This study examined the prevalence of gastrointestinal symptoms and their relationship to depressive symptoms and anxiety traits in young adults seeking outpatient psychiatric care. We found a larger burden of gastrointestinal symptoms in patients compared with healthy controls. gastrointestinal symptom severity was positively associated with overall depressive symptom burden and the severity of individual depressive symptoms. Consistent with previous results (34), trait anxiety correlated with gastrointestinal symptom burden independent of the effects from depressive symptom severity, bulimia nervosa gender and BMI.
Patients with IBS are known to have a high psychiatric co-morbidity. This connection between IBS and psychiatric co-morbidity appears to be bidirectional, with a high prevalence of IBS diagnosis and IBS symptoms in psychiatric patients, especially in patients with mood and anxiety disorders (7, 35). In this study, gastrointestinal symptom burden correlated with depressive symptom severity, a finding in accordance with previous evidence (36). One large Korean study, however, reported that IBS was more common in patients with mild depression than in those with severe depression (37). Our current study included only outpatients and therefore may not generalise to inpatients with severe depression. The correlation between the total MADRS-S score and the total GSRS-IBS score in our study showed a larger effect size in controls than in patients. Exaggerated gastrointestinal symptoms may cause a greater impact on mood and function in an otherwise healthy individual than in a psychiatric patient who also suffers from depression or anxiety.
We identified different subgroups within the studied patient population. One subgroup of patients (cluster 4) had a high level of gastrointestinal symptoms (fast and slow bowel and disturbed appetite) together with high trait anxiety and high levels of depressive symptoms. In contrast to cluster 4, patients in cluster 1 did not score high on any of the factors and thus they may constitute a different subgroup of patients, perhaps closer to remission, as it has been shown that patients in remission from recurrent depression do not have more symptoms of IBS than healthy controls (36).
In our study, personality traits reflecting anxiety and stress susceptibility significantly correlated with gastrointestinal symptom burden with the largest effect size for somatic trait anxiety, which is consistent with the proposed presence of somatisation in patients with IBS (38). In animal models, central pathways mediating stress and anxiety have been linked to increased gut sensitivity (39). In patients with IBS, visceral hypersensitivity is a result of several factors, including increased afferent signalling to the brain (40), abnormal descending modulation of pain, and dysfunction of the medial pain system, which is responsible for the emotional aspect of pain (41). Immune activity in the intestinal mucosa or the central nervous system may play a role in the development of visceral hypersensitivity. However, the precise role of immune activity remains contentious (42, 43).
The pivotal question of the causation of disease is the temporal relationship of the onset of symptoms or the making of a classified diagnosis. The use of questionnaires does not focus on this relationship and the long-term observation time needed precludes conclusions as regards to the onset of disease or symptoms. Animal models may be useful to reveal possible etiological factors related to the onset of gastrointestinal symptoms (44–46).
Different theories have been proposed to explain the high co-morbidity of IBS and psychiatric illness in which the GBA plays a central role in mediating this interaction. Alterations of the autonomous nervous system with increased sympathetic and decreased parasympathetic activity can influence perception from the gastrointestinal tract (47). Dysregulation of the HPA axis has also been observed in female IBS patients of which both basal levels of cortisol and stress-induced cortisol levels were elevated compared with healthy controls (48). Moreover, alterations in the gut microbiome have been central in seeking to understand the complex relationship between depression and IBS (49). Significant differences in microbiota composition have been demonstrated in patients with IBS compared with controls (50). The intestinal microbiota can produce neurologically active substances (e.g., gamma-aminobutyric acid and short-chain fatty acids, SCFAs) that can influence immune regulation and the mucosal barrier, but their role in stress-induced behavioural and physiological alterations is poorly understood (51, 52). In mice, administration of SCFAs was found to alleviate stress-induced anhedonia and increased responsiveness to acute stress as well as reversed changes in intestinal permeability caused by psychosocial stress (53). Moreover, breakdown of the mucosal barrier in the gut wall, bacterial translocation and immune activation are believed to result in excessive cytokine production that can affect not only gut functions and the intestinal microflora, but also brain functions and behaviour (54, 55). Elevated pro-inflammatory markers, especially interleukin-1, interleukin-6 and tumour necrosis factor-alpha are seen in patients with depression and we already know that inflammation may induce depression (56).
A limitation of this study is that the patient group is not delimited to a single diagnosis; rather, symptomatic measurements of depression and anxiety levels are analysed, which restricts the possibility to examine differences between individual diagnostic groups. Still, because of the overlap in concomitant diagnoses, specific psychiatric symptoms reflecting different underlying biological mechanisms are probably more relevant. For this reason, the MADRS-S total score, as a measure of the level of depressive symptoms, and the scales of the SSP were used rather than the diagnostic group affiliation to capture these symptoms or behaviours. Here, we wished to investigate the impact of trait anxiety, which is why individual diagnoses of anxiety were not further analysed in the context of gastrointestinal symptoms. Another limitation is that patients completed the SSP questionnaires with ongoing depressive symptoms and a possible state effect cannot be ruled out.
Gastrointestinal symptoms in this study are self-reported. The GSRS-IBS questionnaire was developed to evaluate treatment for IBS and in our study the total score is used as a measurement of symptom burden. This method is likely more inclusive, whereas when the actual diagnosis is used rather than reported symptoms, the propensity to seek medical care must be considered. While the GSRS-IBS total score reflects symptom burden, gastrointestinal symptoms may vary during each week (such as alternating diarrhoea and constipation), which influences the comparison of the total score between individuals. An attempt to visualise this issue is through the cluster analysis in which different groups with a diverse spectrum of symptoms were identified.
Studies have found ameliorated IBS symptoms with SSRI treatment, but also with tricyclic antidepressants (57, 58). Of note, there were no differences in gastrointestinal symptom burden between patients with and without psychotropic medication (antidepressants, including SSRI’s). Indeed, treatment with SSRIs for IBS may not be a “one size fits all” solution, but rather a treatment that only a subpopulation of IBS patients benefits from. In fact, one study reported more IBS symptoms in patients with SSRI treatment (36). The present study design did not allow for distinction from GI side effects from SSRI treatment, why possible benefits may have been cancelled out.
The prevalence of FGIDs is high in patients with eating disorders (59). Patients who met the criteria for anorexia nervosa were excluded because this diagnosis constitutes a very special catabolic state due to starvation, making results difficult to interpret and generalise. Patients with ongoing bulimia were included, although they generally have a high level of self-starvation, but this potential confounder was adjusted for in the generalized linear model and did not influence the results.
Young adults seeking psychiatric care reported more gastrointestinal symptoms than controls, regardless of ongoing psychotropic medication. gastrointestinal symptoms correlated positively with the severity of depressive symptoms and trait anxiety. Although we confirmed significant associations between gastrointestinal and psychiatric symptoms their aetiology is multifactorial, complex and not well understood. The high co-morbidity of mood and anxiety disorders and gastrointestinal symptoms and IBS in early adult life motivates further investigation to identify common denominators in the complex mechanisms underlying these disorders.