Comparing the driving behaviours of individuals with frontotemporal lobar degeneration and those with Alzheimer's disease.

BACKGROUND: Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD). METHODS: The subjects were 28 FTLD and 67 AD patients who visited the Department of Psychiatry, Kochi Medical School Hospital. We conducted semi-structured interviews with their families and caregivers about traffic accident history and changes in patient driving behaviours after dementia onset and then compared the findings between the two groups. RESULTS: Overall changes in driving behaviours were reported in 89% (25/28) and 76% (51/67) of the FTLD and AD patients, respectively (P = 0.17). In the FTLD group, difficulty in judging inter-vehicle distances, ignoring road signs and traffic signals, and distraction were reported in 50% (14/28), 61% (17/28), and 50% (14/28) of patients, respectively, and 75% (21/28) patients had caused a traffic accident after dementia onset. The risk of causing an accident was higher in the FTLD group than in the AD group (odds ratio = 10.4, 95% confidence interval = 3.7-29.1). In addition, the mean duration between dementia onset and a traffic accident was 1.35 years in the FTLD group compared with 3.0 years in the AD group (P < 0.01). CONCLUSIONS: Patients with FTLD were more likely to show dangerous driving behaviours than those with AD, and the risk of causing a traffic accident may be higher in patients with FTLD from an early disease stage.

Impaired musical ability in people with schizophrenia.

BACKGROUND: Assessment of the musical ability of people with schizophrenia has attracted little interest despite the diverse and substantive findings of impairments in sound perception and processing and the therapeutic effect of music in people with the illness. The present study investigated the musical ability of people with schizophrenia and the association with psychiatric symptoms and cognition. METHODS: We recruited patients with chronic schizophrenia and healthy controls for participation in our study. To measure musical ability and cognitive function, we used the Montreal Battery of Evaluation of Amusia (MBEA) and the Brief Assessment of Cognition in Schizophrenia (BACS). We carried out a mediation analysis to investigate a possible pathway to a deficit in musical ability. RESULTS: We enrolled 50 patients and 58 controls in the study. The MBEA global score in patients with schizophrenia was significantly lower than that in controls (p < 0.001), and was strongly associated with both the composite cognitive function score (r = 0.645, p < 0.001) and the negative symptom score (r = -0.504, p < 0.001). Further analyses revealed direct and indirect effects of negative symptoms on musical ability. The indirect effects were mediated through cognitive impairment. LIMITATIONS: The relatively small sample size did not permit full evaluation of the possible effects of age, sex, education, medication and cultural influences on the results. CONCLUSION: Examining the associations between musical deficits, negative symptoms and cognitive imapirment in patients with schizophrenia may identify shared biological mechanisms.

A greater number of somatic pain sites is associated with poor mental health in adolescents: a cross-sectional study.

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.

[Early intervention in an early psychosis outpatient clinic].

The importance of early detection and intervention for psychiatric disorders, such as schizophrenia, is beginning to attract attention based on the results of imaging and psychosocial studies. Unfortunately, Japan still lags markedly behind Western countries and Australia in respect of early detection and intervention. We conducted a collaborative questionnaire survey of mental health among junior and senior high school students, and found that education on psychiatric disorders is not provided in schools and that the detection of these disorders is delayed due to the lack of awareness and accurate information. Early detection and treatment of psychiatric disorders takes more time than regular outpatient care, and an early psychosis outpatient clinic was established at our institution as a special outpatient clinic. The early psychosis outpatient clinic managed by me cannot be involved in visiting schools to carry out educational activities due to manpower problems and other reasons. However, through individual cases, I am aware that cooperation with schools is as important as cooperation with patients' families, not only to treat psychiatric symptoms, but also to check whether students are viewed with discomfort by classmates due to adverse effects of treatment, such as extrapyramidal symptoms. My aim is to improve the mental health of as many children as possible through future activities.

Cost-effectiveness of family psychoeducation to prevent relapse in major depression: results from a randomized controlled trial.

