Affective disorders in five United States communities

Weissman, Myrna M.; Leaf, Philip J.; Tischler, Gary L.; Blazer, Dan G.; Karno, Marvin; Bruce, Martha L.; Florio, Louis P.

doi:10.1017/s0033291700001975

Cited by 584 publications

(221 citation statements)

References 41 publications

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“…These assumptions correspond to a lifetime morbid risk of 6% for diseases included in ASM II and of 1% for BPI (ASM I). 59 An age-dependency of the penetrance was not taken into account, since using 'affecteds-only' treats unaffected individuals as phenotype unknown, which diminishes the effect of quantifying the correct penetrance.…”

Section: Linkage Analysesmentioning

confidence: 99%

A possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25–q26

et al. 2001

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In an attempt to identify susceptibility loci for bipolar affective disorder, we are currently conducting a systematic genome screen with highly polymorphic microsatellite markers at an average marker spacing of 10 cM in a series of 75 families, comprising 66 families from Germany, eight families from Israel, and one family from Italy. The families were ascertained through index cases with bipolar affective disorder. The distribution of diagnoses is as follows: 126 individuals with bipolar I disorder, 40 with bipolar II disorder, 14 with schizoaffective disorder of the bipolar type, 40 individuals with recurrent unipolar depression, 51 with a minor psychiatric diagnosis, and two individuals with a diagnosis of schizophrenia. One hundred and seventy-one individuals are unaffected. Here, we present results from chromosome 10. Linkage analyses using a total of 33 microsatellite markers with parametric and non-parametric methods provided evidence for linkage at chromosomal region 10q25-q26. The highest two-point LOD score (2.86, = 0.05) was obtained for D10S217 using a dominant genetic model and a broad definition of affection status. The GENEHUNTER program localized the putative susceptibility locus within a ca 15-cM interval between markers D10S1483 and D10S217 with a maximum NPL(all) score of 3.12 (P = 0.0013). Positive linkage findings that have been reported by two independent studies further support the hypothesis of a susceptibility gene for bipolar affective disorder on 10q25-q26. Molecular Psychiatry (2001) 6, 342-349.Bipolar affective disorder (BPAD), also known as manic depressive illness, is characterized by severe aberrant mood swings in alternating periods of mania and depression. The disorder is common with a lifetime prevalence of about 1% in all human populations and results in high costs in terms of morbidity as well as mortality. BPAD is substantially responsive to drug treatment, but episodes tend to recur throughout life. Although the etiology and pathophysiology is widely unknown, family, twin and adoption studies argue for a strong genetic determination of the disease. 1 Theories concerning the possible involvement of multiple genes of small effect and/or the occurrence of major allelic effects in epistasis have been advanced. In order to identify genes predisposing to BPAD, in the absence of substantial molecular pathophysiological knowledge, linkage analysis is one of the best available methods. Early linkage studies were conducted in large families and were based on the implausible assumption that a single major gene was responsible for the disorder: loci for BPAD on the X chromosome 2-4 and on chromosome 11p15 5 were reported and attracted considerable attention, but have not withstood molecular studies in independent samples 6-8 as well as updated and extended analyses by the original groups. 9,10 The reason for these inconclusive results were, for the most part, problems concerning diagnosis, ascertainment of pedigrees, statistical analysis, and lack of availability of dense genetic link...

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Section: Linkage Analysesmentioning

confidence: 99%

A possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25–q26

et al. 2001

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“…These assumptions correspond to a lifetime morbid risk of 6% for diseases included in ASM II and of 1% for BPI (ASM I). 37 An age-dependency of the penetrance was not taken into account, since using 'affecteds-only' treats unaffected individuals as phenotype unknown, which diminishes the effect of quantifying the correct penetrance.…”

