Associations Between Genetic Polymorphisms and Psychological Variables in Women With Fibromyalgia: A Cross‐Sectional Study, 2025, Riquelme‐Aguado….

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Associations Between Genetic Polymorphisms and Psychological Variables in Women With Fibromyalgia: A Cross‐Sectional Study, 2025, Riquelme‐Aguado et al.

ABSTRACT

Introduction Fibromyalgia (FM) is a multifactorial syndrome involving chronic pain and psychological distress. Psychological traits such as anxiety, depression, and catastrophising are linked to symptom severity. Genetic variability may contribute to these dimensions through mechanisms related to pain modulation and stress response.

Objectives

To examine associations between selected genetic polymorphisms and psychological variables in women with FM. Methods A cross‐sectional study was conducted in 67 women diagnosed with FM. Pain intensity, FM impact and psychological variables—anxiety, depression and catastrophising—were assessed using validated questionnaires. Saliva samples were collected and 10 SNPs were genotyped ( COMT rs4680, DRD3 rs6280, OPRM1 rs1799971, BDNF rs6265, MAOA rs1137070, FKBP5 rs1360780, IL6 rs1800796, TNF rs1800629, IL10 rs1800896, IFITM3 rs12252). Correlations were assessed using Pearson or Spearman coefficients, and associations were examined using ANOVA or Kruskal–Wallis with Tukey or Mann–Whitney post hoc tests.

Results

Pain intensity correlated with depression ( r = 0.476, p < 0.001), catastrophising ( r = 0.414, p < 0.001), and anxiety ( r = 0.314, p = 0.009). Catastrophising was related to depression ( r = 0.615, p < 0.001), anxiety ( r = 0.453, p < 0.001), and kinesiophobia ( r = 0.445, p < 0.001). BDNF rs6265 was associated with catastrophising ( p = 0.044), OPRM1 rs1799971 with anxiety ( p = 0.030), and MAOA rs1137070 with depression ( p = 0.020).

Conclusions

Psychological variables in FM are interrelated and linked to pain perception. BDNF , OPRM1 and MAOA polymorphisms are associated with indices of psychological vulnerability, underscoring the importance of integrating genetic and psychological perspectives to understand variability in FM. Significance Statement Genetic variability influences psychological vulnerability in fibromyalgia. Specific variants were associated with key psychological traits: BDNF rs6265 with pain catastrophising, OPRM1 rs1799971 with anxiety, and MAOA rs1137070 with depressive symptoms. These findings reveal an interplay between genetic and psychological factors that may guide more personalised strategies for managing fibromyalgia.

 
Fibromyalgia (FM) is a chronic and disabling syndrome, predominantly affecting women, and characterised by widespread pain, fatigue, cognitive dysfunction, and sleep disturbances (Wolfe et al. 2013). Although its aetiology remains unclear, evidence supports a multifactorial origin involving central sensitisation (Or-Borichev et al. 2025), neuroendocrine dysfunction (Demori et al. 2024), and immune alterations (Nizzero et al. 2025).
In this framework, psychological factors such as anxiety, depression, and pain catastrophising are increasingly recognised as integral to FM pathophysiology, shaping symptom expression and trajectory (Bushnell et al. 2013; Ellingson et al. 2018; González-Álvarez et al. 2024; Ji et al. 2018; Karakuş et al. 2025; Malfliet et al. 2017).
This is what you get when you do questionnaire research..
 
I have high pain tolerance (per MD lancing an infected finger) prior to developing FM.
No depression.

However, severe FM has been a monster both daily and over decades.

How blinded these researchers seem to me, to the effects of the illness itself on the brain. The "anxiety, depression, and pain-catastrophizing" framework--is just waiting to be activated in 5+ percent of the population afflicted with FM?

And how unhelpful to PwFM to rehash their theory with each scientific advance.
 
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