[Noncompliance: an overview].
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Attitude to Health↗
Biomedical subjects
K Thau
Publications and source records attributed to K Thau.
Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study.
Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.
Adult↗
Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.
BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.
Adult↗
Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.
OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.
Alleles↗
Polyglutamine tracts: no evidence of a major role in bipolar disorder.
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Base Sequence↗
MAOA: association and linkage studies with lithium responsive bipolar disorder.
A number of association studies have investigated the role of the monoamine oxidase A (MAOA) gene in the susceptibility to bipolar disorder. Although some studies have reported positive findings, there remains some controversy, because results from different studies have not been consistent. A common explanation for inconsistencies between studies is genetic heterogeneity. We have focused on lithium responsive bipolar disorder as a way to reduce heterogeneity. In this study, we investigated the role of MAOA in lithium responsive bipolar patients using association and linkage study designs. The investigation used 138 patients and 108 normal controls. In addition, 25 families were also studied. Our results were not supportive of a major role of MAOA in the predisposition to bipolar disorder.
Alleles↗
Evidence for a role of phospholipase C-gamma1 in the pathogenesis of bipolar disorder.
Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stabilize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a gamma-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 +/- 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients (chi2 = 8.09; empirical P = 0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD = 1.45; empirical P = 0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is implicated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined.
Adult↗
[Psychotropic drugs in pregnancy: uses and risks].
To reduce insecurities concerning the pros and cons of psychopharmacological treatment of mental disorders during pregnancy, recent papers on teratogenic risks of different (groups of) drugs, and on therapeutic strategies of psychiatry disorders were reviewed and the results summarised. Psychotropic medication sometimes increases the risk of congenital malformations. It may cause peripartal toxicity and neurobehavioral changes; on the other hand, these risks have to be weighted against the proven benefits of the drugs. Untreated mental disorders seriously endanger the offspring during pregnancy and after delivery, and hence psychopharmacological treatment may be advisable in spite of the risks involved.
Abnormalities, Drug-Induced↗
How to interpret findings on mortality of long-term lithium treated manic-depressive patients?! Critique of different methodological approaches.
Many studies have shown that patients with affective disorders have a mortality markedly higher than that of the general population. Studies of manic-depressive patients given prophylactic lithium treatment have yielded varying results. Some authors have reported mortalities which were more than four times that of the general population. Others have found mortalities which did not differ significantly from that of the general population. In order to examine these discrepancies we re-analysed the data of a previous study by IGSLI, using three different methods to calculate the Standardised Mortality Ratio (SMR). The data base was enlarged by adding mortality data from two additional centres. The results indicate that the discrepancies may result from the common use of a 'cumulative' approach which produces a distortion of the data if the treatment duration is not taken into consideration properly. An analysis which eliminates this artefact and takes the treatment duration into account ('year-by-year' approach) provides the strongest evidence that the mortality of lithium treated patients is not significantly different from that of the general population.
Adult↗
Mortality of patients who dropped out from regular lithium prophylaxis: a collaborative study by the International Group for the Study of Lithium-treated patients (IGSLI).
Excess mortality has repeatedly been found in patients with recurrent affective disorders. In previous studies our group has shown that during long-term lithium treatment the mortality of such patients is not significantly higher than that of the general population. In the present study, we extended our investigation to 273 patients from the earlier IGSLI cohort who subsequently dropped out from regular lithium prophylaxis. The standardized mortality ratio (SMR) for the whole group was 2.5, significantly higher (P < 0.01) than 1.0, which is the SMR of the general population. Furthermore, the SMR of the patients from each of the participating countries, namely Denmark, Germany and Austria, was significantly higher than 1.0. These findings strengthen the evidence accumulated in previous investigations that regular long-term lithium treatment does in fact markedly reduce the excess mortality of patients with recurrent affective disorders.
Antimanic Agents↗
Adjunctive carbamazepine or lithium carbonate in therapy-resistant chronic schizophrenia.
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Adult↗
Excess cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis.
The mortality of patients suffering from affective disorders is much higher than that of the general population; this excess is due to both suicides and cardiovascular disease. During long-term lithium treatment, the overall mortality has not been found to differ significantly from that of the general population but the question remains whether this lowering, if it is in fact caused by lithium, is due to a reduction in suicide frequency or cardiovascular mortality, or both. We analysed data from 827 previously studied patients and used a procedure that estimated both overall mortality and cause-specific mortalities by single-case analysis. For overall mortality, the ratio of observed deaths (among the patients) to expected deaths (in the general population) was 1.14, which is not significantly different from 1.0; this was also found in our previous analysis. In the whole patient group, comprising 5600 patient years under lithium treatment, seven suicides were observed and 1.3 expected, resulting in a standard mortality ratio of 5.22; this is significantly > 1.0, but markedly lower than that found in patients with affective disorders not given lithium. Cardiovascular mortality was not found to be higher in our patients than in the general population. In view of the fact that a placebo-controlled mortality study under long-term conditions is neither ethically nor practically feasible, our findings cannot prove definitively that long-term lithium treatment counteracts factors responsible for the excess suicide and cardiovascular mortality of affective disorders. However, our observations are compatible with such a notion.
