Pineal gland and schizophrenia: A systematic review and meta-analysis.

Melatonin (MLT), the main hormone of the pineal gland (PG), is assumed to support initiation and maintenance of sleep, and a stable sleep-wake cycle, exerting antioxidative and neuroprotective actions. Evidence demonstrates that sleep and circadian rhythm abnormalities are very common in schizophrenia patients. Some imaging studies suggest structural abnormalities of the PG in these patients as well. We aimed to critically appraise the literature on PG imaging and melatonin secretion in schizophrenia patients, in comparison to matched healthy controls, and to review placebo-controlled trials of add-on exogenous MLT treatment in schizophrenia patients. In this systematic review, twenty-nine studies were included. Meta-analytical evaluation of data was possible only for MLT secretion finding that midnight plasma levels were significantly reduced in individuals with schizophrenia as compared to healthy controls (Hedge`s g = 1.32, p < 0.01). Imaging studies demonstrated greater prevalence of enlarged calcifications (>1 cm) of the PG (2 out of 2 computed tomography studies) and smaller PG volume (2 out of 3 magnetic resonance studies) compared with healthy controls. Anatomic and functional abnormalities of the PG were not associated with duration of illness or with treatment factors, maybe suggesting them to be primary characteristics of the disease and genetically based. Add-on MLT treatment leads to a modest improvement of objective and subjective sleep quality, of metabolic adverse effects of antipsychotics, and of tardive dyskinesia symptoms in schizophrenia patients. It remains to be established whether MLT treatment in prodromal phases of the disease could prevent neurostructural abnormalities.