Integrating sleep-related breathing disorders and epigenetics into the genetic landscape of sleep disturbances in psychotic disorders
Year: 2025
Type: article
Abstract: Recent advances in psychiatric genetics have underscored the role of polygenic scores (PGSs) in shaping sleep phenotypes in individuals with psychotic disorders.The study by Cederlöf et al. (2025) makes an important contribution by leveraging genome-wide association data to disentangle the complex interplay between genetic liability for insomnia, sleep duration, chronotype, and schizophrenia.Their findings offer compelling insights into how distinct genetic risks manifest in both subjective experiences and cognitive performance.Yet, the genetic landscape of sleep in psychosis is even more nuanced than the current framework suggests.Several biologically and clinically relevant dimensions-namely sleep-related breathing disorders (SRBDs), the COMISA phenotype (comorbid insomnia and sleep apnea), and the dynamic influence of epigenetic regulation-warrant deeper integration into this conversation.Obstructive sleep apnea (OSA), the most prevalent SRBD, is significantly underrecognized in psychotic populations despite high clinical relevance.Individuals with schizophrenia are at increased risk for OSA due to overlapping predisposing factors, including antipsychotic-induced weight gain, sedative use, metabolic syndrome, and lifestyle-related variables (Annamalai et al., 2015;Giles et al., 2022).The consequences of untreated OSA-fragmented sleep, intermittent hypoxia, and excessive daytime sleepiness-may mimic, mask, or exacerbate core psychiatric symptoms, such as cognitive impairment and mood instability (Knechtle et al., 2019).Importantly, studies have shown that treatment with continuous positive airway pressure (CPAP) improves psychiatric outcomes, including mood and attention, in individuals with psychotic disorders (Giles et al., 2022).Despite this, genetic models of sleep in psychosis rarely incorporate SRBDs or the emerging polygenic scores for OSA recently developed from population-based cohorts (Liu et al., 2024).Their absence may obscure an important dimension of biological vulnerability.The intersection of insomnia and OSA-referred to as COMISA-represents a distinct and consequential phenotype.Epidemiological data suggest that COMISA is more prevalent than either disorder alone and associated with more severe clinical outcomes, including greater psychiatric symptom burden, metabolic dysregulation, and treatment resistance (Meira, Cruz, & Sweetman, 2025).The co-occurrence of insomnia and OSA creates a synergistic burden through the convergence of hyperarousal, sleep fragmentation, oxidative stress, and HPA axis dysregulation.These mechanisms overlap with known neurobiological signatures of psychosis, including circadian misalignment, impaired slow-wave sleep, and abnormal synaptic plasticity.Importantly, COMISA complicates therapeutic response, as isolated treatments, such as CBT-I or CPAP, often fail unless the dual pathology is addressed comprehensively.It is plausible that COMISA constitutes not just a clinical entity but a genetic and epigenetic endophenotype of psychosis, deserving focused investigation.The lack of consideration of COMISA in Cederlöf et al.'s study may therefore limit the scope of their otherwise valuable findings.While PGSs illuminate inherited predispositions, they do not capture the environmentally responsive layer of gene regulation provided by epigenetics.Mechanisms such as DNA methylation, histone acetylation, and non-coding RNAs mediate the interface between genotype and environment, dynamically shaping gene expression in response to stressors, including sleep loss (Gaine, Chatterjee, & Abel, 2018), hypoxia (Verdikt & Thienpont, 2024), psychosocial stress (Wu, Qu, Zhang, & Liu, 2024), and pharmacological exposure (Werner, Altshuler, Shaham, & Li, 2021).Epigenetic abnormalities have been widely observed in schizophrenia, affecting genes involved in synaptic signaling, neurodevelopment, and circadian regulation (Yang, Sun, Li, & Zhang, 2025).Sleep disorders, such as OSA and insomnia, exert measurable epigenetic effects.Sleep fragmentation in OSA alters methylation in genes related to inflammation and neuronal excitability (Leader et al., 2021), while intermittent hypoxia induces region-specific histone modifications in brain regions central to cognition and psychosis, including the hippocampus and prefrontal cortex (Ou, Zong, & Ouyang, 2023).Likewise, chronic insomnia, through
Source: Psychological Medicine
Authors: Susana Perdigoto, Miguel De Pedro, Miguel Meira e Cruz
Language: English
Topic: Sleep and related disorders
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,550
OpenAlex ID: W4411664934