New molecular genetic findings in the genetics of affective disorders

1997 ◽  
Vol 9 (2) ◽  
pp. 52-54
Author(s):  
D. Souery ◽  
J. Mendlewicz

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.

2000 ◽  
Vol 12 (3) ◽  
pp. 65-68 ◽  
Author(s):  
D. Souery ◽  
I. Massat ◽  
J. Mendlewicz

ABSTRACTAdvances towards the understanding of the etiological mechanisms involved in mood disorders provide interesting yet diverse hypotheses and promising models. In this context, 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. Other studies have reported the presence of anticipation in BPAD. 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) and may represent a genetic factor involved in the transmission of the disorder. In parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, provided additional evidence in favour of the genetic hypothesis in mood disorders. Moreover, these methods have been improved through models to test the gene-environment interactions. While significant advances have been made in this major field of research, it appears that integrative models, taking into account the interactions between biological (genetic) factors and social (psychosocial environment) variables offer the most reliable way to approach the complex mechanisms involved in the etiology and outcome of mood disorders.


1997 ◽  
Vol 12 (S2) ◽  
pp. 63s-69s ◽  
Author(s):  
D Souery ◽  
O Lipp ◽  
B Mahieu ◽  
J Mendlewicz

SummaryThe present article reviews the recent molecular genetic findings in affective disorders. Results of linkage and association studies are discussed in regard to the main limitations of these approaches in psychiatric disorders. On the whole, linkage and association studies contributed to the localisation of some potential vulnerability genes for Bipolar affective disorder on chromosomes 18, 5, 11, 4, 21 and X. The hypothesis of anticipation in affective disorders is also considered in light of interesting results with trinucleotide repeat mutations.


Author(s):  
Pierre Oswald ◽  
Daniel Souery ◽  
Julien Mendlewicz

Advances towards the understanding of the etiological mechanisms involved in mood disorders provide interesting yet diverse hypotheses and promising models. In this context, 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. Other studies have reported the presence of anticipation in BPAD and in unipolar affective disorder (UPAD). In parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, provided additional evidence in favour of the genetic hypothesis in mood disorders. Moreover, these methods have been improved through models to test the gene-environment interactions. In addition to genetic approaches, psychiatric research has focused on the role of psychosocial factors in the emergence of mood disorders. In this approach, psychosocial factors refer to the patient's social life context as well as to personality dimensions. Abnormalities in the social behavior such as impairment in social relationships have been observed during episode of affective disorders, and implicated in the etiology of affective disorders. Further, gender and socio-economic status also emerged as having a possible impact on the development of affective disorders. Finally, the onset and outcome of affective disorders could also be explained by interactions between the social life context and the individual's temperament and personality. The importance of temperament and personality characteristics in the etiology of depression has been emphasized in various theories, although disagreement exists with regard to terminology and the etiology. While significant advances have been done in these two major fields of research, it appears that integrative models, taking into account the interactions between biological (genetic) factors and social (psychosocial environment) variables offer the most reliable way to approach the complex mechanisms involved in the etiology and outcome of mood disorders. This chapter will review some of the most promising genetic and psychosocial hypotheses in mood disorders that can be integrated in interactive models.


1999 ◽  
Vol 11 (2) ◽  
pp. 67-70
Author(s):  
D. Souery ◽  
J. Mendlewicz

Traditional methods used to asses genetic effects, such as twins, adoption and family studies, have demonstrated the role genetic vulnerability factors in the etiology of major psychiatric diseases such as affective disorders and schizophrenia. It remains however impossible, using these methods, to specify the genetic variables involved and the exact mode of transmission of these diseases. New genetic approaches in psychiatry include the use of DNA markers in sophisticated strategies to examine families and populations. Genetic linkage (in families) and allelic association (in unrelated subjects) are the most frequent techniques applied searching for genes in psychiatric diseases. Advances in these methods have permitted their application to complex diseases in which the mode of genetic transmission is unknown. 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 affective disorders. Large multi-centre 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 parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, have been improved, providing validated models to test the gene-environment interactions.