BACKGROUND: Family psychoeducation is a relatively simple and straightforward intervention whose prophylactic effectiveness and cost-effectiveness is well-established for schizophrenia. We have recently demonstrated its effectiveness for unipolar depression, but its cost-effectiveness has never been examined. We hereby report a cost-effectiveness analysis alongside a randomized controlled trial in order to assess its cost-effectiveness for preventing relapse/recurrence in depression. METHODS: Fifty-seven patients diagnosed with major depression and undergoing its maintenance treatment, and their primary family members were randomized to treatment as usual (TAU) only or to TAU plus family psychoeducation, which consisted of four 2-hour multiple-family sessions consisting of didactic lectures about depression (30 minutes) and group discussion and problem solving (60-90 minutes). The economic analyses were undertaken from the perspective of the National Health Insurance (NHI), assuming the most reasonable price of US$50 per psychoeducation session per patient. The main outcome measures included relapse-free days and direct costs to the NHI. RESULTS: The intervention group enjoyed 272 (SD: 7.1) relapse-free days, while the control group spent 214 (SD: 90.8) relapse-free days (Cox proportional hazard ratio=0.17, 95%CI: 0.04 to 0.75, p=0.002). Cost-effectiveness acceptability curves suggested that the family psychoeducation has 90% or more chances of being cost-effective if the decision-maker is prepared to pay US$20 for one additional relapse-free day. This cost-effectiveness finding was robust when the price for family psychoeducation ranged between 50% to 150% of the baseline scenario in sensitivity analyses. If a relapse-free day is considered to be worth $30 or more, all the pricing scenarios have a close to 100% probability of being cost-effective. CONCLUSION: Family psychoeducation is effective in the relapse prevention of depression and is highly likely to be cost-effective if a relapse-free day is valued as US$20 or more. TRIAL REGISTRATION: UMIN-CTR (UMIN000005555).

Not only body weight perception but also body mass index is relevant to suicidal ideation and self-harming behavior in Japanese adolescents.

Whether a low body mass index (BMI) is directly associated with a high risk of suicidal ideation or self-harming behavior in adolescents is still inconclusive. This study has, therefore, evaluated the relevance of BMI to suicidal ideation and self-harming behavior after controlling for body weight perception (BWP) and other potential confounding factors. BMI, BWP, suicidal ideation, and self-harming behavior were all assessed using a self-report questionnaire administered to 18,104 Japanese adolescents. Potential confounding factors were also evaluated. The data were then analyzed using bivariate and multivariate logistic regression. Low BMI was associated with suicidal ideation and deliberate self-harm when controlling for sex, age, drug use, emotional distress, and BWP. Low BMI may be an independent risk factor for suicidal ideation and deliberate self-harming behavior in Japanese adolescents.

Effects of psychosocial program for preparing long-term hospitalized patients with schizophrenia for discharge from hospital: randomized controlled trial.

AIM: The aims of the present study were to revise the Community Re-entry Program-Japanese version and to review the effectiveness of the revised Program, named the Discharge Preparation Program. METHODS: This study was a randomized controlled trial. The Discharge Preparation Program (DPP) was the intervention condition (n = 26), and the usual rehabilitation program was the control condition (n = 23). Outcome indicators included factors that make patient discharge difficult (which nurses evaluated), psychiatric symptom, knowledge about the illness or medication, and the number of patients who were discharged within 6 months after the end of a program. RESULTS: Significant improvements were found in the score of the 'Issues on treatment compliance' factor and the score of the 'Autistic life' factor, which are subscales of the Discharge Difficulty Scale, for the DPP group, on two-way ANOVA ('Issues on treatment compliance': F = 3.818, P < 0.10; 'Autistic life': F = 4.155, P < 0.05) These factors affected discharge outcome. Thus, the program may be capable of promoting discharge of long-term hospitalized psychiatric patients. With regard to the number of patients discharged in 6 months after the end of a program, there was no significant difference between both groups. CONCLUSION: The present result is in agreement with past studies, and the DPP is useful in discharge support for patients with schizophrenia in Japan.

