Molecular Genetics of Mental Disorders with Particular Reference to Affective 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.


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.


2001 ◽  
Vol 178 (S41) ◽  
pp. s128-s133 ◽  
Author(s):  
Nick Craddock ◽  
Ian Jones

BackgroundA robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes.AimsTo present an overview for clinical psychiatrists.MethodReview of current molecular genetics approaches and emerging findings.ResultsOccasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23–q24, 16p13, 21q22, and Xq24–q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged.ConclusionIt is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.


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.


Author(s):  
Susan C. South ◽  
Ted Reichborn-Kjennerud ◽  
Nicholas R. Eaton ◽  
Robert F. Krueger

The purpose of this chapter is to provide an overview of the behavior and molecular genetics of personality disorder. We begin with a thorough review of findings from the field of behavior genetics of personality pathology, including univariate twin studies, multivariate twin studies, and new models of gene–environment interplay. We then discuss the molecular genetics of personality pathology, including a consideration of candidate gene analysis, linkage analysis, and genome-wide association studies. We focus in particular on research concerning antisocial personality disorder (including antisociality and aggression), borderline personality disorder, schizotypal personality disorder, Cluster B and C personality disorders, and normal personality traits. We then provide a discussion of challenges and future directions with respect to behavior and molecular genetic research. We conclude the chapter with a discussion of the implications of this research for the forthcoming fifth edition of the American Psychiatric Association’s diagnostic manual.


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.


2000 ◽  
Vol 23 (3) ◽  
pp. 549-556 ◽  
Author(s):  
E.Z. Lopes-Machado ◽  
F.A.M. Duarte

The genetics of schizophrenia or bipolar affective disorder has advanced greatly at the molecular level since the introduction of probes for the localization of specific genes. Research on gene candidates for susceptibility to schizophrenia can broadly be divided into two types, i.e., linkage studies, where a gene is found near a specific DNA marker on a specific chromosome, and association studies, when a condition is associated with a specific allele of a specific gene. This review covers a decade of publications in this area, from the 1988 works of Bassett et al. and Sherrington et al. on a gene localized on the long arm of chromosome 5 at the 5q11-13 loci, to the 1997 work of Lin et al. pointing to the 13q14.1-q32 loci of chromosome 13 and to the 1998 work of Wright et al. on an HLA DRB1 gene locus on chromosome 6 at 6p21-3. The most replicated loci were those in the long arm of chromosome 22 (22q12-q13.1) and on the short arm of chromosome 6 (6p24-22). In this critical review of the molecular genetic studies involved in the localization of genes which modulate the predisposition to schizophrenia the high variability in the results obtained by different workers suggests that multiple loci are involved in the predisposition to this illness.


Author(s):  
Mahesh Tilwani

Background and Aim: Alcohol Dependence Syndrome has deleterious consequences not only on the patient with Alcohol Dependence Syndrome but also on the members of his family. The psychopathology in wives of patients with Alcohol Dependence Syndrome is a largely neglected area in psychiatric research. Aim of the present study was to evaluate the frequency and nature of psychiatric disorders in wives of patients with Alcohol Dependence Syndrome. Materials and Methods: A total of 177 wives, 100 wives of patients with Alcohol Dependence Syndrome and 77 wives of patients with Bipolar Affective Disorder- current episode mania were evaluated. Tools used were ICD-10 AM symptom checklist and modules for assessment of psychiatric morbidity and diagnosis was made based on The International Classification of Diseases – (Diagnostic Research Criteria DCR-10). Results: Psychiatric disorders are diagnosed in 75% of the wives of patients with alcohol dependence syndrome out of which 45% have dysthymia, 12% have mild depressive episode, 8% have adjustment disorder- prolonged depressive reaction, 5% have moderate depressive episode and 5% have anxiety disorder unspecified. Conclusion: The present study concludes that the wives of patients with Alcohol Dependence Syndrome have significant psychiatric morbidity when compared to wives of patients with Bipolar Affective Disorder-current episode mania. The most common psychiatric disorder is dysthymia.


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