[show abstract][hide abstract] ABSTRACT: This study examined the relations of genetic variants in catechol-O-methyltransferase (COMT) gene, including rs737865 in intron 1, rs4680 in exon 4 (Val158Met) and downstream rs165599, to schizophrenia and its related neurocognitive functions in families of patients with schizophrenia. Totally, 680 individuals from 166 simplex (166 affected members and 354 nonpsychotic first-degree relatives) and 46 multiplex families (85 affected members and 75 nonpsychotic first-degree relatives) were interviewed using Diagnostic Interview for Genetic Studies, administered Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT), and drawn for venous blood. Both categorical (dichotomizing families on affected members’ neurocognitive performance) and quantitative approaches toward the WCST and CPT performance scores were employed using the family-based association test and the variance components framework, respectively. Both false discovery rate and permutations were used to adjust for multiple testing. The genotypes of rs4680 were associated with both the WCST and CPT performance scores in these families, but not with schizophrenia per se in either whole sample or subgroup analyses. Meanwhile, the other two single nucleotide polymorphisms were differentially associated with the two tasks. For WCST indexes, regardless of subgroup analyses or quantitative approach, only rs737865 exhibited moderate associations. For CPT indexes, rs737865 exhibited association for the subgroup with deficit on CPT reaction time, whereas rs165599 exhibited association for the subgroup with deficit on CPT d′ as well as quantitative undegraded d′. Our results indicate that the genetic variants in COMT might be involved in modulation of neurocognitive functions and hence conferring increased risk to schizophrenia.
[show abstract][hide abstract] ABSTRACT: A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
[show abstract][hide abstract] ABSTRACT: In order to evaluate the linkage of schizophrenia to loci at chromosome 15q, we genotyped six microsatellite markers at chromosome 15q11-14 in 52 Taiwanese schizophrenic families. Two phenotype models (narrow: DSM-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other nonaffective psychotic disorders) were used to define the disease phenotype. Maximum nonparametric linkage scores (NPL scores) of 3.33 (P = 0.0003) and 2.96 (P = 0.0008) were obtained at the marker D15S976 under broad and narrow models, respectively. Positive linkage results were also observed at the marker D15S1360, previously reported to have significant linkage to a neurophysiological deficit of schizophrenia, with NPL scores of 2.71 (P = 0.003) and 2.78 (P = 0.002) under broad and narrow models, respectively. The results provide suggestive linkage evidence of schizophrenia to loci at chromosome 15q13-14 in an ethnically distinct Taiwanese sample.
American Journal of Medical Genetics 01/2002; 105(8):658-61.
[show abstract][hide abstract] ABSTRACT: The well-established role of genetic factors in the etiology of schizophrenia together with reports of allelic association with cPLA2, a phospholipase-A(2) gene, a reported increase of phospholipase-A(2) activity, and the phospholipase-A(2) hypothesis of Horrobin et al. [1995: Med Hypotheses 45:605-613] strongly support cPLA2 (PLA2G4A) and sPLA2 (PLA2G1B) as candidate genes for schizophrenia. In search for allelic association between these phospholipase-A(2) genes and schizophrenia, two samples of Chinese and European origins, in total 328 unrelated schizophrenic patients and their parents, were investigated using Falk and Rubinstein's haplotype relative risk method. Both genes showed marginally significant evidence for association in the total sample (P <or= 0.05), which, however, did not survive the Bonferroni correction for multiple testing. In conclusion, our results do not provide support for the phospholipase-A(2) hypothesis of schizophrenia. Additional studies will be necessary to rule out a possible confounding effect of niacin sensitivity as postulated by Hudson et al. [1999: Biol Psychiatr 46:401-405].
American Journal of Medical Genetics 05/2001; 105(3):246-9.
[show abstract][hide abstract] ABSTRACT: This study investigated the association between T/C polymorphism, at position 102, of the 5-hydroxytryptamine 2A receptor gene and alcoholism with and without behavior problems. Eighty-five subjects (45 men, 40 women) with alcohol abuse, 75 subjects (51 men, 24 women) with alcohol dependence, and 70 normal control subjects (21 men, 49 women) participated in the study. The results show that the frequency of the homozygous T102 genotype was significantly lower in the group of male alcohol abuse with behavior problems than in the female group (chi(2) = 4.072, df = 1, P < 0.05) and the allele frequency of T102 was also lower in the male group than in the female group (chi(2) = 4.187, df = 1, P < 0.05). Of the male alcohol abuse subjects, the group with behavior problems was found to have lower frequencies of the T102 allele than the group without behavior problems (chi(2) = 4.328, df = 1, P < 0.05). In conclusion, this study demonstrates that alcoholism is heterogeneous and male alcohol abuse with behavioral problems was associated with T/C 102 polymorphism of the 5HT2A receptor gene. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:797-800, 2000.
