Cleona R. Allen

Prospective Study of Prodromal Features for Bipolarity in Well Amish Children

OBJECTIVE A prospective study of psychiatrically well Amish children to determine differences in the frequency and pattern of clinical features that may be prodromal for bipolar I disorder. METHOD Children with a bipolar I parent (n = 100) and children of well parents in a matched control sample (n = 110) were assessed annually for 7 years with semistructured interviews covering medical/developmental features and symptoms/behaviors that are possibly prodromal for bipolarity. Randomized histories of these 210 children were evaluated blindly by 4 clinicians for independent ratings of risk for bipolarity. RESULTS Thirty-eight percent of the children of bipolar parents were rated as at risk compared with 17% of children in the control sample. Most control sample children with risk ratings had well parents with a bipolar sibling (i.e., family history positive). Children with family histories negative for mental illness rarely received even a low risk rating. Clinical features significantly (p <or=.05) more frequent among children of a bipolar parent included mood lability, low energy, anxious/worried, hyper-alert, attention problems/distractible and school role impairment, easily excited, sensitivity, somatic complaints, and stubborn/determined. CONCLUSION Mini-clusters of early possible predictors suggest a natural history of episodic prodromal features rather than the chronic symptom pattern sometimes described for children at risk for bipolar disorder.

Linkage of bipolar affective disorders to markers on chromosome 11p is excluded in a second lateral extension of Amish Pedigree 110

Linkage between markers on chromosome 11p and bipolar affective disorders can be excluded in a second large lateral extension of the original Amish Pedigree 110. These results, together with previous negative linkage findings, suggest that there is not one single gene on 11p conferring susceptibility for bipolar affective disorders among the Old Order Amish.

The impact of diagnoses on genetic linkage study for bipolar affective disorders among the amish

The influence of diagnostic decisions and onset of illness for previously unaffected persons in a genetic linkage study are key elements in the research interface of psychiatry and molecular biology. The Amish Study has documented this process and reports its procedural methods for diagnosis of bipolar affective disorders and the impact of diagnosis on lod scores with recommendations for future family linkage study using recombinant DNA techniques.

Update on the search for DNA markers linked to manic-depressive illness in the old order amish

In this report we describe our efforts to identify a gene involved in bipolar illness using a large, multigenerational Old Order Amish pedigree with many affected individuals. The original collection of cell lines from Amish pedigree 110 has been extended to include 169 individuals. We have used over 250 markers spaced at approximately 20 centiMorgans that detect restriction length fragment polymorphisms, but no LOD scores greater than 3 have been obtained from pairwise linkage analyses. We are expanding our collection of cell lines from both normal and affected family members and updating our diagnostic data as we continue our systematic screening of the genome for a gene involved in bipolar illness.

One Form of Bipolar Affective Disorder is Mapped to Chromosome 11

Geneticists have long recognized the power of genetic linkage as a tool in understanding complex traits, but lack of adequate numbers of genetic markers in humans has been a barrier to the use of genetic linkage to understand complex human disorders. The discovery of large numbers of genetic markers identifiable directly in the DNA—the restriction fragment length polymorphisms (RFLPs)—and the rapidly developing international effort to map the human genome have removed that barrier. Genetic linkage can now be used routinely to identify major loci responsible for complex human disorders as the first step toward understanding the etiology and pathogenesis of a disorder. Here we briefly review the evidence for a major locus causing bipolar affective disorder and discuss some of the implications of the finding.