Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption.

Alcoholism has always been a major public health concern in Taiwan, especially in the aboriginal communities. Emerging evidence supports the association between DNA methylation and alcoholism, though very few studies have examined the effect of chronic alcohol consumption on the epignome. Since 1986, we have been following up on the mental health conditions of four major aboriginal peoples of Taiwan. The 993 aboriginal people who underwent the phase 1 (1986) clinical interviews were followed up through phase 2 (1990-1992), and phase 3 (2003-2009). Selected individuals for the current study included 10 males from the phase 1 normal cohort who remained normal at phase 2 and became dependent on alcohol by phase 3 and 10 control subjects who have not had any drinking problems throughout the study. We profiled the DNA methylation changes in the blood samples collected at phases 2 and 3. Enrichment analyses have identified several biological processes related to immune system responses and aging in the control group. In contrast, differentially methylated genes in the case group were mostly associated with susceptibility to infections, as well as pathways related to muscular contraction and neural degeneration. The methylation levels of six genes were found to correlate with alcohol consumption. These include genes involved in neurogenesis (NPDC1) and inflammation (HERC5), as well as alcoholism-associated genes ADCY9, CKM, and PHOX2A. Given the limited sample size, our approach uncovered genes and disease pathways associated with chronic alcohol consumption at the epigenetic level. The results offer a preliminary methylome map that enhances our understanding of alcohol-induced damages and offers new targets for alcohol injury research.

Incidence of first onset alcohol use disorder: a 16-year follow-up in the Taiwanese aborigines.

PURPOSE: To investigate the incidence and cumulative risk of first onset alcohol use disorder (AUD) in a 16-year follow-up among Taiwanese aboriginal populations. METHODS: Participants included in this study were cohort subjects free from any AUD at phase 1 survey (n = 428 for DSM-3-R and 451 for DSM-4) of the Taiwan aboriginal study project conducted in 1986-1988. They were reassessed approximately 16 years later, with a response rate of 98.8 %. A Chinese version of the WHO schedules for clinical assessment in neuropsychiatry was employed to assess the lifetime drinking history and AUD. RESULTS: Age-standardized annual incidence rates of AUD in all groups were 2.26 and 1.75 % according to DSM-3-R and DSM-4, respectively. The overall incidence rates of AUD were comparable to most of other studies in Caucasian populations, but the sex ratios of women to men were higher in this study (1:2-3) than in the latter (1:6). The incidence of AUD was higher with DSM-3-R than with DSM-4 criteria in this study, attributable to the exclusion of physical/psychological harm in DSM-4 alcohol abuse. The cumulative risks of DSM-4 AUD in this study were very high, being 72.2 ± 19.8 for men and 48.7 ± 8.2 for women up to the age of 65 years. CONCLUSIONS: High incidence rates and cumulative risks of AUD in Taiwanese aborigines demand effective prevention strategy.

Mortality and suicide after self-harm: community cohort study in Taiwan.

BACKGROUND: Little is known about outcomes after self-harm in East Asia. AIMS: To investigate mortality after self-harm in a Taiwanese population. METHOD: Between 2000 and 2003, 1083 individuals who self-harmed were identified through a population self-harm register in Nantou County, Taiwan, and followed until 2007 for date and cause of death on a national mortality database. RESULTS: In total, 145 individuals died, 48 through suicide. The risks of all-cause and suicide mortality in the first year were 4.7% and 2.1% respectively, representing 8- and 131-fold age- and gender-standardised increases. Male gender and older age were independent risk factors for both suicide and non-suicide mortality. Use of more lethal methods in the index episode was associated with higher mortality but this was accounted for by gender. CONCLUSIONS: Results in this sample support the recommendation that people with a history of recent self-harm should be a major target for suicide prevention programmes.

Non-fatal repetition of self-harm: population-based prospective cohort study in Taiwan.

