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.

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.

[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.

[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.

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 of family dynamic structure and parental rearing style with male larcenists].

OBJECTIVE: To explore the association of parental rearing style and family dynamic structure with male larcenists. METHODS: A questionnaire survey was undertaken in 280 male imprisoned larcenists and 420 healthy controls with a General Information Questionnaire and EMBU (Egna Minnen Beträlffande Uppfostran). RESULTS: Statistically significant differences were found between the two groups in the following items: 'only child in the family', 'not lived with father before age 5', 'father died', 'mother died', 'both parents died', 'parents divorced', 'lived with father only (mother absence) before age 5', 'adult with father alive (mother died)' and 'adult with mother alive (father died)'. The two groups also experienced significant differences in 'emotional warmth', 'severe punishment', 'over-intervention from both parents', 'favored child from mother', 'father rejection' and 'father over-protection'. CONCLUSION: Men with single father (mother absence) before age 5 and those who have experienced death of any parents, 'emotional warmth', 'severe punishment', 'over-intervention from both parents', 'favored child from mother', 'father rejection' and 'father over-protection' are more likely to commit theft crime.

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.

Interaction among genes influencing ethanol metabolism and sex is association with alcohol use disorders in a Tibet population.

Associations between alcohol use disorders and polymorphisms of genes influencing ethanol metabolism have been widely reported, but gene-gene and gene-sex interaction studies have rarely been examined. Using a set of samples collected during an epidemiological study of alcohol use disorders AUDs in a Tibetan population in China, we performed a case-control study to investigate the relationship between the functional polymorphisms of genes influencing ethanol metabolism and AUDs. The sample included 383 individuals with an AUDIT score >or=10 and 350 control subjects with the AUDIT score

[A twin study on intelligence and processing speed heritability of children and adolescent].

OBJECTIVE: To explore the effects of the genetic and environmental factors on intelligence of children and adolescent from the Southwest China Prospective Twin Registry (SCPT). METHODS: The intelligence was investigated by using the Wechsler Intelligence Scale for Children (C-WISC) in 333 twin pairs aged 6-16 years. The effects of genetic and environmental factors on IQ were analyzed by using structural equation modeling (SEM) and correlation analysis method. The effects in different sex and age groups in this population were also investigated. RESULTS: Genetic influence accounted for 0.43 of total IQ variance and 0.37 of verbal IQ in 6-16 years old children and adolescent, but there was no significant genetic effect on performance IQ. The heritability of children aged 10-16 years was higher than that of those aged 6-10 years (total IQ: 0.82 vs 0.00, verbal IQ: 0.80 vs 0.00, performance IQ:0.51 vs 0.00). In males the heritability of verbal IQ (0.47) was higher than that in females (0.05). The shared environmental influences accounted fo r the majority of variance of performance IQ in both males and females. CONCLUSION: There is moderate heritability on the total IQ and verbal IQ, while shared environmental factors played important roles on the variance of performance IQ. The heritability of IQ, verbal IQ and performance IQ are higher in older children and adolescent than that in younger children.

[Brain structure abnormality as genetic endophenotype of schizophrenia].

OBJECTIVE: To explore the role of genetic factors in the brain structural variation by using magnetic resonance imaging scan in schizophrenic patients and their unaffected siblings, and to provide experimental evidence for identifying endophenotype of schizophrenia. METHODS: The optimized voxel-based morphometry (OVBM) was used to process the brain magnetic resonance images in 15 first episode drug-naive schizophrenic patients, 19 unaffected siblings of the patients and 38 normal control subjects. The data were analyzed by using general linear model. RESULTS: Compared to the normal control subjects, significant decreases of gray matter was observed in first episode drug-naive schizophrenia in bilateral temporal lobe, bilateral occipital lobe, left insula, left frontal lobe superior frontal gyrus and right lentiform nucleus medial globus pallidus. Significant increases of gray matter in bilateral parietal lobe, bilateral limbic lobe cingulate gyrus in patients group while compared to controls were also found. In unaffected siblings, significant decreases of gray matter was observed in the right temporal lobe, bilateral occipital lobe, left insula, and left frontal lobe precentral gyrus, and significant increases of gray matter were found in left parietal lobe and bilateral cerebellum posterior lobe. Increased gray matter in left parietal lobe precuneus was found in first episode drug-naive schizophrenia when compared with their unaffected siblings. CONCLUSION: There were similar brain structure abnormalities between the first episode drug-naive schizophrenia and their unaffected siblings. Genetic factor may play important role in brain structural abnormality in schizophrenia, which suggested that the brain structural change might be a genetic endophenotype of schizophrenia.

Correlation and familial aggregation of dimensions of psychosis in affected sibling pairs from China.

