Psychiatric Epidemiology and Mental Health Service in the Tibet Autonomous Region of the People's Republic of China.

Little is known internationally about the psychiatric epidemiology and mental health services in Tibet. This article reviews the relevant research of psychiatric epidemiology and mental health services in the Tibet Autonomous Region (TAR), P. R. China. There is a substantive number of people suffering from mental disorders and psychological problems in an area with a general lack of modern mental health institutions and professionals.

The development and validation of Huaxi emotional-distress index (HEI): A Chinese questionnaire for screening depression and anxiety in non-psychiatric clinical settings.

BACKGROUND: Depression and anxiety among general hospital patients are common and under-recognized in China. This study aimed toward developing a short questionnaire for screening depression and anxiety in non-psychiatric clinical settings, and to test its reliability and validity. METHODS: The item pool which included 35 questions about emotional distress was drafted through a comprehensive literature review. An expert panel review and the first clinical test with 288 general hospital patients were conducted for the primary item selection. The second clinical test was performed to select the final item in 637 non-psychiatric patients. The reliability and validity of the final questionnaire were tested in 763 non-psychiatric patients, in which 211 subjects were interviewed by psychiatrists using Mini International Neuropsychiatric Interview (MINI). Multiple data analysis methods including principal components analysis (PCA), item response theory (IRT), and receiver operating characteristic (ROC) curve were used to select items and validate the final questionnaire. RESULTS: The series selection of items resulted in a 9-item questionnaire, namely Huaxi Emotional-distress Index (HEI). The Cronbach's α coefficient of HEI was 0.90. The PCA results showed a unidimensional construct. The area under the ROC curve (AUC) was 0.88 when compared with MINI interview. Using the optimal cut-off score of HEI (≥11), the sensitivity and specificity were 0.880 and 0.766, respectively. CONCLUSIONS: The HEI is considered as a reliable and valid instrument for screening depression and anxiety, which may have substantial clinical value to detect patients' emotional disturbances especially in the busy non-psychiatric clinical settings in China.

Genome-Wide Association of Heroin Dependence in Han Chinese.

Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field.

Anti-N-methyl-d-aspartate receptor encephalitis in a patient with a 7-year history of being diagnosed as schizophrenia: complexities in diagnosis and treatment.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a form of autoimmune encephalitis associated with antibodies against the NR1 subunits of NMDARs. Although new-onset acute prominent psychotic syndromes in patients with NMDAR encephalitis have been well documented, there is a lack of case studies on differential diagnosis and treatment of anti-NMDAR encephalitis after a long-term diagnostic history of functional psychotic disorders. The present study reports an unusual case of anti-NMDAR encephalitis. The patient had been diagnosed with schizophrenia 7 years earlier, and was currently hospitalized for acute-onset psychiatric symptoms. The diagnosis became unclear when the initial psychosis was confounded with considerations of other neurotoxicities (such as neuroleptic malignant syndrome). Finally, identification of specific immunoglobulin G NR1 autoantibodies in the cerebrospinal fluid and greater effectiveness of immunotherapy over antipsychotics alone (which has been well documented in anti-NMDAR encephalitis) indicated the diagnosis of anti-NMDAR encephalitis in this case. Based on the available evidence, however, the relationship between the newly diagnosed anti-NMDAR encephalitis and the seemingly clear, long-term history of schizophrenia in the preceding 7 years is uncertain. This case report illustrates that psychiatrists should consider anti-NMDAR encephalitis and order tests for specific immunoglobulin G NR1 autoantibodies in patients presenting with disorientation, disturbance of consciousness, cognitive deficit, dyskinesia, autonomic disturbance, or rapid deterioration, even with a seemingly clear history of a psychiatric disorder and no specific findings on routine neuroimaging, electroencephalography, or cerebrospinal fluid tests in the early stage of the illness.

[Difference in brain surface area between first-episode familial and sporadic schizophrenia and its association with COMT gene polymorphisms].