Identification of stomatal-regulating molecules from de novo arylamine collection through aromatic C-H amination.

Stomata-small pores generally found on the leaves of plants-control gas exchange between plant and the atmosphere. Elucidating the mechanism that underlies such control through the regulation of stomatal opening/closing is important to understand how plants regulate photosynthesis and tolerate against drought. However, up-to-date, molecular components and their function involved in stomatal regulation are not fully understood. We challenged such problem through a chemical genetic approach by isolating and characterizing synthetic molecules that influence stomatal movement. Here, we describe that a small chemical collection, prepared during the development of C-H amination reactions, lead to the discovery of a Stomata Influencing Molecule (SIM); namely, a sulfonimidated oxazole that inhibits stomatal opening. The starting molecule SIM1 was initially isolated from screening of compounds that inhibit light induced opening of dayflower stomata. A range of SIM molecules were rapidly accessed using our state-of-the-art C-H amination technologies. This enabled an efficient structure-activity relationship (SAR) study, culminating in the discovery of a sulfonamidated oxazole derivative (SIM*) having higher activity and enhanced specificity against stomatal regulation. Biological assay results have shed some light on the mode of action of SIM molecules within the cell, which may ultimately lead to drought tolerance-conferring agrochemicals through the control of stomatal movement.

Family psychoeducation for major depression: randomised controlled trial.

BACKGROUND: The value of family psychoeducation for schizophrenia has been well established, and indications for its use have recently expanded to include bipolar affective disorder. However, no study to date has adequately examined its use in depression. AIMS: To examine family psychoeducation in the maintenance treatment of depression and to investigate the influence of the family's expressed emotion (EE) on its effectiveness. METHOD: Of 103 patients diagnosed with major depression and their primary family members, 57 pairs provided written informed consent. The pairs were randomly allocated to the intervention (n = 25) or control (n = 32). One family in the intervention group and two in the control group withdrew their consent after randomisation. The intervention group underwent four psychoeducation sessions consisting of didactic lectures about depression and group problem-solving focusing on how to cope in high-EE situations. Patients did not attend these sessions. Patients in both the intervention and control groups received treatment as usual. The families' EE levels were evaluated through Five-Minute Speech Samples. The primary outcome was relapse. RESULTS: Time to relapse was statistically significantly longer in the psychoeducation group than in the control group (Kaplan-Meier survival analysis, P = 0.002). The relapse rates up to the 9-month follow-up were 8% and 50% respectively (risk ratio 0.17, 95% CI 0.04-0.66; number needed to treat 2.4, 95% CI 1.6-4.9). In Cox proportional hazard analysis, baseline EE did not moderate the effectiveness of the intervention. CONCLUSIONS: Family psychoeducation is effective in the prevention of relapse in adult patients with major depression.

Effect of a family psychoeducational program on relatives of schizophrenia patients.

AIMS: Family psychoeducational programs have been shown to be effective in terms of knowledge acquirement and relapse prevention, but few studies have looked at whether one mode of educational method is more effective than another. The aim of the present study was to compare several modes of educational approaches and to elucidate which mode of education is more effective. METHODS: A total of 110 relatives of 95 patients with schizophrenia received three types of family psychoeducational programs between January 1995 and September 2003: a small group with two sessions (P1), a large group with nine sessions (P2), and a large group with five sessions (P3). In addition to the demographic data, acquired knowledge was measured using the modified Knowledge About Schizophrenia Interview (KASI), family expressed emotion (EE), and relapse episodes. RESULTS: Overall there were significant increases in many KASI subcategory scores after the three programs, in mothers in particular. The change in KASI scores indicated that the low EE group was able to be highly educated and that the relatives of non-relapsers were more effectively educated. As for the mode of the family psychoeducational program, the P1 and P2 groups surpassed the P3 in terms of knowledge acquired. CONCLUSIONS: Effects of family psychoeducation may depend not on the number of members or sessions but on the time spent on the program per member.

