Disability associated with mental disorders in metropolitan China: an application of the quantile regression approach.

Recently active mental disorders are associated with substantial disability, but there is little research on residual disability once symptoms have subsided. The aim of this study is to estimate the degree to which recent disability might be due to recent or past history of mental disorders using a quantile regressions (QR) model that makes it possible to study the full range of disability. Data were from cross-sectional surveys of Chinese living in Beijing and Shanghai, China (n=1628). The World Health Organization Disability Assessment Schedule and the WHO Composite International Diagnostic Interview were used to assess recent disability and common mental disorders, respectively. Recently active mental disorders are found to be associated with elevated levels of disability, especially for current substance use disorder. Anxiety disorders stand out with high levels of disability. Individuals at the higher disability levels show large variations in their disability levels. These epidemiological estimates from China add to the evidence based on the global burden of neuropsychiatric disorders, quantifying the hypothesized influence of recently active and past disorders with the novel QR approach. In future studies, we hope to complete more detailed studies of the causal role of mental disorders in the development of disability.

Perceived barriers to mental health treatment in metropolitan China.

OBJECTIVES: This community-based study examined perceived barriers to the initiation of mental health treatment among individuals with anxiety, mood, and alcohol use disorders. METHODS: Face-to-face interviews were conducted with 5,201 respondents in Beijing and Shanghai using the World Mental Health Composite International Diagnostic Interview. Perceived barriers to initiating treatment from various health practitioners were examined among 211 individuals who met criteria for 12-month DSM-IV disorders and did not receive treatment. RESULTS: Most respondents (92%) with DSM-IV disorders perceived a low need for treatment. Among respondents who perceived a need, 47% reported structural barriers and 83% reported attitudinal barriers. Respondents who had severe mental disorders and perceived a need reported more structural barriers (72%) than attitudinal barriers (65%). Lack of knowledge about service availability was the most common structural barrier. CONCLUSIONS: Future studies should examine the reasons for perceived low need for treatment and other treatment barriers among people with mental disorders.

Individual and societal impact on earnings associated with serious mental illness in metropolitan China.

To evaluate individual-level and societal-level losses of income associated with serious mental illness in metropolitan China, a multi-stage probability survey was administered to adults aged 18-70 years in Beijing and Shanghai. We used data to estimate individual-level expected earnings from a model that included information about the respondents' education level, marital status, age, and gender. Expected earnings were compared to observed earnings among respondents with mental illness and serious disability. The result shows that the 12-month prevalence of such serious mental illness was 0.6%. Its impact on earnings was significant in the total sample and was higher for males (76% of gender-specific expected salary was lost) than for females (32%). When projected to societal level, the annual impact was estimated to be 466 million Renminbi (RMB 8.27=USD 1), less than 0.2% of the gross domestic product (GDP) of the two cities. Serious mental illness was associated with a substantial decrease in individual-level earnings, but the burden that resulted from societal-level loss of earnings was not large enough to help drive mental health policy and programs in China.

Impaired role functioning and treatment rates for mental disorders and chronic physical disorders in metropolitan China.

OBJECTIVES: To compare impairments in role functioning and treatment rate of mental disorders and chronic physical disorders in the general population of metropolitan China. METHOD: Face-to-face household interviews of 5201 people aged 18 to 70 years in Beijing and Shanghai were conducted from November 2001 to February 2002, using a multistage household probability sampling method. The World Mental Health version of the Composite International Diagnostic Interview (WMH-CIDI) was used for assessing sociodemographic characteristics, diagnoses, and treatment. The Sheehan Disability Scale (SDS) was used to measure disorder-specific role impairment. RESULTS: Respondents generally attributed greater impairment to mental disorders than to chronic physical disorders, although there were some variations among specific disorders. This general pattern was supported by within-person comparison of impairment associated with a mental disorder versus any chronic physical disorder. Depression, generalized anxiety disorder, and specific phobia were the most impairing mental disorders. Diabetes, headaches, and asthma were the most impairing physical disorders. Comorbid mental and physical disorders were associated with more severe impairment. A much lower percentage of respondents with mental disorders (3.0%) than chronic physical disorders (42.8%) received treatment in the previous 12 months. CONCLUSION: Common mental disorders were associated with greater impairment than chronic physical disorders but were markedly undertreated. They warrant prioritization in the allocation of healthcare resources in China.

Associations of cohort and socio-demographic correlates with transitions from alcohol use to disorders and remission in metropolitan China.