Section: Linkage Analysesmentioning

confidence: 99%

Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families

et al. 1999

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Previously reported linkage of bipolar affective disorder to DNA markers on chromosome 18 was reexamined in a large sample of German bipolar families. Twenty-three short tandem repeat markers were investigated in 57 families containing 103 individuals with bipolar I disorder (BPI), 26 with bipolar II disorder (BPII), nine with schizoaffective disorder of the bipolar type (SA/BP), and 38 individuals with recurrent unipolar depression (UPR). Evidence for linkage was tested with parametric and non-parametric methods under two definitions of the affected phenotype. Analysis of all 57 families revealed no robust evidence for linkage. Following previous reports we performed separate analyses after subdividing the families with respect to the sex of the transmitting parent. Fourteen families were classified as paternal and 12 families as maternal. In 31 families the parental lineage of transmission of the disease could not be determined ('either' families). Evidence for linkage was obtained for chromosomal region 18p11.2 in the paternal families and for 18q22-23 in the 'either' families. The findings on 18p11.2 and 18q22-23 support prior evidence for susceptibility loci in these regions. The parent-of-origin effect on 18p11.2 is confirmed in our sample. The delineation of characteristics of 'either' families requires further study.Although the etiology of bipolar affective disorder is unknown, strong support for an important genetic component comes from the results of family, twin, and adoption studies. 1 Linkage studies of bipolar disorder to date have provided suggestive evidence in favor of locus heterogeneity. Promising chromosomal regions suggested by recent linkage studies include regions on chromosome 18.Berrettini et al 2 first reported linkage of bipolar disorder to a region near the centromere on chromosome 18p in 22 families using the affected-sib-pair (ASP) method and the affected-pedigree-member (APM) method. Parametric LOD score analysis of all 22 families revealed negative LOD scores. However, individual families yielded LOD scores Ͼ1 assuming dominant or recessive genetic models. Confirmatory evidence for a bipolar susceptibility locus in this chromosomal region was found by Stine et al. 3 Both parametric LOD score analysis and ASP analysis supported linkage in their study of 28 families. In addition, the same study reported a second susceptibility locus on the long arm of chromosome 18 (18q21). Interestingly, linkage to loci on both 18p and 18q was strongest in those families, in which the father or one of the father's siblings was affected, suggesting a parent-of-origin effect operating in bipolar disorder. Gershon et al 4 re-analyzed the 18p marker data of Berrettini et al 2 by the sex of the transmitting parent. Although no kindred with limited paternal transmission was observed, ASP analysis yielded highly significant excess allele sharing in the pedigrees with mixed maternal-paternal transmission (in different pedigree branches) but not in pedigrees with exclusively maternal transmission confirmin...

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“…1 Dysregulation of synaptic signaling in limbic and associated cortical and subcortical areas has been hypothesized to be central in the cyclical changes in behavioral states from mania to depression. 2 It has been hypothesized that dysfunction of many neurotransmitter systems, including the cholinergic muscarinic system, is involved in bipolar disorder.…”

Section: Introductionmentioning

confidence: 99%

Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents

Bymaster

Felder

2002

Mol Psychiatry

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The evidence for the involvement of cholinergic muscarinic receptors in mania and depression is reviewed. Small pilot trials with cholinesterase inhibitors and muscarinic agonists suggest that stimulation of muscarinic receptors may produce an antimanic effect, possibly by activation of muscarinic M 4 receptors. It is concluded that it is not likely that currently used mood stabilizers, such as lithium, valproic acid and carbamazepine, work directly through muscarinic receptor mechanisms. Furthermore, the evidence indicates that antipsychotic agents used for mania are working through the common mechanism of antagonism of dopamine D 2 receptors, and interactions with muscarinic receptors do not play a key role. Finally, it is hypothesized that olanzapine has robust antimanic activity, due to blockade of dopamine D 2 receptors and antagonism of other monoaminergic receptors. Olanzapine may normalize mood due to antidepressant-like activities, such as 5-HT 2A receptor antagonism and increasing cortical norepinephrine and dopamine.

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Affective disorders in five United States communities

Cited by 584 publications

References 41 publications

A possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25–q26

A possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25–q26

Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families

Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents

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