Physical and Psychological Effects of Bariatric Surgery on Obese Adolescents: A Review

The worldwide obesity crisis is not isolated to adults; rather, obesity in adolescents has reached epidemic levels as well. Bariatric surgery continues to be one of the most effective treatments for obesity, both in adults and adolescents, with new evidence continually emerging; however, research surrounding outcomes of these procedures in younger patients is limited in comparison with data available for adults. Further, it is important to examine psychological aspects of obesity in adolescents, as well as effects of surgery on mental health endpoints. Conditions such as anxiety, depression, anger, and disruptive behavior show increased prevalence among obese adolescents, but minimal research exists to examine changes in such conditions following bariatric surgery. Additionally, there is growing evidence of a bidirectional relationship between sleep (quality; disorders) and the development of obesity, and the effects of this relationship are particularly pronounced in the vulnerable adolescent population. This review aims to compile and discuss the results of literature within the last 5 years with regard to overall efficacy of bariatric surgery specifically in adolescent patients in terms of weight and body mass index (BMI) reduction, hormonal changes, and co-morbidity resolution, as well as data surrounding sleep and psychological outcomes. Race, ethnicity, and socioeconomic status were also examined. From this review, we conclude that current research supports bariatric surgery in adolescents as an effective method of treatment for obesity and related co-morbidities; however, minimal long-term data exists to adequately assess efficacy and trends into adulthood. These areas are ripe for future study.


INTRODUCTION
Clinical obesity in adults is characterized by a body mass index (BMI) more than 30 kg/m 2 , and it is the result of multiple, combined factors such as genetics, cultural influences, socioeconomic status (SES), and mental health (1). Over the last four decades, worldwide obesity rates have nearly tripled, and in 2016, close to two billion adults over the age of 18 were overweight or obese-roughly 40 percent of the global population (2). Further, obesity increasingly impacts younger individuals, with 340 million overweight or obese children and adolescents under the age of 19 (2). In children and adolescents, ages 5 to 19, a BMI-for-age more than one standard deviation higher than the World Health Organization (WHO) growth median is considered overweight, and greater than two standard deviations is considered obese (2). Complicating matters further sustainable results, and a measurable impact on lifetime health expenditures and related co-morbidities (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). Klebanoff et al. (4) noted a significant increase of 0.199 in Quality Adjusted Life Years (QALYs) at 3 years post-bariatric surgery, and lifetime costeffectiveness beginning at 5 years post-intervention. Any surgical procedure innately entails risk; however, evidence of long-term physical and psychological benefits, as discussed herein, supports the notion that the rewards, in this case, outweigh the risks.

MATERIALS AND METHODS
For this review, a search was conducted to compile recent data on bariatric surgery outcomes in adolescent patients with regard to weight loss, co-morbidity remission or resolution, sleep, and psychology (Figures 1, 2). Race and socioeconomic status were also examined. Primary studies that examined subjects aged 0-20 and conducted within the past 5 years were considered, and both short-and long-term outcomes were evaluated, using search terms including "bariatric surgery in adolescents" and "obesity in adolescents." Both single and multi-center studies were considered. Though an attempt was made to include studies that used the same or similar metrics for assessing outcomes, measurement variation between studies made doing so impractical. Thirteen primary studies were evaluated, encompassing a total of 1,287 adolescents ( Table 1). Baseline age and BMI ranged from 14 to 19 years and 35 to 91, respectively. The dominant gender was female, and sleeve gastrectomy and Roux-en-Y gastric bypass were the mostperformed procedures.

RESULTS
Overall, significant decreases in weight and BMI were noted across studies, as were beneficial hormonal alterations (Tables 2-4). In terms of co-morbidities, obstructive sleep apnea (OSA), osteoarthritis, type 2 diabetes mellitus, hypertension, and kidney dysfunction showed significant resolution of up to 95% in some cases; while dyslipidemia, depression, and anxiety showed modest or variable improvement (Tables 2-4). Long-term data beyond 6 years was not available, and data beyond 2 years was limited, highlighting the need for further longitudinal examination in this area, particularly concerning developmental and metabolic changes that occur from adolescence to adulthood.

