Abstract
Background: Schizophrenic patients commonly suffer from sleep disorders which are associated with acute disease severity, worsening prognoses and a poorer quality of life. Research is attempting to disentangle the complex interplay between schizophrenia and sleep disturbances by focusing not only on demographic and clinical characteristics, but also on the identification of genetic factors. Methods: Here, we performed a systematic literature review on the topic of genetic variations in sleep-disordered schizophrenic patients in an attempt to identify high quality investigations reporting scientifically sound and clinically useful data. For this purpose, we conducted a thorough search of PubMed, ScienceDirect and GoogleScholar databases, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our search yielded 11 eligible studies. Certain genetic variations were reported to be associated with schizophrenia-related sleep disorders. Antipsychotic-induced restless legs syndrome was linked to polymorphisms located on CLOCK, BTBD9, GNB3, and TH genes, clozapine-induced somnolence was correlated with polymorphisms of HNMT gene, while insomnia was associated with variants of the MTNR1 gene. Conclusions: There are significant genetic associations between schizophrenia and co-morbid sleep disorders, implicating the circadian system, dopamine and histamine metabolism and signal transduction pathways.
Highlights
Sleep disorders are extremely prevalent among diagnosed schizophrenics, affecting almost 80%of patients [1]
Given that both schizophrenia and sleep disorders have been linked to dysfunction in specific neural circuits including dopaminergic and serotoninergic pathways [10], and that both are characterized by a strong genetic component with shared genetic loci [11,12], research is increasingly focusing on detecting genetic variations which are associated with their co-occurrence
Our analysis indicated that GNB3 participates in a variety of signaling pathways, such as protein kinase A, IL-8, IL-1, Gaq, phospholipase C, Tec kinase, G beta gamma, a-adrenergic, Gas, Gai, opioid, and glutamate receptor signaling, while MTNR1A in melatonin, BTBD9 in dopamine signaling, HNMT in histamine degradation, Tyrosine hydroxylase (TH) in protein kinase A and opioid signaling pathway and CLOCK in circadian rhythm, adipogenesis and sirtuin signaling pathway
Summary
Sleep disorders are extremely prevalent among diagnosed schizophrenics, affecting almost 80%of patients [1]. They constitute a source of clinical concern since they are associated with greater symptom severity, increased relapse rates, worse prognoses, and a diminished quality of life [2,3] In this context, there have been several studies focusing on the epidemiology, clinical characteristics, and pathogenic mechanisms underlying schizophrenia-related sleep disturbances [4,5,6]. Methods: Here, we performed a systematic literature review on the topic of genetic variations in sleep-disordered schizophrenic patients in an attempt to identify high quality investigations reporting scientifically sound and clinically useful data. For this purpose, we conducted a thorough search of PubMed, ScienceDirect and GoogleScholar databases, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Conclusions: There are significant genetic associations between schizophrenia and co-morbid sleep disorders, implicating the circadian system, dopamine and histamine metabolism and signal transduction pathways
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