BACKGROUND: Repeated self-harm is relatively common and is linked with an elevated risk of eventual suicide. There has been no study of this involving a large sample from the Far East. AIMS: To estimate the risk over the medium term of non-fatal repetition of self-harm and identify predictive factors in those carrying out self-harm. METHOD: A total of 970 individuals who had self-harmed were recruited from a community-based suicide behaviour register system in Nantou, Taiwan from July 2000 to February 2003. Information regarding demography and suicide methods was collected. Individuals were followed-up until December 2005 to examine the risk of repeated self-harm and independent predictive factors. RESULTS: Ninety cohort members had repeated self-harm during the follow-up period (accounting for 131 repeated self-harm episodes in all). The cumulative risks were 5.7% for the first year, 7.8% for the second year and 9.5% for the fourth year. The risk was highest within the first year after the self-harm event. Independent risk factors included female gender and self-cutting as well as self-poisoning with drugs. Effect of younger age was mediated through the choice of methods. CONCLUSIONS: Individuals with self-harm have a high risk of repetition, especially within the first year. Suicide prevention strategies need to focus on intervening with this population to reduce their repetition.

Effect of media reporting of the suicide of a singer in Taiwan: the case of Ivy Li.

BACKGROUND: Suicide attempters are known to be vulnerable to the influence of media reporting of suicide events. This study investigates possible influences of media reporting of a celebrity suicide on subsequent suicide attempts and associated risk factors among suicide attempters. METHODS: Sixty-three suicide attempters registered in a surveillance system of Taipei City Suicide Prevention Center were assessed using a structured interview soon after media reporting of the suicide of a young female singing star. RESULTS: Forty-three (68%) respondents had encountered with the suicide news. Among them, 37% reported being influenced by the media reporting on their subsequent suicide attempts. Men (adjusted OR 6.36, 95% CI 1.29-31.44) and younger age groups (adjusted OR 4.93, 95% CI 1.04-23.45) were more susceptible to the media reporting. There was a positive modeling effect in method of suicide (charcoal burning) (adjusted OR 7.27, 95% CI 6.31-168.66). CONCLUSIONS: This study has provided further evidence for suicide imitation among vulnerable people encountered with media reporting of celebrity suicide, and for the need to actively restrain reporting of suicides to decrease the imitation effect.

Development of a Chinese version of the Suicide Intent Scale.

This study established the psychometric properties of the Chinese version of the Suicide Intent Scale (SIS) in a clinic- and community-based sample of 36 patients and 592 respondents, respectively. Results showed that the Chinese SIS demonstrated good inter-rater and test-retest reliability. Factor analysis generated three factors (Precautions, Planning, and Seriousness) explaining 92.9% of the total variance with high internal consistency. It was moderately correlated with depressive symptoms. Results suggest that the Chinese SIS is a reliable and valid instrument for use in assessing the extent of suicidal intention among subjects with deliberate self-harm in ethnic Chinese populations.

Psychiatric consultation for post-liver-transplantation patients.

AIM: This report describes the clinical characteristics of referral inpatients who received liver transplantation and the surgeon's concordance with the psychiatric consultation. METHODS: During a 4-year period, psychiatric consultation was arranged for 30 post-liver-transplantation inpatients at Kaohsiung Chang Gung Memorial Hospital. A psychiatrist assessed these patients and made psychiatric diagnoses according to the Diagnostic and Statistical Manual, 4th edition. The clinical data were routinely collected via modified MICRO-CARES software. At the end of the 4-year study period, all the medical records of these 30 inpatients were reviewed. RESULTS: Psychiatric diagnosis was made in 70% of the patients (n = 21) in three major categories, including delirious state (n = 8), depressive disorder (n = 5), and anxiety/dyssomnia (n = 8). All these conditions were improved by psychiatric management. We found that the consultee's concordance with recommended drug prescriptions was high with antidepressants in depressive patients and low with antipsychotics in patients with delirium. Moreover, anxiolytics were frequently prescribed in post-transplant inpatients before psychiatric consultation. CONCLUSION: These findings suggest that psychiatric consultation is beneficial to inpatients after liver transplantation, especially those with depression and delirium.

A community-based study of case fatality proportion among those who carry out suicide acts.