OBJECTIVE: To assess the association of impairment of surface area of first-episode schizophrenia(SZ) with polymorphisms of COMT gene, and the difference in the impaired patterns between familial patients with schizophrenia(FPS) and sporadic patients with schizophrenia(SPS). METHODS: Ninety-eight patients with first-episode SZ(FPS=40, SPS=58) and 78 healthy controls were recruited. COMT gene was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Participants were scanned for 3.0T magnetic resonance images. Freesurfer software was used to analyze the difference in brain surface area between SZ and controls, its association with COMT genotypes, and the difference between SPS, FPS and control groups. Multiple tests were corrected using a Monte Carlo simulation at P<0.05. RESULTS: Compared with controls, SZ showed decreased surface area in right occipital cortex and left prefrontal cortex. No association was found between COMT polymorphisms and whole brain area difference. Among the three subgroups, SPS showed smaller left prefrontal area compared with both FPS and control groups. Patients with SPS also showed significant area reduction in right occipital lobe compared with controls. CONCLUSION: Surface area impairment can be found in those with first-episode SZ, but without association with COMT gene polymorphisms. The SPS have more severe area impairment than FPS, indicating that SPS and FPS may be attributed to different etiological mechanisms.

Contingent negative variation in patients with deficit schizophrenia or bipolar I disorder with psychotic features: measurement and correlation with clinical characteristics.

BACKGROUND: Schizophrenia is a highly heterogeneous disease. Event-related potentials have been regarded to establish intermediate phenotypes of schizophrenia. Our previous study found that patients with deficit schizophrenia (DS) are relatively homogeneous and show a significantly longer onset latency of contingent negative variation (CNV) expectancy wave. AIMS: To further examine CNV in patients with first-episode and drug-naïve DS or bipolar I disorder (BP I) with psychotic features, and also investigate correlations between CNV and clinical characteristics in DS and BP I. METHOD: We elicited a CNV using an alarm (S1)-imperative (S2) paradigm in 30 DS patients or 33 BP I with psychotic features as well as 40 healthy controls. RESULTS: CNV amplitude was significantly smaller and reaction time significantly longer in the DS and BP I groups than in healthy controls. Post-imperative negative variation (PINV) interval was significantly shorter in the DS group than in healthy controls. The onset latency of CNV expectancy wave was significantly longer and PINV area significantly smaller in the DS group than in the other groups. In the DS group, CNV amplitude and PINV interval correlated negatively with the subscale of negative symptoms on the Positive and Negative Syndrome Scale (PANSS); CNV amplitude also correlated negatively with disease duration. In the BP I group, CNV amplitude and reaction time showed no correlation with clinical features. CONCLUSIONS: CNV amplitude is a common trait marker for psychosis. The onset latency of CNV expectancy wave appears to be a specific trait marker and may be used to identify candidate genes for DS.

Long-term benzodiazepine use in patients with major depressive disorder in China.

PURPOSE: There have been no data about long-term benzodiazepine (BZD) use and its correlates in patients with major depressive disorder (MDD) in China. This study aimed to examine the prevalence of long-term BZD use (more than three months) and its demographic and clinical correlates in Chinese patients with MDD. DESIGN AND METHODS: A total of 1,192 patients with MDD were examined in 10 mental health centers in China. Patients' socio-demographic and clinical characteristics and prescriptions for psychotropic drugs were recorded using a standardized form. FINDINGS: A large portion of patients (36.2%) received long-term BZD treatment. Univariate analyses revealed that long-term BZD users were older, poorer, and had more impaired occupational functioning than patients not taking BZDs. Long-term BZD users had fewer psychotic symptoms and took less antipsychotic drugs. In multivariate analyses, long-term BZD use was independently associated with older age and more severe impaired occupational functioning; long-term BZD users were less likely to receive antipsychotic medications and traditional antidepressants (tricyclic antidepressants, tetracyclic antidepressant, and monoamine oxidase inhibitors). PRACTICE IMPLICATIONS: Long-term BZD use was common in patients with MDD in China. A host of demographic and clinical factors were independently associated with long-term BZD use.

