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author:("Okazaki, fuji")
1.  Proteomic Analysis of Lymphoblastoid Cells Derived from Monozygotic Twins Discordant for Bipolar Disorder: A Preliminary Study 
PLoS ONE  2013;8(2):e53855.
Bipolar disorder is a severe mental illness characterized by recurrent manic and depressive episodes. In bipolar disorder, family and twin studies suggest contributions from genetic and environmental factors; however, the detailed molecular pathogenesis is yet unknown. Thus, identification of biomarkers may contribute to the clinical diagnosis of bipolar disorder. Monozygotic twins discordant for bipolar disorder are relatively rare but have been reported. Here we performed a comparative proteomic analysis of whole cell lysate derived from lymphoblastoid cells of monozygotic twins discordant for bipolar disorder by using two-dimensional differential in-gel electrophoresis (2D-DIGE). We found approximately 200 protein spots to be significantly differentially expressed between the patient and the co-twin (t test, p<0.05). Some of the proteins were subsequently identified by liquid chromatography tandem mass spectrometry and included proteins involved in cell death and glycolysis. To examine whether these proteins could serve as biomarkers of bipolar disorder, we performed Western blot analysis using case–control samples. Expression of phosphoglycerate mutase 1 (PGAM1), which is involved in glycolysis, was significantly up-regulated in patients with bipolar disorder (t test, p<0.05). Although PGAM1 cannot be regarded as a qualified biomarker of bipolar disorder from this preliminary finding, it could be one of the candidates for further study to identify biomarkers of bipolar disorder.
doi:10.1371/journal.pone.0053855
PMCID: PMC3567087  PMID: 23408933
2.  A greater number of somatic pain sites is associated with poor mental health in adolescents: a cross-sectional study 
BMC Psychiatry  2013;13:30.
Background
Identifying indicators of poor mental health during adolescence is a significant public health issue. Previous studies which suggested an association between the number of somatic pains and depression have mainly focused on adults or have employed samples with a narrow age range. To date, results from previous studies have been inconsistent regarding the association between somatic pain and academic impairment. Therefore, the main aims of the present study were to 1) investigate the association between the number of somatic pain sites and poor mental health using a community sample of adolescents aged 12 to 18 years and employing a simple method of assessment, and 2) examine the association between the number of somatic pain sites and perceived academic impairment.
Methods
Data analysis was conducted using a large cross-sectional survey of adolescents in grades 7 to 12. The one-month prevalence rates for three sites of somatic pain including head, neck and shoulders, and abdomen were examined. Poor mental health was evaluated using the General Health Questionnaire, and perceived academic impairment was measured using a self-report questionnaire.
Results
A total of 18,104 adolescents participated in the survey. A greater number of pain sites was associated with poor mental health, and this association was consistent across age and gender. There was no difference in effect on mental health between any of the pain sites. Although there was an association between the number of somatic pain sites and perceived academic impairment, the results suggested that the association was mediated by poor mental health.
Conclusions
Simple reporting methods for assessing the number of pain sites may be a feasible indicator of poor mental health in adolescents. Professionals working with adolescents should consider the possibility of poor mental health, especially when students report multiple somatic pains.
doi:10.1186/1471-244X-13-30
PMCID: PMC3598352  PMID: 23327684
Number; Somatic pain site; Poor mental health; Adolescents; Males and females; Academic impairment
3.  Help-seeking behavior among Japanese school students who self-harm: results from a self-report survey of 18,104 adolescents 
Background:
The aim of this study was to determine the prevalence of and factors associated with poor help-seeking among adolescents who self-harm and to explore the resources used for help.
Methods:
A cross-sectional survey using an anonymous questionnaire was conducted in 47 junior and 30 senior high schools in Japan. Adolescent self-harm was defined as an adolescent who had harmed himself or herself in the previous year, as in previous studies reported in Western countries. Poor help-seeking was defined as not consulting anyone despite reporting current psychological or somatic complaints. Information about sociodemographic and psychological factors possibly associated with help-seeking, such as suicidal thoughts, depression, anxiety, and psychotic-like experiences, was also collected. Regression analyses were performed to examine associated factors.
Results:
A total of 18,104 students (8620 aged 12–15 years, 9484 aged 15–18 years), accounting for 93% of all students in the relevant student classes, participated in the study. Two hundred and seventy-six (3.3%) junior and 396 (4.3%) senior high school students reported having self-harmed. Of these, 40.6% of adolescents in junior and 37.6% in senior high schools were classified as poor help-seeking. Poor help-seeking with regard to self-harm was significantly more common in those who reported not having consulted anyone about psychological problems (odds ratio 9.2, 95% confidence interval 4.6–18.4 in juniors; odds ratio 9.9, confidence interval 5.5–17.9 in seniors) and in those with current suicidal ideation (odds ratio 2.0, confidence interval 1.0–3.7 in juniors; odds ratio 1.9, confidence interval 1.1–3.4 in seniors). Family members were approached significantly less often as a resource for help by students who self-harmed than by those who did not, and school nurses were more often consulted by those who did self-harm.