BACKGROUND: A number of studies with conflicting results have examined the familiality of schizophrenia syndromes in Western populations. AIMS: The objective of this study was to determine, using clinical data from concordant sibling pairs, whether symptom dimensions and other clinical characteristics of schizophrenia show familial aggregation and are therefore potentially useful traits in genetic studies. METHOD: We measured clinical and demographic features, and symptom dimensions of schizophrenia in 137 families from China who had two or more affected members with schizophrenia. Within-sibling pair correlation was assessed with intraclass correlation coefficient and kappa statistics. RESULTS: Global functioning, positive, disorganisation and dysphoric symptoms, premorbid schizotypal and schizoid traits, premorbid social adjustment, type and age at illness onset all showed significant evidence of familial aggregation. DSM-IV schizophrenia subtypes were also found to be familial. CONCLUSIONS: This is the first study in a large non-European population to confirm that schizophrenia dimensions and clinical characteristics show significant familiality, implying possible heritability. This supports their use in the delineation of homogeneous subsets for future genetic studies.

An epidemiological survey of alcohol use disorders in a Tibetan population.

We performed an epidemiological survey in order to detect the prevalence of alcohol use disorders in a sub-group of the population of Tibet. The Alcohol Use Disorders Identification Test (AUDIT) questionnaire, the Severity of Alcohol Dependence Questionnaire (SADQ), and a 12-item version of the General Health Questionnaire (GHQ12) were used to obtain epidemiological data on alcohol use disorders and to assess the severity of 'problem drinking' and general mental health status. The AUDIT is a reliable and valid screening tool for both alcohol abuse and dependence in the Tibetan population to identify individuals with alcohol use problems. The cut-off points were set to be 10 and 13 of the AUDIT scores as a diagnostic discriminator of alcohol abuse and alcohol dependence, respectively, with both sensitivity and specificity>0.84. The prevalence of alcohol abuse, was 2.7% (female: 2.0%; male: 6.2%), alcohol dependence 13.5% (female: 7.6%; male: 25.4%) and alcohol use disorders 16.2% (female: 9.6%; male: 31.6%). Age and sex were the main factors affecting an individual's alcohol use and general mental health status. The epidemiological data on alcohol use disorders documented in this project may be helpful in future work seeking more valid causal inferences or interpretations related to this prevalent health problem in Tibet.

[Examining the comorbidity of attention deficit and hyperactivity disorder and conduct disorder in a population-based twin sample].

OBJECTIVE: To examine three possible causes of the relationship between attention deficit and hyperactivity disorder and conduct disorder: additive genetic factors(A), common environmental factors(C) and individual-specific environmental factors(E). METHODS: One hundred and forty pairs of twins from the Southwestern China Twin Registry were examined with the parent-rated Strength and Difficulties Questionnaire (SDQ). The cross-twin within-variable, within-twin cross-variable and cross-twin cross-variable correlations were calculated. Using structural equation modelling, bivariate models were fitted. The best fitting model was chosen based on likelihood and parsimony. RESULTS: The observed phenotypic correlation between HYPER and COND was 0.44 (95% CI: 0.09, 0.27), with genetic factors accounting for about 70% of the observed correlation. Bivariate model fitting quantified the genetic correlation between HYPER and COND at 0.76 (95% CI: 0.31, 1) and the individual-specific environmental correlation at 0.28 (95% CI: 0.02, 0.51). CONCLUSION: In children, three different genetic factors may exist: one that solely affects the liability to hyperactivity behaviour, one that has only an effect on conduct behaviour and one that influences both hyperactivity and conduct behaviour. Our results suggests that most of the environmental factors that increase the risk of hyperactivity behaviour do not influence conduct behaviour and vice versa.

PRODH gene is associated with executive function in schizophrenic families.

The aim of this study was to investigate the relationship between polymorphisms in the PRODH and COMT genes and selected neurocognitive functions. Six SNPs in PRODH and two SNPs in COMT were genotyped in 167 first-episode schizophrenic families who had been assessed by a set of 14 neuropsychological tests. Neuropsychological measures were selected as quantitative traits for association analysis. The haplotype of SNPs PRODH 1945T/C and PRODH 1852G/A was associated with impaired performance on the Tower of Hanoi, a problem-solving task mainly reflecting planning capacity. There was no significant evidence for association with any other neuropsychological traits for other SNPs or haplotypes of paired SNPs in the two genes. This study takes previous findings of association between PRODH and schizophrenia further by associating variation within the gene with performance on a neurocognitive trait characteristic of the illness. It fails to confirm previous reports of an association between COMT and cognitive function.

Functional polymorphism of CYP2E1 gene and alcohol use disorders in a Tibetan population.

OBJECTIVE: To investigate the relationship between the CYP2E1*c1/*c2 polymorphism and alcohol use disorders, and the potential influence of the CYP2E1*c1/*c2 polymorphism on the severity and dimensions of alcohol use disorders in Tibetan. METHODS: Three hundred and forty Tibetans with Alcohol Use Disorders Identification Test (AUDIT) score >or=10 and another 315 matched control subjects with AUDIT score

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.

