Abstract
Background:
Brain-derived neurotrophic factor (BDNF) is associated with the development of different psychiatric conditions, including eating disorders (EDs).
Objectives:
To investigate the salivary BDNF’s ability to act as a potential biomarker for detecting the risk of developing EDs among young females.
Design and methods:
A cross-sectional study was carried out in Amman, Jordan, with a total of 216 nutrition students completing the Eating Attitudes Test-26 (EAT-26) to assess the risk of developing EDs, the Cohens’ Perceived Stress Scale-10 (PSS-10) to measure stress levels, and the International Physical Activity Questionnaire-Short Form (IPAQ-SF) to assess physical activity levels. Dietary intake was analyzed using a semiquantitative food frequency questionnaire. A nested sample of 34 females from both extreme EDs was selected and tested for salivary BDNF levels.
Results:
The nested sample of 34 female nutrition students 22.00 (2.75) years old with body mass index (BMI) of 23.60 (3.35) kg/m2 were divided into two groups; 18 students were at lower risk, while 16 were at higher risk of developing EDs. The salivary BDNF levels did not differ significantly between the low-risk and high-risk groups (391.03 (128.17), 339.15 (102.52), and p = 0.347, respectively). BMI, PSS-10 score, and total metabolic equivalent (MET) were significantly different between the two groups. No associations were found between salivary BDNF levels and BMI, PSS-10 score, MET, or different food groups. The odds ratio for the risk of BDNF-related EDs was 1.07 (95% CI, 1.03–1.10) in the higher-risk group versus the lower-risk group.
Conclusion:
BDNF is not a robust biomarker of risk for EDs. The changes in salivary BDNF levels could reflect individual ED eating patterns rather than indicating a direct causative role in the disorder’s development. According to our results, psychiatric consultation for ED detection remains the gold standard for diagnosis and treatment.
Keywords: brain-derived neurotrophic factor, dietary intake, disordered eating risk, perceived stress levels, metabolic equivalent, young nutritionist Jordanian female adults
Introduction
Eating disorders (EDs) are a group of serious psychiatric illnesses characterized by abnormal eating patterns that result in social behaviors that have a significant impact on individuals’ quality of life and ability to interact socially. 1 Patients with EDs often endure emotional distress, anxiety, depression, and potential health problems. 2 With EDs, they frequently struggle to maintain healthy body weight and/or body image, engage in frequent dieting, and may experience weight-related anxiety. 3 Common EDs are binge ED, bulimia nervosa (BN), and anorexia nervosa, with worldwide prevalence rates among females of 3.4%, 1.7%, and 3.6%, respectively. 4 These disorders pose a significant mental health challenge and can have devastating consequences for those who suffer from them, including substantial economic costs. 5
From an etiological perspective, many factors contribute to the development of EDs.6,7 Disordered eating (DE) behaviors can often precede the development of full-blown EDs.8–11 Behaviors such as restrictive dieting, skipping meals, and purging after eating can indicate unhealthy relationships with food and body image.8–11 Although not meeting the diagnostic criteria for EDs, these DE patterns put individuals at greater risk for developing anorexia nervosa, BN, or binge ED in the future.8,11
Recent research has focused on the potential role of brain-derived neurotrophic factor (BDNF) in disease progression. 12 BDNF is a protein that has been linked to the development of several psychiatric conditions, including EDs. 13 A recent systematic review showed that a lower level of BDNF is linked to a low incidence of EDs 13 and plays an important role in the growth and survival of neurons in the brain. 14 BDNF is widely distributed in many regions of the brain, including the hippocampus, a critical regulatory center for eating behaviors. 15 Salivary BDNF is indicative of the peripheral BDNF pool rather than the central BDNF pool. 16 Salivary BDNF levels are thought to mainly indicate the quantity of BDNF in the overall circulation, as BDNF can move from the bloodstream to saliva through either passive diffusion or active transport pathways. 17 Furthermore, BDNF affects the differentiation and function of adipocytes, therefore affecting the metabolism of adipose tissue and the release of adipokines. 18 BDNF controls numerous behaviors associated with the regulation of food intake by acting in both the appetite and satiety centers of the brain. 19 BDNF gene expression is regulated by endogenous and exogenous stimuli, such as stress, brain injury, physical activity, diet, and medications such as antidepressants. 20
