. Comparing the two groups, the mean P-score at the end of the game and the mean total score were significantly higher in the ASP group, while the rate of selection of cooperative choice in both groups did not differ significantly. The classification of the shape of the graph according to fluctuation of the P-score revealed that in the ASP group only 2 cases (6.9%) showed continuous decrease of P-score compared to 8 control cases (28.6%) demonstrating similar results. However, the reasons were thought to be different: ASP subjects presumably selected card 2 because of a preference for the number itself, whereas control subjects preferentially chose this card to enhance their chance of winning the competition. It is often difficult to diagnose ASP in the young especially when they lack the distinctive clinical features of ASD in early childhood. Given the limited number of objective tools to evaluate the cognitive characteristics of ASP subjects, the PD game might be a useful diagnostic support tool for ASP.

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.