New biomarkers are needed to better distinguish between major depressive disorder (MDD) and bipolar disorder (BD). With the goal of discovering at least 1 of those biomarkers, the researchers of a study recently published in the Nordic Journal of Psychiatry examined the effect of neuropeptides orexin-A (ORX-A), ghrelin (GRL), and neuropeptide Y (NPY) on hypersomnia and hyperphagia. Both symptoms are more common in people with BD.

The researchers recruited 24 patients with BD and 45 patients with MDD who were admitted to the Gazi University School of Medicine Psychiatry Outpatient Clinic between January 2019 and January 2020 and compared them with 36 patients without either BD or MDD who comprised the control group. All patients were aged between 18 and 65 years.

The main outcome analyzed was NPY level. Exclusion criteria included major neurologic diseases, chronic illnesses, and other conditions that affected sleep and appetite. Participants completed multiple psychological assessments and provided blood samples for analysis.

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The researchers found people with BD scored higher on the Emotional Eating subscale than people with MDD. A total of 9 patients with BP experienced daytime sleepiness vs 6 in the MDD group.

Looking at neuropeptides, the researchers found that people with BD had significantly lower NPY levels than people with MDD. Patients in both the BD and MDD groups had significantly lower levels of all neuropeptides studied compared with the control group. They believe stress response is at least partly associated with this finding. The researchers evaluated patients with MDD, and low NPY levels were exhibited regardless of antidepressant drug use.

Although the researchers state that antidepressant treatment may have influenced the study results, they could not withdraw treatment because most had moderate to severe depression with suicidal thoughts. The researchers were also not aware of the relationship between neuropeptide blood levels and central neuropeptide activities. Taking measurements only in the morning may have limited the assessment of biomarker variation.

Although this small study indicates a relationship between NPY and BD and MDD, “longitudinal studies are needed to show the relationship between symptom severity by monitoring patients before and after treatment,” the researchers noted.


Ünler M, Ertek IE, Afandiyeva N, Kavutçu M, Yüksel N. The role of neuropeptide Y, orexin-A, and ghrelin in differentiating unipolar and bipolar depression: a preliminary study, Nord J Psychiatry. 2022;76(3):162-169. doi:10.1080/08039488.2022.2048887

This article originally appeared on Psychiatry Advisor