PT - JOURNAL ARTICLE AU - Stephen V. Gliske TI - A new theory of gender dysphoria incorporating the distress, social behavioral, and body-ownership networks AID - 10.1523/ENEURO.0183-19.2019 DP - 2019 Dec 02 TA - eneuro PG - ENEURO.0183-19.2019 4099 - http://www.eneuro.org/content/early/2019/12/02/ENEURO.0183-19.2019.short 4100 - http://www.eneuro.org/content/early/2019/12/02/ENEURO.0183-19.2019.full AB - When postmortem studies related to transgender individuals were first published, little was known about the function of the various identified nuclei. Now, over two decades later, significant progress has been made associating function with specific brain regions, as well as in identifying networks associated with groups of behaviors. However, much of this progress has not been integrated into the general conceptualization of gender dysphoria in humans. We hypothesize that in individuals with gender dysphoria, the aspects of chronic distress, gender atypical behavior, and incongruence between perception of gender identity and external primary sex characteristics are all directly related to functional differences in associated brain networks. We evaluated previously published neuroscience data related to these aspects and the associated functional networks, along with other relevant information. We find that the brain networks that give individuals their ownership of body parts, that influence gender typical behavior, and that are involved in chronic distress are different in individuals with and without gender dysphoria, leading to a new theory—that gender dysphoria is a sensory perception condition, an alteration in sense of gender influenced by the reflexive behavioral responses associated with each of these networks. This theory builds upon previous work that supports the relevance of the body ownership network and that questions the relevance of cerebral sexual dimorphism in regards to gender dysphoria. However, our theory uses a hierarchical executive function model to incorporate multiple reflexive factors (body ownership, gender (a)typical behavior, and chronic distress) with the cognitive, reflective process of gender identity.Significance Our new model highlights connections between multiple dimensions of gender dysphoria and behavioral neuroscience data, explaining the experience of gender dysphoria using relevant neural substrates and networks. This biology/symptom-based approach provides an updated theory of gender dysphoria, fostering new hypotheses to advance basic understanding of the condition. This theory may lead to therapies which directly address the underlying biology rather than just the subjective symptoms. Such therapies may also be more effective at reducing comorbid conditions (e.g., depression or suicide), given the possibility of a common, underlying biological cause.