The association between dyslipidaemia and types of antipsychotic medications among patients with chronic schizophrenia.

This cross sectional study aimed to explore the association between dyslipidaemia and types of antipsychotics in 100 patients with chronic schizophrenia. Lipid profile, weight, height and waist circumference together with other relevant factors were measured. We found there was a high rate of dyslipidaemia among patients with chronic schizophrenia treated with antipsychotics (66%), however there was no significant difference found between typical or atypical antipsychotics (OR=1). All sociodemographic and clinical factors were not significantly associated with dyslipidaemia. Only non-Malays were found to have significant dyslipidaemia (p<0.1). Effective management is needed to deal with the dyslipidaemia in this group.

BDNF and DARPP-32 genes are not risk factors for schizophrenia in the Malay population.

A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and g.1238delG of DARPP-32 were genotyped in the Malay population in 200 patients with schizophrenia and 256 healthy controls. Analysis of allele and genotype frequencies in these two groups revealed no significant association of BDNF or DARPP-32 polymorphisms with schizophrenia in Malays. This is the first such association study in the Malay population.

The National Mental Health Registry (NMHR).

The National Mental Health Registry (NMHR) collects information about patients with mental disorder in Malaysia. This information allows us to estimate the incidence of selected mental disorders, and to evaluate risk factors and treatment in the country. The National Mental Health Registry (NMHR) presented its first report in 2004, a year after its establishment. The report focused on schizophrenia as a pioneer project for the National Mental Health Registry. The development of the registry has progressed with data collected from government-based facilities, the academia and the private sector. The 2003-2005 report was recently published and distributed. Since then the registry has progressed to include suicides and other mental illnesses such as depression. The NMHR Report 2003-2005 provides detailed information about the profile of persons with Schizophrenia who presented for the first time to various psychiatry and mental health providers throughout Malaysia. More detailed description regarding pharmacotherapy is reported and few cross tabulations done in an effort to provide better understanding and more clinically meaningful reports.

Properties of the temperament and character inventory in a Chinese sample.

OBJECTIVE: To determine the influence of language and culture on the temperament and character (TCI) measure in a Chinese sample. METHOD: We translated the TCI into Mandarin and had a non-psychiatric sample of Malaysian Chinese subjects complete the TCI at baseline and at a 1-month retest, with subsets completing English or Mandarin versions alternatively or on both occasions. Analyses examine the TCI factor structure and any impact of language and culture on TCI scoring. RESULTS: We identified age, gender, occupation and language effects on TCI scale scores. Test-retest reliability was high and not compromised by language. Scale internal consistency was also high. Factor analyses of separate sets of TCI scales corresponded strongly to the structure identified in the TCI development studies. CONCLUSION: The results indicate that TCI is likely to have applicability to Chinese subjects, and argue against properties being constrained by the English language or by western culture.

Do the Chinese somatize depression? A cross-cultural study.

BACKGROUND: A large literature argues for the Chinese--whether in mainland China or elsewhere--being highly likely to express depression somatically, leading to predictable detection and diagnostic difficulties. If true, detection might be assisted if a set of somatic proxies of depression were identified, and this was the principal initial objective in mounting this study. METHODS: We studied two sets of depressed outpatients, one of Malaysian Chinese and the other of Australian Caucasians, matched by age and sex. We identified the prime symptom nominated by them when they first sought assistance, and required them to complete an inventory of both somatic and cognitive symptoms, and rank the three items they judged as most capturing their distress. RESULTS: The Chinese were distinctly more likely to nominate a somatic symptom as their presenting complaint (60% vs 13%), while the Australian subjects were more likely to nominate depressed mood, cognitive and anxiety items. Responses to the inventory established that the Chinese did score somewhat higher on a somatic set of items, but differed far more distinctly in being less likely to affirm cognitive items of depression, resulting in significantly lower total inventory scores. Variation across the contrast samples in acknowledging the presence of symptoms did not relate simply to the prevalences of those symptoms. CONCLUSIONS: Our failure to identify a culture-specific somatic factor as a proxy of depression, together with establishing a high rate of somatic and related items (e. g. insomnia) in both samples, may largely reflect the phenomenon of 'corporization', whereby depressed patients irrespective of culture are more likely to experience and report in response to a 'somatosensory amplification' influence.

Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice.

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR x C57L) F(1) x AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at approximately 20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK. L-Lith1(s). Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L-Lith2(s). Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.

Evaluation and validation of a measure profiling needs and problems of psychiatric patients in the community: a Malaysian study.

BACKGROUND: The Profile of Community Psychiatry Clients (PCPC) was developed in a Sydney-based sample of those with a mental illness as a 35-item measure of likely need for service recognition, review and possible assistance. METHODS: This study has three principal objectives. Firstly, to test the utility of the PCPC measure in a very different region and culture. Secondly, to review the factor structure in an independent sample. Thirdly, to pursue the extent to which the PCPC might serve as a measure of likely need, by obtaining three differing reference viewpoints of need (i.e. clients, their carers, and case managers) and examining responses against PCPC scores. The PCPC was given to a sample of 333 Malaysian clients living in the community, together with two other measures of morbidity and disability. In addition, case managers, family members and clients were requested to directly rate the level of need for service assistance. RESULTS: A principal components analysis favoured a six-factor solution, with PCPC factor scores and total scores intercorrelated with subscale and total scores on the Life Skills Profile (LSP) and Health of the Nation Outcome Scales (HoNOS). The correlation coefficients supported the concurrent validity of the derived PCPC scales. Family members rated the clients' needs as greater than did case managers who, in turn, rated severity of needs greater than the clients themselves. Most importantly, PCPC scores correlated more highly than did LSP and HoNOS scores with need estimates derived by all three rating groups, providing strong support for the PCPC meeting its objective as a measure of putative need. In addition, a refined 23-item version of the PCPC was derived, which retained the capacity of the PCPC to correlate strongly with needs estimates. CONCLUSIONS: This Malaysian study supports the use of the PCPC in a culture where service provision and family support for those with a mental illness vary considerably from Western regions, while its validation as a measure of need for service is supported.

Congenital heart disease in mice deficient for the DiGeorge syndrome region.

The heterozygous chromosome deletion within the band 22q11 (del22q11) is an important cause of congenital cardiovascular defects. It is the genetic basis of DiGeorge syndrome and causes the most common deletion syndrome in humans. Because the deleted region is largely conserved in the mouse, we were able to engineer a chromosome deletion (Df1) spanning a segment of the murine region homologous to the human deleted region. Here we describe heterozygously deleted (Df1/+) mice with cardiovascular abnormalities of the same type as those associated with del22q11; we have traced the embryological origin of these abnormalities to defective development of the fourth pharyngeal arch arteries. Genetic complementation of the deletion using a chromosome duplicated for the Df1 DNA segment corrects the heart defects, indicating that they are caused by reduced dosage of genes located within Df1. The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. These mutants represent a mouse model of a human deletion syndrome generated by chromosome engineering.

Engineering a mouse balancer chromosome.

Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs.

Development of a measure profiling problems and needs of psychiatric patients in the community.

We argue the advantages of a measure profiling common problems faced by psychiatric patients in the community and indicating a likely need for service recognition, review and possible assistance. We describe the development of such a measure, the 35-item Profile of Community Psychiatry Clients (PCPC), and the identification of four relevant domains. Component scales assess coping limitations, behavioural problems, levels of social support and organic problems. High test-retest reliability was established, and a number of tests of the measure's validity were undertaken. Discriminant validity was established by demonstrating that those case managed by a community mental health service returned significantly higher scale scores than a comparison group who, while having a similar diagnostic profile, were not case managed. Additionally, scale scores were associated with a number of categorical and dimensional validators reflecting aspects of service need, and distinctly with service costs. We demonstrate that PCPC scores correspond with scores generated by the Life Skills Profile (LSP), a measure of disability, and examine the extent to which PCPC scales correspond to those contained in the Health of the Nation Outcome Scales (HoNOS). We argue for the scale's capacity to provide both a profile of central problems faced by patients and their likely need for community-based service assistance.

