The association of leptin secretion with cognitive performance in patients with eating disorders
Introduction
Anorexia nervosa (AN) is characterized by restrictive eating patterns, being underweight, and the fear of gaining weight. Patients with AN are capable of suppressing food intake, even in the presence of strong physiological signals of hunger. Bulimia nervosa (BN) is characterized by regular episodes of binge eating with loss of control followed by compensatory behaviors such as vomiting or laxative use in an effort to control weight. Binge eating and loss of control also occur in binge eating disorder (BED) but are not followed by compensatory behaviors; obesity or overweight are common (APA, 2013). High vs. low behavioral inhibitory control defines the clinical phenotypes of AN vs. BN and BED.
Inhibitory control is the ability to suppress or interrupt a response (Bari and Robbins, 2013). Although various experimental paradigms can be used to assess inhibitory control, go/no-go tasks are often used in eating disorder (ED) research to assess the ability to inhibit a response that has not been initiated. Commission errors (i.e., failures to inhibit “no-go trials”) and reaction times for “go-trials” are measures of performance in go/no-go tasks. Systematic reviews of research in this area have indicated that, in comparison to controls, BN and BED are associated with inhibitory control deficits in go/no-go tasks (Wu et al., 2013; Lavagnino et al., 2016). In addition, greater inhibitory control deficits have been noted for disorder-relevant stimuli (e.g., food) in BN (Wu et al., 2013) and BED (Kittel et al., 2015; Giel et al., 2017). However, inhibitory control deficits are also associated with obesity (Lavagnino et al., 2016; Giel et al., 2017) and findings regarding inhibitory control in BED are mixed and ambiguous (e.g., Svaldi et al., 2015, Manasse et al., 2016, Kittel et al., 2017). Studies applying food stimuli have not been conducted with AN participants, but emotional stimuli have been shown to inhibit responses in a go/no-go task (Hildebrandt et al., 2016).
Representing the opposite side of inhibitory control, increased cognitive control and inflexibility may be responsible for the rigid eating behaviors seen in AN. In neuropsychological investigations, set-shifting paradigms are used to assess cognitive flexibility. Set-shifting is the ability to shift thoughts and actions in response to changing contexts. In EDs, set-shifting has frequently been assessed with perseverative errors in the Wisconsin Card Sorting Test (WCST; Heaton et al., 1993) and task completion time in the Trail Making Test (TMT; Reitan, 1992). Impaired set-shifting abilities have been documented for patients with AN (e.g., Holliday et al., 2005, Lang et al., 2014, Westwood et al., 2016, Smith et al., 2018). However, differing methodologies have yielded discrepant results (Lang et al., 2014). In the systematic review by van den Eynde et al. (2011), two studies showed impaired set-shifting, using the WCST, in BN and BED compared to controls; two other studies found no differences. In the most comprehensive meta-analysis conducted, Wu et al. (2014) claim that poor set-shifting is present across all EDs compared to controls (Wu et al., 2014). Mixed results were yielded in the review by Kittel et al. (2015). Set-shifting deficits were found in BED, as compared to obese individuals using the TMT, and in obese patients with BED, as compared to obese individuals using the WCST; furthermore, there were no differences in the WCST between patients with BED and normal-weight controls (Kittel et al., 2015). Patients with BN performed worse than controls in both the TMT and WCST in the meta-analysis conducted by Hirst et al. (2017), although no evidence of set-shifting impairments was found in certain singular studies (e.g., Zakzanis et al., 2010). In the most recent systematic review on set-shifting across EDs, including 12 previous systematic reviews (six of which were meta-analytic reviews), Smith et al. (2018) concluded there is little evidence for set-shifting differences between ED diagnostic groups. Specific set-shifting tasks may be responsible for the varied results mentioned above (Wu et al., 2014; Smith et al., 2018). Moreover, age may be a significant factor. Westwood et al. (2016) focused on the WCST and found effect sizes for deficits in set-shifting in AN were greater in adults, as compared to children and adolescents.
It remains unclear whether neuropsychological impairments across EDs function as etiopathogenetic or maintenance factors (Smith et al., 2018). Impaired neuropsychological performance has been linked to hormonal alterations regarding the hypothalamus-pituitary-adrenal axis and the hypothalamus-pituitary-gonadal axis, mostly in AN (e.g., Sherwin, 2007, Chui et al., 2008, Buehren et al., 2011). Similar studies in BN and BED have not been conducted. Studies examining the association between appetite-regulating hormones and neuropsychological performance in EDs are also lacking.
