Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are many risk factors associated with vulnerability to suicidal behaviour, and the results of family studies, twin studies and adoption studies suggest that they include a genetic predisposition. Moreover, this gentic susceptibility may be specific and independent of the genetic susceptibility to psychiatric disorders associated with suicidal behaviour (e.g., bipolar disorders, schizophrenia, alcoholism). Several groups have carried out association studies using a "candidate gene strategy", with the goal of identifying the genes involved in susceptibility to suicidal behavior. There is compelling evidence from research in biological psychiatry that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of suicidal behavior, and the results of association studies suggest that the gene coding for tryptophan hydroxylase, which is the serotonin synthesis enzyme, and the serotonin transporter gene are involved in susceptibility to suicidal behavior. Furthermore, these genes may influence the suicidal phenotype through different gene-gene interactions and gene-early environment interactions. Current studies aim to identify either the precise phenotypes associated with genes for vulnerability to suicidal behaviour or the intermediate phenotypes (e.g., impulsivity, anger dyscontrol) associated with these genes.
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PMID:[Implication of genes of the serotonergic system on vulnerability to suicidal behavior]. 1553 46

The incidence of aggressive behavior in patients with schizophrenia is higher than in the general population. Among particular gene polymorphisms posited to be involved in psychiatric disorders, the catecholamine-O-methyltransferase (COMT) and serotonin transporter (5-HTTPR) genes have been the focus of recent research on aggression. In this study, we hypothesized that both the COMT and the 5-HTTPR genotypes may be dependent on and related to aggression in Korean patients with schizophrenia. The subjects were 168 unrelated male schizophrenic patients diagnosed according to DSM-IV. Among two psychiatric hospital staff and medical university students, 158 unrelated male subjects with no lifetime history of psychiatric disorders were recruited to establish the COMT and 5-HTTPR genotype distribution in the general population. All episodes of aggression from the last discharge to readmission were rated. The Total Overt Aggression Scale (OAS) score (sum of the scores of all episodes of aggression), highest OAS score (highest individual episode score, 0-16), OAS category, and OAS category score (mean score within each category) were recorded. There were statistically significant effects of COMT genotype on the mean OAS 4 (physical aggression against other people) score and the highest OAS score. The most predictive was the OAS 4 score. There was a statistically significant effect of 5-HTTPR genotype on mean total score. Thus, the COMT gene is associated with the severity of aggression and with physical aggression against other people, whereas the 5-HTTPR gene is associated with the summary score of all episodes of aggression.
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PMID:Association of aggressive behavior in Korean male schizophrenic patients with polymorphisms in the serotonin transporter promoter and catecholamine-O-methyltransferase genes. 1557 82

Increasing focus is being given to identify possible combinations of genes related to specific clinical phenotypes. In our sample of 814 patients comprising 114 with schizophrenia, 416 with bipolar affective disorder and 284 with unipolar affective disorder, we studied interactions between the tryptophan hydroxylase (TPH), the serotonin transporter (5-HTTLPR), and the dopamine receptor (DRD4) genes in relation to five major psychiatric symptomatology scores. There was significant interaction between the TPH and the 5-HTTLPR genes. With an increasing number of short (s) alleles of 5-HTTLPR, the scores for delusions, disorganization and negative symptoms were significantly decreasing among subjects having the TPH genotype AA but increasing among subjects having the TPH genotype AC, yielding the highest scores for the combinations AA x ll and AC x ss. Since high scores on just delusions, disorganization and negative symptoms but low scores on excitement and depression were found among subjects with schizophrenia, we conducted comparisons among the three diagnostic categories and controls as regards the combined TPH x 5-HTTLPR genotype distribution. Schizophrenia subjects had a significantly different distribution of the genotype combination for TPH x 5-HTTLPR as compared to 241 controls or to unipolar or bipolar subjects, and had significantly higher frequencies of AA x ll and of AC x ss. Thus, an interaction between TPH and 5-HTTLPR genes constitutes susceptibility to schizophrenia, thereby yielding apparent relationships between the major psychiatric symptomatology scores and genotype combinations in samples that are obtained by pooling schizophrenia with other diagnostic categories.
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PMID:Interaction between the tryptophan hydroxylase gene and the serotonin transporter gene in schizophrenia but not in bipolar or unipolar affective disorders. 1562 7