A double blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics.

The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient. Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were randomised to receive either zuclopenthixol acetate or haloperidol. They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the same medication, no other anti-psychotic was given for the duration of the study. 50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating (p < 0.001). There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study. Both groups had minimal side effects. Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic.

Prevalence of emotional and behavioural problems in Johor Bahru District school children--comparing three geographical areas.

This is a cross sectional community study in Johor Bahru District. The aim of this study is to estimate the overall prevalence of emotional and behavioural deviance among the school children in three different geographical areas, and to identify their correlates. This paper presents the findings of phase one of a two-stage procedure involving a total of 589 children aged 10-12 years. Using the cut-off point validated locally, the prevalence of deviance on the parental scale was 40% in the rural school, 30.2% in the agricultural resettlement (Felda) school and 32.3% in the urban school. On the teachers' assessment, the prevalence of deviance was 40.8% in the rural school, 10.8% in the Felda School and 8.9% in the urban school. There was significantly higher prevalence of deviance in the rural school on the teachers' scale. In the rural school, significantly higher prevalence of deviance was found among boys.

Audit of new long-stay patients in Permai Mental Hospital, Johor.

We report a cross-sectional descriptive study of 90 new long-stay patients (NLS) (i.e. those who had been resident for six months to three years in Permai Mental Hospital, Johor) and studied from April to June, 1995. The age of this sample ranged from 18 to 85 years. Two subgroups were observed (i.e. younger NLS patients aged 18 to 34 years and older NLS patients aged 35 to 85 years). Among the younger NLS patients, the commonest diagnosis was schizophrenia (51.2%), followed by mental retardation with related problems (24.4%). Sixty-one percent of these younger patients had a history of serious violence or dangerous behaviour. Older NLS patients were likely to have a diagnosis of schizophrenia (79.6%), followed by mood disorder (6.1%) and dementia (4.1%). Forty seven percent of these older group had history of danger to others and 57.1% were at moderate or severe risk of non-deliberate self-harm. Focusing on the schizophrenic patients, all of them had some form of psychopathology, either positive, negative or general symptoms and about one-fourth were assessed to pose a risk for aggression.

Strain distribution pattern for SSLP markers in the SWXJ recombinant inbred strain set: chromosomes 1 to 6.

We typed 147 simple sequence length polymorphisms in the SWXJ recombinant inbred (RI) strain set spanning Chromosomes (Chrs) 1-6. The strain distribution pattern for these loci was combined with data from 18 previously typed loci for SWXJ, resulting in new chromosome maps for this RI set, with an average density of 3.5 cM between loci. This is the first systematic effort to develop a more highly resolved genetic map for the SWXJ RI set and thereby improves the usefulness of this genetic tool for mapping genes underlying both simple and complex genetic disorders.

Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice.

The prevalence of cholesterol gallstones differs among inbred strains of mice fed a diet containing 15% (wt/wt) dairy fat, 1% (wt/wt) cholesterol, and 0.5% (wt/wt) cholic acid. Strains C57L, SWR, and A were notable for a high prevalence of cholelithiasis; strains C57BL/6, C3H, and SJL had an intermediate prevalence; and strains SM, AKR, and DBA/2 exhibited no cholelithiasis after consuming the diet for 18 weeks. Genetic analysis of the difference in gallstone prevalence rates between strains AKR and C57L was carried out by using the AKXL recombinant inbred strain set and (AKR x C57L)F1 x AKR backcross mice. Susceptibility to gallstone formation was found to be a dominant trait determined by at least two genes. A major gene, named Lith1, mapped to mouse chromosome 2. When examined after 6 weeks on the lithogenic diet, the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.88) was downregulated as expected in the gallstone-resistant strains, AKR and SJL, but this enzyme failed to downregulate in C57L and SWR, the gallstone-susceptible strains. This suggests that regulation of the rate-limiting enzyme in cholesterol biosynthesis may be pivotal in determining the occurrence and severity of cholesterol hypersecretion and hence lithogenicity of gallbladder bile. These studies indicate that genetic factors are critical in determining gallstone formation and that the genetic resources of the mouse model may permit these factors to be identified.