Conclusion:
Around 40% of adolescents who self-harmed in the previous year did not seek help. School-based mental health should screen students at risk of self-harm, and educate school nurses about preventative care.
doi:10.2147/NDT.S37543
PMCID: PMC3509995  PMID: 23209369
self-harm; adolescence; help-seeking; prevention; Japan
4.  Post-hospitalization course and predictive signs of suicidal behavior of suicidal patients admitted to a psychiatric hospital: a 2-year prospective follow-up study 
BMC Psychiatry  2012;12:186.
Background
Suicidal patients admitted to a psychiatric hospital are considered to be at risk of suicidal behavior (SB) and suicide. The present study aimed to seek predictors of SB recurrence of the high-risk patients by examining their post-hospitalization course.
Method
The design was 2-year prospective follow-up study of patients consecutively admitted with SB to a psychiatric center in Tokyo. The DSM-IV diagnoses and SB-related features of subjects were determined in structured interviews. Subsequently, the subjects underwent a series of follow-up assessments at 6-month intervals. The assessment included inquiries into SB recurrence, its accompanying suicidal intent (SI) and SF-8 health survey. Analyses of serial change over time in the follow-up data and Cox proportional hazards regression analyses of SB recurrence were performed.
Results
106 patients participated in this study. The dropout rate during the follow-up was 9%. Within 2 years, incidences of SB as a whole, SB with certain SI (suicide attempt) and suicide were 67% (95% CI 58 - 75%), 38% (95% CI 29 - 47%) and 6% (95% CI 3 - 12%), respectively. Younger age, number of lifetime SBs and maltreatment in the developmental period were predictive of SB as a whole, and younger age and hopelessness prior to index admission were predictive of suicide attempt. Regarding diagnostic variables, anxiety disorders and personality disorders appeared to have predictive value for SB. Additionally, poor physical health assessed during the follow-up was indicated as a possible short-term predictor of SB recurrence.
Conclusions
This study demonstrated a high incidence of SB and suicide and possible predictors of SB recurrence in the post-hospitalization period of psychiatric suicidal patients. Specialized interventions should be developed to reduce the suicide risk of this patient population.
doi:10.1186/1471-244X-12-186
PMCID: PMC3549906  PMID: 23114285
Suicide attempt; Self-injurious behavior; Follow-up studies; Psychiatric hospitals; Mental disorders
5.  Irregular Bedtime and Nocturnal Cellular Phone Usage as Risk Factors for Being Involved in Bullying: A Cross-Sectional Survey of Japanese Adolescents 
PLoS ONE  2012;7(9):e45736.
Purpose
A number of studies have tried to identify risk factors for being involved in bullying in order to help developing preventive measures; however, to our knowledge, no study has investigated the effect of nocturnal lifestyle behavior such as sleep pattern or cellular phone usage. In the present study, we aimed to investigate the relationship between school bullying and sleep pattern or nocturnal cellular phone usage in adolescents. The effect of school size on school bullying was also examined.
Methods
Data from the cross-sectional survey of psychopathologies conducted for 19,436 Japanese students from 45 public junior high schools (7th–9th grade) and 28 senior high schools (10th–12th grade) were analyzed.
Results
Bullying status was significantly associated with irregular bedtime (OR = 1.23 and 1.41 for pure bullies and bully-victims, respectively) and e-mail exchange or calling after lights-out (OR = 1.53 and 1.31 for pure bullies and bully-victims, respectively) after controlling domestic violence and substance usage. In addition, school size was significantly associated with the increased risk of bullying in junior high school students (OR = 1.13 for bully-victims).
Conclusions
The present results suggested that sleep pattern and nocturnal cellular phone usage might be risk factors for being involved in school bullying in adolescents. Although further accumulation of data is needed, progressive trend towards nocturnal lifestyle and increasing usage of cellular phone might impair the well-being of adolescents. School-based interventions for lifestyle including sleep pattern and cellular phone usage may be encouraged to reduce school bullying.
doi:10.1371/journal.pone.0045736
PMCID: PMC3446940  PMID: 23029211
6.  Season of birth effect on psychotic-like experiences in Japanese adolescents 
A number of studies have investigated seasonality of birth in schizophrenia. Most of the studies have consistently observed an excess of winter births, often associated with decreased summer births. We postulated that psychotic-like experiences (PLEs), subclinical hallucinatory and delusional experiences, may also be affected by birth season. In the present study, we assessed the season of birth effect on the prevalence of PLEs using data from the cross-sectional survey of 19,436 Japanese adolescents. As a result, significant excess of winter births was observed in the prevalence of PLEs, accompanied by a decreased proportion of summer births. The odds ratios for the prevalence of PLEs were estimated to be 1.11, which was on the same order with those for the development of schizophrenia in the previous meta-analytic studies. To our knowledge, this is the first to show the seasonality of birth in the prevalence of PLEs and implicate the winter birth effect on subclinical stage of schizophrenia.
