A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder

<p>Abstract</p> <p>Background</p> <p>Lithium is an effective treatment for Bipolar Disorder (BD) and significantly reduces suicide risk, though the molecular basis of lithium's effectiveness is not well understood. We seek to improve our understanding of this effectiveness by posing hypotheses based on new experimental data as well as published data, testing these hypotheses in silico, and posing new hypotheses for validation in future studies. We initially hypothesized a gene-by-environment interaction where lithium, acting as an environmental influence, impacts signal transduction pathways leading to differential expression of genes important in the etiology of BD mania.</p> <p>Results</p> <p>Using microarray and rt-QPCR assays, we identified candidate genes that are differentially expressed with lithium treatment. We used a systems biology approach to identify interactions among these candidate genes and develop a network of genes that interact with the differentially expressed candidates. Notably, we also identified cocaine as having a potential influence on the network, consistent with the observed high rate of comorbidity for BD and cocaine abuse. The resulting network represents a novel hypothesis on how multiple genetic influences on bipolar disorder are impacted by both lithium treatment and cocaine use. Testing this network for association with BD and related phenotypes, we find that it is significantly over-represented for genes that participate in signal transduction, consistent with our hypothesized-gene-by environment interaction. In addition, it models related pharmacogenomic, psychiatric, and chemical dependence phenotypes.</p> <p>Conclusions</p> <p>We offer a network model of gene-by-environment interaction associated with lithium's effectiveness in treating BD mania, as well as the observed high rate of comorbidity of BD and cocaine abuse. We identified drug targets within this network that represent immediate candidates for therapeutic drug testing. Posing novel hypotheses for validation in future work, we prioritized SNPs near genes in the network based on functional annotation. We also developed a "concept signature" for the genes in the network and identified additional candidate genes that may influence the system because they are significantly associated with the signature.</p

The Process of Becoming a Sexual Black Woman: A Grounded Theory Study

Black females in the United States disproportionately suffer from STDs, including HIV. Understanding the sociocultural conditions that affect their risk is essential to developing effective and culturally relevant prevention programs. METHODS: In 2016-2017 in Madison, Wisconsin, 20 black females aged 19-62 completed interviews that explored the sociocultural conditions associated with sexual development and STD/HIV risk. Interviews were guided by grounded theory; open, axial and selective coding and constant comparative analysis were used to identify developmental phases and relevant sociocultural conditions. RESULTS: Three phases of becoming a sexual black woman were identified: Girl, when participants reported beginning to understand their sexuality; Grown, marking a transition to adulthood, when participants began to feel more self-sufficient yet still grappled with their emerging sexuality; and Woman, when participants developed a strong sense of self and took ownership of their bodies. Two sociocultural conditions affected progression through these phases: stereotype messaging and protection (both self-protection and protecting others). Negative life events (e.g., sexual trauma) and early sexualization reportedly affected sexual development, and STD experience influenced self-perceptions of sexuality and sexual behavior, often leading to self-protective behaviors. Older participants reported strategies to protect young black females from negative sexual experiences. CONCLUSION: Interventions at multiple levels of the social ecology throughout the life course may help reduce STD/HIV risk among black women in the United States. Future research should include examination of the experiences of black females younger than 18 and evaluation of the protective strategies employed by older black females