Genetic overlap between polycystic ovary syndrome and bipolar disorder: The endophenotype hypothesis

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Center for Neuroscience in Women's Health, 401 Quarry Road, Stanford, CA 94305, United States. bowenj@stanford.
Medical Hypotheses (Impact Factor: 1.15). 07/2009; 73(6):996-1004. DOI: 10.1016/j.mehy.2008.12.056
Source: PubMed

ABSTRACT Polycystic Ovary Syndrome (PCOS) is a polygenic disorder caused by the interaction of susceptible genomic polymorphisms with environmental factors. PCOS, characterized by hyperandrogenism and menstrual abnormalities, has a higher prevalence in women with Bipolar Disorder (BD). Theories explaining this high prevalence have included the effect of PCOS itself or the effect of drugs such as Valproate, which may cause PCOS either directly or indirectly. Incidentally, metabolic abnormalities are observed in both bipolar and PCOS patients. Endophenotypes such as insulin resistance, obesity, and hyperglycemia are common among BD and PCOS patients, suggesting some degree of pathophysiological overlap. Since both BD and PCOS are complex polygenetic diseases, the endophenotype overlap may be the result of common genetic markers. This paper postulates that shared clinical endophenotypes between PCOS and BD indicate common pathophysiological platforms and will review these for the potential of genetic overlap between the two disorders.

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    ABSTRACT: The insulin receptor substrate gene-1 (IRS-1) polymorphisms have been incriminated in insulin resistance; a frequent finding in polycystic ovary syndrome (PCOS). The commonest polymorphism associated with insulin resistance is gly972arg. Another polymorphism is the ala512 pro. This study aimed at elucidating the association of the gly972arg and the ala512pro polymorphisms of the IRS-1 gene with PCOS in Egyptian females. We employed a case–control study. The two polymorphisms were analyzed in 62 PCOS Egyptian female patients and 43 age-matched controls using a PCR-RFLP strategy. Fasting insulin, plasma glucose, and testosterone were analyzed by routine analytical methods and calculation of the homeostasis model assessment (HOMA) and the quantitative sensitivity check index (QUICK I) were done based on the results of the fasting insulin and glucose. It was found that 6.5% of the PCOS cases showed the Gly972Arg genotype. The Gly972Arg in IRS-1 polymorphism was not associated with PCOS (p = 0.556). A positive association was found between the gly972arg and the HOMA quartiles (p = 0.01). PCOS patients with the 972gly/arg genotype had higher glucose (p = 0.040), insulin (0.000), HOMA (0.000), and lower QUICK I (0.023) than PCOS with wild 972arg/arg genotype. Patients of PCOS with the 972gly/arg genotype were more insulin resistant than other patients with the wild genotype. Neither the patients nor the controls showed the mutant ala512pro genotype. Screening for gly972arg genotype can be based on the HOMA quartile ranking. The ala512pro genotype was not found in studied Egyptian women.
    Comparative Clinical Pathology 12/2011; 21(6). DOI:10.1007/s00580-011-1350-0
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    ABSTRACT: Many precise aspects of the etiology and pathophysiology of mental disorders are still unknown. Susceptibility to these disorders depends in part on variability in the genome sequence among individuals. The genotype, a given environment, a specific epigenetic profile and stochastic factors affect the phenotype, which includes body structures, physiological processes, and behavior. Since the access to the Central Nervous System is generally difficult and in most cases there are still no biological tests that necessarily contribute to diagnosis, psychiatric phenotypes are usually limited to clinical symptoms and functioning. Therefore, researchers are currently seeking alternatives to facilitate the identification of genetic risk factors. One strategy is to identify measurable biological, cognitive, and behavioral markers, intermediate phenotypes, or endophenotypes, which in the best case may be simpler than general psychiatric diagnoses, ideally with a precise biological meaning and a more direct relationship with the action of specific genes. Endophenotypes have been very useful in other fields of medicine. Currently, there are several proposed criteria and specifications for endophenotypes. Examples of possible types of endophenotypes or biomarkers, as well as treatment response phenotypes in some psychiatric disorders will be discussed in this review.
    Salud Mental 06/2013; 36(3):181-188. · 0.42 Impact Factor
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    ABSTRACT: Objective: Temperament originates in the brain structure, and individual differences are attributable to neural and physiological function differences. It has been suggested that temperament is associated with metabolic syndrome (MetS) markers, which may be partly mediated by lifestyle and socioeconomic status. Therefore, we aim to compare MetS prevalence between different affective temperamental profiles for each season in bipolar patients. Methods: Twenty-six bipolar type-I patients of a specialized outpatient mood disorder unit were evaluated for MetS according to new definition proposed by the International Diabetes Federation in the four seasons of a year. Temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego - autoquestionnaire version (TEMPS-A). Results: The proportions of MetS were 19.2, 23.1, 34.6, and 38.5% in the summer, fall, spring, and winter, respectively. Only depressive temperament scores were higher (p = 0.002) during the winter in patients with MetS. Conclusion: These data suggest that depressive temperament profiles may predispose an individual to the development of MetS in the winter.
    Revista Brasileira de Psiquiatria 04/2013; 35(2):131-5. DOI:10.1590/1516-4446-2011-0746 · 1.64 Impact Factor


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May 16, 2014