Mice study sheds light on the mechanisms underlying sex differences in psychiatric conditions

Conditions such as Tourette syndrome (TS), schizophrenia, and Attention-Deficit/Hyperactivity Disorder (ADHD) have sex differences with unknown mechanisms. These sex-specific mechanisms may inform the development of more effective treatments. In a new JNeurosci paper, Meghan Van Zandt and Christopher Pittenger used mice to shed light on the mechanisms underlying sex differences in these psychiatric conditions. 

Prior to this study, the researchers knew that these neurological disorders are characterized by altered dopamine signaling in the same brain network. Additionally, human genetic studies implicate a natural compound called histamine in dysregulating dopamine signaling to potentially underlie at least TS. Thus, Van Zandt and Pittenger examined sex differences in how histamine interacts with dopamine signaling in this brain network. 

By manipulating histamine signaling in mice, the researchers discovered that histamine had opposite effects on dopamine levels in males and females: Histamine decreased dopamine in males and increased dopamine in females. In females, this effect was influenced by the estrous cycle. The researchers also found sex differences in the mechanisms through which histamine regulated dopamine levels. 

According to the authors, this study may inform treatment development, suggesting that sex-specific treatments targeting different histamine receptors may effectively correct dopamine signaling in TS, schizophrenia, and ADHD.