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1.  Associations between Lifetime Traumatic Events and Subsequent Chronic Physical Conditions: A Cross-National, Cross-Sectional Study 
PLoS ONE  2013;8(11):e80573.
Associations between lifetime traumatic event (LTE) exposures and subsequent physical ill-health are well established but it has remained unclear whether these are explained by PTSD or other mental disorders. This study examined this question and investigated whether associations varied by type and number of LTEs, across physical condition outcomes, or across countries.
Cross-sectional, face-to-face household surveys of adults (18+) were conducted in 14 countries (n = 38, 051). The Composite International Diagnostic Interview assessed lifetime LTEs and DSM-IV mental disorders. Chronic physical conditions were ascertained by self-report of physician's diagnosis and year of diagnosis or onset. Survival analyses estimated associations between the number and type of LTEs with the subsequent onset of 11 physical conditions, with and without adjustment for mental disorders.
A dose-response association was found between increasing number of LTEs and odds of any physical condition onset (OR 1.5 [95% CI: 1.4–1.5] for 1 LTE; 2.1 [2.0–2.3] for 5+ LTEs), independent of all mental disorders. Associations did not vary greatly by type of LTE (except for combat and other war experience), nor across countries. A history of 1 LTE was associated with 7/11 of the physical conditions (ORs 1.3 [1.2–1.5] to 1.7 [1.4–2.0]) and a history of 5+ LTEs was associated with 9/11 physical conditions (ORs 1.8 [1.3–2.4] to 3.6 [2.0–6.5]), the exceptions being cancer and stroke.
Traumatic events are associated with adverse downstream effects on physical health, independent of PTSD and other mental disorders. Although the associations are modest they have public health implications due to the high prevalence of traumatic events and the range of common physical conditions affected. The effects of traumatic stress are a concern for all medical professionals and researchers, not just mental health specialists.
PMCID: PMC3864645  PMID: 24348911
2.  Lithium in Tap Water and Suicide Mortality in Japan 
Lithium has been used as a mood-stabilizing drug in people with mood disorders. Previous studies have shown that natural levels of lithium in drinking water may protect against suicide. This study evaluated the association between lithium levels in tap water and the suicide standardized mortality ratio (SMR) in 40 municipalities of Aomori prefecture, which has the highest levels of suicide mortality rate in Japan. Lithium levels in the tap water supplies of each municipality were measured using inductively coupled plasma-mass spectrometry. After adjusting for confounders, a statistical trend toward significance was found for the relationship between lithium levels and the average SMR among females. These findings indicate that natural levels of lithium in drinking water might have a protective effect on the risk of suicide among females. Future research is warranted to confirm this association.
PMCID: PMC3863886  PMID: 24225643
lithium; suicide rate; Japan
4.  Disability Mediates the Impact of Common Conditions on Perceived Health 
PLoS ONE  2013;8(6):e65858.
We examined the extent to which disability mediates the observed associations of common mental and physical conditions with perceived health.
Methods and Findings
WHO World Mental Health (WMH) Surveys carried out in 22 countries worldwide (n = 51,344 respondents, 72.0% response rate). We assessed nine common mental conditions with the WHO Composite International Diagnostic Interview (CIDI), and ten chronic physical with a checklist. A visual analog scale (VAS) score (0, worst to 100, best) measured perceived health in the previous 30 days. Disability was assessed using a modified WHO Disability Assessment Schedule (WHODAS), including: cognition, mobility, self-care, getting along, role functioning (life activities), family burden, stigma, and discrimination. Path analysis was used to estimate total effects of conditions on perceived health VAS and their separate direct and indirect (through the WHODAS dimensions) effects.
Twelve-month prevalence was 14.4% for any mental and 51.4% for any physical condition. 31.7% of respondents reported difficulties in role functioning, 11.4% in mobility, 8.3% in stigma, 8.1% in family burden and 6.9% in cognition. Other difficulties were much less common. Mean VAS score was 81.0 (SD = 0.1). Decrements in VAS scores were highest for neurological conditions (9.8), depression (8.2) and bipolar disorder (8.1). Across conditions, 36.8% (IQR: 31.2–51.5%) of the total decrement in perceived health associated with the condition were mediated by WHODAS disabilities (significant for 17 of 19 conditions). Role functioning was the dominant mediator for both mental and physical conditions. Stigma and family burden were also important mediators for mental conditions, and mobility for physical conditions.
More than a third of the decrement in perceived health associated with common conditions is mediated by disability. Although the decrement is similar for physical and mental conditions, the pattern of mediation is different. Research is needed on the benefits for perceived health of targeted interventions aimed at particular disability dimensions.
