Department of Psychiatry, Penn State Milton S Hershey Medical Center, Hershey, PA, USA.
Sleep Research and Treatment Center, Penn State Milton S Hershey Medical Center, Hershey, PA, USA.
Bipolar Disord. 2018 Feb;20(1):27-34. doi: 10.1111/bdi.12529. Epub 2017 Aug 23.
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.
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.
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.
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.
慢性低度炎症与有症状的双相情感障碍（BD）和慢性失眠有关。睡眠障碍是躁狂和抑郁发作的特征之一。我们研究了细胞免疫激活标志物新蝶呤（neopterin）和色氨酸（TRP）途径的炎症副产物犬尿氨酸（KYN）对 BD 总睡眠时间与抑郁严重程度之间关系的影响。
招募了 21 名有症状的 BD 参与者和 28 名健康对照者（HC），并在常规临床护理期间对其进行随访。在基线和症状缓解后，通过活动记录仪对参与者进行为期 1 周的客观总睡眠时间测量，并采集血液样本来测量色氨酸（TRP）、犬尿氨酸（KYN）、KYN/TRP 比值和新蝶呤（neopterin）水平。使用卡方检验、独立 t 检验和分层线性多元回归模型进行统计分析。
总睡眠时间与抑郁严重程度呈正相关，与躁狂严重程度呈负相关。与 HC 相比，BD 患者的 TRP 明显降低。当考虑总睡眠时间和体重指数（BMI）时，KYN、TRP 和 KYN/TRP 比值与抑郁严重程度相关。在急性有症状的 BD 参与者中，KYN/TRP 比值与躁狂症状呈负相关趋势，控制 BMI 和总睡眠时间。新蝶呤与睡眠或情绪严重程度无关。在常规临床护理后，BD 患者的临床症状明显减轻，但睡眠表型或生物标志物没有显著差异。
炎症、睡眠和情绪密切相关。未来对 BD 中炎症对睡眠影响的研究可能会导致临床结果的标志物。