The elevated prevalence of EDs/DE among females may be associated with a range of biological, psychological, and societal variables. 11 An underlying biological element that could contribute to this phenomenon is the distinct control of BDNF levels between males and females. 21 Studies indicate that females generally have elevated amounts of circulating BDNF in comparison to males, perhaps impacting their vulnerability to EDs.13,21 In which a decrease in BDNF levels may impede the development of new brain pathways, affecting the individual’s ability to regulate their eating habits and eventually leading to the manifestation of EDs. 22 In conditions such as anorexia nervosa, decreased levels of BDNF contribute to variations in synapse plasticity and neurogenesis, contributing to the pathophysiology of the disease. 13 Low BDNF levels may also contribute to changes in behavior, mood, and stress that can lead to changes in eating habits, such as emotional eating, thereby increasing the consumption of sweet and fatty food and increasing the risk of developing EDs. 23 It remains unclear whether these reductions in BDNF levels may merely represent an accompanying epiphenomenon to malnourishment or have causal consequences for nerve and synapse growth and plasticity. 24 On the other hand, physical activity may increase the circulating levels of BDNF. 25 The relationship between BDNF and EDs/DE is complex. Nonetheless, the potential role of BDNF in the development and recovery of EDs/DE suggests that BDNF is an important component of the pathophysiology of these disorders. 26
University students enrolled in health-related majors—particularly those in nutrition and dietetics—appear particularly vulnerable to DE behaviors. This vulnerability may be due to increased exposure to food- and body-related knowledge, heightened body image awareness, and internalization of dietary control ideologies promoted in their curriculum. A recent study found that between 4% and 32% of nutrition and dietetics students are at high risk for developing EDs. 27 These findings strongly justify the inclusion of this population as a relevant target group for early ED risk screening. Therefore, the aims of this study were threefold. First, we aimed to identify the proportion of young females with nutritional backgrounds (university students) at EDs (i.e., the prevalence of DE) using clinically validated measures, Second, we aimed to measure salivary BDNF levels in young females who appear to be at ‘low risk’ and those at ‘high risk’ of EDs. Third, we investigated whether measuring BDNF levels can help in identifying the risk (low vs high) of developing EDs. We hypothesized that BDNF could determine the risk of ED among healthy adults.
Materials and methods
Study design
A cross-sectional multistage study was conducted in Jordan to assess the prevalence of DE and to examine salivary BDNF levels as a potential biomarker for ED risk. The reporting of this study conforms to the STROBE statement for observational studies 28 (Supplemental Material 1). The multistage design allowed for an initial screening of a large sample to identify individuals at ‘high or low risk’ to develop EDs, followed by a more in-depth analysis of a subset of high- and low-risk participants.
This study was approved by the Research Ethics Committee of the University of Jordan (Decision ID: UOJ-REC-03-56). Written informed consent was obtained from all participants before their enrollment in the study.
Stage 1: The prevalence of ‘high-risk’ versus ‘low-risk’ EDs
A total of 216 participants were recruited. The inclusion criteria for participants were as follows: (1) female, (2) healthy (free from known medical conditions), (3) aged 18–25 years, and (4) studying nutrition and dietetics at the University of Jordan/Nutrition and Food Technology Department between January and December 2023. The exclusion criteria were: (1) male participants, (2) during menstrual period, (3) pregnant and lactating, (4) use of any medication in the past 7 days, and (6) a known history of psychiatric disorders.
In the first stage, we collected demographic information, including age, height, and weight, to compute the body mass index (BMI) for all 216 participants. They completed the Eating Attitudes Test-26 (EAT-26) questionnaire to assess the risk of developing EDs using an online questionnaire distributed through various recruitment strategies, such as social media advertisements, word-of-mouth, and professional contacts. All the data were coded and stored in a secure Google Drive accessible only to the researchers.