AIMS: To examine socio-demographic associations of transitions from alcohol use to disorders and of remission from disorders in metropolitan China. DESIGN AND SETTING: Face-to-face interviewing by trained lay-interviewers on a multi-staged, clustered sample from the general population of Beijing and Shanghai, China. PARTICIPANTS: A total of 5201 adults aged 18-70 years and with household registration. MEASUREMENTS: World Mental Health version of Composite International Diagnostic Interview. FINDINGS: Lifetime prevalence estimates for alcohol use, regular use (at least 12 drinks in a year), DSM-IV abuse and dependence with abuse were 65.4%, 39.5% (60.4% of ever-drinkers), 4.6% (11.6% of regular users) and 0.9% (20.4% of lifetime alcohol abusers), respectively. These estimates were higher among respondents from the recent cohort; 64.3% and 36.9% respondents with a history of lifetime abuse and dependence respectively had remitted. The number of socio-demographic associations for the onset of each transitional stage decreased from alcohol use to alcohol dependence. Onset of ever-use was more common in respondents who were male, 18-50 years of age, with middle education level and never married, but less common among the previously married and students. First onset of regular use among those with ever-use was more common in respondents who were male, less than 50 years of age and never married, but less common in students. Being male and less than 50 years of age was associated with more alcohol abusers among regular users. CONCLUSION: This study was the first to reveal in a Chinese population that qualitatively different risk factors might operate during the different stages of progression from alcohol use to disorders. Further research is needed to clarify the mechanisms underlying these differences in order to guide prevention programmes.

[The establishment of an animal model of gut-brain interaction in irritable bowel syndrome for the evaluation of visceral sensation, motility and psychological behavior.].

OBJECTIVE: To develop a gut-brain interaction animal model of IBS which combines multiple factors including behavior, visceral sensation and motility. METHODS: Setting up a multifactor interactional animal model (chronic acute combining stress model, CACS) based on a chronic unpredictable mild stress model of depression (CUMS) while combined with wrap restraint stress (WRS), changes of some indexes were recorded including motility (granules of defecating, time of defecating), visceral sensitivity (spontaneous contraction of abdominal striated muscles) and behavior/mind (sucrose consumption, body weight). G protein subunits were measured by Western blot in both hippocampus and prefrontal cortex simultaneously. RESULTS: (1) Compared with the state before stress given, defecating granules increased, defecating time of glassie from rectum shorten, number of abdominal contraction increased, and sucrose consumption decreased in CACS, however, neither significant change was found on defecating behavior in CUMS nor on sucrose consumption in WRS;(2) Compared with the control group, some G protein submits expression decreased in both CACS and CUMS (P < 0.05), while no significant changes of any G protein subunits were found in WRS. CONCLUSION: The CACS animal model was a new, brain-gut interaction model, which can mimic part of human symptoms of IBS very well.

Association of SNPs and haplotypes in APOL1, 2 and 4 with schizophrenia.

Prior work found the APOL1, 2 and 4 genes, located on chromosome 22q12.3-q13.1, to be upregulated in brains of schizophrenic patients. We performed a family-based association study using 130 SNPs tagging the APOL gene family (APOL1-6). The subjects were 112 African-American (AA), 114 European-American (EA), 109 Chinese (Ch) and 42 Japanese (Jp) families with schizophrenia (377 families, 1161 genotyped members and 647 genotyped affected in total). Seven SNPs had p-values<0.05 in the APOL1, 2 and 4 regions for the AA, EA and combined (AA and EA) samples. In the AA sample, two SNPs, rs9610449 and rs6000200 showed low p-values; and a haplotype which comprised these two SNPs yielded a p-value of 0.00029 using the global test (GT) and the allele specific test (AST). The two SNPs and the haplotype were associated with risk for schizophrenia in African-Americans. In the combined (AA and EA) sample, two SNPs, rs2003813 and rs2157249 showed low p-values; and a three SNP haplotype including these two SNPs was significant using the GT (p=0.0013) and the AST (p=0.000090). The association of this haplotype with schizophrenia was significant for the entire (AA, EA, Ch and Jp) sample using the GT (p=0.00054) and the AST (p=0.00011). Although our study is not definitive, it suggests that the APOL genes should be more extensively studied in schizophrenia.

Lifetime prevalence and inter-cohort variation in DSM-IV disorders in metropolitan China.

