Current viewpoints on DSM-5 in Japan.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, and its official Japanese version was published in 2014. The Japanese Government uses classifications from the 10th revision of the I nternational C lassification of D iseases (ICD-10) to categorize disorders and determine treatment fees. However, since the publication of the DSM-III, the use of the DSM system has become prevalent in research and educational settings in Japan. In addition to traditional psychiatry, both the ICD and the DSM are taught by many Japanese medical schools, and virtually all clinical research and trials refer to the DSM to define targeted disorders. Amid the current backdrop in which the reputation of the DSM-5 is being established, the editorial board of P sychiatry and C linical N eurosciences has asked Japanese experts across 12 specialties to examine the structure of the DSM-5, including the following categories: Neurodevelopmental Disorders, Schizophrenia Spectrum Disorders, Major Depression, Bipolar Disorders, Obsessive-Compulsive Disorders, Somatic Symptom Disorder, Eating Disorders, Substance-Related and Addictive Disorders, Gender Dysphoria, and Neurocognitive Disorders. Although opinions were only obtained from these selected experts, we believe that we have succeeded, to a certain extent, in presenting views that are representative of each specialty.

Clinical Features of Japanese Males with Anorexia Nervosa.

BACKGROUND: Anorexia nervosa (AN) is a mental disease with a high mortality rate, and progresses to a serious state, even in males; however the characteristics of male AN patients, including the sex ratio in Japan and the consultation behavior, have not yet been clarified. Therefore, the objective of the present study was to investigate the clinical characteristics of Japanese male AN patients, with the aim of achieving early interventions. METHODS: A total of 2015 AN patients, 60 males and 1955 females, were extracted from 4606 eating disorder patients who consulted Osaka City University Hospital for 34.5 years. The sex ratio was examined, and clinical features, mainly those related to consultation behavior, were compared between males and females. The rate of early drop-outs from outpatient treatments was also determined in male AN patients. RESULTS: The male ration in AN patients was 3.0%, which was markedly lower than generally considered. No significant sex difference was noted in the mean age at the time of consultation or delays in treatment. The rate of weight loss from the premorbid to lowest body weight was similar between males and females. Regarding social backgrounds, the employment rate was higher in males than in females. Male AN patients were more likely to initially consult the psychiatry department. Furthermore, the rate of early drop-outs from outpatient treatments appeared to be higher among males than females. CONCLUSIONS: The male ratio in Japanese clinical AN patients was low. Consultation between may be restricted in males more than in other countries because eating disorders are considered to be female diseases. Male AN is physically severe, similar to female AN; therefore, early interventions were considered important. Educational programs for eating disorders not only in the general public, but also in school and companies may promote early interventions. Treatments that considered sex differences need to be developed in order to prevent early drop-outs.

Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population.

The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653-0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557-0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

Anxiety in children with high-functioning pervasive developmental disorder.

BACKGROUND: Anxiety symptoms in children with pervasive developmental disorder (PDD) often appear to be not as severe as those in children with anxiety disorders or often appear to be the core features of PDD, and therefore, they do not meet the diagnostic criteria for anxiety disorders. In this study, we assessed anxiety broadly in line with dimensions of anxiety and not with an operational categorical diagnosis. The objective of this study was to reveal that children with high-functioning PDD have more anxiety than children in the general population. METHODS: Forty-six children with high-functioning PDD (6-15 years old) were assessed for total anxiety and six subcategories of anxiety, including separation anxiety, generalized anxiety, social phobia, panic/agoraphobia, physical injury fears, and obsessive-compulsiveness. Anxiety in children with high-functioning PDD was compared to that in children of the general population and to that in children with anxiety disorders in a previous study. RESULTS: Children with high-functioning PDD had significantly more symptoms of total anxiety and all subcategories of anxiety except for social phobias than children in the general population, and had significantly fewer symptoms of total anxiety, separation anxiety, generalized anxiety, and social phobias than children with anxiety disorders. CONCLUSIONS: As anxiety in children with high-functioning PDD does not always meet diagnostic criteria for an anxiety disorder, psychiatrists must pay much attention to anxiety and not only depend on diagnostic criteria in order to not miss the chance of treating these children.

