Fig. 2. Orexin action in phenotypes relevant to mental health.

This illustration depicts orexins actions in phenotypes relevant to mental health, as discussed in the preclinical portion of this review. Activity of orexin cells or orexin signaling is depicted on the x axis is labeled (increasing from left to right) and the expression of each behavioral phenotype is depicted on the y axis (increasing from bottom to top). Most behavioral phenotypes are more pronounced with higher orexin action (eg higher arousal, appetite, addictive-like behaviors, anxiety-like behaviors, and fear), whereas some behavioral phenotypes have a curvilinear relationship with orexin action (cognitive function, depressive-like behavior), and one behavioral phenotype shows a negative relationship with orexin action (pain). These relationships are all based on evidence from current literature, but it is possible that further experiments could change the way these relationships are portrayed. For example, perhaps some of these relationships are not linear, and if tested when orexins were at much lower or higher levels, would demonstrate curvilinear relationships. These differing relationships between orexin action and phenotypes relevant to mental health may be reflective of differential orexin receptor expression/function and/or brain circuitry involved. All of these phenotypes can be observed in humans and would then contribute to a clinical diagnosis of stress-related mental illnesses such as Major Depressive Disorder and Anxiety Disorders.