Evaluating the links between schizophrenia and sleep and circadian rhythm disruption

Abstract

Sleep and circadian rhythm disruption (SCRD) and schizophrenia are often co-morbid. Here, we propose that the co-morbidity of these disorders stems from the involvement of common brain mechanisms. We summarise recent clinical evidence that supports this hypothesis, including the observation that the treatment of SCRD leads to improvements in both the sleep quality and psychiatric symptoms of schizophrenia patients. Moreover, many SCRD-associated pathologies, such as impaired cognitive performance, are routinely observed in schizophrenia. We suggest that these associations can be explored at a mechanistic level by using animal models. Specifically, we predict that SCRD should be observed in schizophrenia-relevant mouse models. There is a rapidly accumulating body of evidence which supports this prediction, as summarised in this review. In light of these emerging data, we highlight other models which warrant investigation, and address the potential challenges associated with modelling schizophrenia and SCRD in rodents. Our view is that an understanding of the mechanistic overlap between SCRD and schizophrenia will ultimately lead to novel treatment approaches, which will not only ameliorate SCRD in schizophrenia patients, but also will improve their broader health problems and overall quality of life.

Non-dipping nocturnal blood pressure and psychosis parameters in Parkinson disease

“…A possible mechanism might be related to dopamine which is a common neurotransmitter related to psychosis and circadian rhythms [47] and of course to PD pathology [48] and could therefore be a plausible link between the three entities. The role of dopamine in psychosis and PD has been well studied [48][49][50] but is also gaining increasing awareness within the field of circadian rhythm disruption.…”

“…The role of dopamine in psychosis and PD has been well studied [48][49][50] but is also gaining increasing awareness within the field of circadian rhythm disruption. [47] A link between schizophrenia and sleep and circadian rhythm disruptions (SCRD) via common neurotransmitters such as dopamine has already been proposed. [43] An explanation for this would be that dopamine mediates the relationship between psychosis and Cholecystokinin (CCK), a peptide hormone, which possibly plays a role in sleep regulation [47].…”

“…[47] A link between schizophrenia and sleep and circadian rhythm disruptions (SCRD) via common neurotransmitters such as dopamine has already been proposed. [43] An explanation for this would be that dopamine mediates the relationship between psychosis and Cholecystokinin (CCK), a peptide hormone, which possibly plays a role in sleep regulation [47]. CCK furthermore activates orexin, a neurotransmitter that has an effect on wakefulness.…”

“…CCK furthermore activates orexin, a neurotransmitter that has an effect on wakefulness. [47] It however remains unclear if a similar association exists within PD. The reasons for a causation between a pathological loss of the nocturnal BP fall and psychological symptoms in PD warrants further evaluation.…”

Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy

“…Increased levels of PER1, a negative regulator of circadian rhythm, might lead to decreased transcriptional activity of the BMAL1-CLOCK heterodimer, thereby slowing down circadian oscillations. GSK3-β also plays a role in the post-translational regulation of molecular clock components, targeting BMAL1 for degradation at the end of the circadian cycle and stabilizing Rev-ErbA, a negative regulator of BMAL1 transcription (Pritchett et al, 2012). Model B suggests that circadian rhythm deregulation in collagen VI myopathies is an independent event acting as a secondary modifier of disease severity.…”