Elevated Plasma Orexin A Levels in a Subgroup of Patients with Schizophrenia Associated with Fewer Negative and Disorganized Symptoms

Background: Orexin A and B, a pair of hypothalamic neuropeptides also named hypocretin 1 and 2, play a role in the regulation of arousal, appetite, reward, attention, and cognition. Animal studies showed that antipsychotics can activate orexin neurons in a manner correlated with their weight gain liability. However, little is known about the role of orexin in patients with schizophrenia. This study aimed to investigate the correlation of plasma orexin level with clinical symptom profile, neurocognitive functioning and weight gain liability of the antipsychotics taken in patients with schizophrenia.

Methods: We measured plasma levels of orexin A in 127 patients with schizophrenia and 34 healthy controls by radioimmunoassay. In patients, we assessed clinical symptoms on the Positive and Negative Syndrome Scale and executive function by the Wisconsin Card Sorting test (WCST), and examined their associations with plasma orexin A level.

Results: Patients with schizophrenia had a significantly higher mean orexin A level than healthy controls (60.7±37.9 vs. 38.8±15.5pg/ml). Patients were divided into two subgroups based on their orexin A levels that were distributed in two clusters divided by 80pg/ml. Patients in the high-orexin subgroup had significantly fewer negative and disorganized symptoms, and tended to have fewer perseverative errors, more failure to maintain set yet comparable category achieved on the WCST than the normal-orexin subgroup. There was no significant difference in orexin A levels among patients taking antipsychotics with different weight gain liabilities.

Conclusion: Higher level of orexin A seems to be related to favorable clinical symptom profiles of schizophrenia, but the causal relationship needs further clarification.