The basis of suicidal behavior (SB) is complex and multifactorial. Numerous risk factors have been identified. Epidemiological genetics studies (family studies, twin studies, adoption studies) suggest that there is a genetic basis to SB and that this genetic basis is specific and independent from the genetic factors implicated in predisposition to psychiatric disorders associated with SB (bipolar disorder, schizophrenia, alcoholism). Recently, new molecular genetics tools have been designed to identify the genetic factors that predispose certain individuals to disorders of complex etiology. Biological psychiatry studies have suggested that the physiopathology of SB involves dysfunctioning of the serotonin system. The first genetic association studies tested candidate genes encoding proteins involved in serotonin metabolism. The results of these studies suggest that the gene coding for the limiting enzyme in the synthesis of serotonin, tryptophan hydroxylase (TPH), and the gene encoding the serotonin transporter are involved in predisposition to SB. Furthermore, it is likely that these genes interact with each other and with environmental factors (early) and that they have different phenotypic consequences. One of the main aims of studies currently underway is to identify the precise phenotypes associated with genes that predispose to SB or intermediate phenotypes (impulsivity, inability to control anger, etc.).
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PMID:Suicidal behavior: relationship between phenotype and serotonergic genotype. 1564 80

The article reviews literature on methods for meta-analysis of genetic linkage and association studies, and summarizes and comments on specific meta-analysis findings for psychiatric disorders. The Genome Scan Meta-Analysis and Multiple Scan Probability methods assess the evidence for linkage across studies. Multiple Scan Probability analysis suggested linkage of two chromosomal regions (13q and 22q) to schizophrenia and bipolar disorder, whereas Genome Scan Meta-Analysis on a larger sample identified at least 10 schizophrenia linkage regions, but none for bipolar disorder. Meta-analyses of pooled ORs support association of schizophrenia to the Ser311Cys polymorphism in DRD2 and the T102C polymorphism in HTR2A, and of attention deficit hyperactivity disorder to the 48-bp repeat in DRD4. The 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4) may contribute to the risk of bipolar disorder, suicidal behavior, and neuroticism, but association to the lifetime risk of major depression has not been shown. Meta-analyses support linkage of schizophrenia to regions where replicable associations to candidate genes have been identified through positional cloning methods. There are additional supported regions where susceptibility genes are likely to be identified. Linkage meta-analysis has had less clear success for bipolar disorder based on a smaller dataset. Meta-analysis can guide the prioritization of regions for study, but proof of association requires biological confirmation of hypotheses about gene actions. Elucidation of causal mechanisms will require more comprehensive study of sequence variation in candidate genes, better statistical and meta-analytic methods to take all variation into account, and biological strategies for testing etiologic hypotheses.
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PMID:Meta-analysis in psychiatric genetics. 1580 92

Fifty-nine patients, 21 women and 38 men, with ICD-10 diagnosis of schizophrenia (F20.0), attack-like type, were treated with olanzapine during 28 weeks (8-weeks of acute and 20-weeks of maintenance therapy). Evaluation of clinical symptoms measured by the Positive and Negative Syndromes scale (PANSS) revealed that female patients responded better to therapy as compared to male ones, with PANSS total, PANSS negative and PANSS general psychopathological scores being significantly reduced (p < 0.006) in females after 1 week of the treatment and in males--after 2 weeks. In the female group, a reduction of PANSS total score by 50% in the acute stage of treatment qualified as a very good response was observed in 7 (33%) patients and in the male group--in 1 (2.7%). The between-groups difference was highly significant (p = 0.002). When examined for a rate of 3H-serotonin uptake into platelets, density of sites of 3H-imipramine binding on the whole platelets, platelet serotonin level and levels of high- also low-molecular weight forms of platelet immunoreactive serotonin transporter protein, a significant decrease of the platelet serotonin level, comparing to controls, was detected in the female group before treatment. During the treatment, this parameter gradually increased up to control level. Other parameters did not change significantly for 28-weeks of therapy and did not differ from the control values. There were positive correlations between the levels of platelet serotonin before treatment and subsequent reduction of the PANSS total and positive subscale scores in the female group. In responders with a very good treatment-related response, the serotonin level in the platelets before treatment was higher compared to the values in resistant patients: 5.4 +/- 2.5 and 2.7 +/- 1.3 nmol/10(9) cells, respectively. Relative risk (RR) of unfavorable treatment outcome in patients with initially reduced levels of platelet serotonin was approximately twice lower (RR = 1.83; Cl 95% 1.1-34.9) than that in patients with normal or elevated levels of platelet serotonin. The results suggest that selection of patients with initial higher level of platelet serotonin before olanzapine treatment can reduce the risk of non-responding to therapy by 36%.
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PMID:[Parameters of platelet serotonin system in patients with schizophrenia treated with olanzapine: a search for the serotonergic predictors of therapeutic efficacy]. 1582 26

