Aetiology Of Bipolar Affective Disorder Research Articles

New molecular genetic findings in the genetics of affective disorders.

Molecular genetics has now been widely incorporated into genetic epidemiological research in psychiatry. Affective disorders and, in particular, bipolar affective disorder (BPAD) have been examined in many molecular genetic studies which have covered a large part of the genome. Specific hypotheses such as mutations have also been studied. Most recent studies indicate that several chromosomal regions may be involved in the aetiology of BPAD. These include genes on chromosomes 18, 21, 4, 5, 11 and X. Other studies have reported the presence of anticipation in BPAD and in unipolar affective disorder (UPAD). This phenomenon describes the increase in clinical severity and decrease in age of onset observed in successive generations. This mode of transmission correlates with the presence of specific mutations (trinucleotide repeat sequences). Associations with these mutations have been reported in different populations of BPAD-patients and may represent a genetic factor involved in the transmission of the disorder. These findings are all preliminary and require to be confirmed. Large multi-centres and multi-disciplinary projects are currently underway in Europe and in the US and hopefully will improve our understanding of the genetic factors involved in affective disorders. In addition, genetic approaches used in psychiatry are being combined with an assessment of non-genetic susceptibility factors. The investigation of interactions between gene and environment is one of the most promising areas dealing with complex multi-factorial diseases such as the affective disorders.

5-HT 2A receptor and bipolar affective disorder: association studies in affected patients

The aim of this study was to investigate the possible involvement of genetic variation in serotonin receptors in the aetiology of bipolar affective disorder. The 5-HT 2A receptor gene was systematically screened for genetic variants by single strand conformation polymorphism (SSCP) methods in subjects with bipolar affective disorder. Four polymorphisms (two structural changes, Thr25Asn and His452Tyr, and two silent polymorphisms, 102-T/C and 516-C/T) which had previously been found in patients with schizophrenia and control subjects were detected. No novel polymorphisms were found in patients with bipolar affective disorder. These polymorphisms were genotyped in a sample of 129 patients and 252 controls of German origin and 176 patients and 182 controls of British origin. No strong associations were found between any of these polymorphisms and bipolar affective disorder. Genetic variation at the 5-HT 2A receptor gene does not play a major role in the pathogenesis of the disorder.

Fragile Site Analysis in Bipolar Affective Disorder

Family, twin and adoption studies have shown that genetic factors have an important role in the etiology of bipolar affective disorder. In this study, 30 bipolar cases whose diagnoses were determined by the Pychiatry department and 15 healthy individuals were compared with respect to fragile sites. APC, BrdU, FUdR and MTX were used as fragile site inducers. No significant difference was found between the rates of fragile sites observed in the patient and control groups. The fragile sites that were observed most freguently in the patient group were 1q21, 1q44, 2q32, 6p22, 6p26 and 10q25. No fragile site accumulation could be found on chromosomes 11 and X, where gene locuses are likely to exist. Nor was any cytogenetic association found between FXS and bipolar disorder. It was determined that age and sex do not influence the frequency of fragile sites.

A weak association between TH and DRD2 genes and bipolar affective disorder in a Spanish sample.

Genetic factors play an important role in the aetiology of bipolar affective disorder (BP). So far, results of linkage studies have been largely disappointing. We have searched for a possible association between polymorphic DNA markers of two candidate genes (tyrosine hydroxylase, TH; dopamine D2 receptor gene, DRD2) and BP in a population from central Spain. Our results are consistent with the existence of a weak association between these two genes and BP, in such a way that TH and DRD2 could be considered as minor genes contributing to susceptibility.

Genetic analysis of manic-depressive illness.

Two threshold models, a single locus model, and two combined models are fitted to data on familial incidence of bipolar affective disorder in 194 nuclear families ascertained through a bipolar proband. The relative fit of alternative transmission models is tested by a likelihood ratio chi-square with the degrees of freedom defined by the difference in the number of parameters estimated by each model. All parameters are estimated by the method of maximum likelihood. The simplest threshold model, permitting only a single background familial correlation, is found to provide a statistically poorer fit than any of the alternative models, and may be rejected as a model for the etiology of bipolar affective disorder. The four remaining models are statistically indistinguishable. It is suggested, however, that the involvement of a major locus in the etiology of this disorder deserves further scrutiny since any of the models incorporating a major locus, with or without a multifactorial background, are consistently associated with greater likelihoods than the complex threshold model. It is also noted that diagnostic criteria are critical in the analysis. In the present study, relatives of probands are considered affected if a diagnosis of bipolar or unipolar affective disorder is present. When only bipolar relatives are considered affected, none of the transmission models may be rejected. Finally, the results of these analyses are found to be independent of the ascertainment parameter.