High levels of Nesfatin-1 in relation to the dysfunction of the hypothalamic–pituitary–adrenal and hypothalamus–pituitary–thyroid axes in depressed patients with subclinical hypothyroidism

Abstract

Despite the increasing amount of evidence suggesting a relationship between depression and subclinical hypothyroidism (SCH), the exact mechanism underlying this relationship remains unclear. The main purpose of this study was to investigate the roles of plasma Nesfatin-1 levels and dysfunction of the hypothalamic–pituitary–adrenal (HPA) and hypothalamus–pituitary–thyroid (HPT) axes in the comorbidity of depression and SCH. Dysfunctions of the HPA and HPT axes were detected by measuring plasma corticosterone and thyroid-stimulating hormone (TSH) concentrations, respectively. Subjects in the patient group were selected from patients hospitalized at the Anhui Mental Health Center, and subjects in the control group were recruited from healthy volunteers. Healthy control subjects were matched to the patients in terms of weight and body mass index. The Hamilton Depression Rating Scale was administered to both the groups. The enzyme-linked immunosorbent assay method was used to measure plasma Nesfatin-1, corticosterone, and TSH levels. A radioimmunoassay kit was used for the measurement of the plasma-free triiodothyronine and plasma-free thyroxine. The results showed that the Hamilton Depression Rating Scale scores and average Nesfatin-1, corticosterone, and TSH levels were significantly higher in depressed patients with SCH than in the control group. Moreover, positive relationships were observed between Nesfatin-1 levels and the concentrations of corticosterone (r=0.626, P<0.001) and TSH (r=0.229, P=0.036) in depressed patients with SCH. These findings indicate that Nesfatin-1 is involved in the comorbidity of depression and SCH, and the mechanism underlying this involvement might be related to the dysfunction of the HPA and HPT axes.

Current Understanding of the Role of Nesfatin-1

“…Besides the correlation with self-reported anxiety, circulating NUCB2/nesfatin-1 was also associated with reported depression in a mixed-sex population [ 122 ], with NUCB2/nesfatin-1 levels rising with increasing severity of depression [ 123 , 124 ], and correlated with inflammatory markers such as IL-6 and C-reactive protein as well as corticosterone under these conditions [ 125 ]. Higher NUCB2/nesfatin-1 levels were subsequently shown in patients reporting depression associated with subclinical hypothyroidism [ 126 ], leading to the hypothesis of nesfatin-1 being involved in these symptoms. Also, an animal model of gastric cancer comorbid with depression displayed higher NUCB2/nesfatin-1 peptide levels in the hippocampus, midbrain and plasma compared with undisturbed controls [ 127 ].…”

Differential lipids in pregnant women with subclinical hypothyroidism and their correlation to the pregnancy outcomes

“…They include spontaneous abortion 1 , preeclampsia 2 , placental abruption, premature rupture of membranes, low birth weight 3 , fetal distress, preterm birth 4 , and abnormal neuropsychological and intellectual development 5 . The pathogenesis of SCH remains unclear, despite being associated with nitric oxide (NO) 6 , Nesfatin-1 7 , gene silencing mediated by microRNAs 8 , inactivation of the thyroid-stimulating hormone receptor gene 9 , and the gut–thyroid axis 10 . In summary, SCH during pregnancy has a high incidence, lacks definite symptoms and physical signs, and causes obvious adverse pregnancy outcomes.…”

Association Between Chronic Autoimmune Thyroiditis and Nesfatin-1 Levels

“…Xu et al have shown that nesfatin-1 were positively correlated with TSH in depressed patients with subclinical hypothyroidism. This may be indicate that the mechanism underlying the comorbidity of depression and subclinical hypothyroidism might be related to the dysfunction of the hypothalamus-pituitary-thyroid axis (16). Another study on cases with subclinical and overt hyperthyroidism have not shown a significant change in nesfatin-1 levels (10), but Tohma et al (15) have determined nesfatin-1 levels are remarkably affected by hyperthyroidism.…”