BACKGROUND: This is the first study to examine variation across cohorts in lifetime risk of DSM-IV mental disorders in metropolitan China. METHOD: Face-to-face household interviews of 2633 adults in Beijing and 2568 adults in Shanghai were conducted from November 2001 to February 2002 using a multi-stage household probability sampling method. The Chinese World Mental Health (WMH) Survey Initiative version of the WHO Composite International Diagnostic Interview (WMH-CIDI) was used for assessment. RESULTS: Lifetime prevalence of any disorder was 13.2%. Alcohol abuse (4.7%), major depressive disorder (3.5%), and specific phobia (2.6%) were the most common disorders. The median age of onset was later for mood (43 years) than anxiety (17 years) and substance use (25 years) disorders. Compared to observed lifetime prevalence, the projected lifetime risk as of age 75 years increased by 106% for major depressive disorder (7.2%), and was uniformly higher for all disorders. Relative odds of any lifetime disorder were 4.7 in the most recent cohorts (ages 18-34) compared to the eldest cohorts (ages > or =65). CONCLUSIONS: The findings of this cross-sectional study tally with the view that rapid socioeconomic changes may bring about increasing incidence of mental disorders in China. However, prospective longitudinal studies are needed to confirm if the increase is real. Because of the huge size of the Chinese population, any increase in projected lifetime risk of mental disorders represents an enormous increase in the number of affected individuals.

Twelve-month prevalence, severity, and unmet need for treatment of mental disorders in metropolitan China.

BACKGROUND: Psychiatric epidemiological surveys in China have repeatedly found much lower prevalence estimates than in most other parts of the world. METHOD: Face-to-face household interviews of 5201 subjects (2633 in Beijing and 2568 in Shanghai respectively) were conducted from November 2001 to February 2002 using a multistage household probability sampling method. A Chinese version of the World Health Organization Composite International Diagnostic Interview (CIDI) was used for assessment. RESULTS: Twelve-month prevalence of any DSM-IV mental disorder in metropolitan China is estimated to be 7.0%, with major depressive disorder (2.0%), specific phobia (1.9%), and intermittent explosive disorder (1.7%) the most common disorders. Of these, 13.9% are classified as serious, 32.6% moderate, and 53.5% mild. Only 3.4% of respondents with any disorder sought treatment within the previous 12 months. CONCLUSIONS: Although the general pattern of disorders, risk factors, and unmet need for treatment are similar to those in other countries, a low prevalence of mental disorders is found in metropolitan China. Resolving methodological problems that cause downward bias in estimates, such as stigma-related under-reporting and diagnostic incongruity with a somatopsychic mode of symptom presentation may lead to more accurate and probably higher prevalence estimates in future epidemiological studies. As a low prevalence still translates into an enormous number of people in China, measures are urgently needed to address the huge unmet need for treatment of mental disorders.

An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia.

Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

No association between polymorphisms in three genes of cytochrome p450 family and paranoid schizophrenia in northern Chinese Han population.

We genotyped six SNPs in the genes of p450 family among paranoid schizophrenics and normal controls. All subjects are unrelated Han Chinese. Three showed polymorphic, and no significant differences in allele or genotype frequencies were detected between patients and controls. Thus we obtained no evidence for the involvement of the polymorphisms in paranoid schizophrenia in the population investigated.

An association study between polymorphisms in three genes of 14-3-3 (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein) family and paranoid schizophrenia in northern Chinese population.

We performed an association study between three SNPs in the genes of 14-3-3 family and paranoid schizophrenia. SNP rs983583 G/A in the YWHAZ gene showed significant association with paranoid schizophrenia. Our study indicated that the YWHAZ gene was a potential susceptibility gene for paranoid schizophrenia in the population studied.

No association between polymorphisms in the DDC gene and paranoid schizophrenia in a northern Chinese population.

Several lines of evidence suggest that dysfunctions of neurotransmitters are associated with schizophrenia. DOPA decarboxylase (DDC) is an enzyme involved directly in the synthesis of dopamine and serotonin, and indirectly in the synthesis of noradrenaline. Therefore, the DDC gene can be considered a candidate gene for schizophrenia. We performed an association study between three single nucleotide polymorphisms in the DDC gene and paranoid schizophrenia. However, in our study no significant differences were found in the genotype distributions and allele frequencies between 80 paranoid schizophrenics and 108 controls for any of the polymorphisms. Neither did the haplotypes of the single nucleotide polymorphisms show any association with paranoid schizophrenia. Therefore, we conclude that the polymorphisms studied do not play a major role in paranoid schizophrenia pathogenesis in the population investigated.

Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys.

