Reciprocal interaction between depression and pain: results from a comprehensive bidirectional Mendelian randomization study and functional annotation analysis

Tang, Bowen; Wang, Meng; Hägg, Sara; Burgess, Stephen; Jiang, Xia

doi:10.1097/j.pain.0000000000002305

Cited by 32 publications

(33 citation statements)

References 40 publications

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“…Conversely, chronic facial pain increased the risk of seeking care for depression (i.e., pain → depression only [Supplementary Table S7]). These findings are broadly consistent with other genetic studies concerning depression and chronic pain, which have shown genetic causal relationships between chronic pain and depression, spanning both depression → pain pathways 54–58 and pain → depression pathways. 20,52,55,59 Taken together, our results and previous findings 19,20,27,54,55 raise further intriguing hypotheses, such as that either or both causal directions may exist on a patient sub-group basis.…”

Section: Discussionsupporting

confidence: 91%

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

Farrell

Kho

Campos

et al. 2022

Preprint

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Background: The multifactorial heterogenous nature of chronic pain with its multiple comorbidities presents a formidable challenge in disentangling the aetiology underlying patient symptoms. Methods: Here, we performed genome-wide association studies (GWAS) of eight types of regional chronic pain using UK Biobank data (N=4,037-79,089 cases; N=239,125 controls), followed by bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine (respectively) their genetic correlations and genetic causal proportion (GCP) parameters with 1,492 other complex traits. Findings: We report evidence of a shared genetic signature in common regional chronic pain types, with their genetic correlations and causal directions being broadly consistent across a wide array of biopsychosocial traits. Furthermore, we identified 5,942 significant genetic correlations, of which 570 trait pairs showed evidence of a likely causal association (|GCP| > 0.6; 5% false discovery rate), including 488 traits contributing to chronic pain while 82 were affected by pain. A range of somatic pathologies (e.g., musculoskeletal, visceral), psychiatric factors (e.g., depression, trauma, anxiety, mania, bipolar disorder), socioeconomic factors (e.g., occupation) and other medical comorbidities (e.g., cardiovascular disease) contributed to an increased risk of regional chronic pain. Conversely, each chronic pain type contributed to various other traits such as increased medication use (e.g., analgesics) and risk of ischaemic heart disease and depression. Interpretation: Findings of this data-driven study, through comprehensive analysis of a vast range of biopsychosocial factors, are indicative of a common genetic signature underlying eight regional chronic pain types. We identify a broad range of traits with genetic causal effects upon chronic pain, which may inform development of novel diagnostic and therapeutic strategies, as well as provide convergent support for various existing approaches.

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Section: Discussionsupporting

confidence: 91%

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

Farrell

Kho

Campos

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Our finding that elevated depressive symptoms were associated with pain is consistent with recent literature, but provides an important extension to a middle‐income country 4,5,39,40 . We found evidence of an association between pain and incident elevated depressive symptoms, supporting a bidirectional association of both pain and depression across different study populations 4–6,23,39–42 . Although health factors were fairly consistent by gender, age, and social support differentially impacted pain, suggesting demographic and psychosocial factors may be major drivers of the gender differences observed in pain burden.…”

Section: Discussionsupporting

confidence: 89%

“…Shared risk factors included older age, lower educational attainment, comorbidities, and disability status. This is consistent with a recent Mendelian randomization study which leveraged genetic variants to establish a causal link between depression and pain at specific body sites 23 . More broadly, a literature review cross‐sectionally estimated a 65% mean prevalence of pain symptoms (i.e., self‐reported complaints of pain, chronic pain, or pain scales) in adults with depression in psychiatric and clinical settings.…”

Section: Introductionsupporting

confidence: 84%

“…4,5,39,40 We found evidence of an association between pain and incident elevated depressive symptoms, supporting a bidirectional association of both pain and depression across different study populations. [4][5][6]23,[39][40][41][42] Although health factors were fairly consistent by gender, age, and social support differentially impacted pain, suggesting demographic and psychosocial factors may be major drivers of the gender differences observed in pain burden. Conversely, marital status, consumer durables, and insurance status differentially impacted the risk of elevated depressive symptoms, suggesting that only sociodemographic factors may be major drivers of the gender differences observed in depression burden.…”

