Looking Beyond Anxiety and Depression: Integrating Neurological Factors in Chronic Constipation

We read with great interest the article by Zhao et al. addressing the association between psychological factors and refractory chronic constipation [1]. The authors conducted a retrospective study on 610 patients and demonstrated that anxiety, depression, and somatic symptoms are independent risk factors for treatment-refractory constipation [1]. Their findings highlight the close relationship between psychological disorders and symptom severity as well as quality of life impairment, regardless of therapeutic response [1]. While the study provides valuable insights into the interplay between psychological comorbidities and chronic constipation, several limitations and clarifications should be taken into consideration. In the study, the authors applied rigorous inclusion and exclusion criteria, addressing demographic variables, gastrointestinal comorbidities, systemic diseases, and medication use [1]. Nevertheless, several relevant neurological factors were not taken into account. It is well established that central nervous system damage can profoundly influence gastrointestinal motility and bowel function. For example, both ischemic stroke and acquired traumatic brain injury may result in neurogenic bowel dysfunction, frequently manifesting as chronic constipation [2]. Importantly, neuroimaging studies have shown that bilateral lesions involving the precentral gyrus, insula, opercular part of the inferior frontal gyrus, and the inferior parietal lobule, as well as lesions in the right middle frontal gyrus, are significantly associated with impaired bowel function and constipation [3]. These findings underscore the importance of integrating neurological assessment into the evaluation of patients with refractory constipation. Failure to account for such factors may lead to underestimation of potential etiologies, misclassification of patients, and, ultimately, less effective therapeutic strategies. Future research should therefore include neurological conditions and lesion-related factors in order to provide a more comprehensive understanding of the determinants of refractory constipation. Another important aspect that was not addressed in this study is the potential contribution of comorbid conditions that are themselves strongly associated with anxiety and depression. For instance, patients with obstructive sleep apnea syndrome (OSAS) have a markedly higher prevalence of anxiety and depression compared with the general population, independent of sex [4]. More broadly, sleep disorders of various kinds—such as insomnia, poor sleep quality, and reduced sleep duration—are recognized risk factors not only for psychological disturbances but also for gastrointestinal dysfunction [5]. In particular, accumulating evidence indicates that sleep disturbances are independently associated with an increased risk of chronic constipation [6]. Taken together, these observations suggest that the relationship between psychological disorders and refractory constipation may, at least in part, be mediated or amplified by comorbid conditions such as sleep disturbances. Therefore, a more comprehensive assessment of sleep-related factors could further refine the interpretation of the findings by Zhao et al. and contribute to a more integrated understanding of the biopsychosocial mechanisms underlying chronic constipation. Another relevant factor that warrants consideration is the presence of neuromuscular disorders, which can significantly impact gastrointestinal function. For example, patients with conditions such as myotonic dystrophies and Duchenne muscular dystrophy exhibit a high prevalence of chronic constipation [7, 8]. Moreover, the pharmacological treatments commonly used in neuromuscular diseases may themselves contribute to bowel dysfunction [7, 8]. Muscle relaxants such as baclofen or tizanidine, frequently prescribed in amyotrophic lateral sclerosis or spasticity, as well as certain calcium channel blockers and diuretics like furosemide, can exacerbate constipation [7, 8]. Conversely, some therapies may alleviate constipation or even cause the opposite effect; for instance, pyridostigmine used in myasthenia gravis, by enhancing cholinergic activity, can increase gastrointestinal secretions and motility, potentially leading to diarrhea and thereby masking underlying constipation. Taken together, these observations highlight the complex interplay between neuromuscular pathology, therapeutic interventions, and gastrointestinal function. This underscores the importance of carefully accounting for neuromuscular disorders and their treatments when evaluating patients with refractory constipation, as both the disease process and pharmacological management can significantly modulate bowel symptoms. In conclusion, while the work by Zhao et al. provides valuable insights into the role of psychological factors in refractory chronic constipation, a more comprehensive approach that also considers neurological, neuromuscular, and sleep-related contributors could further refine our understanding and improve patient management. Integrating these multidimensional factors into both research and clinical practice may ultimately lead to more precise, individualized, and effective therapeutic strategies for patients suffering from chronic constipation. The author declares no conflicts of interest. This article is linked to Zhao et al. papers. To view these articles, visit https://doi.org/10.1111/nmo.70162.