Patients with bulimia nervosa (BN) have bulimic and depressive symptoms, which have been associated with abnormalities in the neuroendocrine and vagal systems. Subjects included twenty-four female drug-free outpatients with BN that were selected from patients seeking treatment for eating behavior in our hospital along with twenty-five age-matched healthy females who served as controls. We investigated ghrelin and leptin levels, cardiac vagal tone and sympathovagal balance, frequency of sets of binge-eating and vomiting episodes per week and the Profile of Mood States (POMS) depression scale in BN before and after a 16-week administration of the serotonin selective reuptake inhibitor (SSRI) paroxetine combined with cognitive–behavioral therapy. Compared to controls, the BN group had higher ghrelin levels and resting cardiac vagal tone, and lower leptin levels and resting cardiac sympathovagal balance before treatment, although there was a significant difference between the two groups for the body mass index (BMI). The elevated ghrelin levels (301.7 ± 18.9 pmol/l, mean ± SEM vs. 202.8 ± 15.6 pmol/l, P < 0.01), cardiac vagal tone (2246.4 ± 335.5 ms2 vs. 1128.5 ± 193.3 ms2, P < 0.01), frequency of sets of binge-eating and purging episodes and T scores for the POMS depression scale were all significantly decreased after treatment despite similar BMI, percent body fat and leptin levels. In close association with cardiac vagal function and ghrelin recoveries, abnormal eating behavior and depressive symptoms improved, indicating the usefulness of these indexes in the assessment of clinical condition and therapeutic efficacy in BN.
Ghrelin was originally discovered in the rat and human stomach and stimulates growth hormone secretion (Kojima et al., 1999 and Takaya et al., 2000), increases food intake (Tschöp et al., 2000 and Asakawa et al., 2001) and enhances appetite (Wren et al., 2001). This is an orexigenic and gastrointestinal peptide that antagonizes leptin action (Inui, 2001) and which has a role in the regulation of eating behavior and energy metabolism in the central nervous system (Shintani et al., 2001 and Nakazato et al., 2001) via the vagal system (Masuda et al., 2000, Asakawa et al., 2001 and Date et al., 2002). Recent studies have found that fasting ghrelin levels in patients with bulimia nervosa (BN) are increased (Tanaka et al., 2002, Kojima et al., 2005 and Fassino et al., 2005). In addition, we have shown that increased ghrelin concentrations may be associated with binge-eating and vomiting behavior (Tanaka et al., 2003a and Tanaka et al., 2004). A few studies have shown that BN patients have decreased fasting leptin concentrations (Jimerson et al., 2000 and Brewerton et al., 2000) and elevated cardiac vagal tone (Kennedy and Heslegrave, 1989 and Rissanen et al., 1998), which suggest that BN patients may have neuroendocrine and vagal system abnormalities. In addition, Rissanen et al. (1998) have shown that the use of the serotonin selective reuptake inhibitor (SSRI) fluoxetine combined with self-monitoring that is based on cognitive–behavioral treatment normalizes the elevated cardiac vagal tone in BN patients. Furthermore, BN patients have been reported to respond to treatment with the SSRI fluoxetine (Fluoxetine Bulimia Nervosa Collaborative Study Group, 1992, Goldbloom and Olmsted, 1993 and Goldstein et al., 1995). The aim of this study was to examine ghrelin and leptin levels and cardiac vagal tone in subjects before and after a pharmacologic treatment program, which administered SSRI paroxetine in combination with cognitive–behavioral therapy.