American Journal of Medical Genetics 12/2000; 96(6):797-800.
[show abstract][hide abstract] ABSTRACT: The main purpose of the study was to examine the hypothesis that the postpartum period represents a time of increased risk for depression. The other psychosocial variables on stress, social support and self-esteem were also measured. Adult women, ranging in age from 22 to 45 years, comprised two samples: 148 postnatal women (22 to 44 years) and 148 controls (22 to 45 years). Five sets of instruments were used to collect data: the Demographic Data Form, the Perceived Stress Scale, the Interpersonal Support Evaluation List, the Coopersmith's Self-Esteem Inventory, and the Beck Depression Inventory. Although the postnatal group tended to have a higher rate of depression, the difference was not statistically significant. No significant differences in stress, social support, self-esteem or depression were found between these two groups. However, postnatal women reported significantly higher somatic symptoms of depression than controls. Results of the stepwise multiple regression indicated that the best subset to predict postpartum depression was self-esteem, stress, postnatal complication and work status. The best subset to predict depression of controls included self-esteem, social support, socioeconomic status and stress. Our data indicate that the psychosocial health status of postnatal women is not significantly different from the controls, although the postnatal women complain more about the loss of bodily functions. The possible explanations deserve further research.
The Kaohsiung journal of medical sciences 04/2000; 16(3):156-61. · 0.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous studies have indicated possible linkage of schizophrenia with chromosome 6p21-24. In an attempt to replicate these findings, we studied the linkage of schizophrenia with nine markers on chromosome 6p21-24 in 39 Taiwanese schizophrenic nuclear families with at least two affected siblings. Two diagnostic models (narrow: Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other nonaffective psychotic disorders) were used to define the disease phenotypes. With the broad and narrow diagnostic models, the marker D6S296 produced maximum two-point lod scores of 1.46 (straight theta = 0.2) and 1.35 (straight theta = 0. 2), respectively, in the recessive inheritance model. Assuming locus heterogeneity, a multipoint lod score of 0.85 was obtained between markers D6S296 and D6S277 under the narrow/recessive model. Maximum nonparametric lod scores of 1.25 ( p= 0.09) and 1.36 (p = 0.08) were observed, but still not statistically significant, at D6S296 in the narrow and broad diagnostic models, respectively. Both two-point analysis of the dominant model (lod score 0.85) and nonparametric analysis (lod score 1.25) showed a mild peak lod score appeared at marker D6S 285 as well. The results add some support to the suggestive linkage of schizophrenia with markers in the regions of chromosome 6p22 and 6p24 in an ethnically distinct Taiwanese sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:74-78, 2000.
American Journal of Medical Genetics 03/2000; 96(1):74-8.
[show abstract][hide abstract] ABSTRACT: To examine the differences in psychiatric co-morbidity between hospital and incarcerated groups of heroin addicts in Taiwan.
Life-time prevalence of DSM-III-R-based coexisting psychiatric disorders, including personality disorders, were surveyed.
A psychiatric hospital and two prisons.
Two hundred and sixty heroin users who were incarcerated in prisons, and 47 heroin users who voluntarily sought help in a psychiatric hospital were interviewed by board-certified psychiatrists.
Using two psychometric instruments, the Psychiatric Diagnostic Assessment (PDA) and the Structured Interview for DSM-III-R Personality Disorders (SIPD-R), psychiatric co-morbidity was assessed.
Different life-time rates of coexisting psychiatric disorders among heroin addicts in different settings were found: 83% of hospital subjects and 66% of incarcerated subjects were diagnosed as having at least one coexisting axis I or II disorder. The most prevalent coexisting DSM-III-R defined axis I disorders were additional substance use disorders (alcohol and methamphetamine), while the axis II disorder was antisocial personality disorder. The hospital group had a significantly higher prevalence rate of mood disorder (p < 0.001), paranoid personality disorder (p < 0.05) and antisocial personality disorder (p < 0.001) than the incarcerated group.
We suggest that heroin addicts with coexisting psychiatric disorders receive relevant psychiatric treatment. Those with personality disorders, especially the antisocial type, should be considered for specialized therapeutic community programmes instead of incarceration.
[show abstract][hide abstract] ABSTRACT: There are few cross-national comparisons of the rates of suicide ideation and attempts across diverse countries. Nine independently conducted epidemiological surveys using similar diagnostic assessment and criteria provided an opportunity to obtain that data.
Suicide ideation and attempts were assessed on the Diagnostic Interview Schedule in over 40000 subjects drawn from the United States, Canada, Puerto Rico, France, West Germany, Lebanon, Taiwan, Korea and New Zealand.
