RESUMEN
BACKGROUND: Recent psychiatric literature, while indicating a high incidence of postpartum depression, contains a few clinical reports which support our observations that women with episodic bipolar disorder often remain well without treatment during pregnancy. Our retrospective study statistically examines the clinical course of 28 women with RDC typical bipolar disorder, type I, who became pregnant prior to receiving successful lithium prophylaxis. METHODS: We derived all data from the International Group for the Study of Lithium-treated Patients (IGSLI) database of excellent lithium responders. Data were compared both intraindividually, using data from three 9-month periods - immediately prior to pregnancy, pregnancy and postpartum - and interindividually, using never-pregnant women as controls. RESULTS: Intraindividual data show that women with typical bipolar disorder, type I, experience significantly fewer and shorter recurrences during pregnancy than either before or after. Interindividual comparisons indicate that the recurrence risk during pregnancy is markedly lower than the clinical course would predict. Moreover, the few recurrences observed during pregnancy all took place in the last 5 weeks. LIMITATIONS: Limiting cases to lithium responsive patients could have reduced heterogeneity and perhaps generalizability. CONCLUSIONS: The findings, nonetheless, indicate a marked improvement of the clinical course of typical bipolar disorder, type I, lithium-responsive, during pregnancy. Exploring the underlying protective mechanisms may lead to new understanding of the pathophysiology of mood disorders and to new approaches to treatment and prevention.
Asunto(s)
Antimaníacos/uso terapéutico , Trastorno Bipolar/prevención & control , Trastorno Bipolar/fisiopatología , Carbonato de Litio/uso terapéutico , Complicaciones del Embarazo/fisiopatología , Adulto , Depresión Posparto/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Recurrencia , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Expresión Génica/genética , Litio/uso terapéutico , Receptores de GABA/genética , Transmisión Sináptica/genética , Alelos , Trastorno Bipolar/genética , Femenino , Ligamiento Genético , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genéticaRESUMEN
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.
Asunto(s)
Trastorno Bipolar/genética , Hormona Liberadora de Corticotropina/genética , Encefalinas/genética , Ligamiento Genético/genética , Precursores de Proteínas/genética , Adulto , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/etiología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Litio/uso terapéutico , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
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.
Asunto(s)
Trastorno Bipolar/genética , Mapeo Cromosómico , Péptidos/genética , Adulto , Anciano , Alelos , Antimaníacos/uso terapéutico , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Femenino , Pruebas Genéticas , Humanos , Carbonato de Litio/uso terapéutico , Masculino , Persona de Mediana Edad , Repeticiones de Trinucleótidos/genéticaRESUMEN
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.
Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/genética , Ligamiento Genético/genética , Litio/uso terapéutico , Monoaminooxidasa/genética , Alelos , Femenino , Humanos , MasculinoRESUMEN
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.
Asunto(s)
Trastorno Bipolar/enzimología , Trastorno Bipolar/genética , Isoenzimas/genética , Isoenzimas/metabolismo , Polimorfismo Genético , Fosfolipasas de Tipo C/genética , Fosfolipasas de Tipo C/metabolismo , Adulto , Edad de Inicio , Trastorno Bipolar/tratamiento farmacológico , Femenino , Frecuencia de los Genes , Genes Dominantes , Genes Recesivos , Ligamiento Genético , Marcadores Genéticos , Genotipo , Humanos , Litio/uso terapéutico , Escala de Lod , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Fosfolipasa C gamma , Valores de Referencia , Estadísticas no ParamétricasRESUMEN
In a review of the literature the author outlines the basic ethical problems of contemporary European gerontopsychiatry, as apparent at international congresses of gerontopsychiatric societies in Berlin (1993 and 1994) and Amsterdam (1994). Ethical dilemmas include in the first place abuse of old people, ethics of drug trials with insane patients and the right of a dignified death of psychiatric patients in general and insane patients in particular. The author holds a critical view of the legalization of euthanasia. A substantial part of the paper is devoted to the development of discussions regarding the legalization of euthanasia in Holland. It seems that as long as euthanasia will be restricted to the terminal stages of generalized malignities, it could be adopted also in other European countries incl. the Czech Republic. The author has a very critical and negative attitude to frequently practised dysthanasia, not only in the mentally healthy but also in psychiatric patients. He refutes inadequate medical intervention from the sphere of heroic medicine in particular in insane patients in the terminal stages of degenerative brain diseases.
Asunto(s)
Ética Médica , Psiquiatría Geriátrica , Anciano , República Checa , Eutanasia Pasiva , HumanosRESUMEN
The paper offers a brief outline of the current state of geriatric psychiatry and psychopharmacology in Canada and partially in the USA. Major trends are described in clinical care, in organization and education, along with some basic historical comments. The important role of self-help groups is sketched. The contents of recent major scientific meetings illustrate the increasing emphasis in research in ageing, geriatric psychiatry and geriatric psychopharmacology. The developments are characterized by intimate connections between basic and applied research, and between clinical observations and experimental neurobiology. The analysis of developments in the current practice and research offers some insight into upcoming treatment strategies. The next decade in geriatric psychiatry will probably belong in particular to molecular biology, genetic, psycho-immunology and psychopharmacology.
Asunto(s)
Psiquiatría Geriátrica , Psicofarmacología , Anciano , Canadá , Servicios de Salud para Ancianos , HumanosRESUMEN
The author reflects critically on some shortcomings of the contemporary not always indicated increase of institutionalized death in old age. The relief of relatives from the physical and mental strain associated with nursing in the home is in many instances heavily paid for by emotional deprivation and psychological suffering of the dying person away from his home. The attending doctor should therefore consider more carefully all risks of hospitalization in particular the hastened onset of death (the so-called phenomenon of transplantation and translocation shock) against its possible advantages. Under conditions of hospital or institutional treatment it is important to improve systematically the emotional support of patients dying without their family (trained health workers, psychologists and clergymen) or facilitate legislatively and de facto the integration of the closest relatives in the process of dying.
Asunto(s)
Anciano , Atención Domiciliaria de Salud , Hospitalización , Cuidado Terminal , HumanosRESUMEN
Recent epidemiological studies of mania suggest that admissions correlate with length of day and sunlight. As well, seasonal affective disorder--a depression occurring in winter, is reported to respond to light therapy and it has been proposed that supersensitivity to light is a trait-marker of manic-depressive illness. Dark adaptation threshold (D.A.T.)--a measure of night vision--was assessed in 19 euthymic manic-depressive patients stabilized on lithium, and in 19 drug-free healthy controls. The D.A.T. was significantly raised in the patients taking lithium. It is concluded that lithium induces subsensitivity to light.
Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Adaptación a la Oscuridad/efectos de los fármacos , Litio/efectos adversos , Adulto , Anciano , Femenino , Humanos , Litio/uso terapéutico , Masculino , Persona de Mediana Edad , Umbral SensorialRESUMEN
The 21 HLA-A and -B antigens were typed in 38 patients with the senile form of Alzheimer's disease and 301 healthy individuals. No statistically significant difference was found in the frequency of HLA antigens after correction of P.
Asunto(s)
Enfermedad de Alzheimer/genética , Antígenos HLA/genética , Anciano , Demencia/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
The results concerning the association of HLA antigens with ITP, pernicious anaemia, hemangiomas and Alzheimer's disease are compared with those of other authors and the causes for differences are discussed. The different number of examined patients does not seem to be the main cause of those differences. Selecting of the correct method for statistical evaluation and the differences in the criteria for diagnosing the disease are more important. The unsubstantial differences in the homogeneity of the patients group and controls are negligible.