Psychological Endpoints
Most patients retained symptomatic or non-symptomatic status from baseline to 2 years, and remission was more prevalent than the development of new symptomology across studies. Anxiety, depression, disruptive behavior, and anger all decreased significantly at 2 years, contrasted by increases in mood, selfesteem, and self-concept at the same time point, reflected in IWQOL-Kids, BDI, and perceived confidence scores.

BARIATRIC SURGERY: OVERVIEW OF PROCEDURES AND RISKS
Three primary methods of bariatric surgery are commonly performed: Roux-en-Y gastric bypass, sleeve gastrectomy, and the adjustable gastric band. Among these, gastric bypass is generally considered the "gold standard, " with the bulk of evidence in the long-and short-term landing in favor of the procedure for its safety and efficacy (27,48). In the gastric bypass procedure, a 30-milliliter stomach pouch is created by dividing the stomach in half, to which surgeons connect a portion of the small intestine, which has also been divided (48). With a smaller stomach, less food is consumed; and with a shortened small intestine, fewer nutrients are absorbed (48). Additionally, the altered digestive route significantly impacts gut hormones such as ghrelin, leptin, and glucagon-like peptide 1 (GLP-1), resulting in suppression of hunger and stimulation of satiety (48). Those who are not candidates for gastric bypass due to BMI restrictions or severity of co-morbidities, usually undergo a sleeve gastrectomy, which removes 80 percent of the stomach (48), and has been shown to be more effective than the adjustable gastric band (27). In adjustable gastric banding, a reversible procedure, surgeons install an inflatable band around the upper stomach. This leaves only a small area of stomach above the band, thereby reducing the quantity of food the stomach can accommodate (48). Gastric banding, however, has decreased in popularity due to the more dramatic results of the bypass and sleeve methods.
A young person is eligible for bariatric surgery if he/she has a BMI >40, or a BMI >35 with associated clinical illness(es), such as type 2 diabetes, hypertension, chronic liver disease, obstructive sleep apnea (OSA), or cardiac deficits (22,23,49). Additionally, most surgical centers require psychological evaluation lasting 1 month or longer to determine the patient's ability to adhere to dietary guidelines and follow-up after surgery (49), and the patient's insurance must pre-authorize the procedure, creating a barrier for some patients. The most common procedures in these patients are the sleeve gastrectomy and gastric bypass, and patients must have a full team in place prior to surgery, including the surgical staff, nutritional support, psychological support, and an exercise specialist (49).
Risks associated with bariatric surgery in adolescents are magnified by the extent of related co-morbidities, and multiple studies support early intervention to minimize risk of complications (22,23,33,49). Following surgery, patients may face absorption defects, particularly involving micronutrients such as B-vitamins, vitamin D, and calcium, highlighting the necessity for proper nutritional support from family members and specialists (49). Patients should consider ongoing psychological care following surgery, as there is not yet enough long-term data to rule out adverse mental health ramifications (49), or to rule in significant positive change.

