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    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.162397.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Opinion Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Elucidating the interrelations between fibromyalgia, anxiety, and depression in Rheumatoid arthritis and Osteoarthritis: Implications for patient care and the need for in-depth research</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: awaiting peer review]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Raza</surname>
                        <given-names>Ahmed Asad</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0004-2930-8188</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Akhtar</surname>
                        <given-names>Syed Owais</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Zehra</surname>
                        <given-names>Syeda Farwa</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0003-7608-5661</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Samadi</surname>
                        <given-names>Abedin</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0007-8614-3924</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan</aff>
                <aff id="a2">
                    <label>2</label>Department of Medicine, Kabul University of Medical Sciences Abu Ali Sina, Kabul, Afghanistan</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:abedinsamadi4@gmail.com">abedinsamadi4@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>1</day>
                <month>4</month>
                <year>2025</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2025</year>
            </pub-date>
            <volume>14</volume>
            <elocation-id>373</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>21</day>
                    <month>3</month>
                    <year>2025</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Raza AA et al.</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/14-373/pdf"/>
            <abstract>
                <p>Osteoarthritis (OA) and rheumatoid arthritis (RA) are prevalent, debilitating conditions causing significant joint pain and functional impairment. OA affects over 30% of the global population, while RA impacts around 1%, with risk factors including age, sex, and smoking. Both disorders are frequently accompanied by psychological issues such as anxiety and depression, which exacerbate physical symptoms and lead to additional health problems. Fibromyalgia, often co-occurring with OA and RA, further complicates these conditions with symptoms like widespread pain and stiffness. This creates a vicious cycle where pain and inflammation contribute to worsening anxiety and depression, further impairing quality of life. The interplay of these conditions results in severe physical, emotional, and social consequences, including restricted mobility and increased economic burden due to healthcare costs and reduced work capacity. Current research highlights significant comorbidity but is limited by small sample sizes and reliance on self-reported data. There is a critical need for larger, more comprehensive studies to explore these interactions and inform integrated treatment strategies. Enhanced awareness and holistic care approaches are essential to improving outcomes for patients with these chronic conditions.</p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Fibromyalgia; osteoarthritis; rheumatoid arthritis; anxiety; depression</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec1" sec-type="intro">
            <title>I. Introduction</title>
            <p>Rheumatic disorders include many different types, and the most prevalent painful and disabling diseases worldwide are osteoarthritis and rheumatoid arthritis, that lead to pain, swollen joints, and progressive damage to articular cartilage.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>,
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>Osteoarthritis (OA) is a well-known cause of disability, with an estimated global prevalence of more than 30%. Further, its prevalence is increasing because of rapid population growth. Risk factors for OA include person factors (age, sex, obesity, and genetics) and joint factors (deformity, malalignment, and injury) that interact in an intricate manner. Roughly 10% of those over 55 have painful, incapacitating osteoarthritis (OA), of which 25% are severely impaired.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>,
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> Rheumatoid arthritis (RA) is a persistent inflammatory illness that can lead to joint degradation and impairment. The prevalence of RA is approximately 1% worldwide. The majority of cases of RA are in older women. Risk factors include smoking as main environmental factor.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <p>In individuals with OA and RA psychological discomfort, such as sadness, anxiety, or low mood, has been linked to increased pain levels. A 7-year follow-up study found a connection between OA and personality problems, substance addiction, and affective diseases (such as depression and bipolar disorder).
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup>
            </p>
            <p>In addition to discomfort, the patient&#x2019;s functional deterioration results in additional health issues. An increased risk of cardiovascular disease, osteoporosis, obesity, and psychological issues is associated with a wmore sedentary lifestyle. Fibromyalgia which is also an additional problem associated with OA and RA has multiple symptoms like tachycardia, dyspnea, anxiety, stress and stiffness throughout the body which significantly impair quality of life and result in huge degree of functional impairment. In Europe, the frequency of FM is 2.5%, with a 3:1 female-to-male ratio.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>,
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup>
            </p>
        </sec>
        <sec id="sec2">
            <title>II. The vicious trio: Fibromyalgia, anxiety and depression in arthritis</title>
            <p>The fibromyalgia-depression and anxiety-pain relationships have long been associated, particularly as part of the triad with rheumatoid arthritis (RA) or osteoarthritis. These factors not only exist side-by-side, but actually influence and worsen each other to create a neverending cycle of patient misery. Pain itself is anxiety and depression enhancing, as observed in the largely pain syndromes RA/OA alongside fibromyalgia.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> The relentless stream of pain signals can also saturate the nervous system, triggering anxiety and a sense of desperation that not infrequently seem to intensify side by side with the pain. In addition, inflammation which is another common factor plays an important role in this crosstalk. Higher levels of inflammatory cytokines, which we see in both RA/OA and fibromyalgia, have been associated with changes n brain chemistry that can lead to anxiety- or depression-like moods.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup>
            </p>
            <p>Apart from the physical connections, a psychological and emotional connection of having to live with RA/OA sure are an inviting medium for mental health repercussions. The erratic nature of these diseases, the physical constraints they impose and their often-invisible presence combine to create feelings of anxiety or depression and despair. This is even more problematic because the signs and symptoms of each overlap so it can be hard to tell where one condition stops while another starts. For example, the tiredness that is a cardinal UCTD symptom &#x2014; and present to some extent in all three conditions liste d above&#x2013; can certainly make concentration difficult (even when anxious or depressed) mean you get irritable very easily; deprived of energy over prolonged periods it can have an impact on mood. A particularly common feature of both fibromyalgia and the comorbid anxiety disorders is sleep disturbances that may serve to compound pain perception, increase fatigue, as well as contribute to feelings of hopelessness often seen in depression.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup>
            </p>
        </sec>
        <sec id="sec3">
            <title>III. The potentially life-changing consequences for patient</title>
            <p>This comorbidity of fibromyalgia, anxiety and depression has a significantly negative influence on the physical function of patients with rheumatoid arthritis (RA) or osteoarthritis (OA), as well their emotional health status, social functioning and economic costs. These individuals also often have physical pain, and be exquisitely tender to even minor forms of touch. Acute pain, combined with the fatigue and stiffness that define these types of conditions can greatly restrict movement even at very low grades &#x2014; what would otherwise be mild activities like walking or takeoff.
