This study aimed to compare adult women of varying weight categories in terms of symptoms of generalised anxiety disorder and depression assessed via the PHQ-9 and GAD-7 questionnaires, respectively. We hypothesised that there is an association between body weight and questionnaire scores, with increasing significance as BMI rises. Additionally, we hypothesised that the use of anti-obesity medication and bariatric surgery status would impact GAD-7 and PHQ-9 scores.
As we anticipated, both GAD-7 and PHQ-9 scores demonstrated a positive correlation with BMI. This is consistent with prior studies using these assessment tools [22, 23, 24] and aligned with meta-analyses indicating a relationship between body weight and depressive and anxiety disorders [6, 7]. This connection is complex, with current understanding suggesting an interplay between psychological and biological pathways [6]. Obesity contributes to heightened psychological distress. Cultural norms surrounding beauty ideals may amplify body dissatisfaction and lower self-esteem, both of which are linked to depression and anxiety [7, 25, 26]. Women with obesity are more likely to be dissatisfied with their weight and experience social problems as compared to women of culturally acceptable weight [27]. Disrupted eating patterns, eating disorders, and physical discomfort stemming from obesity elevate depression risk and psychological distress [28, 29]. Sleep disturbances are also significant as sleep loss can contribute to the maintenance and/or exacerbation of anxiety and depression [30]. Notably, disruption of sleep associated with major depressive episodes is a significant factor in weight gain [31]. Looking at the pathophysiology, obesity can be understood as a chronic low-grade inflammation of fatty tissue, and activating inflammation pathways could lead to developing depression and anxiety [32, 33, 34]. Obesity often involves dysregulation of the hypothalamic-pituitary-adrenal axis, a well-established factor in both of the disorders [35, 36]. Its chronic activation is associated with chronically stressful or traumatic experiences; immunosuppression; and alteration in monoaminergic pathways, including noradrenaline, dopamine and serotonin. Increased body weight also increases the risk of insulin resistance, potentially leading to brain alterations and heightened depression risk [37]. Dysregulated mesolimbic dopamine signalling is implicated in both obesity and major depressive disorder (MDD), with individuals showing alterations in dopamine receptor availability and responsivity to rewards [38].
The scores also showed a negative correlation with age. This is in line with different studies using GAD-7 [39, 40]. For PHQ-9, this may be due to the relatively young age of the participants. In a study on 15,847 participants, the average values of the PHQ-9 total scores followed a reverse U-shaped pattern: starting low during young adulthood, increasing during middle adulthood, and then decreasing during older adulthood [41]. Since the average age of our participants was 38.89 (SD = 9.00), we might have only observed a part of this trajectory. Similar correlations for both questionnaires might be due to the fact that there are a few similar items in both the subscales, regarding being restless, having difficulty sleeping or relaxing. In addition, both depression and anxiety symptoms are part of the same mood disorder category, share a common domain of negative affect, and share a cognitive process with negative bias in information processing. This finds confirmation in other research utilising these tools [42, 43].
In our study, patients undergoing semaglutide treatment demonstrated reduced scores for both anxiety and depression symptoms. While evidence supporting this correlation in other studies is limited, there is more comprehensive data regarding liraglutide which is also a GLP-1 agonist. In randomised controlled phase 2 and 3a trials with patients on a 3.0 mg dose, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs. 2.9 ± 3.1 for liraglutide vs. placebo improved to 1.8 ± 2.7 vs. 1.9 ± 2.7, respectively, at treatment end, supporting the neuropsychiatric safety of this class of medication [44]. In another study involving women with PCOS undergoing liraglutide 1.8 mg treatment, psychological health markers improved compared to the control group after the treatment [45]. It’s worth noting that psychiatric adverse events from using incretin medications are generally rare, and when studied, comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide [46]. However, there have been reports of semaglutide-associated depression, which resolved after withdrawing the medication [47]. Recently, there have been concerns about the impact of anti-obesity medication on mental health, specifically after patients prescribed semaglutide have anecdotally reported suicidal ideations [48]. This has spurred European regulatory agencies to investigate this potential association. However, comprehensive studies have not supported these claims, as semaglutide was associated with a lower risk of suicidal thoughts than other anti-obesity and anti-diabetes drugs [49].
Women who underwent bariatric surgery screened less frequently for anxiety in our study. Recent meta-analysis from 2022 also suggests improvement in mood symptoms after post-bariatric surgery [50]. The pooled proportion of patients with anxiety symptoms reduced from 24.5% pre‐operatively to 16.9% post‐operatively. There were significant reductions in Generalised Anxiety Disorder Assessment‐7 score by 0.54. The pooled proportion of depressive symptoms reduced from 34.7% pre‐operatively to 20.4% post‐operatively. There were also significant reductions in the Patient Health Questionnaire‐9 score. The mean follow‐up duration of post‐bariatric surgery was 34 months. It’s important to underline that our study didn’t specify when the surgery took place. Several studies have reported less favourable long‐term mental health outcomes post‐bariatric surgery, with some stating that the initial improvement of depressive symptoms was not sustained beyond the first postoperative year [51]. The prevalence of post-bariatric surgery depression is also relatively high with almost one in five patients affected by it. Depression might be related to weight regain, eating disorders, and quality of life [52]. Additionally, it is suspected that long-term malabsorption might be related to the incidence of major depressive disorder after bariatric surgery, but the possible causal relationship between nutritional deficiency after bariatric surgery and major depressive disorder needs more investigation [53].
The evidence of moderate research shows that the risk of suicide and self-harm increases after bariatric surgery [54]. Thus, we are not drawing arbitrary conclusions from our observations and are convinced that this area requires further research.
The authors are aware of the limitations of this study, starting with the lack of representativeness of the study group and inability to reach individuals without internet access or outside of themed support groups. Some studies have suggested that depression can influence the validity of self-reported BMI in the obese population and that women especially underestimate their BMI [54]. Moreover, this study was cross-sectional and as such no causal pathways could be investigated. We had no information on previous medical history including the use of antidepressant medication. We were also unaware of the timeframe of use of anti-obesity medication or bariatric surgery. Finally, it's important to note that while the PHQ-9 and GAD-7 are cost-effective screening instruments, they are not sufficient substitutes for a clinical diagnosis of depression and anxiety, respectively. Psychological support for participants was not provided.