In this study, the standardized and validated Arabic translation of the EAT-26 was used. 29 The EAT-26 is divided into three subscales, dieting, bulimia, and food obsession/oral control, with responses scored on a 6-point scale ranging from 0 (never) to 6 (always); the sum of EAT-26 scores ranges from 0 to 78. A score of 20 or above was classified as indicating a higher risk, while a score of less than 10 was classified as indicating a lower risk. 30 The EAT-26, developed by Garner and colleagues in 1982, is the most widely used instrument for predicting the development of EDs. 31 The EAT-26 is an enhanced variant of the EAT-40, with high levels of validity and test–-retest reliability for both adolescents and adults. The EAT-26 has demonstrated good sensitivity and specificity for identifying ED risk. An initial validation study of the EAT-26 among patients with anorexia nervosa and BN revealed 89% sensitivity and 84% specificity for anorexia nervosa and 91% sensitivity and 97% specificity for BN when using a cutoff score of 20. 32
Stage 2: Measuring BDNF and other factors for those at ‘high risk’ versus at ‘low risk’ of developing EDs
A nested sample of 34 females was selected based on their EAT-26 scores. Participants with scores in the upper quartile (above the 75th percentile; high-risk group, n = 16) and those in the lower quartile (below the 25th percentile; low-risk group, n = 18) were included. This selective sampling approach, though reducing the overall sample size to 34, allowed for maximizing the contrast in eating attitudes and behaviors between the two groups. By comparing BDNF levels in these extremely high and low-scoring groups, the authors could more stringently test for potential differences in this neurotrophin related to ED psychopathology.
Participants in this stage were asked to provide a salivary BDNF mouth swab and complete other questionnaires, such as the Arabic version of Cohen’s PSS-10 scale (PSS-10) to assess participants’ stress, 33 The international physical activity questionnaire-short form (IPAQ-SF) to assess participants’ physical activity, 34 and the semiquantitative food frequency questionnaire (FFQ) to analyze dietary intake. 35
For the BDNF test, 34 females were asked to perform passive saliva collection to determine BDNF levels. Saliva samples were collected by mouth swabbing with a cotton stick and then stored in tubes from all participants in the morning following an overnight fast. Particular attention was given to ensuring the absence of the menstrual cycle in the same month during which the EAT-26 questionnaire was completed. The salivary samples were stored at −20°C for 30–40 days with no protease inhibitor added per the manufacturer’s kit instructions, which ensured the stability of BDNF without the inhibitors. We used a BDNF ELISA kit (CV%: 12%) to measure BDNF levels in the saliva (GenoChem World, Valencia).36,37 Saliva samples were used for BDNF detection due to their noninvasive collection and time savings for young females.
The perceived stress score PSS-10 is a 10-item questionnaire designed to evaluate self-reported stress. 33 Each question is scored from 0 (never) to 5 (very often), with a total possible score ranging from 0 to 40. A higher score indicates a high level of stress. 38
The IPAQ-SF, a validated tool for estimating physical activity among adults, was used to quantify the participants’ physical activity levels. 34 This survey evaluated the frequency and duration of physical exercise and divided it into three categories: mild, moderate, and vigorous. All continuous scores are expressed in MET minutes/week.
The FFQ was used to assess the regularity of food consumption in the five major food categories. In six categories (rarely or never, once to three times/month, three to six times/week, once to two times/week, twice/day, once/day), participants were asked how frequently they had generally consumed the 30 primary food items.38,35 Our FFQ was previously validated in Arabic populations. 35
All questionnaires are available in Supplemental Material 2.
Statistical methods
Descriptive statistics are presented as the median and interquartile range (IQR) for continuous variables, and counts and percentages were used to summarize categorical data in the study. Reporting descriptive statistics in this manner (i.e., median and IQR) allows for appropriate characterization of the data given its nonnormal distribution, enabling suitable interpretation of the results for the reader.
