Are Circadian Disturbances a Core Pathophysiological Component of Schizophrenia?

Abstract

<jats:p> Schizophrenia is a multifactorial disorder caused by a combination of genetic variations and exposure to environmental insults. Sleep and circadian rhythm disturbances are a prominent and ubiquitous feature of many psychiatric disorders, including schizophrenia. There is growing interest in uncovering the mechanistic link between schizophrenia and circadian rhythms, which may directly affect disorder outcomes. In this review, we explore the interaction between schizophrenia and circadian rhythms from 2 complementary angles. First, we review evidence that sleep and circadian rhythm disturbances constitute a fundamental component of schizophrenia, as supported by both human studies and animal models with genetic mutations related to schizophrenia. Second, we discuss the idea that circadian rhythm disruption interacts with existing risk factors for schizophrenia to promote schizophrenia-relevant behavioral and neurobiological abnormalities. Understanding the mechanistic link between schizophrenia and circadian rhythms will have implications for mitigating risk to the disorder and informing the development of circadian-based therapies. </jats:p>

Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues

“…Similar to the comorbidity of sleep disruption, circadian misalignment, and psychotic and cognitive symptoms in patients [ 49 , 71 , 107 – 110 ], we found that circadian disruption and recognition memory impairment co-occurred in GluA1-deficient mice. Recent patient studies suggest that the extent of sleep and circadian disruption may precede the onset, as well as predict the severity, of psychotic and cognitive symptoms in clinical and healthy populations [ 108 – 112 ]. This raises the possibility that ameliorating sleep and circadian disruption may improve various symptoms of schizophrenia [ 113 ].…”

Chronotype, circadian rhythm, and psychiatric disorders: Recent evidence and potential mechanisms

“…Schizophrenia is a multifactorial disorder defined by abnormalities in one or more of five domains, namely delusions, hallucinations, disorganized thinking or speech, grossly disorganized, or abnormal motor behavior, and negative symptoms ( Arlington and Publishing, 2013 ). Circadian rhythm disruption may be a risk factor for schizophrenia by affecting the disorder onset and severity of symptoms ( Delorme et al, 2020 ). Some previous reviews have suggested little evidence linking chronotype and schizophrenia ( Ahn et al, 2008 ; Kivela et al, 2018 ; Taylor and Hasler, 2018 ).…”

Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner

“…We previously reported that circadian disruption could act as another environmental risk factor for schizophrenia ( Bhardwaj et al, 2015 ; Delorme et al, 2020 ). Circadian disruptions are disturbances of circadian rhythms, which are near 24 h endogenous rhythms governing metabolism, body temperature, hormone secretion, and many more physiological variables and systems ( Bollinger and Schibler, 2014 ).…”