Relationships between occupational stress and depressive symptoms among prison officers in Japan.

BACKGROUND: The relationships between occupational stress and depressive symptoms in prison officers have rarely been studied in Japan. Thus, we analyzed the associations between occupational stress factors and depressive symptoms among Japanese prison officers. METHODS: This was a cross-sectional study involving 426 male prison officers (20-60-year-old). Depressive symptoms were assessed using the Zung Self-Rating Depression Scale. Using this scale and a cut-off point of 50, the subjects were divided into the "depressive group" and "non-depressive group". Occupational stress was evaluated using the Generic Job Stress Questionnaire. Comparisons among the groups were performed with multiple logistic regression analysis. RESULTS: Of the 426 subjects, 107 were included in the depressive group. After adjusting for demographic and occupational variables, higher scores for the physical environment, role ambiguity, and quantitative workload and a lower score for social support from co-workers were found to be associated with an increased odds ratio of depressive symptoms. CONCLUSIONS: The physical environment, role ambiguity, quantitative workload, and social support from coworkers are associated with depressive symptoms in Japanese prison officers. We hope that educating prison officers about the results of this study and organizational/individual-based improvement strategies will reduce their risk of depression.

No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese.

The Met66 allele of the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785-1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one-way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.

Evaluation of therapeutic response to donepezil by positron emission tomography.

BACKGROUND: Donepezil hydrochloride (Donepezil) is an acetylcholinesterase inhibitor (AChEI) that is used for the symptomatic treatment of Dementia of the Alzheimer's Type (DAT). Recently, the effects of AChEI in patients with DAT have been investigated using positron emission tomography (PET) or single photon emission computed tomography (SPECT). This study is to evaluate the usefulness of fluorine-18-fluorodeoxyglucose (FDG)-PET in assessing the therapeutic response of Donepezil to DAT using Regions of Interest (ROI) analysis. METHODS: The participants included eleven outpatients diagnosed as having DAT according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The patients were performed FDG-PET before initiating Donepezil therapy and after 12 weeks of medication. Cognitive change was measured using the Japanese version of the Alzheimer's disease Assessment Scale cognitive subscale (ADAS-J cog) and the group was divided into Responders and Non-responders based on these results. We used FDG-PET to investigate glucose metabolism of the brain and measured FDG uptake in the ROI set in each lobe of the brain. Then the ratios of the post-treatment uptake to pre-treatment uptake were determined. RESULTS: In the Responders, the mean ratios in the frontal, temporal, occipital, parietal, and temporoparietal lobes were 2.18, 1.62, 1.15, 1.12, and 1.09 respectively. The mean ratios of the Non-responders were 0.69, 0.88, 0.75, 0.98, and 0.68 respectively. Significant differences were found between the ratios of the Responders and Non-responders in the frontal and occipital lobes (p < 0.05). CONCLUSIONS: These findings suggest that FDG-PET could be useful for the evaluation for monitoring response to Donepezil.

A case series of aripiprazole augmentation of selective serotonin reuptake inhibitors in treatment-refractory obsessive compulsive disorder.

OBJECTIVE: For the obsessive compulsive disorder (OCD) patients refractory to selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, such as risperidone, or olanzapine have been found effective in the augmentation of SSRIs. However these atypical antipsychotics may cause a number of safety concerns associated with body weight or metabolic changes. We sought to investigate the efficacy and safety of a novel atypical neuroleptic aripiprazole as an augmenting agent for the treatment-resistant OCD. METHODS: Eleven patients who had previously been assessed as poorer responders (<10% reduction of Y-BOCS) to both adequate SSRI monotherapy such as fluvoxamine or paroxetine and the subsequent atypical antipsychotic augmentation of SSRIs were included in this study. The addition of aripiprazole to ongoing SSRIs was continued for at least 12 weeks in the subjects except for one who dropped out during the period. RESULTS: The mean maximum daily dosage of aripiprazole in the completers was 10.9 ± 3.4 mg/day. Seven of 10 completers exhibited significant reduction of Y-BOCS (>35%) accompanying a few adverse events. CONCLUSIONS: This preliminary study supports the notion that adding aripiprazole to SSRIs could be a valid and effective strategy for treatment-resistant OCD patients. Thus it points towards the need of further controlled and longitudinal studies.