The Mann‒Whitney test was used to compare the differences between the high-risk ED group and the low-risk ED group. This statistical analysis method is appropriate for nonparametric data and can be used to compare two independent groups. By utilizing this statistical test, we were able to determine whether there were significant differences in BDNF levels between the two groups of participants. Spearman’s rank correlation was used to explore relationships between different study variables. The Spearman’s rank correlation coefficient is an important statistical measure used in this study to explore relationships between different variables being analyzed. It measures the strength and direction of the linear relationship between two continuous variables, allowing researchers to quantify the degree of association between variables such as BDNF levels, age, and BMI. Calculating correlations helps identify which variable pairs are more strongly related and may warrant further investigation into potential causal relationships. Understanding these interrelationships provides a crucial context for interpreting the overall study findings and results, as correlations can guide more advanced modeling techniques, such as logistic regression, used to predict ED risk based on BDNF while controlling for other factors. The risk of ED based on BDNF was predicted using logistic regression analysis after adjustments for age and BMI. The odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) are reported. The R Statistical Computing program (version R 4.3.2) was used to perform the statistical analyses for this study, with significance set at p < 0.05.
Results
Results of Stage 1: The prevalence of ‘high-risk’ versus ‘low-risk’ EDs
A total of 250 female university students participated in this stage, and 216 provided usable responses (response rate 90%). The median age was 23 years (IQR = 4.00 years), and the BMI was 22.51 kg/m2 (IQR = 4.95 kg/m2). The median EAT-26 score for the total sample was 14 (IQR = 11.00). The 25th percentile for the EAT-26 score was 10.00, the 50th percentile (median) was 14.00, and the 75th percentile was 21.00. Of the 216 participants, 60 (28%) were classified as at high risk of EDs with EAT-26 scores of 20 or above. The remaining 156 participants (72%) were classified as having a low risk of EDs, with EAT-26 scores less than 20.
Results of Stage 2: Measuring BDNF and other factors for those at ‘high risk’ versus at ‘low risk’ of developing EDs
The second stage included 34 participants with the lowest scores (i.e., from the 25th percentile for EAT-26 scores with an EAT-26 score of approximately 10) who were labeled ‘low-risk’ (n = 18), and participants with the highest scores (i.e., from the 27th percentile for EAT-26 scores with an EAT-26 score above 21) who were labeled ‘high-risk’ (n = 16).
The demographic characteristics of the 34 participants included in stage 2 are presented in Table 1. The median age was 22.94 years (IQR = 4.82). The median weight was 64.85 kg (IQR = 13.07), and the median height was 162.75 cm (IQR = 6.83), resulting in a median BMI of 24.44 kg/m2 (IQR = 4.24). 39 The median salivary concentration of BDNF was 390.91 pg/ml (IQR = 101.81).
Table 1.
Demographic characteristics of participants involved in stage 2 of the study (n = 34).
| Variable | Median (IQR) |
|---|---|
| Age | 22.00 (2.75) |
| Weight (kg) | 60.50 (12.75) |
| Height (cm) | 164.50 (9.75) |
| BMI (kg/m2) | 23.60 (3.35) |
| Highest weight ever (kg) | 69.50 (22.20) |
| BDNF Conc. (pg/ml) | 335.10 (390.10) |
Note: Data are expressed as the median and interquartile range (IQR). BMI: body mass index, BDNF: brain-derived neurotrophic factor.
The demographic, anthropometric, and other variables, including the PSS-10 score, MET/week, and food group consumption, were compared between the two groups categorized as lower risk and higher risk.
Table 2 shows that the median differences between the two groups, lower risk and higher risk, in terms of EDs, BMI, and PSS-10 score, were significantly different (p = 0.011 and p = 0.02), with higher values within the higher-risk group, which had higher BMIs and PSS-10 scores, than within the lower-risk group. BDNF levels did not differ significantly between the two groups. Only fat intake differed significantly, p = 0.004, with lower consumption in the high-risk group. Other food groups showed no statistical differences p > 0.05).
Table. 2.