Polymorphisms of genes in neurotransmitter systems were associated with alcohol use disorders in a Tibetan population.

Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD). However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281) with an alcohol use disorder identification test (AUDIT) score ≥10, as well as healthy controls (N = 277) with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05). After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881) in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881) showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD.

[Epidemiological survey on neuropsychiatric disorders in Tibet of China: neuroses, alcohol-related disorders, mental retardation and epilepsy].

OBJECTIVE: To investigate the prevalence of four common neuropsychiatric disorders in Tibet, with an aim to providing information support to health planning. METHODS: The survey was carried out in four regions of Tibet. The sampling strategy was adapted from that of a national psychiatric epidemiological survey in China in 1982 and 1993. The Neurosis Screening Inventory, Screening Inventory for Alcohol Dependence and Related Problems, Child Intelligence Screening Inventory, and a questionnaire for the Detection of Epileptic Seizures were administered to the respondents through face to face interview. Those with a positive response and 10% of those with a negative response were further interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders (research version) (SCID-I ). Anxiety disorders and alcohol used disorders were diagnosed according to the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV). Hysteria and mental retardation were diagnosed according to the International Classification of Diseases, 10th edition (ICD-10), and the Chinese Classification of Mental Disorders, 3rd edition (CCMD-3). RESULTS: The point prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 56%, 4. 06%, 0. 28% and 0. 68%, respectively. The lifetime prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 62%, 4. 24%, 0. 28% and 0.72%, respectively. CONCLUSION: Alcohol-related disorders and neuroses are the two common mental health problems in Tibet. Mental retardation and epilepsy are the two serious neuropsychiatric disorders affecting Tibetan children and adolescence. These disorders should be identified as priorities in the reginonal health planning in Tibet.

Advanced paternal age increases the risk of schizophrenia and obsessive-compulsive disorder in a Chinese Han population.

Using the Structured Clinical Interview for DSM-IV, patient and non-patient version (SCID-P/NP), this study investigated 351 patients with schizophrenia, 122 with obsessive-compulsive disorder (OCD), and 238 unrelated healthy volunteers in a Chinese Han population. The relative risks posed by advanced paternal age for schizophrenia and OCD in offspring were computed under logistic regression analyses and adjusted for the participant's sex, age and co-parent age at birth. Compared to the offspring with paternal age of 25-29 years old, the relative risks rose from 2.660 to 10.183 in the paternal age range of 30-34 and ≥35. The relative risks for OCD increased from 2.225 to 5.413 in 30-34 and ≥35. For offspring with paternal age of <25, the odds ratios of developing schizophrenia and OCD were 0.628 and 0.289 respectively, whereas an association between increased maternal age and risk for schizophrenia/OCD was not seen. Interaction analysis showed an interaction effect between paternal age and maternal age at birth. Such a tendency of risk affected by parental age for schizophrenia and OCD existed after splitting out the data of early onset patients. Sex-specific analyses found that the relative risks for schizophrenia with paternal age of 30-34 and ≥35 in male offspring were 2.407 and 10.893, and in female offspring were 3.080 and 9.659. The relative risks for OCD with paternal age of 30-34 and ≥35 in male offspring were 3.493 and 7.373, and in female offspring 2.005 and 4.404. The mean paternal age of schizophrenia/OCD patients born before the early 1980s was much greater than that of patients who were born after then. The findings illustrated that advanced paternal age is associated with increased risk for both schizophrenia and OCD in a Chinese Han population, prominently when paternal age is over 35. Biological and non-biological mechanisms may both be involved in the effects of advanced paternal age on schizophrenia and OCD.

Hair cortisol level as a biomarker for altered hypothalamic-pituitary-adrenal activity in female adolescents with posttraumatic stress disorder after the 2008 Wenchuan earthquake.

