Are the arginine vasopressin V1a receptor microsatellites related to hypersexuality in children with a prepubertal and early adolescent bipolar disorder phenotype?

Objective: To examine family-based transmission of the number of 5' flanking arginine vasopressin V1a receptor (AVPR1A) microsatellites, which include [(GATA)(14)] and complex [(CT)(4)-TT-(CT)(8)-(GT)(24)] repeats, in probands with a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP). Preferential transmission of the number of AVPR1A microsatellite repeats to hypersexual and uninhibited people-seeking probands was hypothesized, based on reports from preclinical work in the literature.

Methods: Probands were 83 participants in an ongoing controlled study of PEA-BP. The PEA-BP phenotype was defined by DSM-IV mania with at least one of the cardinal symptoms of mania (elation and/or grandiosity) to avoid diagnosing mania only by symptoms that overlapped with those for attention-deficit hyperactivity disorder (ADHD). Comprehensive assessment of the probands included separate Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) interviews of parents about their children and of children about themselves. Hypersexuality and uninhibited people-seeking were assessed from the corresponding WASH-U-KSADS items. Microsatellite genotyping of the AVPR1A repeats was conducted using fluorescently labeled primers and detected by laser-induced fluorescence. Alleles were determined with the assistance of semi-automated allele-calling software. There were 32 complete, biological trios (28 informative families) for the GATA repeat and 34 complete, biological trios (30 informative families) for the complex repeat. Data were analyzed using case-control and family-based association methods.

Results: Preferential transmission of AVPR1A GATA or complex repeats was not significant for hypersexuality or uninhibited people-seeking, using the transmission disequilibrium test. Similarly, case-control analyses found no significant associations between hypersexuality or uninhibited people-seeking and the number of AVPR1A GATA or complex repeats. For p < 0.05, there was about 80% power to detect odds ratios of 5.0 and 4.0 (in the family-based analyses) and 3.5 and 2.6 (in the case-control analyses), for allele frequencies of 0.1 and 0.5, respectively.

Conclusion: Preferential transmission of AVPR1A to hypersexual or uninhibited people-seeking probands was not supported.