Biological Sex on the Therapeutic Effectiveness of Various Treatments of Major Depressive Disorder

Abstract

Major Depressive Disorder (MDD) is one of the most prevalent mood disorders in the world. Anatomical differences between male, female, heterosexual, and homosexual individuals such as the hypothalamus and hippocampus cause for larger prevalence of the disorder in females and homosexuals. The purpose of this study was to elucidate the effect of biological sex and sexual orientation on different treatments of MDD. The model organism, Drosophila melanogaster, was used due to its human gene homologs of the 5HT1A, fru, and dsx genes. The 5HT1A gene mutation decreases serotonin which is linked to MDD. The fru gene mutation was used to model homosexuality and the dsx gene mutation was used to model transgender identities. Double and triple cross mutants were made through careful genetic crosses to create a fru, dsx, and 5-HT1A mutant. The hypothesis was, if males, females, fru mutants, dsx mutants, 5HT1A mutants, and combinations of those received different treatments for MDD, then their effectiveness will vary based on the genetic profile of the mutants. The popular antidepressants fluoxetine, sertraline, and lithium chloride were tested as treatments. Behavioral and biochemical tests tested symptoms of MDD such as decreased appetite, decreased activity, decreased serotonin levels. The hypothesis was supported, results showing that variable groups experienced different responses to different treatments. Results demonstrated that lithium chloride was most effective in males, fluoxetine most effective in females, and sertraline most effective in homosexuals. Therefore, drug treatments differ amongst individuals of differing sex and sexual orientation and should be explored in future experiments.