NUCB2/nesfatin-1 Is Associated with Elevated Levels of Anxiety in Anorexia Nervosa

Abstract

Objective: NUCB2/nesfatin-1 is an anorexigenic hormone with elevated levels in obese and decreased levels in anorexia nervosa (AN) patients. Moreover, a role in the regulation of stress and emotions was suggested by several rodent and preliminary human studies. Since anxiety and depression are common comorbidities in AN, we investigated the association of NUCB2/nesfatin-1 with anxiety, depression and perceived stress in AN.

Methods: We analyzed circulating NUCB2/nesfatin-1 levels in 64 female inpatients diagnosed with anorexia nervosa (body mass index, BMI; mean±SD, 14.7±2.3 kg/m2). At the same time anxiety (GAD-7), depression (PHQ-9), stress (PSQ-20) and disordered eating (EDI-2) were measured psychometrically.

Results: No correlation was observed between NUCB2/nesfatin-1 and BMI (r = 0.06, p = 0.70). The study population was divided in patients with low anxiety (n = 32, GAD-7 scores, mean±SD, 7.5±3.3) and high anxiety (n = 32, 16.0±3.0, p<0.001). Patients with high anxiety scores displayed 65% higher NUCB2/nesfatin-1 levels (p = 0.04). This was reflected by a positive correlation of GAD-7 and NUCB2/nesfatin-1-levels (r = 0.32, p = 0.04). Scores of PSQ-20 (73.3±14.3 vs. 48.6±17.2) and PHQ-9 (18.8±5.0 vs. 10.3±5.1) were higher in the high anxiety group (p<0.001) but did not correlate with NUCB2/nesfatin-1 (p>0.05). EDI-2 total score was also higher in the high anxiety group (52.3±14.1 vs. 40.2±16.0, p = 0.02), while no correlations of EDI-2-scores with plasma NUCB2/nesfatin-1 were observed (p>0.05).

Conclusions: Circulating NUCB2/nesfatin-1 levels correlated positively with perceived anxiety, whereas no association with BMI or eating disorder symptoms was observed. NUCB2/nesfatin-1 might be primarily involved in the modulation of anxiety and subsequently in the regulation of eating habits and body weight in AN.

Fig 1. GAD-7, PHQ-9, PSQ-20 and EDI-2 scores and plasma NUCB2/nesfatin-1 levels in anorexic patients.

Patients with high anxiety displayed significantly higher NUCB2/nesfatin-1 levels compared to those with low anxiety (A). This resulted in a positive correlation of NUCB2/nesfatin-1 with anxiety in the whole anorexic patient sample (B), whereas depression scores (C), perceived stress scores (D) and eating disorder symptoms (E) did not correlate with plasma NUCB2/nesfatin-1. Differences between groups were calculated using t-tests. Data are expressed as mean ± standard deviation. * p < 0.05. Distribution of the data was determined by Kolmogorov-Smirnov test. Correlations were determined by Pearson’s or Spearman’s analyses depending on the distribution of the data. Values for r and p are indicated in the graph. Abbreviations: EDI-2, eating disorder inventory; GAD-7, general anxiety disorder questionnaire; NUCB2, nucleobindin2; PHQ-9, patient health questionnaire depression; PSQ-20, perceived stress questionnaire.

Fig 2. PHQ-9 and PSQ-20 scores of anorexic patients with low versus high anxiety.

Patients with high anxiety scores displayed higher total scores in PHQ-9 (A) and PSQ-20 (B). Similarly, the PSQ-20 subscales differed between the two groups with higher scores for “worries” (C), “tension” (D) and “demands” (E) and lower scores for “joy” (F) in the high versus low anxiety group. Differences between groups were calculated using t-tests. Data are expressed as mean ± standard deviation. *** p < 0.001. Abbreviations: PHQ-9, patient health questionnaire; PSQ-20, perceived stress questionnaire.

Fig 3. EDI-2 scores of anorexic patients with low versus high anxiety.

Patients with high anxiety scores displayed a higher EDI-2 total score (A) and higher values of the subscales “perfectionism” (E), “ineffectiveness” (G) and “interoceptive awareness” (H) compared to those with low anxiety, while the subscales “drive for thinness” (B), “bulimia” (C), “body dissatisfaction” (D), “interpersonal distrust” (F) and “maturity fears” (I) did not differ between the two groups. Differences between groups were calculated using t-tests. Data are expressed as mean ± standard deviation. * p < 0.05, ** p < 0.01 and *** p < 0.001. Abbreviations: EDI-2, eating disorder inventory.