Physiological Effects of Bariatric Surgery in Adolescents: Experimental Findings
The dramatic efficacy of bariatric surgery on both weight loss and co-morbidity resolution that is well-documented in adult patients is echoed in available research for children and adolescents. Studies show weight loss of up to 96 percent of excess body weight in the short-term (up to 1 year) and 39.4 percent sustained in the longer-term (up to 6 years), complete resolution or substantial improvement in type 2 diabetes, decreased appetite and increased satiety, and significant resolution of musculoskeletal pain (26,(28)(29)(30)(31)(32)(33).
One large-scale, longitudinal assessment currently being conducted is Teen-LABS (40, 50), a consortium comprised of six clinical sites and a data-coordinating center, gathering information from participating clinical sites to develop a database of surgical outcomes in adolescents. Primary measured surgical outcomes include percent change in BMI, and remission from baseline type 2 diabetes and hypertension, with secondary measured outcomes being incidence of iron and B12 deficiency, and occurrence of abdominal reoperations.
Many of the studies reviewed herein utilize data currently available from this project (4,26,28,33,46). In one such study, Inge et al. (33) reported a decrease in mean weight of 27 percent, a decrease in kidney dysfunction in 86 percent of patients who had such dysfunction at baseline, remission of hypertension in 72 percent, and resolution of dyslipidemia in 66 percent. Weight-related quality of life also showed significant improvement. The researchers did find an increase in iron deficiency in over half of the participants, and 13 percent underwent revision surgeries. This study looked at outcomes after 3 years of followup; consequently, it is one of the longer-term sources of data available.
Inge et al. also performed a secondary study looking exclusively at adolescents with type 2 diabetes, comparing data from Teen-LABS to that from TODAY, a study in which participants were randomized to receive metformin therapy only, metformin therapy in combination with rosiglitazone, or an intensive lifestyle intervention (26,51). A cohort of 30 subjects in the Teen-LABS study showed a decrease in mean hemoglobin A1c concentration from 6.8% at baseline to 5.5% over the course of 2 years, while that in the 63 subjects in the TODAY study increased from 6.4 to 7.8% (26). Further, mean BMI in the Teen-LABS group decreased by 29%, while mean BMI in the TODAY group increased by 3.7% (26). These results offer compelling support for bariatric surgery in these cohorts; however, for accurate comparison, it is necessary to examine prospective studies to eliminate possible confounders and biases.
One such prospective cohort, and another source of long-term data is the ongoing study by Zitsman et al. which recently posted 5-year follow-up data for all 137 study participants regarding BMI and %EWL endpoints (47). Researchers found a mean postlaparoscopic banding decrease in %EWL of 35.5 percent (39.4% standard deviation), and a percent BMI decrease of 36.6 (37.5% standard deviation) at 5 years. Similar results are reported by Olbers et al. in a Swedish nationwide study that also followed participants over 5 years; however, in this cohort, the surgical method evaluated was Roux-en-Y gastric bypass (42), rather than gastric banding. Participants in this study had a mean (95% CI) weight reduction of 36.8 kg (32.8-40.9 kg), and a mean decrease in BMI of 13.1 kg/m 2 (14.5-11.8 kg/ m 2 ). The study also reported significant co-morbidity resolution and a decrease in cardiovascular risk factors over the 5 years; however, researchers noted weight loss of <10 percent in nine participants (11%). These longitudinal studies reflect an even greater degree of efficacy than previously seen in Teen-LABS (40,50), and again highlight the need for further long-term data.

