Rheumatic and musculoskeletal diseases (RMDs) are deeply intertwined with complex affective disorders. Beyond the profound physical burden of chronic pain and functional limitation, patients frequently present with comorbid psychological distress. Emerging evidence suggests that this high comorbidity is not merely a secondary reaction to physical suffering, but is driven by a profound, bidirectional neuroimmunological crosstalk. Systemic inflammation, mediated through the immune-neuroendocrine axis, can directly alter central nervous system function, while psychological distress can conversely precipitate physical symptomatology through central sensitization. Despite this established link, existing investigations predominantly examine anxiety and depression within isolated cohorts. Systematic efforts to quantitatively delineate and compare the psychological landscape across diverse RMD phenotypes remain conspicuously scarce. The primary objective of this study was to conduct a comprehensive systematic review and meta-analysis to map psychological distress levels across seven major RMDs—Fibromyalgia (FM), Systemic Lupus Erythematosus (SLE), Osteoarthritis (OA), Systemic Sclerosis (SSc), Primary Sjögren's Syndrome (pSS), Rheumatoid Arthritis (RA), and Behçet's Disease (BD)—and establish a robust, evidence-based risk hierarchy to identify high-susceptibility subgroups.

The study protocol was prospectively designed and strictly adhered to the PRISMA and MOOSE reporting guidelines. A systematic literature search was conducted across three major electronic databases: PubMed, Web of Science (Core Collection), and the Cochrane Library, from inception to November 2025. The search syntax intersected core domains of the seven specified RMDs and targeted psychological outcomes. To guarantee methodological homogeneity and eliminate the confounding effects of somatic symptoms (e.g., fatigue, pain, insomnia) that frequently overlap with RMD systemic manifestations, inclusion was explicitly restricted to adult observational studies employing the Hospital Anxiety and Depression Scale (HADS) as the psychometric outcome measure. Following rigorous screening and data extraction, a random-effects single-arm meta-analysis was performed using the R statistical environment to calculate the pooled effect sizes (ES) and mean scores for the specific patient cohorts. Heterogeneity was evaluated using Cochran’s Q test and the I² statistic, supplemented by predefined subgroup analyses and methodological quality assessments.

The final analysis incorporated 109 independent studies, yielding a cumulative cohort of 14,351 patients. Methodological quality across included studies was robust. The meta-analytic pooling demonstrated a substantial and clinically significant psychological burden across the RMD spectrum, yet revealed a highly divergent, disease-specific hierarchy of neuropsychiatric impairment.

For anxiety symptoms, the severity ranked in the following descending order: FM exhibited the most profound impairment (ES: 1.63), followed by pSS (ES: 0.88), BD (ES: 0.76), SLE (ES: 0.65), RA (ES: 0.51), OA (ES: 0.36), and SSc (ES: -0.12).

For depressive symptoms, FM (ES: 1.48) and BD (ES: 0.89) exhibited the highest levels of distress. Intra-disease comparisons unveiled distinctive neuropsychiatric signatures. FM demonstrated a severe, high-burden profile driven primarily by central sensitization. Conversely, conditions like pSS and SLE exhibited an anxiety-predominant profile. Notably, BD presented a unique depression-predominant signature, distinguishing it from other RMDs; this is likely attributable to its profound Th1/Th17-mediated systemic vasculitis and endothelial activation, creating a vascular-inflammatory "double hit" that severely compromises blood-brain barrier integrity in mood-regulating subcortical circuits.

Furthermore, comparative analysis highlighted that the overall psychological burden in FM was approximately three times higher than that observed in RA. Subgroup analyses indicated that while female predominance served as a macroscopic risk amplifier across certain connective tissue diseases, severe psychological distress remained highly pervasive across all age strata. Potential limitations of this study include an inherent English-language publication bias and the potential for residual indirect somatic overlap despite the use of HADS, although comprehensive sensitivity analyses confirmed the statistical robustness of these findings.

Anxiety and depression are highly prevalent systemic manifestations across all major RMDs, but their severity and phenotypic expression vary significantly by specific disease type. Patients with FM, BD, and pSS represent uniquely high-risk populations characterized by severe psychological morbidity. Recognizing these distinct profiles necessitates a paradigm shift in rheumatological care, moving away from generic, uniform screening toward a stepped-care, phenotype-tailored framework. Routine integration of somatic-independent psychometric instruments like the HADS, coupled with targeted neuropsychiatric interventions for high-susceptibility phenotypes, is imperative to optimize holistic, patient-centered clinical management and disrupt the debilitating cycle of physical and mental deterioration.