Lithium Levels in Tap Water and the Mental Health Problems of Adolescents: An Individual-Level Cross-Sectional Survey.

OBJECTIVE: We investigated the association between lithium level in tap water and mental health problems, including depressive symptoms, anxiety, and aggressive and suicidal behaviors, in a general population of adolescents using a large individual-level dataset. METHODS: A school-based, cross-sectional survey was conducted in Kochi Prefecture in Japan between 2008 and 2009. Students in 24 public junior high schools were asked to anonymously complete a self-report questionnaire. The main outcome measures were mental health problems, including those on the 12-item General Health Questionnaire, interpersonal violence, bullying, destructive behavior, self-harm, and suicidal ideation. Samples were collected from sources that supplied drinking water to schools, and lithium levels were measured using atomic absorption spectrophotometry. The associations of lithium levels with mental health problems were examined using a generalized linear mixed model with schools as the fixed effect. Potential confounding factors were also added into the model. RESULTS: A total of 3,040 students among 3,311 students responded to the self-report questionnaire (response rate, 91.8%). The mean lithium concentration in tap water was 0.48 µg/L (SD = 0.52; range, 0.01 to 2.10; skewness = 2.01; kurtosis = 4.04), and it was relatively low compared with previous studies. In multivariable regression analysis, lithium level in tap water had an inverse association with depressive symptoms (P = .02) and interpersonal violence (P = .02) but not with suicidal behaviors (suicidal ideation, P = .82; self-harm, P = .46). CONCLUSIONS: Lithium level in tap water was inversely associated with depressive symptoms and interpersonal violence among a general population of adolescents and may have antidepressive and antiaggressive effects.

Vulnerability of synaptic plasticity in the complexin II knockout mouse to maternal deprivation stress.

The alterations in brain function and structure seen in schizophrenia are mediated by genetics as well as vulnerability due to environmental factors. Postmortem studies in schizophrenic patients have shown that expression of complexin II, which is involved in neurotransmitter release at central nervous system synapses, is decreased in the brain. We examined the physiological characteristics of complexin II gene-deficient mice subjected to maternal deprivation stress to determine whether psychological stress during the early stage of life affected the development of brain function. We compared the electrophysiological properties of CA1 hippocampal pyramidal neurons and spatial memory in the Morris water maze test in the wild-type mouse and the homozygous mutant. In the non-stressed mouse, no significant differences in transsynaptic responses and synaptic plasticity or spatial memory were seen, suggesting that complexin II does not play a critical role in transmitter release or synaptic plasticity under these conditions. In contrast, under conditions of maternal deprivation stress, the knockout mouse showed a significant decrease in post-tetanic potentiation and LTP induction and a significant impairment in Morris water Maze test compared to the wild-type mouse, suggesting that complexin II plays a significant role in neurotransmitter release and synaptic plasticity under this pathological condition. Taken together, these results show that mice lacking complexin II are vulnerable to maternal deprivation stress, which raises the possibility that the complexin II gene may be a factor in the onset of schizophrenia.

[Dementia and driving: present status of drivers with dementia and response of their family's care in Japan].

As a result of the growing proportion of drivers aged 65 years and older, it is estimated that the number of elderly drivers with dementia is increasing in Japan. Since June 2002, if a driver is found to be "demented", his/her driving license shall be revoked in Japan. However, there are no consensus guidelines for demented drivers. Between September 1995 and September 2001, we evaluated 30 drivers with dementia (19 males and 11 females, mean age of 69.4 years) in out patients clinic of the Kochi Medical School Hospital and related hospitals. Clinical Diagnosis was Alzheimer's disease in 20, vascular dementia in 3, mixed type dementia in 2, frontotemporal lobar degeneration in 4, other type dementia in 1. We analyzed their driving behavior and family's attitude. Seventy-three point three percent of 30 drivers with dementia continued to drive after diagnosis. In follow-up periods, number of drivers continuing driving was decreased to 13 (43.3%), while six drivers (27.3%) had a traffic accident or violation. Our study suggests that several important medical and social factors should be considered for the management of drivers with dementia. A consensus medical guideline for demented drivers has to be established.