Psychology in the Obese Adolescent: Experimental and Observational Findings
Recent evidence suggests that bariatric surgery has a significant and positive impact on the psychological co-morbidities of obese teenagers. A study by Schmitt et al. examining the outcomes of laparoscopic adjustable gastric banding, in addition to noting positive physiological outcomes (Tables 1-3), also gathered data on the perceived reasons for the onset of obesity in the adolescent patients (45). According to the responses, more than half of the participants attributed the start of their weight gain to a single, deleterious life event (45), such as divorce or a parental suicide, and the same proportion presented with a psychiatric history at baseline. In addition, study participants noted teasing (n = 11), decreases in selfesteem (n = 7), body dissatisfaction (n = 14), anxiety (n = 5), and attempted suicide (n = 1) as triggers of current psychological distress. This study found an improvement in depressive symptoms and social isolation at 1 year post-surgical intervention, and results from Psychosocial PedsQL evaluations noted statistically significant improvement at both 1 and 2 year endpoints in emotional functioning, social functioning, and school functioning (45). However, the study was performed in a specialty obesity center with a cohort of only 16 subjects, so it is not necessarily generalizable to the population as a whole. Jarvholm et al. examined a cohort of Swedish adolescents, aged 13-18, in an attempt to determine if the positive psychological outcomes observed in research available for adult patients were mirrored in these younger patients at 2-years post-surgery (44). According to Jarvholm et al. (44), anxiety, depression, anger, and disruptive behavior all decreased significantly at 2 years post-bariatric surgery in a cohort of 88 adolescents, using Beck Youth Inventory (BYI) scores. Additionally, self-esteem and self-concept improved significantly at 1 year post-surgery, with stabilization occurring by the 2-year mark.
Hunsaker et al. (43) found less dramatic improvement over 2 years, with most of the subjects maintaining their symptomatic psychological status; however, remission or improvement was more common than the occurrence of new symptomology. These findings were mirrored by Zeller et al. (46); however, this study utilized Youth Self-Report (YSR) and Adult Self-Report (ASR) examinations, which have the potential to introduce bias. The study had a follow-up period that lasted as long as 6 years, however, making it one of the longest-term studies currently available for analysis. It is important to note the difficulty of evaluating psychological improvement, as studies measure according to clinical diagnosis, which does not always apply uniformly across individuals. Further, self-reported methods are often employed, resulting in potential bias. More study, particularly long-term and objective, is needed to clearly assess the mental health changes, though initial results in both adult and adolescent studies lend strong evidence to the efficacy of bariatric surgery on psychological endpoints.

Sleep Quality and Disorders in the Obese Adolescent: Experimental Findings
Sleep disorders such as obstructive sleep apnea (OSA), circadian rhythm disorders, and poor sleep quality show a high prevalence in obese adolescents (17). He et al. found that habitual sleep variability is significantly associated with abdominal and visceral obesity (17), and even more compelling, that 20 percent of the association with visceral adiposity can be attributed to carbohydrate intake, an effect more clearly delineated in a recent review by St-Onge et al. (18). Additionally, due to a delay in melatonin release during the adolescent years, teenagers are more prone to sleep restriction resulting from the delayed sleep onset, combined with the early start of the typical school day (17). Such short sleep duration can lead to weight gain and eventual obesity, due to an increase in neuronal reward responses to unhealthy foods, potential alterations in hormonal activity (leptin, ghrelin, GLP-1, orexins), and the increased time awake that leads to higher caloric intake (18)(19)(20). Similarly, in a randomized, crossover, sleep restriction-extension paradigm, Beebe DW et al. reported that adolescents with chronic sleep restriction tend to consume high glycemic index foods, and that such sleep restriction could cause lasting changes in dietary habits that increase the risk of obesity into adulthood (52). Many obese adolescents also experience varying degrees of OSA (37), and according to findings by Talib et al. OSA is closely related to BMI Z-score (3.7 vs. 3.4; P = 0.003) (53).
Mounting evidence suggests that bariatric surgery is instrumental in reversing or minimizing the impact on sleep caused by obesity (36,37), and can even be beneficial in stabilizing hormonal factors that interfere with proper sleep structure (38). According to findings by Amin et al. (38), apnea hypoxia index (AHI) decreased post-surgery from 15.8 events per hour at baseline to 9.1 events per hour at 5 weeks postsurgery. In the same cohort, leptin levels decreased significantly and orexin levels increased significantly, demonstrating an early alteration in hormone activity following surgical intervention. Ashrafian et al. (37) found similar improvements in OSA in their recent meta-analysis, noting significantly stronger results in those who received bariatric surgery vs. traditional weight loss interventions. In one of the few studies examined that focused on gastric banding, Zitsman et al. (34) utilized polysomnography to diagnose 35.8% of study subjects (49 patients) with OSA, and the researchers noted a resolution of OSA in 17 of those patients post-surgery. It is important to note, however, that complication rates in this study were more prevalent than in studies investigating sleeve and bypass techniques, and improvement in OSA was measured by self-report rather than formal re-testing. Few studies are available that examine the changes in OSA following bariatric surgery in adolescents specifically-and even fewer look at the long-term efficacy; consequently, more data is needed prior to definitive conclusions regarding the positive outcomes noted here.