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup> However, this never give-up attitude can only last so long before becoming exhausting and wearing &#x2014; physically to act in spite of the suffering and potential disaster; mentally from stripping your humanity away voiding self-esteem into a deep emotional hole.</p>
            <p>Socially, they can stop participating in activities that gave them joy before, like feeling judged or inadequate compared to their friends. These individuals are made to feel more detached from their society, compounding the sense of loneliness and depression that further perpetuates their misery. Economically, it can be just as &#x2013; if not more destructive. These conditions are unpredictable, and maintaining regular employment can be challenging &#x2014; resulting in economic hardship. In addition, managing multiple chronic conditions often requires costly medications, therapies, and trips to the doctor- necessary expenses that can create financial constraints on individuals as well as their families. They are especially difficult to diagnose and treat. Despite their overlapping symptomatology that often results in misdiagnosis or delayed treatment&#x2014;clinicians targeting the most overt symptoms without recognizing the disordered systems these characteristics emerge from. As a result, the pain is seldom adequately managed, and the mental health issues underlying many of these claims are never addressed in any meaningful way; time after time we hear from patients who have become trapped in an endless cycle of misery followed by disappointment.</p>
        </sec>
        <sec id="sec4">
            <title>IV. The need for research and awareness &amp; potenitial solution</title>
            <p>A recent retrospective study in a tertiary healthcare setting found that about 40% of patients with osteoarthritis (OA) and 36% with rheumatoid arthritis (RA) had at least one comorbidity.
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup> However, the study has notable limitations that underscore the need for further investigation. Its cross-sectional design restricts the ability to track disease onset and progression over time. Additionally, data were collected from a single rheumatology clinic, which may limit the applicability of the findings to other settings or populations. The focus on patients receiving specialized care could also skew results, potentially overestimating the prevalence of severe comorbidities like anxiety, depression, and fibromyalgia compared to other studies, which report lower prevalence rates for these conditions
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup>; 18-24% prevalence of fibromyalgia in RA patients
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>
                </sup> and 17.6% prevalence of anxiety in RA patients
                <sup>
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> and 19.9% prevalence of depression in OA patients.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>
                </sup>
            </p>
            <p>The study&#x2019;s reliance on self-reported data without objective clinical measures introduces potential bias, and it did not consider factors such as socioeconomic status, healthcare access, or psychological support. Furthermore, it did not compare comorbidity rates in OA and RA patients with age- and sex-matched individuals in the general population, missing an opportunity for context.
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup>
            </p>
            <p>Given these limitations and the complexity of comorbidities associated with OA and RA, further research is crucial. More comprehensive studies are needed to address these gaps and explore a broader range of comorbidities, as previous research has identified various conditions linked to OA and RA although there is limited data to support the evidence.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>,
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> OA has been linked with several co-morbids such as vascular diseases, metabolic conditions, rheumatic diseases and neurological disorders
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup> meanwhile RA has been linked with cardiovascular, respiratory, neurological and gastrointestinal conditions
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> so it would be better to include all the co-morbids and outcomes under one roof and do a extensive research from worldwide by having a meta analysis of the datas from all over the world not being heterogeneous. This would be impactful and raise awareness among healthcare professionals and the public for early diagnosis and effective management, ultimately improving patient outcomes.</p>
        </sec>
        <sec id="sec5" sec-type="conclusion">
            <title>V. Conclusion</title>
            <p>The intricate interplay between fibromyalgia, anxiety, and depression in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) underscores the urgent need for a comprehensive approach to patient care. The coexistence of these conditions not only exacerbates physical pain but also significantly impairs emotional well-being, social functioning, and overall quality of life. The compounded effects of these comorbidities create a vicious cycle that can lead to a downward spiral in both physical and mental health.</p>
            <p>To address this pressing issue, it is imperative to increase awareness among healthcare providers and the general public. Early diagnosis and a holistic, integrated treatment approach are essential for managing these complex cases effectively. Furthermore, there is a critical need for more in-depth research that explores the full spectrum of comorbidities associated with RA and OA, utilizing larger, more diverse patient populations and objective clinical measures.</p>
            <p>By investing in research and adopting a multidisciplinary approach to treatment, we can significantly improve the quality of life for patients suffering from these chronic conditions. Let us work together to ensure that individuals with RA and OA receive the comprehensive care they need, freeing them from the additional burdens of fibromyalgia, anxiety, and depression. Prioritizing holistic care is not just a medical necessity but a moral imperative, with the potential to transform the lives of millions worldwide.</p>
        </sec>
        <sec id="sec6">
            <title>Ethics and consent</title>
            <p>Ethical approval and consent were not required.</p>
        </sec>
    </body>
    <back>
        <sec id="sec9" sec-type="data-availability">
            <title>Data availability statement</title>
            <p>No data are associated with this article.</p>
        </sec>
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