Prenatal sensitization in a mouse model.
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Animals↗
Biomedical subjects
B Ahrens
Publications and source records attributed to B Ahrens.
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↗
Omega-3 fatty acids--the missing link?
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Arrhythmias, Cardiac↗
Death in the emergency department.
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Attitude of Health Personnel↗
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↗
Psychopathological assessment and diagnosis. A study of specificity of single symptoms.
The importance of single symptoms in the diagnostic process has not been adequately studied, mainly because of the complexity of the information involved. The aim of the present study is to investigate the interconnection between psychopathological assessment and diagnostic classification, with the aid of a nonparametric, inductive pattern recognition method. Using the concept of inductive logic and a theory of inductive knowledge acquisition, a model has been developed to describe psychopathological assessment and diagnostic classification. Based on a comprehensive psychopathological assessment in 837 patients with 14 different diagnoses, classification values were calculated for specific symptoms in different diagnostic groups. Furthermore, nonparametric statistical procedures have advantages over discriminant analytic approaches: more information is utilized in differentiating the groups and differentiations can be made between more groups, whereby the rate of correctly classified cases is comparable with discriminant analytic approaches. The pattern recognition method appears to illustrate the multidimensional, medical decision-making in a comprehensible way.
Adult↗
Mortality studies and the effectiveness of drugs in long-term treatment.
In scientific observations on the utilization of drugs under routine treatment conditions in patients with affective disorders, one of the main problems is the establishment of criteria for measuring treatment effectiveness. As the mortality risk of such patients is considerable, the mortality rate is an important outcome criterion for determining the long-term effectiveness of medication administered in routine treatment settings. Mortality studies are typical phase IV studies; the researcher does not interact with the treatment procedure, he only observes the results of treatment with respect to death rates. As lithium treatment is of increasing importance and interest as a major prophylactic agent in recurrent affective disorders and is by its nature a long-term treatment, such a therapy provides an excellent field for observations of effectiveness under long-term treatment conditions. Mortality studies can take into account various factors, such as type of treatment setting, treatment regimen, drop-out analysis, and comparison between times on and off treatment. Results from several mortality studies on lithium-treated patients are reported in order to demonstrate the methodology and outcome of long-term observation of drug treatment. Mortality studies conducted within the framework of phase IV studies and particularly within the concept of pharmacoeconomics can help to demonstrate the effectiveness of long-term treatment, and are an important methodological adjunct to controlled clinical trials.
Antimanic Agents↗
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↗
Suicidality in hospitalized patients with a primary diagnosis of personality disorder.
In this investigation the frequency and clinical importance of suicidal behavior in patients with a primary diagnosis of personality disorder was studied. The sample was drawn from a group of over 8000 psychiatric inpatients admitted to a university psychiatric hospital. Only patients with a primary diagnosis of personality disorder were included. In the subgroup of 226 patients with this diagnosis, it was found that the rate of suicidality was almost as great as that of patients with a primary diagnosis of major affective disorder (39% as opposed to 41%), despite the absence in all but 3% of these patients of an additional diagnosis of affective disorder. Further, this figure was considerably higher than that for all psychiatric inpatients (24%). Suicidal patients had more suicide attempts in their history and had a more serious depressive syndrome, despite the fact that only 3% fulfilled the criteria for major affective disorder. The conclusion which can be drawn is that a high degree of suicidality should not be regarded as exclusively linked to a primary diagnosis of major affective disorder.
Adult↗
Is there a suicidality syndrome independent of specific major psychiatric disorder? Results of a split half multiple regression analysis.
Biological findings such as low 5-HIAA levels in cerebrospinal fluid (CSF) in suicidal patients compared to non-suicidal patients independent of the type of psychiatric disorder indicate a broad basis for suicidality. It is therefore important to ask whether a suicidality syndrome can be delineated on a phenomenological level, and whether it is independent of specific major psychiatric disorders which are otherwise considered to be aetiologically different. This paper reports on a study of 2383 schizophrenic and 1920 depressive unselected patients with and without suicidality. They were assessed during the first 24 h after admission to a psychiatric in-patient facility using a comprehensive psychopathological assessment (AMDP system). Using multiple variance analysis and logistic regression analysis based on single symptoms, for both suicidal and non-suicidal patients it was shown that a suicidality syndrome independent of the underlying illness can be delineated. In schizophrenia as well as in major affective disorders it was found that hopelessness, ruminative thinking, social withdrawal and lack of activity are core symptoms of this suicidal syndrome. The finding of a suicidality syndrome, not associated with a specific major affective disorder, indicates the need to identify this syndrome, which should be seen as an independent dimension and diagnosed separately, and not regarded merely as a secondary symptom of major psychiatric disorders, particularly affective disorders.