The median differences between the low-risk and high-risk groups.
| Variable | Low-risk group (n = 18) |
High-risk group (n = 16) |
p-value | |
|---|---|---|---|---|
| Age | 22 (1.5) | 22.5 (4) | 0.834 | |
| Weight (kg) | 58.5 (9) | 66.5 (11) | 0.104 | |
| Highest weight ever (kg) | 62 (13.75) | 73 (23.25) | 0.166 | |
| BMI (kg/m2) | 23.13 (3.34) | 25.16 (4.35) | 0.011* | |
| Height (cm) | 166 (10.13) | 162 (8) | 0.233 | |
| BDNF Conc. (pg/ml) | 391.03 (128.17) | 339.15 (102.52) | 0.347 | |
| PSS-10 | 15.5 (10) | 24.5 (7.75) | 0.02* | |
| Total MET/week | 1192.5 (2114.63) | 4693.5 (6895.5) | 0.003* | |
| Macronutrient consumption | ||||
| Carbohydrates | Starchy foods (grains) (%) | 23.21 (6.76) | 21.1 (10.26) | 0.574 |
| Vegetables (%) | 15.19 (5.4) | 11.68 (15.79) | 0.534 | |
| Dairy (milk) (%) | 7.24 (11.48) | 9.29 (13.56) | 0.772 | |
| Fruits (%) | 11.01 (16.16) | 9.73 (9.25) | 0.796 | |
| Starchy foods (tubers) (%) | 4.04 (5.94) | 5.63 (15.08) | 0.581 | |
| Protein | Protein (animal-based) (%) | 17.01 (8.52) | 14.78 (14.23) | 0.704 |
| Protein (plant-based) (%) | 4.29 (8.37) | 4.65 (7.39) | 0.512 | |
| Fat | Oils (%) | 11.01 (10.98) | 4.65 (12.35) | 0.004* |
Note: Data are expressed as the median and interquartile range (IQR). BMI: body mass index, BDNF: brain-derived neurotrophic factor, PSS-10: perceived stress score, MET/week: metabolic equivalent/week.
p < 0.05
Table 3 shows the Spearman’s rank correlation coefficient that was used to assess the relationships between the study variables. A significant positive correlation was found between BMI and total MET (rho = 0.40, p = 0.020), while no significant correlations were found between BDNF levels and BMI, PSS-10 score, MET, or different food groups. Table 4 shows that the odds ratio for the risk of BDNF-related EDs was 1.07 (95% CI, 1.03–1.10) in the ‘high-risk’ group versus the ‘low-risk’ group.
Table 3.
Spearman’s rank correlation between the study variables.
| BMI | BDNF | CHO % | VEG % | MILK % | FRUITS % | OTHER CHO % | ANIMAL P % | PLANT P % | FAT % | MET/WEEK | PSS-10 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BMI | — — |
|||||||||||
| BDNF | −0.14 0.446 |
— — |
||||||||||
| CHO % | −0.03 0.861 |
0.08 0.636 |
— — |
|||||||||
| VEG % | −0.23 0.181 |
−0.14 0.426 |
0.17 0.336 |
— — |
||||||||
| Milk % | 0.07 0.708 |
0.12 0.499 |
−0.35*
0.045 |
−0.45**
0.008 |
— — |
|||||||
| Fruit % | 0.13 0.448 |
−0.17 0.333 |
−0.20 0.257 |
0.28 0.109 |
−0.05 0.769 |
— — |
||||||
| Other CHO% | −0.02 0.923 |
−0.16 0.369 |
−0.29 0.094 |
−0.26 0.139 |
−0.18 0.299 |
−0.19 0.284 |
— — |
|||||
| Animal p % | 0.26 0.144 |
0.03 0.888 |
−0.07 0.680 |
−0.37*
0.031 |
0.01 0.975 |
−0.43*
0.012 |
−0.21 0.236 |
— — |
||||
| Plant p % | −0.28 0.114 |
−0.06 0.741 |
−0.15 0.403 |
0.11 0.551 |
−0.26 0.141 |
0.01 0.967 |
−0.04 0.818 |
−0.05 0.758 |
— — |
|||
| Fat % | −0.10 0.583 |
0.28 0.109 |
−0.13 0.456 |
−0.19 0.276 |
−0.11 0.543 |
−0.35*
0.044 |
0.27 0.121 |
−0.12 0.489 |
−0.22 0.219 |
— — |
||
| MET/week | 0.40*
0.020 |
−0.22 0.204 |
−0.21 0.225 |
0.25 0.162 |
−0.04 0.816 |
0.08 0.642 |
−0.04 0.829 |
−0.05 0.775 |
0.25 0.154 |
−0.10 0.555 |
— — |
|
| PSS−10 | 0.02 0.905 |
−0.17 0.347 |
−0.09 0.624 |
0.05 0.795 |
−0.05 0.762 |
0.09 0.626 |
0.30 0.083 |
−0.14 0.445 |
−0.04 0.829 |
−0.11 0.540 |
0.33 0.058 |
— — |
Note: Spearman’s rank correlation rho (upper value) and p-value (lower value). BMI: body mass index, BDNF: brain-derived neurotrophic factor, CHO: carbohydrate, PSS-10: perceived stress score; MET/week: metabolic equivalent/week.