OBJECTIVE: To investigate the case fatality proportion and associated factors in those carrying out suicide acts in Nantou, Taiwan. METHOD: Data from 1,171 suicide acts (including 973 with deliberate self harm and 198 completed suicides), identified between July 2000 and February 2003, were collected from a population suicide register in Nantou County, Taiwan. Case fatality proportion and the independent effects of demographic factors and suicide method on case fatality were investigated. RESULTS: The overall case fatality proportion was 16.9%, with higher proportions in men (26.3%) and in those aged 65 and over (37.9%). Hanging was the most lethal method (fatality proportion = 81.5%); pesticide was both commonly used and associated with a high case fatality (fatality proportion = 26.3%). Only age (increased with age) and suicide method were found to be independently associated with the risk of fatality. CONCLUSIONS: Suicide method and older age are independent predictors of the fatality of suicide acts. Suicide prevention strategy and clinical assessment ought to take into account of these two factors. Diminution of pesticide toxicity and control of access to pesticides are important considerations for suicide prevention in rural Taiwan.

Was the economic crisis 1997-1998 responsible for rising suicide rates in East/Southeast Asia? A time-trend analysis for Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand.

In 1997-1998 a widespread economic crisis hit the economies of many East/Southeast Asian countries; its impact on suicide rates across the region has not been systematically documented. We investigated the impact of the Asian economic crisis (1997-1998) on suicide in Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand. Suicide and population data for the period 1985-2006 were extracted from the World Health Organisation's mortality database and Taiwanese mortality statistics. Sex-specific age-standardised suicide rates for people aged 15years or above were analysed using joinpoint regression. Trends in divorce, marriage, unemployment, gross domestic product (GDP) per capita and alcohol consumption were compared with trends in suicide rates graphically and using time-series analysis. Suicide mortality decreased in the late 1980s and early 1990s but subsequently increased markedly in all countries except Singapore, which had steadily declining suicide rates throughout the study period. Compared to 1997, male rates in 1998 rose by 39% in Japan, 44% in Hong Kong and 45% in Korea; rises in female rates were less marked. Male rates also rose in Thailand, but accurate data were incomplete. The economic crisis was associated with 10,400 more suicides in 1998 compared to 1997 in Japan, Hong Kong and Korea. Similar increases in suicide rates were not seen in Taiwan and Singapore, the two countries where the economic crisis had a smaller impact on GDP and unemployment. Time-series analyses indicated that some of the crisis's impact on male suicides was attributable to increases in unemployment. These findings suggest an association of the Asian economic crisis with a sharp increase in suicide mortality in some, but not all, East/Southeast Asian countries, and that these increases were most closely associated with rises in unemployment.

Acculturation, psychiatric comorbidity and posttraumatic stress disorder in a Taiwanese aboriginal population.

BACKGROUND: This study investigates acculturation and other antecedent psychiatric and socio-environmental risk factors for posttraumatic stress disorder (PTSD) in one aboriginal group (the Bunun) exposed to an earthquake disaster in Taiwan. METHOD: Respondents (n = 196) were assessed 5 months after the disaster, using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry and the Taiwan Aboriginal Acculturation Scale. RESULT: Four risk factors exerted independent effect on the risk of PTSD, including magnitude of the earthquake, subsequent traumas, antecedent major depressive disorder and acculturation status. CONCLUSION: Public mental health programs need to consider the liability to PTSD in populations with different ethnicity and socio-cultural environments.

The influence of media reporting of the suicide of a celebrity on suicide rates: a population-based study.

BACKGROUND: The impact of media reporting of suicides of entertainment celebrities may affect suicide rates due to an imitation effect. We investigated the impact on suicides of the media reporting of the suicide of a male television celebrity. METHODS: All suicides during 2003-2005 in Taiwan (n = 10,945) were included in this study. A Poisson time series autoregression analysis was conducted to examine whether there was an increase in suicides during the 4-week period after extensive media reporting of the celebrity suicide. RESULTS: After controlling for seasonal variation, calendar year, temperature, humidity and unemployment rate, there was a marked increase in the number of suicides during the 4-week period after media reporting (relative risk = 1.17, 95% CI 1.04-1.31). The increase was in men (relative risk = 1.30, 95% CI 1.14-1.50) and for the individuals using the same highly lethal method (hanging) as the TV actor did (relative risk = 1.51, 95% CI 1.25-1.83). However, the age groups in which the increase occurred were younger than the age of the celebrity. CONCLUSIONS: The extensive media reporting of the celebrity suicide was followed by an increase in suicides with a strong implication of a modelling effect. The results provide further support for the need for more restrained reporting of suicides as part of suicide prevention strategies to decrease the imitation effect.