The lifetime prevalence rates/100 for suicide ideation ranged from 2.09 (Beirut) to 18.51 (Christchurch, New Zealand). Lifetime prevalence rates/100 for suicide attempts ranged from 0.72 (Beirut) to 5.93 (Puerto Rico). Females as compared to males had only marginally higher rates of suicidal ideation in most countries, reaching a two-fold increase in Taiwan. Females as compared to males had more consistently higher rates for suicide attempts, reaching a two- to three-fold increase in most countries. Suicide ideation and attempts in most countries were associated with being currently divorced/separated as compared to currently married.
While the rates of suicide ideation varied widely by country, the rates of suicide attempts were more consistent across most countries. The variations were only partly explained by variation in rates of psychiatric disorders, divorce or separation among countries and are probably due to cultural features that we do not, as yet, understand.
Psychological Medicine 02/1999; 29(1):9-17. · 5.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Borna disease virus (BDV), a negative-strand RNA virus, has been reported to be associated with severe psychiatric disorders. The association is mainly based on the findings that patients with schizophrenia and depression have a higher seroprevalence rate of BDV-specific antibodies than controls. In addition, psychiatric patients were also found to have a higher detection rate of BDV transcripts in their blood than controls. By using an improved Western blot analysis, we first demonstrated that Chinese schizophrenic patients from Taiwan also have a higher seroprevalence of BDV-specific antibodies than controls (12.1% vs 2.9%, P< 0.001), providing support to the positive association between BDV and psychiatric disorders in our population. Because of the contagious nature of viral infection, we further examined patients' family members and mental health workers, who have close contact with patients. We found that both groups also have a higher seroprevalence of BDV-specific antibodies, 12.1% and 9.8%, respectively, than controls. This finding provides some evidence for a possible human-to-human transmission of Borna disease virus. Our finding needs further independent verification from other research groups and the clinical relevance of this preliminary observation deserves further study.
[show abstract][hide abstract] ABSTRACT: Background. There are few cross-national comparisons of
the rates of suicide ideation and attempts
across diverse countries. Nine independently conducted epidemiological
surveys using similar
diagnostic assessment and criteria provided an opportunity to obtain that
Psychological Medicine 12/1998; 29(01):9 - 17. · 5.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: The authors investigated whether nonpsychotic relatives of schizophrenic probands have an elevated risk of deficits in sustained attention as measured by the Continuous Performance Test (CPT), whether such deficits are associated with specific factors of schizotypy, and whether poor CPT performance by probands predicts poor performance by their relatives. In addition, the heritability of CPT performance in the families of schizophrenic probands was estimated.
The study subjects were 60 schizophrenic probands, 148 of their first-degree relatives, 20 normal comparison probands, and 42 of the comparison probands' first-degree relatives. Subjects completed undegraded and 25% degraded sessions of the CPT and were interviewed with use of the Chinese version of the Diagnostic Interview for Genetic Studies. Subjects' CPT sensitivity indexes, d', were standardized against those of a community sample of 345 subjects, with adjustment for age, sex, and level of education.
On average, the d' values of the relatives of schizophrenic probands were lower than those of the relatives of comparison probands but higher than those of schizophrenic probands. Lower sensitivity indexes among the relatives of schizophrenic patients were associated with the interpersonal dysfunction and disorganization factors of schizotypy but not the cognitive/perceptual factor. When schizophrenic probands were divided into two subgroups by a cutoff of -3.0 for adjusted z score on the CPT, the d' values of relatives of probands with CPT deficits were lower than those of relatives of probands without deficits. The estimated heritability of performance on the CPT ranged from 0.48 to 0.62.
Sustained attention deficit may be a genetic vulnerability marker for schizophrenia, and it may be more useful in linkage analysis than traditional phenotype definitions of schizophrenia.
American Journal of Psychiatry 10/1998; 155(9):1214-20. · 14.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dopamine D4 receptor (DRD4) gene polymorphisms are associated with various pharmacologic activities. This study investigated whether polymorphisms of 48-bp tandem repeats in the exon 3 of the DRD4 gene are related to neuroleptic response.
The neuroleptic response at the acute stage of schizophrenia was assessed in 80 (48 men, 32 women) schizophrenic patients. The negative symptoms at remission were also rated. DRD4 genotype was established using the polymerase chain reaction. Patients with genotypes containing an allele with only two repeats (2-2, 2-3, 2-4, 2-6) were assigned to group I (n = 38). Those homozygous for four 48-bp repeats were assigned to group II (n = 42).