Race, Ethnicity, and Socioeconomic Status: Experimental and Epidemiological Findings
As with the vast majority of medical procedures, socioeconomic status (SES) plays a role in patient eligibility due to quality of insurance, cost of support structures and specialists, proximity to high-quality facilities, and availability of transportation/lodging when necessary. Because obesity has been strongly linked to those of lower SES and has a disproportionate impact on Black and Hispanic adolescents when compared with non-Hispanic whites (11,41,(54)(55)(56), considering not only SES, but also race, ethnicity, and geographic location is important when examining the accessibility of bariatric surgery for some of the most at-risk populations. In reviewing the current literature, very few studies specifically focus on these areas with regard to bariatric surgery outcomes in adolescents. Gullick et al. (56) examined both race and SES in relation to bariatric surgery outcomes, finding similar improvements in comorbidities, but lower weight loss in African American subjects than European Americans at 1, 2, and 5 year endpoints. The study, however, enrolled 74.4 percent European Americans, and only 25.6 percent African Americans, and it also studied adult, rather than adolescent, subjects. Based on the evidence, it appears that SES may be a bigger predictor of outcomes than ethnicity; however, not enough data exist to make a definitive conclusion (55,56). What can be assessed is that those of lower SES or living in rural areas further from reputable medical centers, have more post-operative complications and lower success rates than those with better access to resources (11).
Perez et al. found that age-adjusted severe obesity rates were higher in minority adolescent groups: black adolescents have a rate of 8.6% and Hispanic adolescents a rate of 8.4%, while white adolescents have less than half that rate at 4.1% (P = 0.03) (57). The researchers also found that white adolescents utilize bariatric surgery at a much higher rate than black or Hispanic patients, and that there is a paradoxical relationship with regard to insurance type (57): minority patients are even less likely to undergo weight loss surgical procedures if they carry Medicaid rather than private insurance; however, white patients with Medicaid are much more likely to undergo such procedures than those insured by private carriers. Though the reasons for such dichotomy are as of yet unclear, what Perez et al. pointed out was that the solution is far more complex than a simple expansion of government-sponsored health insurance. As with many complicated issues, there are several components at play here, including cultural context/norms, health education, and physical access to care. Each must be examined specifically within the context of the adolescent population to determine future public health measures that could mitigate such disparity and ensure a more equitable distribution of care.

CONCLUSION
For decades, bariatric surgery has been considered a highly effective treatment method for adults with morbid obesity and related co-morbidities; however, efficacy and safety in children and adolescents, particularly with regard to metabolic profiles, psychology and sleep disorders, has not been adequately evaluated, especially for long-term outcomes. The data presented in this review lends further support to the continued use of bariatric surgery in adolescents, with an emphasis on the need for further long-term data and more extensive data on metabolic changes in this population post-surgery. In compiling this review, it is important to note the limitation in making adequate comparisons, as metrics used to determine endpoints of obesity, such as BMI, percent excess weight loss (%EWL), percent weight loss (%WL), and total weight loss, are not uniformly measured across studies. Additionally, this review examined a wide range of factors regarding bariatric surgery and adolescent obesity, though a lengthy review could easily be written for each individual aspect. As the obesity epidemic shows no signs of decline, findings in this area will become increasingly vital to health care professionals and policy makers alike.
Note: The BASIC trial, the first randomized, controlled trial looking at bariatric surgery as a treatment for adolescents for whom lifestyle interventions have failed, is in its early stages, and could provide useful long-term data in the future, including insights into psychosocial outcomes (58). Additionally, several clinical trials and prospective cohort studies are currently pending completion, recruiting, or generating results. Findings from these projects could yield the much-needed information regarding the long-term safety and efficacy of bariatric surgery in younger patients that this paper has found to be currently lacking.

AUTHOR CONTRIBUTIONS
CR designed and conducted research, analyzed data, wrote the paper, primary responsibility for final content, read, and approved the final manuscript.