BACKGROUND: The present study evaluated the accumulated changes in hair cortisol levels of patients with posttraumatic stress disorder (PTSD) attributed to the 2008 Wenchuan earthquake in China. METHODS: Sixty-four female adolescents from two townships who experienced the earthquake were recruited 7 months after the disaster, including 32 subjects with PTSD (PTSD group) and 32 subjects without PTSD (non-PTSD group). Twenty matched adolescents were recruited from an area that was not affected significantly by the earthquake as the control group. Hair cortisol concentrations were measured by the electrochemiluminescence immunoassay in each 3-cm segment of hair sample from the scalp. RESULTS: There was no significant difference at the baseline hair cortisol level in the three groups before the traumatic event (p > .6). Hair cortisol levels changed over time and differed among groups (p = .0042). The hair cortisol levels among the PTSD and non-PTSD subjects were elevated, suggesting increasing levels in response to stress. However, these two groups differed in their response. The non-PTSD subjects showed a significantly higher cortisol level than the PTSD group between month 2 and month 4 (p = .0137) and also between month 5 and month 7 (p = .0438) after the traumatic event. CONCLUSIONS: This study revealed a blunted response curve to the disaster among PTSD subjects compared with subjects without PTSD. These findings suggest that hair cortisol level could be used to assess the integrated hypothalamic-pituitary-adrenal activity over a period of months after traumatic events and be used to serve as a biomarker in patients with PTSD.

Use of clozapine for the treatment of schizophrenia: findings of the 2006 research on the china psychotropic prescription studies.

OBJECTIVE: Clozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. METHODS: Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10 provinces with differing levels of economic development. RESULTS: Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36±128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. CONCLUSION: Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.

Normative data on a battery of neuropsychological tests in the Han Chinese population.

In order to develop normative data of a battery of neuropsychological tests in the mainland Chinese population, we examined the performance of 15 neuropsychological tests in 465 healthy subjects (231 males and 234 females) in a population-based cohort study. The years of education were ranged between 1 and 23 years, and ages were ranged between 16 and 75 years old. The 15 neuropsychological tests cover five domains of neurocognitive functions including attention and speed of information processing, memory and learning, verbal function, visual constructive abilities, and executive function. We also assessed the effects of gender, age, educational attainment on the performance of these neuropsychological tests. The results showed that, as expected, educational attainment and age are the two main factors affecting performance in these tests. Educational attainment has the strongest predictive effect on all tests, while the majority of tests selected in this study are also affected by age at examination to varying degrees. The presented normative data will be useful for future studies in related clinical research, and be of value in transcultural neuropsychological studies.

Gender-specific interactions between alcohol metabolism genes and severity of quantitative alcohol-related-traits in a Tibetan population.

Association between genes influencing alcohol metabolism and alcohol use disorders (AUD) has been extensively studied, but the effect of interactions between these genes and AUD have rarely been tested. Our previous case-control study in a Tibetan population noted that the positive association between c2 allele of cytochrome P4502E1 (CYP2E1) gene and AUD might only exist in males who are homozygotes for 1 alleles of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B) genes, but this interaction did not reach statistical significance. Using the same set of data, the present study was aimed at exploring interactions between these genes and quantitative alcohol-related-trait scores (QARTs), and whether these are influenced by gender. The sample included 383 AUD cases with the alcohol use disorders identification test (AUDIT) score ≥10 and 350 normal controls with the AUDIT score ≤5. QARTs were measured using three factors from AUDIT. Possible associations of QARTs with interactions among genotypes of ALDH2 1/ 2, ADH1B1/2 and CYP2E1 c1/c2 and sex were analyzed in AUD cases and normal controls separately. The subjects with 2 alleles of ALDH2 or/and ADH1B had significantly lower scores of alcohol intake among controls but had significantly higher scores of alcohol related problems among cases. The score of alcohol intake in male cases who are homozygous for ALDH2 1 and ADH1B 1 and with CYP2E1 c2 allele was significantly higher than that of other cases. These findings suggest that interactions between genes influencing alcohol metabolism are influenced by gender and might affect QARTs differently between the milder-/non-drinkers and AUD cases.

Factors that influence the prescription of antipsychotics for patients with schizophrenia in china.