Thirteen (34.2%) of the 38 group I subjects and 26 (61.9%) of the 42 group II subjects had good neuroleptic response during acute stage treatment (chi 2 6.12, df = 1, p < .02). In remission, the rates of negative symptoms of blunt affect, avolition, and global negative rating were higher in group I than in group II. This was more prominent in men than in women.
The presence of homozygous four 48-bp repeats in both alleles in exon 3 of the DRD4 gene is associated with good neuroleptic response during acute treatment, and with a lower prevalence of negative symptoms at remission, especially in male schizophrenic patients.
[show abstract][hide abstract] ABSTRACT: Seventy DSM-III schizophrenic patients were assessed for positive and negative symptoms using Andreasen's scales for the assessment of positive and negative symptoms (SANS and SAPS) on admission. The correlation structure of the items in the SANS and SAPS was explored in dimension and item levels by use of correlation plots through a distinct analytical method displaying the proximity matrix. The results revealed at least three major dimensions of symptoms delineated as Negative Symptoms, Disorganized Thoughts and Delusions and Hallucinations. The latter two dimensions were derived from the SAPS, while Negative Symptoms comprised most of the items in the SANS. Items in Disorganized Thoughts were more correlated to Negative Symptoms than to the other items in the SAPS. 'Loss of ego boundary' delusions and experience of auditory hallucinations appeared as two sub-clusters in the group of Delusions and Hallucinations. The relative independence of persecutory, grandiose, religious, somatic and reference delusions gives support to the concept that paranoid schizophrenia stands as a distinct clinical subtype of schizophrenia. The graphical method introduced here well expresses the information of correlation matrix and is useful for exploring inter-item or inter-cluster associations.
Psychiatry Research 03/1998; 77(2):121-30. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Continuous Performance Test (CPT) has been modified to be used widely as a potential vulnerability marker of schizophrenia. In genetic analyses of schizophrenia, well-established norms for the CPT are essential in choosing a suitable threshold of CPT for classifying subjects as affected or unaffected. In this study, we investigated the performance of 115 adolescents and 345 adults, randomly sampled from a community, on two sessions of the CPT 1-9 (undegraded and 25% degraded). The results showed that an older age was associated with a decreasing hit rate and sensitivity (d'), while a higher level of education was associated with an increasing hit rate and d' for both sessions of the CPT. Men had higher hit rates and d' than women for the degraded CPT. A practice effect during the second session of the CPT was noted among 20 to 33 percent of the subjects. Poorer CPT performance was associated with schizotypy measured by the Perceptual Aberration Scale and the Schizotypal Personality Questionnaire. Thus, in assessing CPT performance among schizophrenia patients or high-risk populations, we must compare their results to age-, education-, and sex-corresponding norms. The data presented in this report will be valuable in this regard.
[show abstract][hide abstract] ABSTRACT: Variation in the number of tandem repeats of a 48 base pair (bp) unit was found in the gene of the dopamine D4 receptor (DRD4). The number of repetitions of the 48bp unit was shown to influence the binding of clozapine, which suggests that different alleles may function differently in vivo and affect the pathogenesis of schizophrenia. Genotypes of DRD4 polymorphism were analyzed for 47 schizophrenic probands who had at least one living sibling with a diagnosis of schizophrenia, 35 unaffected siblings of the schizophrenic proband, 42 sporadic schizophrenic patients, and 43 healthy controls without a family history of psychosis. There was no significant difference in genotypic or allelic distributions among the four groups. Significant differences in the frequencies of two- and seven-repeats alleles between the Chinese and Caucasians controls were noted. The present study did not support that a particular allele or genotype of the 48bp-repeat of DRD4 was associated with schizophrenia.
American Journal of Medical Genetics 08/1997; 74(4):412-5.
[show abstract][hide abstract] ABSTRACT: We examined the relationships between symptom dimensions derived from factor analytic studies of schizophrenic symptoms and sustained attention deficits. Four factors, negative, delusion/hallucination, disorganization, and excitement, were yielded from factor analysis on 14 items of the Positive and Negative Syndrome Scale (PANSS) among 60 Chinese inpatients with acute schizophrenia. The negative dimension was associated with lower sensitivity index (d') while the excitement dimension was associated with higher d' on the Continuous Performance Test (CPT) after sex, age and education were adjusted for in multiple linear regressions. The positive dimension affected only response criterion (ln beta) and was not associated with the d' on the CPT. In contrast, the summed scores of PANSS Positive and Negative scales did not have significant correlations with d' on the CPT. Thus, the discriminant validity of these symptom dimensions of schizophrenia is supported by their correlations with CPT performance indices.
Schizophrenia Research 07/1997; 25(3):211-9. · 4.59 Impact Factor