A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Differential impacts of duration of untreated psychosis (DUP) on cognitive function in first-episode schizophrenia according to mode of onset.

BACKGROUND: The mode of onset and the course of schizophrenia illness exhibit substantial individual variations. Previous studies have pointed out that the mode of onset affects the duration of untreated psychosis (DUP) and clinical outcomes, such as cognitive and social functioning. This study attempted to clarify the association between the DUP and clinical features, taking the different modes of onset into consideration, in a prospective longitudinal study examining patients with first-episode schizophrenia. METHODS: This study was conducted in six areas of Japan. Patients with first-episode schizophrenia were followed for over 18 months. Cognitive function, psychopathology, and social functioning were assessed at baseline and at 6, 12, and 18-month follow-up points. RESULTS: We identified 168 patients and sufficient information was available to determine the DUP and the mode of onset for 156 patients (92.9%): 79 had an acute onset, and 77 had an insidious onset. The DUP was significantly associated with quality of life (QOL), social functioning, and cognitive function at most of the follow-up points in the insidious-onset group. The DUP and negative symptoms at baseline were significant predictors of cognitive function at the 18-month follow-up in the insidious-onset group. CONCLUSIONS: The present results further support the hypothesis that the DUP affects QOL, social functioning, and cognitive function over the course of illness, especially in patients with an insidious onset. Effective strategies for detecting and caring for individuals with insidious onset early during the course of schizophrenia will be essential for achieving a full patient recovery.

Psychotic-like experiences are associated with suicidal feelings and deliberate self-harm behaviors in adolescents aged 12-15 years.

OBJECTIVE: Psychotic disorders are a significant risk factor for suicide, especially among young people. Psychotic-like experiences (PLEs) in the general population may share an etiological background with psychotic disorders. Therefore, the present study examined the association between PLEs and risk of suicide in a community sample of adolescents. METHOD: Psychotic-like experiences, suicidal feelings, and self-harm behaviors were studied using a self-report questionnaire administered to 5073 Japanese adolescents. Depression and anxiety were evaluated using the 12-item General Health Questionnaire (GHQ). RESULTS: The presence of PLEs was significantly associated with suicidal feelings (OR = 3.1, 95% CI = 2.2-4.5) and deliberate self-harm behaviors (OR = 3.1, 95% CI = 2.0-4.8) after controlling for the effects of age, gender, GHQ-12 score, victimization, and substance use. Suicidal feelings and behaviors were more prevalent in subjects with a greater number of PLEs. CONCLUSION: Psychotic-like experiences may increase the risk of suicidal problems among adolescents.

Effects of a one-hour educational program on medical students' attitudes to mental illness.

A new 1-h educational program was developed to change attitudes towards mental illness, and was conducted on 95 first-year medical students in order to investigate its effects on their attitudes towards mental illness, using a pre- and postquestionnaire study design. A similar study without the program was conducted on 94 first-year medical students as controls. After the program, more students replied that they would accept former patients on relatively close social distance items. Favorable attitudinal changes were observed in terms of 'psychiatric services', 'human rights of the mentally ill', 'patients' independence in social life', and 'cause and characteristics of mental illness'. In contrast, no significant change was observed in the control group. These results suggest that attitudes towards mental illness could be changed favorably by this program.

Expressed emotion of families and the course of mood disorders: a cohort study in Japan.

BACKGROUND: Findings on expressed emotion (EE) of the family and the course of mood disorders have not been consistent. There has also been no report on these problems from Asia. METHODS: The subjects were 32 patients diagnosed to have mood disorders on the basis of DSM-IV and ICD-10 and 36 principal members of their families. EE was evaluated using Camberwell Family Interview (CFI). A cohort study was conducted for 9 months after discharge of the patients. The patients were divided into a high-EE group and a low-EE group using a few cut-off points concerning the number of critical comments (CCs) and emotional over-involvement (EOI), the 9-month relapse risks were compared, and the relapse risk ratio and its 95% confidence interval were calculated. Also, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and the optimal cut-off point was evaluated. Multiple logistic regression analysis was performed to control the effects of potential confounding factors. RESULTS: When the subjects with three or more CCs, or an EOI score of three or higher were regarded as a high-EE group, and the others as a low-EE group, the nine-month relapse risks were 83.3% (5/6) and 19.2% (5/26), respectively, and the relapse risk ratio (95% confidence interval) was 4.3 (1.8-12.2). The values of the validity parameters were the highest with these cut-off points. The effect of EE was also significant on multiple logistic regression analysis. LIMITATIONS: Small sample size and severity of the patients. CONCLUSIONS: Families' EE based on CFI correlated with relapse also in Japan.

Expressed emotion and psychoeducational intervention for relatives of patients with schizophrenia: a randomized controlled study in Japan.

The benefit of single-family treatment (SFT) in addition to short educational sessions (SES) consisting of multiple-family treatment was investigated. The study design was a randomized controlled study. Subjects were 30 patients suffering from schizophrenia with at least one of their family members showing high expressed emotion (EE) in the Camberwell Family Interview. After the SES, the patients were randomly allocated to two groups: those who received routine individual outpatient treatment and those who received additional SFT and routine treatment. The two groups were followed for 9 months after discharge, and the relapse risks were compared. The relapse risk was lower in the SES+SFT group than in the SES group (23.1% vs. 35.3%). However, the difference was not significant. When high-EE families were classified into those with many critical comments (high-CC) or a high score of emotional overinvolvement (high-EOI), the relapse risk was 0% in the patients living with a high-CC family not only in the SES+SFT group but also in SES group. In the patients living with a high-EOI family, the relapse risk was lower in the SES+SFT group than in the SES group (42.9% vs. 60.0%). These findings suggest that high-EE families should receive at least SES, and additional SFT should be given to families with specific needs.