Correlations between the offensive subtype of social anxiety disorder and personality disorders.

AIMS: Recent studies have revealed the possibility that the offensive subtype of social anxiety disorder (SAD) may no longer be a culture-bound syndrome; however, detailed clinical pictures have never been reported. This study investigated the differences between the offensive and non-offensive subtypes of SAD in terms of the background and axis I and II comorbidity. METHODS: A total of 139 patients with SAD based on DSM-IV criteria were studied by conducting a semi-structured interview including the Structured Clinical Interview for DSM-IV axis I and II disorders, and the Liebowitz Social Anxiety Scale. RESULTS: Fifty-two (37%) patients were classified with the offensive subtype. There were no significant differences in most demographic variables and axis I lifetime comorbidity between offensive and non-offensive subtype patients. On logistic regression analysis, offensive subtype patients showed a more frequent history of parental physical abuse, higher Liebowitz Social Anxiety Scale scores, and more frequently exhibited obsessive--compulsive personality disorders than non-offensive subtype patients. CONCLUSION: Yamashita (1977) reported that the majority of offensive subtype patients were doted on by their parents, although current offensive subtype patients are more likely to have had a troubled childhood, show severer forms of SAD, and more frequently exhibit an inflexible personality. This study suggested that the offensive subtype might not be essentially different from the non-offensive subtype (quantitative rather than qualitative).

[Eating disorders in the workplace].

The prevalence of eating disorders (ED) has increased and these are intractable disorders that require prolonged treatment. The workplace is an important life scene for the patients, but there are few reports available about the current status and correspondence to ED in workplace. Based on a survey of 1248 enterprises, we discuss the cognition of each form of ED. In addition, the background, eating behaviors, and job stress of 2004 workers were also surveyed. Based on these responses, workers who were supposed to demonstrate anorexia nervosa (AN), bulimia nervosa (BN), or night eating syndrome (NES) were identified. The same survey was conducted among outpatients with ED, and the findings were compared with those of a healthy control group. The terms ED, AN, and BN were highly acknowledged in the workplace, but recognition of NES was low. In addition, the prevalence of workers suspected of AN, BN, or NES were 0.27%, 0.21%, and 12.9%, respectively. Based on comparisons of job stress in working ED patients with job stress in workers without ED, and comparisons of job stress in NES workers with job stress in workers without eating problems, specific job stressors were supposed to be associated with ED. These findings indicate the importance of learning appropriate techniques for coping with job stress and the necessity of recognizing abnormal eating behaviors in the workplace.

[Current situation of drug dependence and task against it].

According to several kind of nationwide surveys and censuses, the 3rd epidemic methamphetamine abuse/dependence still continues since 1995. Methamphetamine is still most popular drug among people with drug abuse/dependence despite strict legal restriction. The majority of these are repeat offenders. This indicates the need for development of medical treatment targeting drug dependence and for its social support system. At the same time, abuse of cannabis, narcotics, MDMA has increased and non-regulatory drugs such as designer drugs emerged mainly among young people, while solvent abuse/dependence is dramatically decreased. Benzodiazepine dependence occur in patients taking therapeutic doses of benzodiazepine. The elderly patients are most vulnerable to benzodiazepine dependence. Education of benzodiazepine dependence and development of the withdrawal program are needed.

Frontal hypoperfusion in depressed patients with dementia of Alzheimer type demonstrated on 3DSRT.