OBJECTIVE: To investigate the patterns of antipsychotic use in China and to analyze the factors that influence antipsychotic prescriptions. METHODS: A standardized survey was conducted from May 20 to 24 2002 in five different regions of China with varying economic levels. The patterns of antipsychotic medication use were analyzed in a sample of 4,779 patients with schizophrenia. The survey gathered information on demographic characteristics, clinical profiles, and antipsychotic medications prescribed. Multiple logistic regression was used to analyze factors related to patterns of antipsychotic medication use. RESULTS: A plurality of patients with schizophrenia was treated with clozapine (39%); this was followed by risperidone, sulpride, chlorpromazine, perphenazine, and haloperidol. More than 56.3% of patients were treated with only one atypical antipsychotic. The mean daily dose of chlorpromazine was 365±253 mg (mean±standard deviation), and 6.5% of patients were treated with depot injections of typical antipsychotic medications. A total of 73.7% (n=3,523) of patients with schizophrenia received monotherapy, 24.8% (n=1,183) received two antipsychotics, 1.1% (n=52) received three antipsychotics, and one received four different antipsychotics. Patients often simultaneously received other classes of medications including anticholinergic agents, benzodiazepines, ß-blockers, antidepressants, and mood stabilizers. Economic status and clinical symptoms were the main factors that contributed to the patterns of antipsychotic prescription. CONCLUSION: The present study suggests that atypical antipsychotic medications, especially clozapine, are the primary psychiatric treatments of choice in the management of schizophrenia in China. Moreover, the economic status and clinical profile of the patient are the major factors affecting the prescription of antipsychotic medication.

Premorbid tobacco smoking is associated with later age at onset in schizophrenia.

Rates of cigarette smoking in individuals with schizophrenia well exceed those in the general population and in other mental illnesses. In the present study, we examined the relationship between smoking status, clinical characteristics and cognitive functions in 230 male Chinese schizophrenia patients. They were interviewed by experienced psychiatrists using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (SCID-P). Clinical symptoms were rated using the Positive and Negative Syndrome Scale (PANSS), and the Revised Tolerance Questionnaire (RTQ) used to evaluate the severity of nicotine dependence. Nine neuropsychological tests were used to assess cognitive function. We found that never-smokers had a younger age at examination and earlier onset and longer duration of illness than smokers and ex-smokers. The age of initiation of regular smoking in patients was significantly earlier than their age of illness onset. We found that longer duration of illness was significantly associated with higher RTQ scores. Ex-smokers with schizophrenia performed significantly more poorly on the Stroop C test than smokers. The results imply that smoking may affect cognitive function and illness onset time in patients with schizophrenia.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and age of onset in schizophrenia.

Different lines of evidence indicate that methylenetetrahydrofolate reductase (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine metabolism, are associated with increased vulnerability to several heritable developmental disorders. Opposing views are expressed considering the possible association between MTHFR and susceptibility for schizophrenia. In order to evaluate if age of onset could explain some of this discrepancy we investigated the relationship between two functional MTHFR gene polymorphisms and age at onset in this disorder. Scandinavian patients (n = 820) diagnosed with schizophrenia, schizoaffective disorder, and schizophreniform disorder were investigated. Two functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133) were genotyped and the effect of MTHFR polymorphisms on the age of onset was examined with survival analysis. In an attempt to replicate the findings from the Scandinavian sample, the association between rs1801133 and age at onset was also analyzed in Chinese high-risk families, with two or more affected siblings (n = 243). Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T) significantly affected age at onset of schizophrenia in a dose-dependent manner (P = 0.0015), with lower age of onset with increasing numbers of the mutant T-allele. There was no evidence of rs1801131 (A1298C) affecting age of onset in schizophrenia. Within the Chinese high-risk families carriers of the MTHFR 677T allele showed earlier age at onset than siblings being homozygous for the wild-type allele (P = 0.008). The MTHFR C677T polymorphism may play a role as a modifying factor for age of onset in schizophrenia.