The Autism-Spectrum Quotient in university students: pattern of changes in its scores and associated factors.

INTRODUCTION: Support to university students with autism spectrum disorders (ASD) is becoming increasingly important. To determine the validity of the Autism-Spectrum Quotient (AQ) for ASD screening of university students, we conducted longitudinal measurements of the AQ in a large sample of university students and investigated the possibility of changes in the AQ and associated factors. METHODS: The AQ, University Personality Inventory (UPI), and the willingness of the students to be interviewed were determined at admission in students from four departments of Kochi University; the AQ was determined again in the second year. Changes in the AQ and associated factors were analyzed statistically. RESULTS: The number of valid responses in the initial survey was 3427 (87.2%). The AQ was significantly higher in the group with high UPI scores (F = 156.08, P < 0.001). Of the 486 students interviewed at admission, 22 had suspected ASD. The sensitivity/specificity of the AQ for ASD was 81.8%/92.0%. A total of 319 (11.0%) students responded to the second-year survey, which revealed significant decrease of the AQ in the group with high AQ values at admission. DISCUSSION: The AQ measured at admission was correlated with the UPI score, regardless of the sex or department; in the second survey, the scores decreased significantly in those with high AQ values at admission, suggesting that an unstable mental state can produce a temporary increase of the AQ scores.

Hippocampal subfield volumes in first episode and chronic schizophrenia.

BACKGROUND: Reduced hippocampal volume in schizophrenia is a well-replicated finding. New imaging techniques allow delineation of hippocampal subfield volumes. Studies including predominantly chronic patients demonstrate differences between subfields in sensitivity to illness, and in associations with clinical features. We carried out a cross-sectional and longitudinal study of first episode, sub-chronic, and chronic patients, using an imaging strategy that allows for the assessment of multiple hippocampal subfields. METHODS: Hippocampal subfield volumes were measured in 34 patients with schizophrenia (19 first episode, 6 sub-chronic, 9 chronic) and 15 healthy comparison participants. A subset of 10 first episode and 12 healthy participants were rescanned after six months. RESULTS: Total left hippocampal volume was smaller in sub-chronic (p = 0.04, effect size 1.12) and chronic (p = 0.009, effect size 1.42) patients compared with healthy volunteers. The CA2-3 subfield volume of chronic patients was significantly decreased (p = 0.009, effect size 1.42) compared to healthy volunteers. The CA4-DG volume was significantly reduced in all three patient groups compared to healthy group (all p < 0.005). The two affected subfield volumes were inversely correlated with severity of negative symptoms (p < 0.05). There was a small, but statistically significant decline in left CA4-DG volume over the first six months of illness (p = 0.01). CONCLUSIONS: Imaging strategies defining the subfields of the hippocampus may be informative in linking symptoms and structural abnormalities, and in understanding more about progression during the early phases of illness in schizophrenia.

Validity of a five-minute speech sample for the measurement of expressed emotion in the families of Japanese patients with mood disorders.

Both the Camberwell Family Interview (CFI) and the Five-Minute Speech Sample (FMSS) have been used to define expressed emotion (EE), but the validity of the FMSS relative to the CFI in mood disorders has not been evaluated. In our study, the FMSS and the CFI were performed on the same day in close family members of inpatients with mood disorders within 2 weeks after their admission. The ratings obtained from the CFI were then used to estimate the validity of the FMSS, which was defined by sensitivity and specificity on the basis of the overall evaluation of EE. Validity was also assessed by including borderline ratings of 'low EE' in the category of 'high EE.' Based on the overall evaluation, sensitivity and specificity were 66.7 and 96.8%, respectively. When borderline low EE was included in high EE, the sensitivity and specificity were 100 and 90.3%, respectively. The validity of definitions of EE by the FMSS relative to the CFI was high in mood disorders. Evaluation of EE by the FMSS, which is clinically applicable to patients with mood disorders, is feasible. The validity of this approach is enhanced when families defined as 'borderline low EE' are included in the high-EE category.

