Fertility and childhood bipolar disorder

University of Louisville, Department of Psychiatry, 501 E Broadway, Suite 340, Louisville, KY 40202, United States.
Medical Hypotheses (Impact Factor: 1.15). 02/2007; 69(3):587-9. DOI: 10.1016/j.mehy.2006.12.055
Source: PubMed

ABSTRACT The observation that the diagnosis of bipolar illness is increasingly being made in the young is fascinating and potentially quite instructive. Several potential reasons have been put forward, which may all play a role. These include increased awareness, a cohort effect, changes in the diagnostic criteria, increased use of stimulants and antidepressants unmasking the illness, and others. It is interesting to note that this increase in recognition of bipolar illness in the young comes about one generation after the introduction of lithium as a therapeutic agent in bipolar disorder. We propose that the introduction of lithium may have increased fertility (broadly defined) of bipolar patients allowing for the expression of genetic anticipation by having a second and third generation of offspring that are affected at earlier ages. A similar phenomenon was seen in schizophrenia after the introduction of phenothiazines for the treatment of psychosis. These pharmacologic and social changes may have all conspired to increase reproductive success of bipolar subjects, giving rise to a new generation of bipolar patients with earlier onset and more severe manifestation of their disorder.

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    ABSTRACT: CONTEXT It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants. OBJECTIVES To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants. DESIGN We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population. SETTING Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register. PARTICIPANTS In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden. MAIN OUTCOME MEASURES Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status. RESULTS Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In the case of depression, this more than compensated for the lower fecundity of affected individuals. CONCLUSIONS Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.
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