PMCID: PMC3675077  PMID: 23762442
5.  Evaluation of the DSM-IV and ICD-10 Criteria for Depressive Disorders in a Community Population in Japan Using Item Response Theory 
The DSM-IV and ICD-10 are both operational diagnostic systems that classify known psychological disorders according to the number of criteria symptoms. Certain discrepancies between the criteria exist and may lead to some inconsistencies in psychiatric research. The purpose of this study was to investigate these differences in the assessment of depression with item response theory (IRT) analyses. The World Mental Health-Japan (WMHJ) Survey is an epidemiological survey of the general population in Japan. We analyzed data from the WMHJ completed by 353 respondents who had either depressive mood or diminished interest. A 2-parameter logistic model was used to evaluate the characteristics of the symptoms of the DSM-IV and ICD-10. IRT analyses revealed that the symptoms about psychomotor activity, worthlessness and self-reproach were more informative and suggestive of greater severity, while the symptoms about dietary habits were less informative. IRT analyses also revealed that the ICD-10 seems more sensitive to the mild range of the depression spectrum compared to the DSM-IV. Although there were some variations in severity among respondents, most of the respondents diagnosed with a severe or moderate depressive episode according to the ICD-10 were also diagnosed with a major depressive episode according to the DSM-IV.
PMCID: PMC3671887  PMID: 20645305
Depression; World Mental Health Japan Survey; DSM-IV; ICD-10; Item Response Theory
6.  Lifetime prevalence of mental disorders and its relationship to suicidal ideation in a Japanese rural community with high suicide and alcohol consumption rates 
The World Mental Health Survey Japan was conducted to address the current status of mental disorders in Japan. Among the various regions covered by the survey were Tendo City and Kaminoyama City in Yamagata Prefecture. The suicide and alcohol consumption rates in Yamagata are higher than the Japanese national average. Many studies have reported that major depressive disorder (MDD), alcohol use disorders (AUDs), and suicidal ideation are related to suicide risk. The prevalence of MDD, AUDs, and suicidal ideation, as well as the association between suicidal ideation and mental disorders must be investigated in order to implement mental health and suicide prevention measures in our community; however, only a few studies have addressed this issue.
The survey involved face-to-face interviews. The study population consisted of 1,684 adult residents, of which 770 (mean age 54.0 ± 17.4 years) who completed the interview process. Mental disorders were assessed using the World Mental Health version of the World Health Organization Composite International Diagnostic Interview.
Among the study population, lifetime prevalence of MDD was 4.4%, which was similar to values reported in previous studies in Japan. Prevalence of AUDs, however, was 10.2%, which was higher those reported previously. We observed a significant association between suicidal ideation and MDD [odds ratio (OR) 7.6], our results showed precisely the opposite association between AUDs and suicidal ideation (OR 0.5, not significant) compared to previous studies.
Although prevalences of MDD and suicidal ideation were not high, this study revealed a high lifetime prevalence of AUDs and a negative association between suicidal ideation and AUDs.
PMCID: PMC3206975  PMID: 21431807
Mental disorders; Suicide; Alcohol; Lifetime prevalence; Describe epidemiology
7.  Early childhood adversity and later hypertension: Data from the World Mental Health Survey 
Although many studies have indicated that psychosocial factors contribute to hypertension, and that early childhood adversity is associated with long-term adverse mental and physical health sequelae, the association between early adversity and later hypertension is not well studied.
Data from 10 countries participating in the World Health Organization (WHO) World Mental Health (WHM) Surveys (N = 18,630) were analyzed to assess the relationship between childhood adversity and adult-onset hypertension, as ascertained by self-report. The potentially mediating effect of early-onset depression-anxiety disorders, as assessed by the WHM Survey version of the International Diagnostic Interview (WMH-CIDI), on the relationship between early adversity and hypertension was also examined.
Two or more early childhood adversities, as well as early-onset depression-anxiety, were significantly associated with hypertension. A range of specific childhood adversities, as well as early-onset social phobia and panic/agoraphobia, were significantly associated with hypertension. In multivariate analyses, the presence of 3 or more childhood adversities was associated with hypertension, even when early-onset depression-anxiety or current depression-anxiety was included in the model.
Although caution is required in the interpretation of self-report data on adult-onset hypertension, the results of this study further strengthen the evidence base regarding the role of psychosocial factors in the pathogenesis of hypertension.
PMCID: PMC3486699  PMID: 20196979
8.  Parental Psychopathology and the Risk of Suicidal Behavior in their Offspring: Results from the World Mental Health Surveys 
Molecular psychiatry  2010;16(12):1221-1233.