Electronic supplementary material
The online version of this article (doi:10.1007/s00787-012-0326-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s00787-012-0326-1
PMCID: PMC3562433  PMID: 22983561
Schizophrenia; Winter birth; Summer birth; Hallucination; Delusion
7.  The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack 
Background
The place where a patient experiences his/her first panic attack (FPA) may be related to their agoraphobia later in life. However, no investigations have been done into the clinical features according to the place where the FPA was experienced. In particular, there is an absence of detailed research examining patients who experienced their FPA at home. In this study, patients were classified by the location of their FPA and the differences in their clinical features were explored (e.g., symptoms of FPA, frequency of agoraphobia, and severity of FPA).
Methods
The subjects comprised 830 panic disorder patients who were classified into 5 groups based on the place of their FPA (home, school/office, driving a car, in a public transportation vehicle, outside of home), The clinical features of these patients were investigated. Additionally, for panic disorder patients with agoraphobia at their initial clinic visit, the clinical features of patients who experienced their FPA at home were compared to those who experienced their attack elsewhere.
Results
In comparison of the FPAs of the 5 groups, significant differences were seen among the 7 descriptors (sex ratio, drinking status, smoking status, severity of the panic attack, depression score, ratio of agoraphobia, and degree of avoidance behavior) and 4 symptoms (sweating, chest pain, feeling dizzy, and fear of dying). The driving and public transportation group patients showed a higher incidence of co-morbid agoraphobia than did the other groups. Additionally, for panic disorder patients with co-morbid agoraphobia, the at-home group had a higher frequency of fear of dying compared to the patients in the outside-of-home group and felt more severe distress elicited by their FPA.
Conclusion
The results of this study suggest that the clinical features of panic disorder patients vary according to the place of their FPA. The at-home group patients experienced "fear of dying" more frequently and felt more distress during their FPA than did the subjects in the other groups. These results indicate that patients experiencing their FPA at home should be treated with a focus on the fear and distress elicited by the attack.
doi:10.1186/1751-0759-6-12
PMCID: PMC3349583  PMID: 22494552
Place of first panic attack; Panic attack symptoms; Subtype of panic disorder; Agoraphobia
8.  Classification of First-Episode Schizophrenia Patients and Healthy Subjects by Automated MRI Measures of Regional Brain Volume and Cortical Thickness 
PLoS ONE  2011;6(6):e21047.
Background
Although structural magnetic resonance imaging (MRI) studies have repeatedly demonstrated regional brain structural abnormalities in patients with schizophrenia, relatively few MRI-based studies have attempted to distinguish between patients with first-episode schizophrenia and healthy controls.
Method
Three-dimensional MR images were acquired from 52 (29 males, 23 females) first-episode schizophrenia patients and 40 (22 males, 18 females) healthy subjects. Multiple brain measures (regional brain volume and cortical thickness) were calculated by a fully automated procedure and were used for group comparison and classification by linear discriminant function analysis.
Results
Schizophrenia patients showed gray matter volume reductions and cortical thinning in various brain regions predominantly in prefrontal and temporal cortices compared with controls. The classifiers obtained from 66 subjects of the first group successfully assigned 26 subjects of the second group with accuracy above 80%.
Conclusion
Our results showed that combinations of automated brain measures successfully differentiated first-episode schizophrenia patients from healthy controls. Such neuroimaging approaches may provide objective biological information adjunct to clinical diagnosis of early schizophrenia.
doi:10.1371/journal.pone.0021047
PMCID: PMC3119676  PMID: 21712987
9.  Comprehensive early intervention for patients with first-episode psychosis in Japan (J-CAP): study protocol for a randomised controlled trial 
Trials  2011;12:156.
Introduction
Comprehensive approaches for patients with psychotic symptoms play essential roles in the symptomatic and functional outcomes of patients, especially during disease onset. In Japan, the shortage of mental health services, particularly for outpatients, and community-based supports has been a major problem. The purpose of this trial is to investigate the effectiveness and affordability of 18-month comprehensive early intervention services for patients with first-episode psychosis compared with typical treatment.