CONTEXT: Little is known about the extent or severity of untreated mental disorders, especially in less-developed countries. OBJECTIVE: To estimate prevalence, severity, and treatment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders in 14 countries (6 less developed, 8 developed) in the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative. DESIGN, SETTING, AND PARTICIPANTS: Face-to-face household surveys of 60 463 community adults conducted from 2001-2003 in 14 countries in the Americas, Europe, the Middle East, Africa, and Asia. MAIN OUTCOME MEASURES: The DSM-IV disorders, severity, and treatment were assessed with the WMH version of the WHO Composite International Diagnostic Interview (WMH-CIDI), a fully structured, lay-administered psychiatric diagnostic interview. RESULTS: The prevalence of having any WMH-CIDI/DSM-IV disorder in the prior year varied widely, from 4.3% in Shanghai to 26.4% in the United States, with an interquartile range (IQR) of 9.1%-16.9%. Between 33.1% (Colombia) and 80.9% (Nigeria) of 12-month cases were mild (IQR, 40.2%-53.3%). Serious disorders were associated with substantial role disability. Although disorder severity was correlated with probability of treatment in almost all countries, 35.5% to 50.3% of serious cases in developed countries and 76.3% to 85.4% in less-developed countries received no treatment in the 12 months before the interview. Due to the high prevalence of mild and subthreshold cases, the number of those who received treatment far exceeds the number of untreated serious cases in every country. CONCLUSIONS: Reallocation of treatment resources could substantially decrease the problem of unmet need for treatment of mental disorders among serious cases. Structural barriers exist to this reallocation. Careful consideration needs to be given to the value of treating some mild cases, especially those at risk for progressing to more serious disorders.

Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families.

Chromosome 22q12 is one of the most promising regions for harboring a risk gene for schizophrenia. We have reported significant linkage of intermediate phenotypes for schizophrenia with markers within or near the beta-adrenergic receptor kinase 2 (ADRBK2, or GRK3) gene, which is highly expressed in dopaminergic pathways in the central nervous system, and mediates homologous desensitization for a variety of neurotransmitters and hormones through phosphorylation of G protein-coupled receptors (GPCRs). A polymorphism in the promoter region of the ADRBK2 was reported to be associated with bipolar disorder. We screened the putative promoter region, and all 21 exonic and flanking intronic regions of the ADRBK2 gene for mutations in 48 schizophrenia probands (including 16 Japanese and 32 Chinese patients), and evaluated the detected polymorphisms and those reported in the JSNP database for associations with schizophrenia in 113 family trios of schizophrenia probands. Four single nucleotide variants in the 5'-UTR/promoter region, and 16 rare variants in exonic and flanking regions, were identified. Among them, the Cys208Ser variant was the only non-synonymous mutation. Cys208Ser was found in one family without cosegregation between the variant and schizophrenia. Moreover, allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms and schizophrenia. The present study indicates that the ADRBK2 gene is unlikely to contribute strongly to schizophrenia susceptibility in this set of families.

Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples.

BACKGROUND: A family based association study in a British sample found the NOTCH4 gene to be associated with schizophrenia; however, all six replication studies failed to confirm the finding. METHODS: We performed a family based association study of NOTCH4 and schizophrenia in 123 trios (16 Japanese and 107 Chinese). In addition to the original study's polymorphisms, we examined four new single nucleotide polymorphisms (SNPs)--SNPs_A, B, C and D--around SNP1 of the original study. We genotyped all samples for SNPs_A-D and for SNP1 and (CTG)n of the original study. RESULTS: We found no significant associations between NOTCH4 and schizophrenia or its subtypes for all polymorphisms, regardless of gender. The finding remained negative when the Chinese sample was analyzed separately. Exploratory analyses suggested that SNP_A may be associated with early-onset schizophrenia and that SNP1 may be associated with schizophrenia characterized by numerous negative symptoms. CONCLUSIONS: NOTCH4 is not a significant susceptibility gene for schizophrenia when clinical heterogeneity is ignored; however, NOTCH4 may be associated with early-onset schizophrenia or schizophrenia with many negative symptoms, but these findings should be interpreted cautiously.

Family-based association study of markers on chromosome 22 in schizophrenia using African-American, European-American, and Chinese families.

Several studies suggest that loci at chromosome 22q11.2-q13 might be linked to susceptibility to schizophrenia. Here we performed family-based association studies on chromosome 22q using 12 DNA microsatellite markers in African-American, European-American, and Chinese pedigrees. The marker D22S683 showed significant linkage and association with schizophrenia in not only the European-American sample but also in a combined sample (European-American and Chinese samples). Notably, D22S683 is located nearby and between D22S278 and D22S283, which have shown linkage and association to schizophrenia in prior reports. However, we found no significant association for the African-American sample. In conclusion, our data provide further support for the idea that the region around D22S683 contains a susceptibility gene for schizophrenia.