Future of genetics of mood disorders research

Merikangas, Kathleen R.; Chakravarti, Aravinda; Moldin, Steven O.; Araj, Houmam; Blangero, John; Burmeister, Margit; Crabbe, John C.; DePaulo, J. Raymond; Foulks, Edward F.; Freimer, Nelson B.; Koretz, Doreen S.; Lichtenstein, William; Mignot, Emmanuel; Reiss, Allan L.; Risch, Neil; Takahashi, Joseph S.

doi:10.1016/s0006-3223(02)01471-3

Cited by 118 publications

(68 citation statements)

References 122 publications

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“…2 The study of these candidate genes is well supported by extensive data from neurochemical, pharmacological, physiological, and animal studies investigating the role of serotonin, its receptors and transporter in the etiology, and treatment of affective disorder. 5 In this study, we reviewed a total of 86 association studies that focused on genetic variation located in these candidate genes.…”

Section: Discussionmentioning

confidence: 99%

“…This is based on considerable evidence suggesting that genes may play a significant role in the predisposition to these disorders. 2 Association studies have been advocated as the method of choice to investigate complex traits such as affective disorders. 3,4 This, together with the relative simplicity involved in the execution of these studies and the recent exponential grow in the amount of available information on genetic variation, has greatly stimulated the proliferation of association studies in psychiatry, including affective disorders.…”

Section: Introductionmentioning

confidence: 99%

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A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders

2003

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The different 5-HT (serotonin) receptors including the serotonin transporter (5-HTT) are candidate genes for affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). They have been investigated in a number of allelic association studies where the individual results have been inconsistent, and therefore, definite conclusions are difficult to make. Systematic reviews using meta-analytical techniques are a reliable method for objectively and reproducibly assessing individual studies and generating combined result. This study aimed at reviewing published studies investigating the association between affective disorders (MDD and BD) and variation at genes coding for serotonin receptors and the serotonin transporter. We performed National Library of Medicine database searches to identify potential studies. More than 430 articles were reviewed and 86 studies met the inclusion criteria for participation in our review. Of these, 41 studies investigated 45 different 5-HT receptor variants and 45 studies investigated at least one of two commonly studied 5-HTT polymorphisms in MDD. Many studies investigated the association between MDD and BD with the 5-HT2A 102 T/C, the 5-HTT promoter 44 bp insertion/deletion and the intron 2 VNTR polymorphisms, and thus, these could be pooled using meta-analytic techniques. The overall odds ratio (OR) for the combined individual results was significant for BD and the two 5-HTT polymorphisms: Mantel-Haenszel weighted OR ¼ 1.14, CI: 1.03-1.26, P ¼ 0.015 for the promoter locus (N ¼ 3467) and Mantel-Haenszel Weighted odds ratio OR ¼ 1.18, CI: 1.05-1.32, P ¼ 0.004 for the VNTR locus (N ¼ 3620). However, sensitivity analysis indicated that, in each case, the overall positive association could be mostly attributed to the large effect of one individual study. Therefore, these results suggest that, although promising, further studies are required to assess appropriately the evidence suggesting an association between BD and 5-HTT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders

2003

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“…Also for the course of disorders, it is unlikely that there exists one single predictor. Accurate prediction of the course of depressive and anxiety disorders requires that psychosocial and biological research paradigms be integrated within a common psychiatric epidemiological framework (Merikangas et al, 2002). The rapid technological advances such as genomics have recently allowed such integration which enables research into the interaction between psychosocial and biological determinants.…”

Section: Rationale 3: Depressive and Anxiety Disorders Should Be Studmentioning

confidence: 99%

The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods

Penninx

Beekman

Smit

et al. 2008

Int J Methods Psych Res

841

737

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“…Indeed, the concordance for BP in monozygotic twins (0.67), when compared with concordance in dizygotic twins (0.10 to 0.20) 11 and the relative risk in first-degree relatives (0.10 to 0.20), 12 strongly suggests that more than one locus is involved. 13 Moreover, genome scans from several groups have been conducted to date on the "BP spectrum" phenotype, with evidence for a "BP" gene locus varying by study, including findings of possible loci on chromosome 18q21-23, [14][15][16][17] chromosome 4p12-13, 18,19 chromosome 13q31-33, 20 and other loci (see section on linkage scans below).…”

Section: Bipolar Disorder Especially the Most Severe Type (Type I) mentioning

confidence: 99%

“…T r a n s l a t i o n a l r e s e a r c h BP-I is the most severe, most reliably diagnosed, 51-53 and most genetic form of BP, 12 yet almost all previous genetic studies of BP have failed to study the BP-I phenotype without clouding the picture by including BP-II and recurrent depression in the phenotype definition. No doubt, a major limitation to performing studies on the most severe phenotype, BP-I, has been the fact that finding families with large sibships, who are intact and agreeable to participate, has been prohibitively difficult in mainstream United States society.…”

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confidence: 99%

3. Genetics of Bipolar Disorder

Bengesser¹,

Reininghaus²

Genetics of Bipolar Disorder

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ipolar affective disorder, type I (BP-I) is a severe mental illness marked by periodic extremes of mood state (manias), as well as (in most cases) episodes of depression and (in many cases) psychosis. The consequences of BP-I are severe, and involve both direct and indirect issues. Rates of suicide in BP-I patients are high, 1,2 and BP-I subjects also suffer from poorer quality of life and lower productivity than unaffected individuals.3 Annual public health costs (combined direct and indirect) of BP have been estimated to be between 24 billion and 45 billion dollars.4,5 BP-I occurs in all populations that have been studied, with lifetime prevalence rates worldwide of the order of one per every 100 individuals. 6 Segregation analyses, adoption studies, and twin studies have consistently shown that, regardless of the population studied, genetic factors play an important role in determining one's risk of developing BP-I. [7][8][9] Since little is known about the actual etiology of BP, it would be a major contribution to our understanding of the pathophysiology of BP if the genes responsible for the neurobiologic changes which underlie this disorder could be identified. The difficulty in finding genetic loci that are involved in BP most likely derives from the complex nature of the illness. When multiple transmission models for BP-I (the most severe form of BP) have been tested, oligogenic epistatic models are found to be the best fit, rather than models which purport one major locus. Craddock et al 10 reviewed epidemiologic, family, and twin studies, and showed that two, three, or four locus models 141T r a n s l a t i o n a l r e s e a r c h B

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Future of genetics of mood disorders research

Cited by 118 publications

References 122 publications

A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders

A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders

The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods

3. Genetics of Bipolar Disorder

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