Methods
This interventional, parallel, single-blinded (open but blinded raters trial) was effectively designed. The participants are patients with a diagnosis of F2 or F3 (International Classification of Disease, 10 th revision), with psychotic symptoms. The inclusion criteria were an age of 15-35 years, onset of psychotic symptoms within 5 years, first-episode psychosis, and residence in the catchment area of each site. Allocation will be conducted equally between case management and standard care groups. After enrollment, standard care will be provided for both groups, and community-based care to promote recovery for 18 months will be provided for the comprehensive approach group. The primary outcome will be the function domain of the global assessment of functioning scores at 18 months after enrollment. Data assessment will be performed at enrollment and 18, 36, and 60 months after enrollment. The target sample size will be 150, and registration will occur from March 1, 2011, to September 30, 2012.
Discussion
This trial will provide promising results about the effectiveness and cost-effectiveness of early intervention services in Japan to improve the quality and quantity of community mental health services.
Trial registration
This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (No. UMIN000005092).
doi:10.1186/1745-6215-12-156
PMCID: PMC3148989  PMID: 21689393
10.  Psychiatric disorders and clinical correlates of suicidal patients admitted to a psychiatric hospital in Tokyo 
BMC Psychiatry  2010;10:109.
Background
Patients admitted to a psychiatric hospital with suicidal behavior (SB) are considered to be especially at high risk of suicide. However, the number of studies that have addressed this patient population remains insufficient compared to that of studies on suicidal patients in emergency or medical settings. The purpose of this study is to seek features of a sample of newly admitted suicidal psychiatric patients in a metropolitan area of Japan.
Method
155 suicidal patients consecutively admitted to a large psychiatric center during a 20-month period, admission styles of whom were mostly involuntary, were assessed using Structured Clinical Interviews for DSM-IV Axis I and II Disorders (SCID-I CV and SCID-II) and SB-related psychiatric measures. Associations of the psychiatric diagnoses and SB-related characteristics with gender and age were examined.
Results
The common DSM-IV axis I diagnoses were affective disorders 62%, anxiety disorders 56% and substance-related disorders 38%. 56% of the subjects were diagnosed as having borderline PD, and 87% of them, at least one type of personality disorder (PD). SB methods used prior to admission were self-cutting 41%, overdosing 32%, self-strangulation 15%, jumping from a height 12% and attempting traffic death 10%, the first two of which were frequent among young females. The median (range) of the total number of SBs in the lifetime history was 7 (1-141). Severity of depressive symptomatology, suicidal intent and other symptoms, proportions of the subjects who reported SB-preceding life events and life problems, and childhood and adolescent abuse were comparable to those of the previous studies conducted in medical or emergency service settings. Gender and age-relevant life-problems and life events were identified.
Conclusions
Features of the studied sample were the high prevalence of affective disorders, anxiety disorders and borderline PD, a variety of SB methods used prior to admission and frequent SB repetition in the lifetime history. Gender and age appeared to have an influence on SB method selection and SB-preceding processes. The findings have important implications for assessment and treatment of psychiatric suicidal patients.
doi:10.1186/1471-244X-10-109
PMCID: PMC3018373  PMID: 21144041
11.  Haloperidol treatment induces tissue- and sex-specific changes in DNA methylation: a control study using rats 
Background
We previously found that there is a subtle difference in the global methylation state of blood leukocyte DNA between male subjects with and without schizophrenia. The aim of the current study was to determine whether this difference was a primary effect of the disease state, or a secondary effect of antipsychotics administered to these patients.
Methods
We examined the methyl cytosine (mC) content of DNA from the leukocytes, brain, and liver of rats using high performance liquid chromatography. A total of 40 male and female rats received for 21 days daily injection of haloperidol or vehicle solution alone.
Results
In control rats injected with buffer only, there was a sex-dependent difference in mC content in leukocyte DNA (male > female; P = 0.028, n = 10), similar to our previous observations in human peripheral leukocytes. No difference in mC content between the sexes was observed in the brain or liver in buffer-treated animals. Haloperidol treatment slightly decreased the mC content of leukocytes in male rats, but unexpectedly, increased the mC content of leukocytes in females. We observed a trend toward a higher level of mC in the liver in both sexes following haloperidol treatment, compared to buffer-treated animals. In contrast, haloperidol treatment resulted in a decrease in mC content in the brain in females, and this difference was statistically significant (P = 0.026).
Conclusion
These results indicate that haloperidol can affect DNA methylation states in the brain, as well as in certain other tissues, and raise the possibility that antipsychotic drugs play a role in the observed disparity in mC content in male subjects with and without schizophrenia.
doi:10.1186/1744-9081-2-37
PMCID: PMC1684254  PMID: 17132176

Results 1-11 (11)