Cardiovascular Diseases↗
Mortality during initial and during later lithium treatment. A collaborative study by the International Group for the Study of Lithium-treated Patients.
We have previously shown that the mortality of patients with recurrent affective disorders in long-term lithium treatment is not higher than that of the general population. In the present study on 471 patients from Denmark and Germany, we examined mortality during the initial year of lithium treatment and during later lithium treatment. During initial lithium treatment, the total mortality was twice as high as in the general population (difference not significant) and the mortality due to suicide 16 times higher. During later lithium treatment, the mortality rates did not differ from those in the general population. Our results indicate that patients with frequent, often severe recurrences, those chosen for prophylactic lithium treatment, are at risk of high mortality, which then diminishes as the prophylactic action of the treatment takes effect.
Adult↗
The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders.
The prophylactic efficacy of carbamazepine slow release (CBZ) at ke different blood levels and lithium carbonate slow release (LI) was compared in a retrospective/prospective, randomized, 2-year open trial. 84 patients with a DSM-III-R diagnosis of recurrent affective disorder who had no prophylactic medication in the 2 years preceding the trial (no LI nonresponders), were randomly allocated to three treatment groups: CBZ low (15-25 mumol/l), CBZ high (28-40 mumol/l) and LI (0.6-0.8 mumol/l). Fifty-eight patients completed the full observation period of 2 years, 26 patients dropped out. There were no statistically significant differences in the efficacy of the prophylactic treatment for bipolar patients. For the unipolar patients, the group with a low CBZ serum level showed no reduction in the duration of episodes. The two other treatment groups seem to be equal in attenuation of a unipolar course of an affective disorder.
Adolescent↗
The effect of long-term lithium treatment on the mortality of patients with manic-depressive and schizoaffective illness.
Clinical research centers in Aarhus, Berlin, Hamilton and Vienna collected mortality data for 827 manic-depressive and schizoaffective patients given lithium treatment for more than 6 months. The average duration of the treatment was 81 months and the total time on lithium 5600 patient-years. For each patient, the mortality risk was calculated by entering the appropriate national life tables for the general population. The number of observed deaths was 44; the number of expected deaths was 49.7. The standardized mortality ratio, 0.89, did not differ significantly from 1.0. The mortality of manic-depressive patients is 2-3 times that of the general population. Our data show that the mortality of manic-depressive and schizoaffective patients given long-term lithium treatment does not differ significantly from that of the general population.
Adult↗
Reduced mortality of manic-depressive patients in long-term lithium treatment: an international collaborative study by IGSLI.
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Bipolar Disorder↗
Three cases of severe mania successfully treated with high-dosage lithium-carbonate.
Three female patients suffering from severe mania, who failed to respond to increasingly high dosages of highly potent neuroleptics, were put on a high-dose regime of lithium carbonate. With rapidly increasing daily doses of lithium carbonate, blood levels of approximately 1.3-1.51 mmol/l were achieved. When high lithium levels had been attained the patients showed a considerable improvement between 75 and 82 percent on the Bech-Rafaelsen Scale. At the same time it proved possible to reduce additional medication. Not toxic effects of lithium carbonate were observed. The consequences for clinical practice (e.g. shortened duration of hospitalization) are discussed.
Adult↗
Temporal stability of diagnostic criteria for functional psychoses. Results from the Vienna follow-up study.
200 first admissions with functional psychoses were interviewed with PSE and rated simultaneously according to different diagnostic criteria (ICD-9, RDC, DSM-III, St. Louis, Taylor, Vienna Research Criteria). At follow-up 7 years later 186 patients could be traced and a course diagnosis was applied to each patient. Temporal stability of diagnostic criteria was calculated for ICD-9, RDC and DSM-III by stability coefficient and kappa values and was used as a criterion for validity. Schizophrenia and affective disorder display considerable stability over time, no matter whether one uses ICD-9, RDC or DSM-III. The data for schizoaffective disorder are less impressive, the stability coefficient is much higher for schizoaffective bipolar than for schizoaffective depressive patients.
Family↗