Prior research suggests that parental psychopathology predicts suicidal behavior among offspring; however, the more fine-grained associations between specific parental disorders and distinct stages of the pathway to suicide are not well-understood. We set out to test the hypothesis that parental disorders associated with negative mood would predict offspring suicide ideation, whereas disorders characterized by impulsive-aggression (e,g., antisocial personality) and anxiety/agitation (e.g., panic disorder) would predict which offspring act on their suicide ideation and make a suicide attempt. Data were collected during face-to-face interviews conducted on nationally representative samples (N=55,299; age 18+) from 21 countries around the world. We tested the associations between a range of parental disorders and the onset and persistence over time (i.e., time-since-most-recent-episode controlling for age-of-onset and time-since-onset) of subsequent suicidal behavior (suicide ideation, plans, and attempts) among offspring. Analyses tested bivariate and multivariate associations between each parental disorder and distinct forms of suicidal behavior. Results revealed that each parental disorder examined increased the risk of suicide ideation among offspring, parental generalized anxiety and depression emerged as the only predictors of the onset and persistence (respectively) of suicide plans among offspring with ideation, whereas parental anti-social personality and anxiety disorders emerged as the only predictors of the onset and persistence of suicide attempts among ideators. A dose-response relation between parental disorders and respondent risk of suicide ideation and attempt also was found. Parental death by suicide was a particularly strong predictor of persistence of suicide attempts among offspring. These associations remained significant after controlling for comorbidity of parental disorders and for the presence of mental disorders among offspring. These findings should inform future explorations of the mechanisms of inter-generational transmission of suicidal behavior.
PMCID: PMC3142278  PMID: 21079606
suicide; parent and family history; intergenerational transmission
9.  Modifications to the WHODAS-II for the World Mental Health Surveys: Implications of Filter Items 
Journal of Clinical Epidemiology  2008;61(11):1132-1143.
The WHODAS-II was substantially modified for use in the World Mental Health Surveys. This paper considers the modified WHODAS-II’s psychometric properties and implications of filter items employed to reduce respondent burden.
Study design and setting
Seventeen surveys in 16 countries administered a modified WHODAS-II to population samples (N=38,934 adults). Modifications included introducing filter questions for four sub-scales and substituting questions on the number of days activity was limited for the Life Activities domain. We evaluated distributional properties, reliability, and validity of the modified WHODAS-II.
Most respondents (77%–99%) had zero scores on filtered subscales. Lower bound estimates of internal consistency (alpha) for the filtered subscales were typically in the 0.70’s, but were higher for the Global scale. Loadings of subscale scores on a Global Disability factor were moderate-to-high. Correlations with the Sheehan Disability Scale were modest but consistently positive, while correlations with SF-12 Physical Component Summary were considerably higher. Cross-national variability in disability scores was observed, but was not readily explainable.
Internal consistency and validity of the modified WHODAS-II was generally supported, but use of filter questions impaired measurement properties. Group differences in modified WHODAS-II disability scores may be compared within, but not necessarily across, countries.
PMCID: PMC3277915  PMID: 18619808
Disability; Measurement; Reliability; Validity; Survey; Epidemiology
10.  Cross-national epidemiology of DSM-IV major depressive episode 
BMC Medicine  2011;9:90.
Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low- to middle-income countries in the World Mental Health Survey Initiative.
Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults.
The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2:1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low- to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed.
MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.
PMCID: PMC3163615  PMID: 21791035
11.  Subtyping Social Anxiety Disorder in Developed and Developing Countries 
Depression and anxiety  2010;27(4):390-403.
Although social anxiety disorder (SAD) is classified in DSM-IV into generalized and non-generalized subtypes, community surveys in Western countries find no evidence of disjunctions in the dose-response relationship between number of social fears and outcomes to support this distinction. We aimed to determine whether this holds across a broader set of developed and developing countries and whether subtyping according to number of performance versus interactional fears would be more useful.
The WHO World Mental Health (WMH) Survey Initiative undertook population epidemiological surveys in 11 developing and 9 developed countries using the Composite International Diagnostic Interview (CIDI) to assess DSM-IV disorders. Fourteen performance and interactional fears were assessed. Associations between number of social fears in SAD and numerous outcomes (age-of-onset, persistence, severity, comorbidity, treatment) were examined. Additional analyses examined associations with number of performance fears versus number of interactional fears.
Lifetime social fears are quite common in both developed (15.9%) and developing (14.3%) countries, but lifetime SAD is much more common in the former (6.1%) than latter (2.1%) countries. Among those with SAD, persistence, severity, comorbidity, and treatment all have dose-response relationships with number of social fears, with no clear nonlinearity in relationships that would support a distinction between generalized and non-generalized SAD. The distinction between performance fears and interactional fears is generally not important in predicting these same outcomes.