Family attitude scale: measurement of criticism in the relatives of patients with schizophrenia in Japan.

Expressed emotion (EE) is traditionally measured with the Camberwell Family Interview (CFI), but the CFI requires considerable time for both execution and evaluation. As an alternative, we investigated the validity of the Family Attitude Scale (FAS), a questionnaire developed for the measurement of EE. The CFI, the FAS, the General Health Questionnaire (GHQ), and the Five-Minute Speech Sample (FMSS) were administered in 57 members of the families of 41 patients with acute episodes of schizophrenia. The relative sensitivity and specificity of EE assessment with the FAS compared with the criticism component of the CFI were 100% and 88.5%, respectively. EE assessment based on criticism as assessed with the FMSS compared with the CFI had a sensitivity of 40.0% and a specificity of 90.4%. The GHQ score tended to be higher in the high-scoring FAS group than in the low-scoring FAS group. The FAS showed excellent validity for the measurement of critical aspects of family attitudes, and the FAS score reflected the state of psychological health of the families.

Effect of depression-related somatic pain on treatment satisfaction and daily living functions.

OBJECTIVE: Recent studies suggest that depression is associated with somatic pain. Despite growing research interest in the topic, the effects of depression-related somatic pain remain unclear. The present study sought to investigate the relationships between depression-related somatic pain, treatment satisfaction, and functions of daily living, and to compare them with the relationships between these factors and mental health measures. METHOD: We administered an Internet-based survey to 663 patients with depression in Japan, including questions about pain symptoms, mental health, functions of daily living, and dissatisfaction with depression treatment. The SF-8 questionnaire was used to assess functions of daily living. We conducted a multiple linear regression analysis to examine the associations between depression-related somatic pain, functions of daily living and treatment satisfaction, and between mental health measures, somatic pain and functions of daily living. RESULTS: An increase per unit in the number of pain symptoms was associated with a 1.04-unit decrease in physical functioning score (P < 0.001), a 0.67-unit decrease in the role functioning-physical score (P < 0.001), and a 0.53-unit decrease in role functioning-emotional score (P = 0.0010). Meanwhile, we found no significant association between the number of pain symptoms and patients' satisfaction with treatment, and no significant association between the number of pain symptoms and social functioning. CONCLUSIONS: These results suggest that even when patients report satisfaction with their treatment, they may be suffering from reduced physical functioning and role functioning. These impairments may escape clinical recognition when clinicians or patients fail to discuss pain symptoms.

Psychoeducation for major depressive disorders: a randomised controlled trial.

Various psychological therapies have been shown to be effective for the treatment of mood disorders. Among them, family psychoeducation has demonstrated efficacy in reducing symptom severity and extending the time to relapse. We tested the efficacy of adding psychoeducation focussed on how to deal with the family's expressed emotion to treatment as usual (TAU) to prevent relapse among patients with remitted major depression. A total of 34 patients with major depressive disorders in full or partial remission were randomised to receive either group psychoeducation over six sessions, each consisting of a didactic lecture and group problem-solving (n=19), plus TAU or TAU alone (n=15). The primary outcome was relapse by Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria. Masked raters administered the Hamilton Rating Scale for Depression-17 (HRSD-17). As many as 18 patients in the intervention group and 14 patients in the control group completed the study. Time to relapse was significantly longer in the intervention group than in the control group, with a risk ratio (RR) of relapse by 9 months of 0.12. At 9 months, there was a significantly greater decrease in the HRSD-17 score in the intervention group than in the control group. We demonstrated the effectiveness of patient psychoeducation on the course and outcome of major depressive disorders.