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Pineal Gland Volume, Sleep Quality, and Psychiatric Disorders: A Systematic Review and Meta-Analysis
Sophie Bolwig1, Kristian H R Jensen1,2
1Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.
Introduction:
Disturbances in sleep and circadian rhythms are features of several psychiatric disorders. The pineal gland regulates these rhythms via melatonin, with pineal gland volume (PGV) serving as a structural proxy. We conducted a meta-analysis to synthesize evidence on differences in PGV between patients with psychiatric disorders and healthy controls and the association between PGV and sleep outcomes.
Method:
Systematic searches of PubMed, Embase, Scopus, and Web of Science were performed (August 2025). Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses using restricted maximum likelihood (REML) estimation were conducted for correlation and group-comparison outcomes. Subgroup analyses were performed by diagnostic category.
Results:
Fourteen studies compared PGV between psychiatric patients and healthy controls, and seven studies examined associations between PGV and sleep outcomes. PGV was significantly lower in patients with psychiatric disorders compared with healthy controls (1055 patients, 712 controls, Hedges' g = -0.54 [-0.68, -0.41], p < 0.001). Reductions were most pronounced in schizophrenia spectrum disorders (g = -0.63 [-0.81, -0.46], p < 0.001), and were approximately twice the magnitude observed in mood disorders (g = -0.33 [-0.59, -0.06], p = 0.027). The pooled association between larger PGV and better sleep was weak and nonsignificant (47 patients, 713 controls, Zr = 0.18 [-0.08, 0.43], p = 0.136), with substantial heterogeneity (I2 = 82%), likely reflecting variability in sleep assessment and study populations.
Conclusion:
Across psychiatric disorders, PGV is reduced relative to healthy controls, with the largest and most consistent reductions observed in schizophrenia spectrum disorders. In contrast, evidence for an association between PGV and sleep outcomes remains inconclusive. These findings suggest that reduced PGV may represent a trait-like structural alteration linked to psychiatric illness, particularly schizophrenia spectrum disorders, rather than a direct marker of sleep disturbance.
Trial Registration:
PROSPERO: CRD420251138624.
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