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No description available.

No description available.

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Early exposure to abuse, neglect, and household dysfunction is linked to long-term detrimental effects on mental and physical health. In the mid-1990s, Kaiser Permanente and the CDC surveyed adults in the community and found a strong and cumulative relationship between the degree of exposure to adverse childhood experiences (ACEs) and risk factors for leading causes of death in adulthood. At present, most research using ACE survey methodology examines community-based adult samples, and populations who experience the greatest number of adversities are largely ignored. An additional factor indicative of household dysfunction that has not been thoroughly explored in the context of ACE survey methodology is foster care placement. Further, little is understood regarding the impact of out-of-home placement on persons with disproportionately high ACE scores and subsequent difficulties with sexual and aggressive behavior. Studies investigating differential risk factors and outcomes could inform prevention, policy, and treatment. As such, the current study seeks to investigate the impact of childhood adversity and out-of- home placement on the onset of aggression and problem sexual behavior using ACE survey methodology in a sample of juveniles receiving residential treatment for sexual misconduct. Data for this study were collected from archival records of children and adolescents who have received sexual offender treatment at a treatment center for male youth (N=120; 88% Caucasian) for periods ranging from one month to more than four years (M=13.68 months, SD=10.96). These participants have a mean age of 14.63 years (SD=1.56; Range: 11 to 17 years) at the time of first admission into the facility. As expected, the adolescents in this study have experienced higher rates of adverse childhood experiences than the general adult population and male adolescents involved in the juvenile justice system previously reported in the literature. Only 2.5% of the current sample experienced no ACEs and 74.2% faced four or more adversities, which is considered to be high risk in the literature. Participants had a mean age at first out-of-home placement of 9 years (SD=5.21) and had an average of 3.7 out-of-home placements at time of admission to the facility. The association of childhood adversities, the number of non-psychiatric out-of-home placements, and age at first out-of-home placement with earlier onset of aggressive and sexual offending behaviors will be investigated using Cox proportional hazard analyses. Behavioral outcomes (e.g., onset of sexual and aggressive behavior problems; substance use; arrest history; and, treatment length) between individuals who were placed in family members’ homes versus those placed in non-familial foster care will also be explored. Implications for prevention and environmental responsiveness will be addressed.

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Sex steroids are important hormones produced in the body to regulate an individual's physiology and behavior in preparation for reproduction. Aromatase (Cyp19a1) is the steroidogenic enzyme that converts aromatizable androgens into bioactive estrogens, and hence is in a pivotal position to mediate reproductive processes and sexual behavior. In mice, evidence from whole body aromatase knockout and estrogen receptor knockout lines has revealed the critical roles of estrogen signalling in ovarian development, gonadotropin signalling, ovulation, and sexual behavior. While the ovaries have high aromatase activity levels and are a major source of circulating estrogens in the female body, they can also be locally produced in tissues via tissue-specific aromatase expression. Of particular interest, the importance of brain-derived estrogens for reproductive processes and sexual behavior is still under study. Teleosts are an amenable model system for understanding the role of brain-derived estrogens in reproduction as they have two aromatase paralogs, cyp19a1a and cyp19a1b, that are highly expressed in the ovary and brain, respectively. In this thesis, I sought to identify the importance of brain-derived estrogens for sexual behaviors and reproductive health in zebrafish using cyp19a1⁻ᐟ⁻ mutant lines and a transgenic cyp19a1b-GFP line. In dyadic sexual behavior assays, female cyp19a1b⁻ᐟ⁻ mutants took 4.1 times longer to initiate spawning behavior with wildtype (WT) males compared to WT females. This suggested a potential impairment in mate identification and assessment in the female cyp19a1b⁻ᐟ⁻ mutants. The importance of the cyp19a1 paralogs for early larval development was revealed by 4 times higher progeny mortality from cyp19a1b⁻ᐟ⁻ mutant female and cyp19a1a⁻ᐟ⁻;cyp19a1b⁻ᐟ⁻ mutant male pairings compared to WT pairings. Gene expression analyses identified significantly lower levels of important neuroendocrine genes including the estrogen receptors and the nonapeptides, arginine vasopressin (avp) and oxytocin, in the telencephalon and hypothalamus of cyp19a1b⁻ᐟ⁻ mutant female compared to WT female brains. I performed acute intraperitoneal injections of Avp and Oxytocin, as well as mixtures of their respective receptor antagonists, in cyp19a1b⁻ᐟ⁻ mutant females to determine if the behavioral impairments could be rescued in adult fish. Arginine vasopressin was found to uniquely recover the delayed oviposition in female cyp19a1b⁻ᐟ⁻ mutants. Immunohistochemistry experiments using the transgenic cyp19a1b-GFP zebrafish line with a zebrafish-validated Avp antibody revealed a close neuroanatomical proximity and contact points between radial glial cell Cyp19a1b-expressing fibres and Avp-immunopositive neurons in preoptic areas. These findings suggest that brain-derived estrogens, via Cyp19a1b activity, might affect female sexual behavior by diffusing to nearby neurons to regulate Avp signalling levels in preoptic areas. Together, these findings establish the importance of cyp19a1b for female zebrafish sexual behavior and identify a positive link between Cyp19a1b and Avp. Future study can help to characterize the estrogen-dependent pathways involved in regulating Avp signalling in the female brain and the extent of evolutionary conservation of this regulation pathway for female sexual behavior across vertebrates.