This study was to aim at investigating the potential interaction for the serotonin receptor gene (5-HTR) 2A and serotonin transporter gene (5-HTTLPR) polymorphisms in the development of schizophrenia, as well as the interaction of the two polymorphisms in relation with symptomatology, family history, age of onset and antipsychotic response. Genomic DNA analysis with polymerase chain reaction (PCR) was used for the genotyping. One hundred and eleven (111) patients with schizophrenia and 172 normal controls participated in the study. We did not find any association between the individual polymorphism and schizophrenia. The significant interaction effect between 5-HTTLPR and 5-HTR2A polymorphisms on the development of schizophrenia as well as on the antipsychotics response, family history, symptomatology and age at onset, was not found. However, subject with 5-HTR2A*TT genotype were found to have lower age of onset, compared to their counterparts (p=0.01). These results suggest that the interaction between 5-HTTLPR and 5-HTR2A polymorphisms may not contribute to susceptibility to schizophrenia as well as some clinical factors such as antipsychotic response, at least in the Korean population.
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PMID:No evidence for interaction between 5-HT2A receptor and serotonin transporter genes in schizophrenia. 1589 80

The serotonin transporter gene (SLC6A4) is a candidate gene for schizophrenia based on serotonin transporter's crucial role in serotonergic neurotransmission. However, association studies have produced conflicting results regarding the association between two common SLC6A4 gene polymorphisms, the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR) polymorphisms, and schizophrenia susceptibility. To further elucidate the putative association between the two SLC6A4 gene polymorphisms and schizophrenia susceptibility, we performed a meta-analysis based on all original published association studies between schizophrenia and the 5-HTTLPR and STin2 VNTR polymorphisms published before April 2004. Our analyses showed no statistically significant evidence for the association between the Short allele of the 5-HTTLPR polymorphism and schizophrenia (random-effects pooled odds ratio (OR)=0.99, 95% Confidence Interval (CI)=0.92-1.07, Z=-0.23, P=0.82) from 19 population-based association studies consisting of 2990 case and 3875 control subjects. However, highly significant evidence for association between the STin2.12 allele of the STin2 VNTR polymorphism (random-effects pooled OR=1.24, 95% CI=1.11-1.38, Z=3.82, P=0.00014) and schizophrenia was found from 12 population-based association studies consisting of 2177 cases and 2369 control subjects. Our meta-analysis suggests that the STin2.12 allele of the STin2 VNTR polymorphism is likely a risk factor for schizophrenia susceptibility. Our data imply that following completion of the International HapMap Project, a comprehensive evaluation of a set of markers that fully characterize the linkage disequilibrium relationships at the SLC6A4 gene should be tested in large well-characterized clinical samples in order to understand the role of this gene in schizophrenia susceptibility.
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PMID:Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. 1594 Feb 96

This study investigated the potential interaction between the polymorphisms of serotonin transporter gene (SLC6A4, a 44 base pair insertion/deletion in the promoter region, 5-HTTLPR) and tumor necrosis factor-alpha gene (TNFA; -238G/A and -308G/A polymorphisms) on the development of schizophrenia, as well as the interaction of the three polymorphisms in relation to symptomatology, family history, onset age and antipsychotic treatment response. Genomic DNA analyses with polymerase chain reaction (PCR) was used for the genotyping. One hundred and fifty-two (152) patients with schizophrenia and 152 normal controls participated in the study. Any associations between the individual polymorphism and schizophrenia were not found. However, marginal association between subjects with both TNFA -238 A allele (genotype AA plus AG) and 5-HTTLPR s allele (ss plus sl) and presence of family history was found (p = 0.023; p = 0.026). The subjects with TNFA -308 AG genotype showed higher change in PANSS total score (p = 0.028). No significant interaction effect between 5-HTTLPR and TNFA -238/-308 polymorphisms either on the development of schizophrenia or on antipsychotics treatment response and psychopathology was found, although a significant interaction effect for subjects carrying TNFA -238 AG and -308 AA genotypes on a positive family history was observed (p = 0.017). These results suggest that the interaction effects between 5-HTTLPR and TNFA -238/-308 polymorphisms gives no significant contribution to the susceptibility to schizophrenia, and is not associated with clinical variables, antipsychotic treatment response and psychopathological features, except for family history of disease, at least in the Korean population.
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PMID:Interaction analysis between 5-HTTLPR and TNFA -238/-308 polymorphisms in schizophrenia. 1625 73

A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been investigated in several genetic association studies, including studies of schizophrenia and suicidality. The current study was designed to examine whether the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with suicide attempts of 290 Caucasian schizophrenic patients. Among these patients, 92 had a history of suicide attempt. No association with history of suicide attempt was found in the multiallelic 5-HTTLPR (p = 0.305), however we found significant association with the intron 2 VNTR polymorphism (p = 0.018). When we performed a haplotype analysis, we found association between suicide attempt and haplotype distribution (p = 0.031). These findings suggest that the intron 2 VNTR polymorphism in serotonin transporter gene may influence suicidal behaviour in schizophrenia.
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PMID:Association study between the novel functional polymorphism of the serotonin transporter gene and suicidal behaviour in schizophrenia. 1627 62


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