The influence of media coverage of a celebrity suicide on subsequent suicide attempts.

OBJECTIVE: To investigate the impact of media reporting of a celebrity suicide on subsequent suicide attempts. METHOD: A Poisson time series autoregression analysis was conducted to examine whether there was a significant increase in suicide attempts during the 3-week period after the start of extensive media reporting of a celebrity suicide. The reporting began on May 2, 2005, and lasted about 17 days. To investigate the influence of media reporting on suicide attempts, a structured interview was conducted with 124 suicide attempters identified from 2 counties in Mid Taiwan who had exposure to the media reporting. RESULTS: After controlling for seasonal variation, calendar year, temperature, and humidity, there was a marked increase in the number of suicide attempts during the 3-week period after media reporting began (adjusted relative risk = 1.55, 95% CI = 1.26 to 1.91). Among 124 suicide attempters exposed to the media reports, 23.4% reported an influence from them. There was no relationship between the attempters' ages and the age of the celebrity or the method, but male attempters had a significantly higher risk for such influence. A considerably higher risk for such influence was found among subjects with a history of suicide attempt(s) in the previous year (odds ratio = 52.3, 95% CI = 5.96 to 459.1). CONCLUSIONS: The extensive media reporting of the suicide of a celebrity was followed by an increase in suicide attempts. The effect was particularly marked in individuals with a recent history of a suicide attempt. The results provide further support for the need for more restrained reporting of suicides as part of suicide prevention strategies and for special vigilance for contagious effects of such reporting on people who have carried out recent suicidal acts.

Correlates of family, school, and peer variables with adolescent substance use in Taiwan.

This study examines adolescent substance use in relation to family, peer and school factors in the context of Taiwan. Information on family characteristics, satisfaction with performance at school, and peer influence was collected using a case-control study in which a two-stage method was applied to ascertain substance use. A set of hypotheses on interrelationships of substance use (tobacco, alcohol, betel, illicit drugs) and influences were tested with a structural equation model. There was a strong negative relation between family factors and peer relationships (p=0.005). Family variables played an important role in motivation and effort to study (p=0.004). High motivation and effort to study (p=0.0012) and good school adjustment (p=0.078) led to higher satisfaction with performance at school. A significant positive association between peer relationships and deviant peer behaviour was observed (p<0.001). Satisfaction with performance at school was negatively related to deviant peer behaviour (p=0.052). The direct effect of deviant peer behaviour was marginally statistically significant (p=0.011) and an indirect effect of family factors on substance use was statistically significant (p=0.041). In conclusion, the study found that a strong family-peer relationship and family influence has a significant effect on substance use.

The influence of media reporting of a celebrity suicide on suicidal behavior in patients with a history of depressive disorder.

BACKGROUND: Few studies have directly assessed the impact of a specific media report in vulnerable people. This study investigates possible influences of media reporting of a celebrity suicide on subsequent suicidal behaviors and associated risk factors among depressive patients. METHODS: Depressive patients (N=461) were assessed through a structured interview soon after extensive media reporting of a celebrity suicide. RESULTS: Among 438 depressive patients exposed to the media report, 38.8% reported an influence on subsequent suicidal behaviors, including 24 (5.5%) with a suicide attempt. The risk of such influence was highest among patients in a severe depressive state just prior to the media report (adjusted OR 7.81, 95% CI 3.28-18.59). Such influence on a subsequent suicide attempt was highest in patients with a most recent suicide attempt within one month prior to the media reports (adjusted hazard ratio 11.91, 95% CI 3.76-37.72). LIMITATIONS: Our finding of the significant media influence may reflect adverse thoughts among more suicidal and depressed individuals. The possible influence of other factors on the findings cannot be ruled out. CONCLUSIONS: This study has provided more convincing evidence suggesting negative influences of media reporting of a celebrity suicide on subsequent suicidal behaviors among depressive patients. Particular attention in terms of potential negative media influences should be paid to patients who are younger and currently depressed and have made a recent suicide attempt.