No evidence is found to support subtyping SAD on the basis of either number of social fears or number of performance fears versus number of interactional fears.
PMCID: PMC2851829  PMID: 20037919
12.  Low-dose lithium uptake promotes longevity in humans and metazoans 
European Journal of Nutrition  2011;50(5):387-389.
Lithium is a nutritionally essential trace element predominantly contained in vegetables, plant-derived foods, and drinking water. Environmental lithium exposure and concurrent nutritional intake vary considerably in different regions. We here have analyzed the possibility that low-dose lithium exposure may affect mortality in both metazoans and mammals.
Based on a large Japanese observational cohort, we have used weighted regression analysis to identify putative effects of tap water-derived lithium uptake on overall mortality. Independently, we have exposed Caenorhabditis elegans, a small roundworm commonly used for anti-aging studies, to comparable concentrations of lithium, and have quantified mortality during this intervention.
In humans, we find here an inverse correlation between drinking water lithium concentrations and all-cause mortality in 18 neighboring Japanese municipalities with a total of 1,206,174 individuals (β = −0.661, p = 0.003). Consistently, we find that exposure to a comparably low concentration of lithium chloride extends life span of C. elegans (p = 0.047).
Taken together, these findings indicate that long-term low-dose exposure to lithium may exert anti-aging capabilities and unambiguously decreases mortality in evolutionary distinct species.
PMCID: PMC3151375  PMID: 21301855
Trace elements; Lithium; Mortality; Longevity; Human; C. elegans
13.  Why Japanese workers show low work engagement: An item response theory analysis of the Utrecht Work Engagement scale 
With the globalization of occupational health psychology, more and more researchers are interested in applying employee well-being like work engagement (i.e., a positive, fulfilling, work-related state of mind that is characterized by vigor, dedication, and absorption) to diverse populations. Accurate measurement contributes to our further understanding and to the generalizability of the concept of work engagement across different cultures. The present study investigated the measurement accuracy of the Japanese and the original Dutch versions of the Utrecht Work Engagement Scale (9-item version, UWES-9) and the comparability of this scale between both countries. Item Response Theory (IRT) was applied to the data from Japan (N = 2,339) and the Netherlands (N = 13,406). Reliability of the scale was evaluated at various levels of the latent trait (i.e., work engagement) based the test information function (TIF) and the standard error of measurement (SEM). The Japanese version had difficulty in differentiating respondents with extremely low work engagement, whereas the original Dutch version had difficulty in differentiating respondents with high work engagement. The measurement accuracy of both versions was not similar. Suppression of positive affect among Japanese people and self-enhancement (the general sensitivity to positive self-relevant information) among Dutch people may have caused decreased measurement accuracy. Hence, we should be cautious when interpreting low engagement scores among Japanese as well as high engagement scores among western employees.
PMCID: PMC2990723  PMID: 21054839
14.  Implications of modifying the duration requirement of generalized anxiety disorder in developed and developing countries 
Psychological medicine  2008;39(7):1163-1176.
A number of western studies have suggested that the 6-month duration requirement of generalized anxiety disorder (GAD) does not represent a critical threshold in terms of onset, course, or risk factors of the disorder. No study has examined the consequences of modifying the duration requirement across a wide range of correlates in both developed and developing countries.
Population surveys were carried out in 7 developing and 10 developed countries using the WHO Composite International Diagnostic Interview (total sample size = 85,052). Prevalence of GAD was estimated using different minimum duration criteria. Age of onset, symptom persistence, subsequent mental disorders, impairment, and recovery were compared across GAD subgroups defined by different duration criteria.
Lifetime prevalence estimates for GAD lasting 1 month, 3 months, 6 months, and 12 months were 7.5%, 5.24%, 4.11%, and 2.95% for developed countries and 2.65%, 1.78%, 1.47%, and 1.17% for developing countries, respectively. There was little difference between GAD of 6 months duration and GAD of shorter durations (1–2 months, 3–5 months) in symptom severity, age of onset, persistence, impairment, or comorbidity. Those with GAD lasting 12 months or more were the most severe, chronic, and impaired of the four duration subgroups.
In both developed and developing countries, the clinical profile of GAD is similar regardless of duration. The DSM-IV 6-month duration criterion is not an optimal marker of severity, impairment, or need for early treatment. Future iterations of the DSM and ICD should consider shortening the duration requirement of GAD.
PMCID: PMC2692366  PMID: 19091158

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