Section: Discussionmentioning

confidence: 99%

“…This is consistent with a recent Mendelian randomization study which leveraged genetic variants to establish a causal link between depression and pain at specific body sites. 23 More broadly, a literature review cross-sectionally estimated a 65% mean prevalence of pain symptoms (i.e., self-reported complaints of pain, chronic pain, or pain scales) in adults with depression in psychiatric and clinical settings. Alternatively, the mean prevalence of concurrent major depression in patients with pain ranged from 13% to 85%, based on the study settings.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The pain and depressive symptoms cascade: A bidirectional analysis of the Mexican Health and Aging Study 2012–2015

Gutierrez

Wong

Milani

2022

Int J Geriat Psychiatry

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Objectives:The association of pain and depression has not been evaluated in lowand middle-income countries, which have a disproportionate burden of pain compared to high-income countries. Methods:Using data from the Mexican Health and Aging Study (baseline, 2012; follow-up, 2015), we examined the bidirectional relationship between pain and depressive symptoms and identified shared predictors among community-dwelling participants ≥60 years (n = 7237). Multivariable logistic regressions models evaluated the association between (1) baseline pain and incident elevated depressive symptoms and (2) baseline depressive symptoms and incident pain, adjusting for demographic, socioeconomic, and health-related factors. Models included inverse probability weights and evaluated interactions by gender.Results: Participants (55.0% women) were on average 69.1 years old. Over half reported no pain (60.7%) and low/no depressive symptoms (67.9%) in 2012, of which, 20.2% reported elevated depressive symptoms and 25.3% self-reported pain in 2015. Baseline pain was associated with higher odds of incident elevated depressive symptoms (aOR 1.65; 95% CI, 1.41-1.93). Baseline elevated depressive symptoms were associated with higher odds of developing pain (aOR 1.57; 95% CI, 1.32-1.87). Age, gender, self-rated health, and activity of daily living limitations were shared risk factors for pain and elevated depressive symptomatology onset.Although the incidence of elevated depressive symptoms and pain was higher in women, there were no statistically significant interactions.Conclusions: Older adults with pain or depression may be at risk for developing the other. These shared predictors could help identify patients in clinical settings, where pain and depression are often overlooked, reducing the cascading risk of this comorbidity.

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Mendelian randomization highlights sleep disturbances mediated the effect of depression on chronic pain

Zhu,

Bi,

Zhu

2024

Brain and Behavior

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IntroductionDepression and chronic pain are significant contributors to the global burden of disease. Previous research has revealed complex relationships between these two conditions, which may be influenced by sleep quality. However, observational studies have limitations, including confounding factors and reverse causation. This study aims to explore the mediating effects of sleep on the relationship between depression and chronic pain using Mendelian randomization (MR).MethodsWe conducted a two‐step, two‐sample MR study using mediation analysis. We obtained major depressive disorder (MDD) Genome‐Wide Association Studdies (GWAS) data from Wray et al.’s GWAS meta‐analysis. Phenotypic data related to sleep were collected from the UK Biobank. Chronic pain data were obtained from the Finnish database.ResultsMR analysis revealed significant genetic associations between MDD and chronic localized pain [IVW: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.16–1.38, p = 2.52 × 10–7] as well as fibromyalgia (IVW: OR = 2.17, 95% CI = 1.34–3.52, p = .002). Genetic susceptibility for MDD was also associated with insomnia (IVW: OR = 1.10, 95% CI = 1.06–1.13, p = 3.57 × 10–8) and self‐reported short sleep duration (IVW: OR = 1.03, 95% CI = 1.00–1.06, p = .047). The mediating effects of insomnia and fibromyalgia on the pathway from depression to chronic regional pain were 1.04 and 1.03, respectively, with mediation proportions of 12.8% and 15.2%. Insomnia mediated the pathway between depression and fibromyalgia with an effect of 1.12, accounting for 15.2% of the total effect.ConclusionThis two‐step MR analysis strengthens the evidence of genetic predictive associations between depression and chronic pain, highlighting the mediating roles of insomnia and short sleep duration. It further elucidates the specific roles of distinct sleep disorders, differentiating insomnia and short sleep duration from other sleep‐related phenotypes.

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Reciprocal interaction between depression and pain: results from a comprehensive bidirectional Mendelian randomization study and functional annotation analysis

Abstract: Supplemental Digital Content is Available in the Text. Mendelian randomization study supports that depression is a causal risk factor for headache and pain at neck/shoulder, back, and abdominal/stomach.

Cited by 32 publications

References 40 publications

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

The pain and depressive symptoms cascade: A bidirectional analysis of the Mexican Health and Aging Study 2012–2015

Mendelian randomization highlights sleep disturbances mediated the effect of depression on chronic pain

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