Elevated Serum Levels of Neopterin at Admission Predicts Depression After Acute Ischemic Stroke: a 6-Month Follow-Up Study

Abstract

Inflammation and cell-mediated immune activation are attributed to the pathogenesis and pathophysiology in depression. Our aim was to test the possible association between serum levels of neopterin and the development of post-stroke depression (PSD) in Chinese patients. The subjects were first-ever acute ischemic stroke patients who were hospitalized at the First Affiliated Hospital of Xinxiang Medical University during the period from December 2012 to December 2013. Clinical information and stroke severity were collected at admission. Neurological and neuropsychological evaluations were conducted at the 6-month follow-up. Serum neopterin levels were measured using fluorometry and a high performance liquid chromatography (HPLC) method. Multivariate analyses were performed using logistic regression models. During the study period, 226 patients were included and finished the 6-month follow-up. Sixty-nine patients (30.5 %) were diagnosed as having major depression at 6 months. Patients with major depression showed higher levels of serum neopterin (21.6[IQR, 18.9-25.7]nmol/L vs. 14.6[IQR, 12.2-18.4]nmol/L, P < 0.0001) at admission. In multivariate analyses, serum neopterin was an independent predictor of PSD at 6 months [odds ratio (OR): 1.952 (95 % CI, 1.358-2.805), P < 0.0001]. With an AUC of 0.850 (95 % CI, 0.797-0.902), neopterin showed a significantly greater discriminatory ability as compared with high-sensitivity C-reactive protein, age, body mass index, and National Institutes of Health and Stroke Scale score. Neopterin is a novel, independent predictor of the development of depression 6 months after stroke. This indicated that the elevated neopterin levels may play a significant role in the pathology of depression and that the pathways leading to inflammation and cell-mediated immune activation warrant further exploration.

Periodontal, metabolic, and cardiovascular disease: Exploring the role of inflammation and mental health

“…Urinary neopterin levels in depressed patients have also been reported to be significantly higher as compared to healthy controls [163, 164]. Similar finding was reported by a more recent study [165], which also indicated that 6-months after an acute ischemic stroke, neopterin could be an independent predictor for the development of major depression. Interestingly, serum neopterin levels were reported to be significantly higher before treatment in anti-psychotic naive schizophrenia-patients, as compared to healthy controls, which reportedly declined significantly after 3 months of treatment with anti-psychotic medications [166].…”

Inflammation and the Silent Sequelae of Stroke

“…Unfortunately, the poor quality of the studies done to date do not allow for a definitive connection between PSD and inflammation to be made. In some studies, early markers of inflammation like CRP [57], ferritin [58], and neopterin [59] were associated with the later development of PSD. High serum levels of leptin at days 7 and 30 after stroke have also shown an association with later development of PSD [60].…”

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

“…One of the inflammatory drivers of this diversion of 5-HT to KYN is neopterin, a catabolic product of guanosine triphosphate that is a marker of cellular immune system activation produced by macrophages upon stimulation by interferon-gamma. 25–28 Increased peripheral KYN results in increased central KYN. KYN is further broken down into quinolinic acid, which potently agonizes the N-methyl-D-aspartate (NMDA)-receptor causing excitotoxic effects through receptor over-activation 29, 30 and inhibits glutamate uptake that causes elevated extracellular glutamate concentrations.…”