CNS Spectrums ◽  
2002 ◽  
Vol 7 (3) ◽  
pp. 196-202 ◽  
Author(s):  
Kezia J. Lange ◽  
Melvin G. McInnis

ABSTRACTAnticipation refers to the increase in disease severity or decrease in age of onset in successive generations. The concept evolved from the theories and dogma of degeneration that were pervasive in psychiatry and medicine in the late 19th century and into the early 20th century. The term was set aside with the criticism of geneticist Lionel Penrose, who argued that anticipation was the result of ascertainment biases. The renewed interest in anticipation followed the identification of its molecular genetic basis in the form of unstable trinucleotide repeats. Subsequently, several diseases have been studied clinically for the presence of anticipation. Although anticipation has been identified in many diseases, including bipolar disorder, only diseases showing a pattern of progressive neurodegeneration have been associated with unstable trinucleotide repeats. This review summarizes the research on anticipation in bipolar disorder and other secular trends in the patterns of the illness such as the cohort effect. The changing nature of bipolar disorder is likely to be a result of combined influences from several genes, some of which are likely to be in a state of flux, as well as environmental or cultural forces that converge to give the clinical picture of anticipation.


Author(s):  
E. D. Kasyanov ◽  
G. E. Maso ◽  
A. O. Kibitov

Affective disorders (recurrent depressive disorder and bipolar affective disorder) are multifactorial and polygenic diseases, which suggests the involvement of multiple neurobiological mechanisms. The phenotype of affective disorders is a heterogeneous group of clinically similar psychopathological symptoms, which also makes it difficult to detect potential biomarkers and new therapeutic targets. To study families at high risk of developing affective disorders using both clinical and molecular genetic approaches can help to study the neurobiological basis of depressive conditions, as well as to identify endophenotypes of affective disorders. The most important criterion for an endophenotype is its heritability, which can be proved only within the framework of the family design of the study. Comprehensive clinical and molecular genetic studies based on family design have the best prospects.


2008 ◽  
Vol 39 (5) ◽  
pp. 763-771 ◽  
Author(s):  
J. G. Fiedorowicz ◽  
A. C. Leon ◽  
M. B. Keller ◽  
D. A. Solomon ◽  
J. P. Rice ◽  
...  

BackgroundSuicide is a leading cause of death and has been strongly associated with affective disorders. The influence of affective disorder polarity on subsequent suicide attempts or completions and any differential effect of suicide risk factors by polarity were assessed in a prospective cohort.MethodParticipants with major affective disorders in the National Institute of Mental Health (NIMH) Collaborative Depression Study (CDS) were followed prospectively for up to 25 years. A total of 909 participants meeting prospective diagnostic criteria for major depressive and bipolar disorders were followed through 4204 mood cycles. Suicidal behavior was defined as suicide attempts or completions. Mixed-effects, grouped-time survival analysis assessed risk of suicidal behavior and differential effects of risk factors for suicidal behavior by polarity. In addition to polarity, the main effects of age, gender, hopelessness, married status, prior suicide attempts and active substance abuse were modeled, with mood cycle as the unit of analysis.ResultsAfter controlling for age of onset, there were no differences in prior suicide attempts by polarity although bipolar participants had more prior severe attempts. During follow-up, 40 cycles ended in suicide and 384 cycles contained at least one suicide attempt. Age, hopelessness and active substance abuse but not polarity predicted suicidal behavior. The effects of risk factors did not differ by polarity.ConclusionsBipolarity does not independently influence risk of suicidal behavior or alter the influence of well-established suicide risk factors within affective disorders. Suicide risk assessment strategies may continue to appraise these common risk factors without regard to mood polarity.


1991 ◽  
Vol 158 (4) ◽  
pp. 485-490 ◽  
Author(s):  
John Snowdon

In a replication of an earlier published study, case notes of 75 elderly in-patients with bipolar affective disorder were examined. Few of the patients had experienced a manic episode before the age of 40. Mean age of onset of affective disorder was 46 years, and first manic episode at 60 years. Cerebral insults before the first manic attacks were recorded in a substantial number of cases, and a family history of mental illness was less common among this group. Bipolar affective disorder is relatively common as a reason for admission of elderly patients.


1984 ◽  
Vol 14 (1) ◽  
pp. 145-149 ◽  
Author(s):  
Peter R. Joyce

SynopsisThe age of onset in bipolar affective disorder was determined in 200 hospitalized patients. The mean age of their first affective syndrome was 28·3 years, and the mean age of first hospitalization was 30·8 years. However, the median age for first affective syndrome was 23 years (26 years for first hospitalization), and the most common age of onset was 15–19 years. Those patients with an early onset, especially if they were first hospitalized for mania, were most likely to have received a diagnosis of schizophrenia.


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