p < 0.05, **p < 0.01.
Table 4.
Logistic regression analysis to predict the risk of EDs based on BDNF.
| 95% CI | ||||||
|---|---|---|---|---|---|---|
| Predictor | Estimate | SE | P | Odds ratio (OR) | Lower | Upper |
| EAT-26 Low–EAT-26 High | 0.07 | 0.02 | <0 .001 | 1.07 | 1.03 | 1.1 |
Note: Adjusted for age and BMI: body mass index, BDNF: brain-derived neurotrophic factor. Unadjusted for the PSS-10: perceived stress score, MET/week: metabolic equivalent/week; FFQ: food frequency questionnaire.
Discussion
The main objective of this cross-sectional study was to provide new insight into the influence of BDNF concentration on susceptibility to ED among young female adults. We hypothesized that salivary BDNF might be associated with EDs 40 in addition to alterations in serum and plasma BDNF levels. 13
In contrast, salivary BDNF levels among our study group did not show such alterations concerning EDs. The BDNF level was within the normal concentration range. This outcome is consistent with the findings of Mandel et al. 41 and Tirassa et al., 42 with median values ranging from approximately 400–200 pg/ml throughout the day. Studies indicate that females generally have elevated amounts of circulating BDNF in comparison to males. 43 Notably, BDNF levels among females are affected by the menstrual cycle. Therefore, the slight changes in BDNF levels in our study could be due to abnormalities in estrogen signaling 22 pathways.
Our findings appear to contradict the anticipated outcome, as there was no statistically significant difference between BDNF levels in EDs in the higher-risk and lower-risk groups. However, a simple correlation between BDNF and factors such as starvation or increased body weight did not exist. 22 Few studies have demonstrated a significant correlation between salivary BDNF and EDs. 44 An inverse correlation has been shown between blood BDNF and AN or BN, and BDNF levels are negatively correlated with the severity of symptoms of EDs.22,45
In the current study, BMI significantly differed between the higher- and lower-risk groups, with higher BMIs observed in the high-risk group. This finding is consistent with several studies showing that obesity and EDs have common maintenance and risk factors, including self-dissatisfaction, dieting, concerns about shape/weight, and unhealthy weight control behaviors, which are very common among young adults.13,22,46 Those who were obese or overweight had a greater clinical impairment and greater pathology of the ED than those who were underweight or healthy weight. 47 Moreover, the high-risk group exhibited increased levels of stress and physical activity. These results are consistent with the findings of Grilo et al., 48 who reported that the occurrence of stressful negative life events and increased social and work stress act as warning signs among women for relapse in remission from BN and other EDs. Additionally, high levels of physical activity in individuals with EDs are due to psychological mechanisms and stress because BN and AN individuals have excessive value for their weight and body shape. 49 Therefore, physical activity is a consequence of a conscious effort to work off calories and achieve the ideal thinness they desire, which makes the thinness drive concept an important motivation to participate in physical activity. Furthermore, a significant positive correlation between BMI and physical activity has been found. 50 In this context, there has been a significant increase in compulsive exercise with high levels of ED symptoms. 51 Therefore, exercise has positive effects on muscle strength and mass. 52
Despite the lack of association between BDNF and physical activity levels, our results showed increased physical activity within the high-risk group, which may have led to an increase in the levels of BDNF. Both BDNF and exercise are associated with improvements in neurogenesis. 45 The expression of BDNF is increased by aerobic exercise in humans due to its effect on the hippocampus by regulating the expression of the BDNF gene. 53