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↗
Age of onset in familial and sporadic schizophrenia.
We have studied the gender and family history differences with regard to age of onset of schizophrenia. These differences have often been viewed as an important clue to the aetiology of the illness. Patients from three centres in Europe and Canada were included in the study. A sample of 1089 subjects was categorized according to the subject's sex, family history of schizophrenia, and the centre. The principal statistical method was analysis of variance. Patients with no family history of schizophrenia had a consistently higher average age of onset. This effect was seen in both male and female subjects across all three groups. These results support the relationship between familial risk and early onset, but no interaction of gender and family history was found.
Adult↗
Suicide attempts, age and duration of illness in recurrent affective disorders.
One of the strongest predictors of suicide is a suicide attempt in the history of the patient. The question, however, is to what extent age and duration of the illness affects the risk of a suicide attempt. In this study, we examined the course of 310 patients with primary affective disorders before lithium prophylaxis and compared the clinical data of those with and without suicide attempts in their history. In a subgroup of 98 patients with suicide attempts, measures for both suicide attempts and inpatient episodes were investigated. Comparing patients with suicide attempts and those without, we found no difference between duration of illness and number of previous episodes between the two groups. However, those with a suicide attempt in their history had an earlier onset of the illness. In the group of 98 suicide attempters, we found no significant correlation between age and rates for both episodes and suicide attempts, which indicates that these rates were not declining as the illness progressed and the patient aged. Dividing the sample into three different age groups, episode rates and rates of attempted suicide were found to be positively correlated in all age groups, again indicating that as long as episodes occur, the suicide risk does not decline. The results are not in favor of findings which suggest that the risk of attempting suicide might manifest itself primarily in the early course of the illness or that suicide attempts in the early course of illness provide a 'cathartic effect' which leads to a lower risk in the later course of the illness. Rather, the findings support the view that the risk of suicide attempts in recurrent affective disorders is unchanged in all age groups and throughout all stages of untreated illness.
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↗
Clinical course of affective disorders: were Emil Kraepelin and Jules Angst wrong?
Returning to the original problem of 'correcting' the earlier findings, it appears that it is not a question of who is right and who is wrong. Kraepelin outlined, and Angst clearly specified, the basic characteristics of the clinical course of unipolar and bipolar affective disorders which unfolds in patients without other pre-existing psychiatric disorders and which is typically episodic. The criteria for diagnosis applied not only cross-sectionally but also longitudinally. Recent studies, on the other hand, have put more emphasis on the standardized cross-sectional approach, and deal with a much broader population in which episodes of affective syndromes develop mainly on the basis of preexisting and chronic psychiatric disturbance, with more frequent recurrences and cycling. In a nutshell, Kraepelin and Angst provided us with a natural history of affective disorders whereas recent studies provide us with the clinical course of a broadly defined cluster of affective syndromes.
Comorbidity↗
Extended survival of patients on long-term lithium treatment.
OBJECTIVE: Findings from a recent international multi-centre trial are compatible with the idea that long-term lithium treatment extends the survival of patients suffering from affective disorders to match the general population. A similar reduction of mortality was found in Canadian patients, although important questions remained to be answered about cardiovascular and suicide mortality, and patient selection. METHOD: Based on data collected in a study (1) from lithium clinics in Canada, Denmark, Germany and Austria, an analysis was carried out of suicide and cardiovascular mortality in patients who received prophylactic lithium treatment. RESULTS: In patients given lithium for two years or longer (n = 641), both suicide and cardiovascular mortality were the same as, or only slightly higher than, in the general population; in patients given lithium for less than two years (n = 186), both mortalities remained high. The reduced mortality is not likely to be the result of selection because the patients who were treated briefly and those treated for a longer time did not differ in important mortality variables. CONCLUSIONS: In addition to its ability to prevent recurrences, prophylactic lithium treatment appears capable of reducing both the excess suicide risk and excess cardiovascular mortality of affective illness.
Adult↗