Schizophrenia as a possible dysfunction of the suprachiasmatic nucleus

Abstract

Psychosis and dreaming have many similarities, including delusions, hallucinations, bizarre thinking and perceptual distortions. This clinical observation has lead us to hypothesize that the suprachiasmatic nucleus (SCN), a hypothalamic center regulating sleep and wakefulness, is involved in the pathogenesis of schizophrenia. Schizophrenic patients have certain sleep architecture characteristics, and distinctive biological markers suggesting abnormity of the SCN, including irregular pattern of melatonin secretion, abnormal actigraphyic studies, D1-dopamine receptors involvement in the process of entraining the SCN and vulnerability to psychotic exacerbation due to jet lag. In addition, SCN lesions in rodents are associated with pathologic day-time sleep pattern, very similar to the sleeping pattern in patients with schizophrenia. We introduce the concept of REM sleep abnormity as a possible etiological factor in development of psychosis. We hypothesize that the proposed dysfunction of the SCN may contribute to schizophrenia through several different, not necessarily mutually exclusive, mechanisms, including "REM sleep (dream) rebound" phenomenon, damaged neuronal pathways connecting SCN to the brain regions affected by schizophrenia, and the SCN dysfunction induced dysregulation of gene expression in different parts of the body, including the brain. Moreover, the influenza virus, which has been implicated in the etiology of schizophrenia, is capable of resetting the SCN, the ultimate processor of light signals, suggesting the explanation for chronological variability of incidence of schizophrenia. Future investigation of the proposed mechanisms will provide the ultimate test of our hypothesis that lesions of the suprachiasmatic nucleus play an important role in the etiology of schizophrenia.