AIMS: Depressive symptoms are common in patients with dementia of Alzheimer type (DAT) and contribute to clinical morbidity. Previous studies have suggested that hypoperfusion in the prefrontal cortex and anterior cingulate gyrus are involved in the pathophysiology of depression in DAT. Using 3-D stereotactic region of interest (ROI) template (3DSRT), fully automated ROI analysis software, the purpose of the present study was to investigate the relationship between depressive symptoms and regional cerebral blood flow (rCBF) in DAT. METHODS: Technetium-99m-ethyl cysteinate dimer ((99m)Tc-ECD) single-photon emission computed tomography (SPECT) and Japanese version of the Neuropsychiatric Inventory (NPI) were carried out in 35 patients diagnosed as having mild-moderate DAT according to DSM-IV. These patients were divided into the depressive group (D group: n = 17) and non-depressive group (ND group: n = 18) using the NPI depression items. All data from SPECT images were analyzed using 3DSRT software. On 3DSRT the perfusion ratios (rCBF of bilateral callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus and hippocampus/cerebellar hemisphere) of each segment were compared between the D group and the ND group. RESULTS: The perfusion ratios of the left callosomarginal segment for the D group were significantly lower (P < 0.05) than those of the ND group. CONCLUSIONS: Hypoperfusion in the left frontal cortex contributes to the expression of depressive symptoms in patients with DAT.

The clinical utility of symptom dimensions in obsessive-compulsive disorder.

Factor analyses in obsessive-compulsive disorder (OCD) have consistently identified several different symptom dimensions. Nevertheless the clinical utility of identifying such symptom dimensions remains somewhat unclear. On the basis of their principal symptoms, 343 OCD patients were divided into four symptom dimension subgroups; 1) contamination/washing, 2) hoarding, 3) symmetry/repeating and ordering, and 4) forbidden thoughts/checking. Clinical variables including 1-year treatment outcome were compared across these patient subgroups. Most patients (74%) could distinctively be categorized as falling into a particular symptom subgroup. The groups were differentially characterized by some demographic and clinical features. For instance, both the symmetry and hoarding groups were significantly associated with decreased global functioning and greater OCD severity. Moreover the hoarding group was significantly more likely than the others to show longer duration of illness, lower rate of marriage, poor insight, and poorer outcome. However, about a quarter of the participants could not be classified definitively into a particular group. Our findings provide partial support for the clinical utility of a simple measure of symptom dimensions in OCD. In clinical settings, however, the limitations of such a simple measure of predominant symptom dimensions should be borne in mind and further work on their validity and utility is needed.

Clinical features and treatment characteristics of compulsive hoarding in Japanese patients with obsessive-compulsive disorder.

INTRODUCTION: Compulsive hoarding has been studied primarily in Western countries. Here we sought to examine compulsive hoarding in Japanese patients with obsessive-compulsive disorder (OCD). The heterogeneous nature of hoarding was also investigated. METHODS: One hundred and sixty-eight OCD outpatients were initially assessed to determine the presence or absence of compulsive hoarding, and whether hoarding was primary or secondary to another symptom dimension for which they had received treatment for 1 year. RESULTS: Of the participants, 54 patients were found to have compulsive hoarding. Hoarders were significantly more likely than non-hoarding patients to have more severe psychopathology including elevated severity of OCD symptoms, poorer insight, higher prevalence of comorbid schizotypal or obsessive-compulsive personality disorder, closer association with symmetry dimension, and poorer treatment outcome. Comparisons of subjects with primary and secondary hoarding found that the former group had more severe clinical features, while the latter group hoarded a wider variety of items, including apparently bizarre ones. CONCLUSION: The prevalence and clinical characteristics of compulsive hoarding in OCD subjects was similar to those reported in Western countries, supporting its trans-cultural consistency. The distinction between primary and secondary hoarding in OCD is clinically useful, and may contribute to the debate about whether hoarding should be a separate diagnostic entity.

A ghrelin gene variant may predict crossover rate from restricting-type anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis.

