Total sleep time and kynurenine metabolism associated with mood symptom severity in bipolar disorder

• Published in: Bipolar disorders 2018-02, Vol.20 (1), p.27-34
• Main Authors: Mukherjee, Dahlia, Krishnamurthy, Venkatesh Bassapa, Millett, Caitlin E., Reider, Aubrey, Can, Adem, Groer, Maureen, Fuchs, Dietmar, Postolache, Teodor T, Saunders, Erika F. H.
• Format: Article
• Language: English
• Subjects: Adult; Affect - physiology; Affective disorders; Biomarkers - blood; Bipolar disorder; Bipolar Disorder - blood; Bipolar Disorder - complications; Bipolar Disorder - psychology; Body mass index; Chi-square test; Depression - blood; Depression - diagnosis; Female; Humans; Immune response; Inflammation; Inflammation - blood; Inflammation - psychology; Insomnia; Kynurenine - blood; kynurenine pathway; Male; Metabolism; Middle Aged; Mood; Neopterin; Neopterin - blood; Outcome Assessment (Health Care); Phenotypes; Regression analysis; Serotonin; Serotonin - metabolism; Sleep; Sleep disorders; Sleep Initiation and Maintenance Disorders - etiology; Sleep Initiation and Maintenance Disorders - psychology; Statistical analysis; Tryptophan; Tryptophan - blood
• ISSN: 1398-5647; 1399-5618
• DOI: 10.1111/bdi.12529

Objective Chronic, low‐level inflammation is associated with symptomatic bipolar disorder (BD) and with chronic insomnia. Disrupted sleep is a feature of episodes of both mania and depression. We examined the effect of neopterin, a marker of cellular immune activation, and kynurenine (KYN), an inflammatory byproduct of the serotonin pathway, on the association between total sleep time and depression severity in BD. Method Twenty‐one symptomatic BD participants and 28 healthy controls (HC) were recruited and followed during usual clinical care. At baseline and after symptomatic recovery, total sleep time was objectively measured with actigraphy for 1 week and blood plasma was collected to measure the serotonin precursor tryptophan (TRP), KYN, the KYN/TRP ratio, and neopterin levels. Statistical analyses were conducted using chi‐square, independent t tests and hierarchical linear multiple regression models. Results Total sleep time was correlated positively with depressive severity and negatively with manic severity. TRP was significantly reduced in BD participants compared to HC. KYN, TRP, and the KYN/TRP ratio were associated with depressive severity when total sleep time and body mass index (BMI) were included in the model. The KYN/TRP ratio trended towards a negative association with mania symptoms, controlling for BMI and total sleep time, in acutely symptomatic BD participants. Neopterin was not associated with sleep or mood severity. After usual clinical care, BD participants showed significantly decreased clinical symptoms but no significant differences in sleep phenotype or biomarkers. Conclusion Inflammation, sleep, and mood are closely intertwined. Future research into the effect of inflammation on sleep in BD may lead to clinical markers of outcome.