B. Ahrens

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.

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.

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.

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.

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 subjects 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.

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.

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.

Psychopathological Assessment and Diagnosis

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.