Reaction time of the Continuous Performance Test is an endophenotypic marker for schizophrenia: a study of first-episode neuroleptic-naive schizophrenia, their non-psychotic first-degree relatives and healthy population controls.

Sustained attention has been proposed as an endophenotype of schizophrenia, and consequently may be useful as a quantitative trait in genetic studies. In the present study, we used the continuous performance test (CPT) to measure sustained attention in 112 first-episode and neuroleptic-naive schizophrenic patients, 296 of their non-psychotic first-degree relatives, and 452 normal controls. Compared with controls, probands with schizophrenia showed worse performance on all measures of CPT. Parents, siblings and offspring of probands were also impaired on 'hit reaction time', an index of psychomotor processing speed of the correct response. Hit reaction time was also independent of the acute clinical features of the disease, indicating it is a trait rather than a state marker. Our findings supported the use of the hit reaction time measure of the CPT as an endophenotype marker for schizophrenia.

Assessing depressive symptoms in persons who die of suicide in mainland China.

BACKGROUND: The potential insensitivity to depression of translated diagnostic instruments makes it difficult to assess the relationship of depressive symptoms to suicide in non-Western cultures. METHODS: Addition of culturally sensitive probes and other modifications were made to the depression section of the Chinese version of the SCID; the standard SCID probes and the expanded-probes are separately used to assess each symptom of depression, the resultant diagnoses and the overall severity of depression. This modified SCID was included in the psychological autopsy interviews with family members and, separately, close associates of 887 suicides and 721 non-suicidal decedents from 23 regions of mainland China. RESULTS: Compared to the standard interview, the expanded-probe method increased reported prevalence of major depressive episode among suicide decedents from 26.4% (234/887) to 40.2% (357/887) and for other deaths from 1.0% (7/721) to 2.1% (15/701). The additional 131 cases identified using the expanded-probe method had substantial social impairment and a greatly elevated risk of suicide compared to those with no depressive symptoms (OR=37.0, 95% CI=17.6-77.6). Inter-observer reliability for major depressive episode between the two independent interviews was greater for the expanded probe method (ICC=0.77 vs. 0.67, P<0.001). For both interview methods there was a strong dose-response relationship between suicide risk and the number and severity of depressive symptoms. LIMITATIONS: This study uses proxy informants to obtain information about the psychological status of deceased subjects; the value of this expanded-probe method for the diagnosis of depression in non-Western cultures needs to be confirmed with living subjects. CONCLUSIONS: Adding culture-appropriate probes about depressive symptoms to standardized diagnostic instruments identifies many Chinese subjects with unrecognized depression. Dimensional measures of depressive symptoms are more powerful predictors of suicide risk than categorical diagnoses.

A quantitative association study between schizotypal traits and COMT, PRODH and BDNF genes in a healthy Chinese population.

Previous studies have suggested that catechol-O-methyltransferase (COMT), proline dehydrogenase (PRODH), and brain-derived neurotrophic factor (BDNF) genes are possible susceptibility genes for schizophrenia. We hypothesized that these genes are also associated with schizotypal traits, which are heritable and related to schizophrenia. We genotyped five single nucleotide polymorphism (SNPs) from the COMT, PRODH and BDNF genes, and performed a series of association analyses between alleles, genotypes or haplotypes, and quantitative schizotypal trait scores derived from the Schizotypal Personality Questionnaire (SPQ), in 465 Chinese healthy subjects. We found that 'years of education' was a major influence on seven out of nine schizotypal components, three schizotypal factors and the total SPQ scores. Molecular genetic analysis of COMT, PRODH and BDNF genes showed no significant effects of any variants on schizotypal components or factors of SPQ after correction for multiple testing, although there were weak association between COMT Val158Met (rs4680G/A) and the odd speech subscale (allele-wise, P=0.04; genotype-wise, P=0.049), between COMT Val158Met (rs4680G/A) and the suspiciousness subscale (genotype-wise, P=0.024), and between BDNF Val66Met and the Factor 2 interpersonal measure (genotype-wise, P=0.027) before correction. Furthermore, we found SNP Val158Met (rs4680) of the COMT gene significantly influenced the scores of some of schizotypal traits including total SPQ score, the disorganization factor and the constricted affect subscale in male subjects only. However, the effect was in the opposite direction of an earlier association with the SPQ reported by Avramopoulos et al. [Avramopoulos, D., Stefanis, N.C., Hantoumi, I., Smyrnis, N., Evdokimidis, I., Stefanis, C.N., 2002. Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele. Molecular Psychiatry 7, 706-711]. We conclude that SNP Val158Met (rs4680) in the COMT gene may be associated with some schizotypal traits in male subjects, but our results are not conclusive.