Prodromal symptoms before onset of manic-depressive disorder suggested by first hospital admission histories.

OBJECTIVE: A priority for research on manic-depressive or bipolar I disorder (BPI) for children and adolescents has been to search for early predictors of the illness. METHOD: Medical record data were reviewed and systematically coded for a sample of 58 adult patients (32 males/26 females) with confirmed diagnoses of BPI to identify prodromal features and possible patterns of symptoms from the Amish Study. RESULTS: The most frequently reported symptoms included episodic changes in mood (depressed and irritable) and energy plus anger dyscontrol, with no significant gender differences. A progression of ages is seen for the most commonly reported symptoms prior to age 16. The time interval was 9 to 12 years between appearance of the first symptoms and onset of a documented BPI syndrome. CONCLUSIONS: The data suggest testable hypotheses about specific symptoms and behaviors that may be useful for the early detection of children at highest risk for developing manic-depressive disorder.

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5. 22 x 10(-4); SIBPAL Pempirical value <3 x 10(-5)) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 10(-3); SIBPAL Pempirical value <1 x 10(-3)) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.

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.

Bipolar affective disorders linked to DNA markers on chromosome 11.

An analysis of the segregation of restriction fragment length polymorphisms in an Old Order Amish pedigree has made it possible to localize a dominant gene conferring a strong predisposition to manic depressive disease to the tip of the short arm of chromosome 11.

Amish Study, I: Affective disorders among the Amish, 1976-1980.

The authors review the goals, methods, sample, and selected epidemiologic findings from a collaborative study of affective disorders among the Amish. This culturally and genetically homogeneous population (N = 12,500) constitutes an excellent research setting for psychiatric epidemiologic and genetic study. Alcoholism, drug abuse, and sociopathy did not complicate the study because they are culturally prohibited. During 1976-1980, 112 active cases of mental illness were identified; 71% received diagnoses of major affective disorder. Equal numbers of men and women received diagnoses of unipolar illness, and slightly more men than women were diagnosed as having bipolar illness.

Amish Study, III: the impact of cultural factors on diagnosis of bipolar illness.

In the Amish Study of affective disorders, 79% of the 28 active bipolar I patients, diagnosed according to Research DIagnostic Criteria, previously had received hospital record diagnoses of schizophrenia. Both cultural and clinical factors hindered correct diagnosis, and cultural influences particularly complicated the interpretation of the manic symptoms of grandiosity and excessive involvement in activities. Other factors central to misdiagnosis were form of thought (flight of ideas), content of thought (grandiose and religious delusions), paranoid features, and the failure to recognize the presence of a manic syndrome.

Amish Study, II: Consensus diagnoses and reliability results.

Reliability of diagnosis is central to genetic research on mental illness. In the Amish Study of affective disorders, consensus diagnoses were derived by a psychiatric board using the Research Diagnostic Criteria (RDC). To verify the reliability of diagnoses, the authors 1) studied how well board members followed RDC procedures, 2) compared diagnoses based on abstracted medical records with those based on full medical records, 3) compared diagnoses based on the two data sources--abstracted medical records and the Schedule for Affective Disorders and Schizophrenia-Lifetime Version--and 4) studied diagnostic stability to determine validity of diagnosis. The results of these substudies demonstrate a high concordance of diagnosis.