Surprisingly, our study did not show a significant difference in the consumption of different food groups between the high- and low-risk groups. The high consumption of artificially sweetened beverages among women with ED is intriguing. 54 High amounts of artificial sweeteners and higher intakes of yogurt and cheese have been demonstrated in nonpregnant women with ED. 55
Associations between BDNF and BMI, stress, or the intake of different food groups were not detected in our study. In contrast, previous studies revealed positive correlations between BDNF serum levels and BMI, suggesting that BDNF concentration changes in the circulation are secondary to the dysregulation of energy balance.44,56 However, one study reported a negative correlation between body weight and BDNF, in which the restriction of caloric intake in overweight individuals was significantly associated with lower BMI and increased BDNF serum levels. 57 The decrease in BDNF levels observed in the circulation of individuals with BN and AN could be a result of the large or low caloric utilization that is induced by purging behaviors or the extreme restriction of food intake often found among individuals with EDs. 19 Leptin is another possible cause of elevated BDNF levels. Compared to controls, individuals with AN have repeatedly been found to have lower leptin serum levels. 58 Further studies should include leptin as a factor for increased BDNF in individuals with ED since Li et al. 57 suggested that BDNF-expressing neurons were targets of leptin and that leptin deficiency decreased BDNF gene expression. 59
In addition, it has been suggested that stress and biological system responses play a role in BDNF changes. 58 Indeed, in animal models, the downregulation of hippocampal BDNF mRNA and neurogenesis, and impaired neuronal branching, is due to chronic stress. 60 Increased levels of proinflammatory cytokines and glucocorticoid hormones, key stress response players, are related to decreased BDNF levels.61,62
Finally, several factors may explain the lack of significant differences in salivary BDNF levels between the low-risk and high-risk ED groups. The fact that BDNF levels in saliva reflect peripheral rather than central nervous system concentrations, potentially limiting their sensitivity as biomarkers for neuropsychiatric conditions, Moreover, BDNF is influenced by various endogenous factors such as hormonal fluctuations, especially estrogen.
Limitation
The study’s limitations were that the small sample size limited the statistical power to detect differences in BDNF levels between groups due to the limited availability of BDNF kits and the fact that female participants was used, rather than both sexes. Therefore, our results do not necessarily represent males. Furthermore, the onset of ED may influence the levels of BDNF. Since BDNF increases with time, increased BDNF could be affected by a long diagnosis period. 62 Accumulating evidence supports the hypothesis that BDNF dysregulation can indirectly increase the risk of developing ED in individuals. Considering that long periods of food restriction induce the expression of BDNF, the change in BDNF levels could also reflect individual ED eating patterns rather than an indication of a direct causative role in the development of the disorder. However, we could not rule out this effect because we did not cover participants’ onset measures. Future research could include more factors and study the associations and their effect on BDNF levels. A post-hoc power analysis (GPower 3.1) revealed 32% power to detect a medium effect size (d = 0.5) at α = 0.05, underscoring the need for larger replication studies.
Conclusion
Salivary BDNF may not appear as a biomarker for ED among young females. The changes in salivary BDNF levels could reflect individual ED eating patterns rather than indicating a direct causative role in the disorder’s development. These results advocate the use of psychiatric consultation for the detection of EDs, emphasizing the need for sophisticated detection beyond biomarkers such as BDNF. As salivary BDNF showed no utility as an ED biomarker in this preliminary study, future work should explore longitudinal designs, larger samples including male and female, and CSF–serum–saliva BDNF correlations to explore the intricate correlation between BDNF and EDs.
