Longitudinal Associations of Serum Orexin-A With Physical Activity and Sleep in Schizophrenia: A Preliminary Study

Orexin-A (OXA) is a neuropeptide that regulates arousal, behavior, and sleep-wake rhythms. While altered OXA levels have been observed in schizophrenia, longitudinal data are limited. This study examined the relationship between changes in serum OXA levels and physical activity, sleep, and psychiatric symptoms in patients with chronic schizophrenia.

Seventeen long-term inpatients with schizophrenia underwent assessments at baseline (T1) and again after 6 months (T2). Serum OXA levels, sleep and activity parameters derived from actigraphy, and psychiatric symptoms (evaluated with the Positive and Negative Syndrome Scale [PANSS]) were collected at both time points. Spearman's correlations were used to analyze associations between the T2-T1 change in serum OXA (ΔOXA) and the corresponding Δ values of each sleep, activity, and PANSS measure, to explore longitudinal associations among these variables.

ΔOXA was positively correlated with Δ step count (ρ = 0.53, p = 0.03) and negatively correlated with Δ time in bed (ρ = -0.50, p = 0.04). No significant associations were found with PANSS scores, other sleep parameters, pharmacotherapy, or body mass index.

In this preliminary longitudinal sample, increases in serum OXA were linked to greater daytime activity and reduced time in bed, suggesting that orexinergic signaling may modulate behavioral regulation in schizophrenia beyond its established role in sleep-wake control. Larger studies, with adjustment for multiple comparisons, are warranted to evaluate OXA as a candidate biomarker or therapeutic target.