Expressed emotion and family distress in relatives of patients with schizophrenia in Japan.

We evaluated the association between distress and expressed emotion (EE) in family members of patients with schizophrenia by the General Health Questionnaire (GHQ), the Camberwell Family Interview (CFI), and the Five-Minute Speech Sample (FMSS). The GHQ score was higher in the high-EE group determined by both the CFI and FMSS. The difference in the GHQ score between high-EE and low-EE groups was more marked for the CFI. Family distress is closely associated with the EE classification, but the EE classification by the CFI more markedly reflected family distress versus the FMSS. Even in relatives with low EE, distress was marked, and therefore, coping with mental health in family members is important.

Evaluation of expressed emotion (EE) status in mood disorders in japan: inter-rater reliability and characteristics of EE.

The reliability of expressed emotion (EE) ratings by the Camberwell Family Interview (CFI) and characteristics of EE were evaluated in families of patients with mood disorders in Japan. The subjects were 27 patients with mood disorders and 31 members of their families. The CFI was carried out with the family members. EE was rated by two raters independently, and the inter-rater reliability was evaluated according to Spearman's correlation coefficient by ranks and the kappa-value. The distribution of subscales of EE in these subjects was compared with that in families of patients with schizophrenia in Japan and families of patients with mood disorders abroad. Concerning critical comments (CC), hostility (H), and emotional over-involvement (EOI), which are important for EE rating, Spearman's correlation coefficient and the kappa-values were 0.4-0.8, and the reliability of EE ratings in mood disorders was not high. The proportion of positive agreement was particularly low in H and EOI. CCs were fewer in families of Japanese patients with mood disorders than in those with schizophrenia or families of American or European patients with mood disorders. Re-evaluation of the inter-rater reliability of EE ratings in mood disorders is needed. Expressed emotion was more suppressed in families of patients with mood disorders than in those of patients with schizophrenia. Expressed emotion was also more reserved in the Japanese subjects than in their Western counterparts.

Validity of a Five-Minute Speech Sample in measuring expressed emotion in the families of patients with schizophrenia in Japan.

The Five-Minute Speech Sample (FMSS) is a brief measure for the assessment of expressed emotion (EE). No prior studies have investigated the validity of the FMSS in comparison to the Camberwell Family Interview (CFI) in Japan. Therefore, we administered the CFI and the FMSS to schizophrenic families in an attempt to evaluate the usefulness of the FMSS. The ratings obtained from the CFI were then used to estimate the validity of the FMSS. The overall agreement of the two methods was 53.8%. We conclude that the FMSS may be a useful screening method for the evaluation of EE. Borderline low-EE subjects may have to be included in the high-EE group to improve the sensitivity.

Expressed emotion of families and negative/depressive symptoms in schizophrenia: a cohort study in Japan.

This study investigated whether the Expressed Emotion (EE) status of families is associated with an increased risk of negative and depressive symptoms in schizophrenia. The subjects were 52 schizophrenic patients from mental hospitals in Kochi, Japan, who satisfied the DSM-III-R or ICD-9 criteria for schizophrenia. The Japanese version of the Camberwell Family Interview was administered to 73 key relatives of the patients within 2 weeks after admission. A certified rater evaluated the EE's status of each family, using an audiotaped interview and its transcript. Using cohort study design, the subjects were followed for 9 months after their discharge and were monitored for negative and depressive symptoms. Trained psychiatrists who were blind to the EE status of the patients' households administered the Brief Psychiatric Rating scale (BPRS) at discharge, and 9 months after discharge. Repeated-measures analyses of variance showed that EE effects were significant in Emotional withdrawal in all subjects, Depressive mood and Total depressive symptoms in non-relapsers. A multiple regression analyses revealed that EE's effect was significant only in Depressive mood in non-relapsers controlling confounding factors. In non-relapsers in positive symptoms, high EE families could make patients depressed. EE's effect on negative symptoms remains to be established.

Critical comments made to schizophrenic patients by their families in Japan.

Critical comments (CCs) are one of the components of expressed emotion (EE), an excess of which is related to relapse. Therefore, CCs could be a target of family psychoeducation. We examined the nature of CCs for clues to family therapy. We classified CCs expressed in the Camberwell Family Interview (CFI) into nine categories: (1) positive symptoms, (2) negative symptoms, (3) compliance with medical care, (4) life problems, (5) socially inappropriate behavior, (6) aggression, (7) rejection, (8) premorbid personality, and (9) other. Positive symptoms were the most frequently commented on (34%). Negative symptoms were not so frequently commented on (11%), as expected. In comparing high-EE and low-EE relatives or relapsers and nonrelapsers, there were no significant differences in the distribution of the nine CC categories. We conclude that positive symptoms should be a main topic of family psychoeducation in such cases.

Expressed emotion and social function.

We examined whether expressed emotion (EE) influenced the social functioning of schizophrenia. Twenty-nine subjects meeting the diagnostic criteria of ICD-9 or DSM-III-R participated in the study. The Camberwell Family Interview was conducted to evaluate EE, and subjects were divided into high EE and low EE groups. The subjects had been followed up for 9 months and their social functioning was compared between the two groups as assessed with the Katz Adjustment Scales. In the high EE group, levels of both performance of socially-expected activities and free-time activities slightly declined at follow-up. In contrast, those in the low EE group improved and the score increase in the level of performance of socially-expected activities was significant (P < 0.05). We confirmed the relationship of families' EE status with social functioning in schizophrenia.