Supplemental Material
Supplemental material, sj-pdf-1-whe-10.1177_17455057251376885 for Salivary BDNF to predict at-risk status of eating disorders in young nutritionist Jordanian females: Results from a preliminary multistage study by Aseel AlSaleh, Hebah Abdalla Ali, Amani Ali Almasri, Razan Mahmoud Omoush, Adam Tawfiq Amawi, Mohammed Ahmed Alkharisi, Seithikurippu R. Pandi-Perumal, Khaled Trabelsi, Hadeel Ghazzawi and Haitham Jahrami in Women's Health
Supplemental material, sj-pdf-2-whe-10.1177_17455057251376885 for Salivary BDNF to predict at-risk status of eating disorders in young nutritionist Jordanian females: Results from a preliminary multistage study by Aseel AlSaleh, Hebah Abdalla Ali, Amani Ali Almasri, Razan Mahmoud Omoush, Adam Tawfiq Amawi, Mohammed Ahmed Alkharisi, Seithikurippu R. Pandi-Perumal, Khaled Trabelsi, Hadeel Ghazzawi and Haitham Jahrami in Women's Health
Footnotes
ORCID iDs: Aseel AlSaleh 
https://orcid.org/0000-0003-4652-2341
Amani Ali Almasri
https://orcid.org/0009-0004-6534-7790
Hadeel Ghazzawi
https://orcid.org/0000-0003-3045-4153
Haitham Jahrami
https://orcid.org/0000-0001-8990-1320
Ethics considerations: This study was approved by the Research Ethics Committee of the University of Jordan (Decision ID: UOJ-REC-03-56).
Consent to participate: Written informed consent was obtained from all participants before their enrollment in the study.
Author contributions: Aseel AlSaleh: Conceptualization; Data curation; Methodology; Resources; Writing - review & editing; Writing - original draft.
Hebah Abdalla Ali: Writing - original draft; Writing - review & editing; Methodology; Conceptualization; Data curation; Resources.
Amani Ali Almasri: Writing - original draft; Writing - review & editing; Conceptualization; Data curation; Resources.
Razan Mahmoud Omoush: Writing - review & editing; Data curation; Resources; Conceptualization; Writing - original draft.
Adam Tawfiq Amawi: Conceptualization.
Mohammed Ahmed Alkharisi: Writing - review & editing; Writing - original draft; Conceptualization.
Seithikurippu R. Pandi-Perumal: Writing - original draft; Writing - review & editing.
Khaled Trabelsi: Writing - review & editing; Conceptualization; Writing - original draft; Methodology; Software.
Hadeel Ghazzawi: Conceptualization; Investigation; Writing - original draft; Writing - review & editing; Methodology; Software; Formal analysis; Project administration.
Haitham Jahrami: Formal analysis; Data curation; Methodology; Conceptualization; Supervision; Project administration; Validation; Investigation; Writing - original draft; Writing - review & editing; Software; Resources.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data availability statement: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Supplemental material: Supplemental material for this article is available online.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplemental material, sj-pdf-1-whe-10.1177_17455057251376885 for Salivary BDNF to predict at-risk status of eating disorders in young nutritionist Jordanian females: Results from a preliminary multistage study by Aseel AlSaleh, Hebah Abdalla Ali, Amani Ali Almasri, Razan Mahmoud Omoush, Adam Tawfiq Amawi, Mohammed Ahmed Alkharisi, Seithikurippu R. Pandi-Perumal, Khaled Trabelsi, Hadeel Ghazzawi and Haitham Jahrami in Women's Health
Supplemental material, sj-pdf-2-whe-10.1177_17455057251376885 for Salivary BDNF to predict at-risk status of eating disorders in young nutritionist Jordanian females: Results from a preliminary multistage study by Aseel AlSaleh, Hebah Abdalla Ali, Amani Ali Almasri, Razan Mahmoud Omoush, Adam Tawfiq Amawi, Mohammed Ahmed Alkharisi, Seithikurippu R. Pandi-Perumal, Khaled Trabelsi, Hadeel Ghazzawi and Haitham Jahrami in Women's Health