Psychiatric and psychosocial predictors of substance use disorders among adolescents: longitudinal study.

BACKGROUND: Few studies have prospectively examined psychosocial and psychiatric predictors of adolescent substance use disorders simultaneously. AIMS: To identify psychosocial and psychiatric predictors of substance use disorders in adolescence. METHOD: School children aged 12 years (s.d.=0.3) free from any substance use disorder at grade 7 (n=428) were assessed in three consecutive years, using a standardised psychiatric interview. Their baseline psychosocial information was also collected. The outcome was the onset age of a substance use disorder. The Cox regression model was used for data analysis. RESULTS: The most significant predictive factors for adolescent substance use disorder included male gender, attention-deficit hyperactivity disorder, conduct disorder and sibling use of tobacco. Three protective factors against such morbidity included living in a household with two parents, a good academic grade at grade 7 and objection to the use of substances. CONCLUSIONS: Early intervention for disruptive behaviour disorders and specific psychosocial risk factors might prevent substance use disorders in early adolescence.

Glutamate decarboxylase genes and alcoholism in Han Taiwanese men.

OBJECTIVE: Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. METHOD: An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. RESULTS: Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. CONCLUSIONS: This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism.

A 3-year panel study of mental disorders among adolescents in Taiwan.

OBJECTIVE: This study investigated the prevalence and changing trends of mental disorders and the effects of gender and urbanization among adolescents in Taiwan. METHOD: A random sample of seventh-grade students (N=1,070) was recruited from one urban and one rural junior high school in which 1,051 (98.2%) and 1,035 (96.7%) were reassessed in the second and third years, respectively. A two-stage case identification was conducted by mental health professionals with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version, supplemented by information from the Child Behavior Checklist. RESULTS: The weighted 3-month prevalence rates across the 3 consecutive years for overall psychiatric disorders were 20.3%, 22.7%, and 14.8%, respectively. The most prevalent psychiatric condition was attention deficit hyperactivity disorder (ADHD) in the first 2 years and substance use disorders in the third. During the 3 years, the rates for ADHD, specific phobia, and social phobia decreased, and the rates for major depression and substance use disorders, conversely, increased. Although conduct disorder, ADHD, and substance use disorders were more prevalent among boys, the rates for major depression, social phobia, specific phobia, and adjustment disorder were higher among girls. Rural adolescents had higher rates of conduct disorder, oppositional defiant disorder, and substance use disorders than their urban counterparts. CONCLUSIONS: Our findings are similar to those of previous studies among adolescents in prevalence rates, changing trends of most mental disorders, and gender effects. The differential changing trends in various diagnostic groups may imply the importance of specific measures for prevention during adolescence.

Development of a chinese version of the Yale-Brown obsessive compulsive scale for heavy drinking.

BACKGROUND: Measurement of craving is an important component in the investigation of the etiology and clinical pictures of alcoholism and dependence of other substances in different cultures. The aim of this study was to develop a Chinese version of the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd-C), the instrument most frequently used in assessing the severity of alcohol craving in Taiwan. METHODS: Four hundred twenty Han Chinese (220 with alcohol use disorders) and 218 Bunun aborigines (150 with alcohol use disorders) in Taiwan were interviewed by mental health professionals with the YBOCS-hd-C and a Chinese version of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry to establish the psychiatric diagnosis. Validity and reliability of the YBOCS-hd-C were examined. RESULTS: The YBOCS-hd-C was found to have acceptable interrater reliability (intraclass correlation, 0.89-0.96), internal consistency (Cronbach's alpha = 0.99), construct validity, concurrent validity, and cross-cultural validity. The correlations between 10 items of the YBOCS-hd-C and 11 items of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry adjusted for age, gender, and ethnicity ranged from 0.39 to 1.00. The YBOCS-hd-C also discriminated effectively among individuals with alcohol dependence, alcohol abusers, and normal drinkers. CONCLUSIONS: This study demonstrated that the YBOCS-hd-C is a reliable and valid instrument for assessing the extent of craving for alcohol in Taiwanese Han and Bunun individuals.