BACKGROUND: Patients with anorexia nervosa restricting type (AN-R) often develop bulimic symptoms and crossover to AN-binge eating/purging type (AN-BP), or to bulimia nervosa (BN). We have reported earlier that genetic variants of an orexigenic peptide ghrelin are associated with BN. Here, the relationship between a ghrelin gene variant and the rate of change from AN-R to other phenotypes of eating disorders (EDs) was investigated. METHODS: Participants were 165 patients with ED, initially diagnosed as AN-R. The dates of their AN-R onset and changes in diagnosis to other subtypes of ED were investigated retrospectively. Ghrelin gene 3056 T-->C SNP (single nucleotide polymorphism) was genotyped. Probability and hazard ratios were analyzed using life table analysis and Cox's proportional hazard regression model, in which the starting point was the time of AN-R onset and the outcome events were the time of (i) onset of binge eating, that is, when patients changed to binge eating AN and BN and (ii) recovery of normal weight, that is, when patients changed to BN or remission. RESULTS: Patients with the TT genotype at 3056 T-->C had a higher probability and hazard ratio for recovery of normal weight. The ghrelin SNP was not related with the onset of binge eating. CONCLUSION: The 3056 T-->C SNP of the ghrelin gene is related to the probability and the rate of recovery of normal body weight from restricting-type AN.

A two-year follow-up study of chronic fatigue syndrome comorbid with psychiatric disorders.

AIMS: Chronic fatigue syndrome patients often have comorbid psychiatric disorders such as major depressive disorders and anxiety disorders. However, the outcomes of chronic fatigue syndrome and the comorbid psychiatric disorders and the interactions between them are unknown. Therefore, a two-year prospective follow-up study was carried out on chronic fatigue syndrome patients with comorbid psychiatric disorders. METHODS: A total of 155 patients who met the Japanese case definition of chronic fatigue syndrome were enrolled in this study. Comorbid psychiatric disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria. Patients with comorbid psychiatric disorders received psychiatric treatment in addition to medical therapy for chronic fatigue syndrome. Seventy patients participated in a follow-up interview approximately 24 months later. RESULTS: Of the 70 patients with chronic fatigue syndrome, 33 patients were diagnosed as having comorbid psychiatric disorders including 18 major depressive disorders. Sixteen patients with psychiatric disorders and eight patients with major depressive disorders did not fulfill the criteria of any psychiatric disorders at the follow up. As for chronic fatigue syndrome, nine out of the 70 patients had recovered at the follow up. There is no significant influence of comorbid psychiatric disorders on the outcome of chronic fatigue syndrome. CONCLUSIONS: Chronic fatigue syndrome patients have a relatively high prevalence of comorbid psychiatric disorders, especially major depressive disorders. The outcomes of chronic fatigue syndrome and psychiatric disorders are independent. Therefore treatment of comorbid psychiatric disorders is necessary in addition to the medical treatment given for chronic fatigue syndrome.

A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting SSRI-refractory obsessive-compulsive disorder.

OBJECTIVE: Although atypical antipsychotic agents have been found effective in the augmentation of serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in short-term trials, there are few data on the effectiveness and safety of these agents in clinical settings over the long term. METHOD: Subjects (N = 46) who responded to selective SRIs (SSRIs) in an initial 12-week trial were continued on SSRI monotherapy plus cognitive-behavioral therapy (CBT) for 1 year. Subjects (N = 44) who failed to respond to SSRIs were randomly assigned to 1 of 3 atypical antipsychotics -- olanzapine, quetiapine, or risperidone -- and were consecutively treated using SSRI + atypical antipsychotics combined with CBT for 1 year. This study was conducted from January 2006 to November 2007 at Osaka City University Graduate School of Medicine Hospital, Japan. RESULTS: Augmentation with atypical antipsychotics reduced mean +/- SD Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores in SSRI-refractory OCD patients (at initial assessment = 29.3 +/- 9.9, after 1 year = 19.3 +/- 6.8). However, compared to SSRI responders (at initial assessment = 25.8 +/- 11.4, after 1 year = 13.7 +/- 4.6), total YBOCS scores in those who required atypical antipsychotic augmentation were initially higher, and they remained at higher levels than those of SRI responders after 1 year of the treatments. CONCLUSIONS: Our work does not sufficiently support the long-term effectiveness of the atypical antipsychotics in the augmentation of SSRIs for treatment-resistant OCD patients. Even though this approach seems useful for some types of OCD patients, such as those with symmetry/ordering and hoarding symptoms, these data emphasize the limitations of the current pharmacotherapeutic options in treatment-refractory OCD, and their chronic use raises a number of safety concerns. TRIAL REGISTRATION: (ClinicalTrials.gov) Identifier NCT00854919.