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Relation between symptoms of insomnia, depression, sleep quality, anti-tumor necrosis factor therapy and disrupted circadian clock genes' expression in inflammatory bowel disease.

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INTRODUCTION Inflammatory bowel diseases (IBD) might be accompanied by emotional disturbances. Circadian rhythm genes, brain and muscle ARNT-Like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein… Click to show full abstract

INTRODUCTION Inflammatory bowel diseases (IBD) might be accompanied by emotional disturbances. Circadian rhythm genes, brain and muscle ARNT-Like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), nuclear receptor subfamily 1 group D member 1 (NR1D1) bear relation to inflammation and psychiatric symptoms, thus might modulate their interactions. OBJECTIVES The study aimed to compare the expressions of BMAL1, CLOCK, NPAS2, NR1D1 mRNA between IBD patients and healthy controls (HC). The association between genes' expressions and disease severity, anti-TNF therapy, sleep quality, insomnia, and depression was evaluated. PATIENTS AND METHODS Eighty-one IBD patients and 44 HC were recruited and divided according to disease activity and IBD type (ulcerative colitis (UC), Crohn's disease (CD)). Questionnaires assessing sleep quality, daytime sleepiness, insomnia, and depression were filled out. Venous blood was collected; IBD subjects who underwent anti-TNF therapy had their blood drawn before and after 14 weeks of treatment. RESULTS The IBD group had decreased expression of all studied genes, but BMAL1 compared to HC. UC individuals with exacerbation had decreased expression of CLOCK and NPAS2 compared to remission group; UC severity was negatively correlated with CLOCK, NPAS2, NR1D1 mRNA. IBD participants with depression symptoms had decreased expression of CLOCK and NR1D1 compared to those without mood disturbances. Poor sleep quality was associated with decreased expression of NR1D1. Biological treatment decreased BMAL1 expression. CONCLUSIONS Disruption of clock genes expressions might constitute a molecular background of sleep disorders and depression in IBD as well as contribute to UC exacerbation.

Keywords: insomnia depression; clock; therapy; sleep quality

Journal Title: Polish archives of internal medicine
Year Published: 2023

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