Constipation may be tied to more than discomfort

A large review links chronic constipation with a higher likelihood of depression, pointing to gut-brain pathways and the need to assess bowel and mental health together.

Depression is among the most prevalent, disabling mental disorders worldwide, contributing substantially to disease burden and mortality. According to recent global estimates, around 350 million people have depression. Chronic constipation is one of the most common gastrointestinal disorders and causes persistent discomfort, disrupting daily activities and psychological well-being.

Evidence suggests that constipation is often accompanied by psychological distress, raising the possibility of a potential association with depression. The gut-brain axis (GBA) may be a plausible biological framework linking depression to constipation. GBA dysregulation has been implicated in mood disorders, especially depression, and functional gastrointestinal disorders.

Moreover, clinical observations reveal that people with bowel disorders often show depressive symptoms. Gut microbiota alterations may be one of the potential mechanisms underlying the coexistence of depression and constipation. However, epidemiological evidence is inconsistent, with no previous comprehensive systematic review and meta-analysis quantitatively synthesizing this observational evidence.

Meta-Analysis Methods And Measures

In the present study, researchers assessed the association between depression and constipation. First, a comprehensive literature search was performed across PubMed, Embase, Cochrane Library, and Web of Science databases using pertinent keywords. Retrieved records underwent title/abstract screening and full-text review to assess eligibility for inclusion.

Observational studies, including cross-sectional and cohort studies, in the general population were included. Relevant data, including study and participant characteristics and analytical data, were extracted from included studies. The Newcastle-Ottawa Scale was used to evaluate the methodological quality of studies.

The primary outcome was depression in people with or without constipation. Further, random effects models were used to calculate pooled odds ratios (ORs), accounting for both between- and within-study variability. For studies with alternative effect measures, the researchers converted effect sizes into log ORs for inclusion in pooled analyses.

The team computed 95% prediction intervals to determine expected effects in future populations. Funnel plots and Egger’s regression test were used to assess publication bias. Sensitivity analyses included excluding studies with alternative effect measures and performing leave-one-out (LOO) analyses. Subgroup analyses were performed by sex, region, age, sample size, study design, and assessment methods.

Constipation Shows Twofold Depression Odds

Database searches identified 8,153 records. Following deduplication and abstract/title screening, 57 records underwent full-text review. Of these, 14 studies were eligible for inclusion; four additional eligible studies were identified through manual screening of references. As such, 18 studies, including three cohort and 15 cross-sectional studies, were included. Nine studies were conducted in North America, six in Asia, two in Europe, and one in Oceania.

Sample sizes across these studies ranged between 913 and 449,459 individuals, with 730,263 participants included overall. Study populations comprised adults, older adults, and adolescents. Studies assessed depression and constipation using different methods, such as self-report instruments, clinical diagnoses, and medical records. Studies had a moderate to high methodological quality. Fifteen studies directly reported ORs, with 13 providing adjusted estimates.

In contrast, three studies used alternative effect measures, such as standardized mean differences and correlation coefficients. The meta-analysis revealed a significant association between constipation and a higher likelihood of depression, using adjusted estimates where available, although there was substantial heterogeneity between studies. In LOO analyses, excluding any study did not impact the statistical significance or pooled effect estimate.

Similarly, the association remained significant after excluding studies that reported alternative effect measures. The 95% prediction interval ranged between 1.32 and 3.27, suggesting that future studies are likely to observe this positive association, although its magnitude may vary by population, study design, and setting. Funnel plots did not show marked asymmetry, and Egger’s test revealed no significant publication bias.

Moreover, the positive association of constipation with depression remained consistent across subgroups. However, it was stronger in Asian and North American studies, among adolescents, in smaller studies, and across studies using self-reported measures of depression. Further, subgroup analyses by the proportion of females, study design, and constipation assessment method found no significant differences, meaning these subgroup patterns should be interpreted cautiously rather than as definitive subgroup-specific effects.

Gut-Brain Care Implications

In sum, the findings reveal that constipation is significantly associated with approximately twofold higher odds of depression, with a pooled OR of 2.08 and 95% CI of 1.84 to 2.34. The magnitude and direction of the association were consistent despite substantial between-study heterogeneity, and sensitivity analyses corroborated the robustness of the results.

However, because most included studies were cross-sectional and all were observational, the findings cannot establish causality or temporal direction. The relationship may also be bidirectional, with constipation potentially contributing to depressive symptoms through gut-brain mechanisms, while depression may promote constipation through behavioral, dietary, neuroendocrine, and autonomic pathways. Residual confounding, including diet quality and lifestyle factors, also remains possible.

Overall, the results highlight the need for integrated mental health and gastrointestinal care, especially in adolescents and young adults with constipation, while supporting further prospective and mechanistic studies to clarify whether gut-brain pathways explain the observed association.

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Journal reference:

• Ren ZY, Guo ZY, Diao Q, Hashimoto K, Yang JJ, Zhang GF (2026). Constipation is associated with an increased risk of depression: A systematic review and meta-analysis of observational studies. Translational Psychiatry. DOI: 10.1038/s41398-026-04138-8. https://www.nature.com/articles/s41398-026-04138-8