New murine polymorphisms detected by random amplified polymorphic DNA (RAPD) PCR and mapped by use of recombinant inbred strains.

Oligonucleotide primers of random sequence that were 12 bases in length, 58% in GC content, and lacking internal palindromes were designed. By random amplified polymorphic DNA (RAPD) PCR, these primers were used to survey for DNA variations between the progenitors of the mouse AXB and BXA recombinant inbred sets (A/J and C57BL/6J). We identified 17 DNA variants detected by 10 primers. Map positions for these variants were determined by comparing their strain distribution patterns in the AXB, BXA recombinant inbred sets with strain distribution patterns of previously published loci. When necessary, BXD and NXSM recombinant inbred sets were also used. These 17 new loci mapped to 12 chromosomes. The 10 primers were also used to survey 20 inbred mouse strains including the progenitors of other recombinant inbred sets and four mouse strains recently inbred from the wild (CAST/Ei, MOLF/Ei, PERA/Ei, and SPRET/Ei).

Strain distribution pattern in AXB and BXA recombinant inbred strains for loci on murine chromosomes 10, 13, 17, and 18.

Strain distribution patterns (SDPs) of selected loci previously mapped to murine Chromosomes (Chrs) 10, 13, 17, and 18 are reported for the AXB, BXA recombinant inbred (RI) strain set derived from the progenitor strains A/J (A) and C57BL/6J (B). The loci included the simple sequence length polymorphisms (D10Nds1, D10Mit2, D10Mit10, D10Mit14, D13Mit3, D13Nds1, D13Mit10, D13Mit13, D13Mit7, D13Mit11, D17Mit18, D17Mit10, D17Mit20, D17Mit3, D17Mit2, D18Mit17, D18Mit9, and D18Mit4), the restriction fragment length polymorphisms Pdea and Csfmr, and the biochemical marker AS-1. These loci were chosen because they map to genomic regions that had few or no genetic markers in the AXB, BXA RI set. Several of these loci also were typed in backcross progeny of matings of the (AXB)F1 to strain A or B. The strain distribution patterns for chromosomes 10, 13, 17, and 18 are reported, and the gene order and map distances determined from the backcross data. The addition of these markers to the AXB, BXA RI strain set increases the genomic region over which linkage for new markers can be detected.

The AXB and BXA set of recombinant inbred mouse strains.

The recombinant inbred (RI) set of strains, AXB and BXA, derived from C57BL/6J and A/J, originally constructed and maintained at the University of California/San Diego, have been imported into The Jackson Laboratory and are now in the 29th to 59th generation of brother-sister matings. Genetic quality control testing with 45 proviral and 11 biochemical markers previously typed in this RI set indicated that five strains had been genetically contaminated sometime in the past, so these strains have been discarded. The correct and complete strain distribution patterns for 56 genetic markers are reported for the remaining RI strain set, which consists of 31 living strains and 8 extinct strains for which DNA is available. Two additional strains, AXB 12 and BXA 17, are living and may be added to the set pending further tests of genetic purity. The progenitors of this RI set differ in susceptibility to 27 infectious diseases as well as atherosclerosis, obesity, diabetes, cancer, cleft palate, and hydrocephalus. Thus, the AXB and BXA set of RI strains will be useful in the genetic analysis of several complex diseases.