Anticipation in bipolar affective disorder

• Published in: American journal of human genetics Vol. 53; no. 2; pp. 385 - 390
• Main Authors: MCINNIS, M. G, MCMAHON, F. J, CHASE, G. A, SIMPSON, S. G, ROSS, C. A, DEPAULO, J. R
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.08.1993
• Subjects: 550900 > Pathology; Adult; Adult and adolescent clinical studies; age; Age Factors; Aged; BASIC BIOLOGICAL SCIENCES; Bias; Biological and medical sciences; bipolar affective disorder; Bipolar Disorder - genetics; Chi-Square Distribution; Child; Cohort Studies; Depression; DNA - analysis; ETIOLOGY; Female; Gene Amplification; GENE MUTATIONS; Genotype; HUMAN POPULATIONS; Humans; Life Tables; linkage analysis; Male; man; Medical sciences; MENTAL DISORDERS; Middle Aged; Mood disorders; MUTATIONS; Pedigree; Phenotype; POPULATIONS 550400 > Genetics; Proportional Hazards Models; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Repetitive Sequences, Nucleic Acid; RFLPS; SCREENING; Severity of Illness Index; statistical genetics; SURVIVAL TIME; Human; Mood disorder; Age of onset; Family study; Pathogenesis; Repeated sequence; Inheritance; Bipolar disorder; Severity score
• ISSN: 0002-9297; 1537-6605

Anticipation refers to the increase in disease severity or decrease in age at onset in succeeding generations. This phenomenon, formerly ascribed to observation biases, correlates with the expansion of trinucleotide repeat sequences (TNRs) in some disorders. If present in bipolar affective disorder (BPAD), anticipation could provide clues to its genetic etiology. We compared age at onset and disease severity between two generations of 34 unilineal families ascertained for a genetic linkage study of BPAD. Life-table analyses showed a significant decrease in survival to first mania or depression from the first to the second generation (P < .001). Intergenerational pairwise comparisons showed both a significantly earlier age at onset (P < .001) and a significantly increased disease severity (P < .001) in the second generation. This difference was significant under each of four data-sampling schemes which excluded probands in the second generation. The second generation experienced onset 8.9-13.5 years earlier and illness 1.8-3.4 times more severe than did the first generation. In additional analyses, drug abuse, deaths of affected individuals prior to interview, decreased fertility, censoring of age at onset, and the cohort effect did not affect our results. We conclude that genetic anticipation occurs in this sample of unilineal BPAD families. These findings may implicate genes with expanding TNRs in the genetic etiology of BPAD.