This pilot study aims to contribute to this knowledge gap by assessing both neuropsychological performance and appetite-regulating hormones in participants with AN, BN, and BED, as well as controls. Appetite-regulating hormones are commonly assessed under standardized (e.g., fasting) conditions, in a single and static baseline procedure. In contrast, this study examines appetite-regulating hormonal systems with a dynamic functional test procedure instead of with a single measure. Since food intake is the physiological stimulus for changes in secretion of the hormones of interest, the paradigm of oral glucose ingestion after an overnight fast employing an oral glucose tolerance test (OGTT) has been applied. In addition to glucose and insulin, the hormones commonly assessed during the OGTT, leptin and ghrelin were also examined as these two appetite-regulating hormones have recently been associated with cognitive performance (e.g., Yin et al., 2018, Chen et al., 2017). The “net” hormonal response during the OGTT was assessed by calculating the area under the curve (AUC), corrected for baseline, since baseline concentrations were expected to significantly differ between groups and thus influence the overall secretion patterns. Additionally, a set-shifting variant of a food vs. neutral stimuli go/no-go task was applied, examining the combined impulsivity control x set-shifting abilities. We included only obese BED patients to assess a phenotype that may be characterized by more distinct impairments in cognitive performance. Not only has poor inhibitory control been associated with high BMI (Stice et al., 2016), but greater impairments in executive function have been found in obese patients with BED, as compared to patients with only BED (e.g., Duchesne et al., 2010, Manasse et al., 2015). Similarly, in the context of food, greater impairments in response inhibition have been observed in obese patients with BED, as compared to obese individuals without BED (e.g., Schag et al., 2013, Svaldi et al., 2014, Hege et al., 2015).
We hypothesized that:
- 1)
Hormone secretion patterns would significantly differ between patients with EDs and controls, and
- 2)
Dysfunctional hormone secretion patterns in patients with AN, BN, and BED would be associated with impaired performance in the applied variant of the go/no-go task. Since there is no previous research associating appetite-regulating peptides with neuropsychological performance in EDs, and findings related to associations between endocrine responses and cognitive performance in different clinical cohorts are inconsistent, no hypotheses related to specific hormones or diagnostic subgroups were formulated.
Section snippets
Study population
Participants were adult female outpatients and inpatients diagnosed with AN (n = 10), BN (n = 10) and BED (n = 10). Participants were recruited during their inpatient stay or outpatient consultation at the Department of Psychosomatic Medicine and Psychotherapy at the University Hospital Erlangen, Germany. Diagnoses of AN, BN, and BED were ascertained during non-standardized, semi-structured clinical interviews conducted by psychologists and physicians with experience in the assessment and
Age, BMI, eating disorder-specific psychopathology
There were no significant differences between the groups regarding age (F3,46 = 2.65, p = 0.06, partial η2 = 0.15). As expected, the ANOVA revealed a significant main effect for group regarding BMI (F3,46 = 50.20, p < 0.001, partial η2 = 0.77), with AN < BN (p = 0.003), AN < CO (p < 0.001), AN < BED (p < 0.001), BN < BED (p = 0.001), and CO < BED (p = 0.001) in corresponding post hoc tests (Games-Howell) (Table 1).
The groups also differed on the EDE-Q (F3,46 = 41.43, p < 0.001, partial η2
Discussion
This study examined female patients with AN, BN, and BED, and female controls, to find that patients with AN differ from controls regarding their “net” (i.e., corrected for baseline concentrations) leptin response during an OGTT. While the four groups being compared did not differ in their neuropsychological performance in a set-shifting go/no-go paradigm with food vs. neutral stimuli, leptin responses in the OGTT were found to be associated with performance in response inhibition toward
Limitations
Limitations of this study include the small number of participants in each group and the resulting limited power to detect differences. However, curves for CEs and RTs in the go/no-go task were remarkably parallel, which might indicate similar results even with a greater number of participants. Another explanation for the failure to detect differences between groups in neuropsychological performance might relate to the significance of mood status on inhibitory control (e.g., Loeber et al., 2018
Conclusions
In summary, we investigated the concentrations of the appetite-regulating hormones ghrelin, leptin, insulin, and glucose in a functional manner, using the OGTT, and their association with neuropsychological performance in a pilot study of ED patients and controls. The primary finding was that the AUC for leptin, corrected for baseline concentrations, differed significantly between AN patients and controls and predicted performance in response inhibition, as indicated by the numbers of CEs in
Declaration of interest
The authors declare that they have no conflict of interest.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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2021, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :There were few differences between people with NW and those with BED on the GNG. Seven studies compared NW and BED groups (Tables 2 and 3) (Kelly et al., 2013; Loeber et al., 2018; Mobbs et al., 2011; Kollei et al., 2018; Oliva et al., 2019; Wollenhaupt et al., 2019; Lyu et al., 2017); five described no between-group differences (Kelly et al., 2013; Kollei et al., 2018; Oliva et al., 2019; Wollenhaupt et al., 2019; Lyu et al., 2017), and the remaining two reported partial differences (i.e., no main effects) (Loeber et al., 2018; Mobbs et al., 2011). One study found that individuals with BED made significantly more errors on the neutral version of the GNG as compared to the food version (Loeber et al., 2018).
Omentin and visfatin in adolescent inpatients with anorexia nervosa; association with symptoms
2021, NeuropeptidesCitation Excerpt :Some of them, such as leptin or ghrelin, have been extensively studied and are known to be involved in AN etiology (Monteleone and Maj, 2013). Furthermore, they regulate hunger and satiety, not only by affecting metabolism but also eating behaviors and emotions (Berner et al., 2019; Rybakowski et al., 2014; Wollenhaupt et al., 2019). However, according to the last metanalysis of adipokines in anorexia nervosa some of these proteins have not been so intensively studied (Karageorgiou et al., 2020) and further research are needed.
- 1
Both authors have contributed equally to this study.
- 2
The present work was performed in fulfillment of the requirements for obtaining the degree “Dr. med.” (MD).