Evidence for the association between psychological stress and peri-implant health among middle-aged and elderly adults: A systemic review

Abstract

BACKGROUND

Chronic psychological stress (CPS) is increasingly recognized for its detrimental effects on systemic and oral health, yet its impact on peri-implantitis remains underexplored.

AIM

To evaluate the evidence linking CPS to peri-implantitis.

METHODS

This systematic review was conducted according to the PRISMA guidelines. Publications searching PubMed, EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov for human studies published in English from 1983 to December 2024. Additionally, quality assessment of selected full-text articles were performed using the modified Newcastle–Ottawa Scale.

RESULTS

From an initial total of 3964 studies, 4 cross-sectional studies comprising 432 participants met the inclusion criteria and consistently demonstrated a positive association between CPS and peri-implantitis. However, the findings are compromised by small sample sizes, study design limitations, methodological heterogeneity, and inadequate adjustment for critical confounders such as smoking and prior periodontitis.

CONCLUSION

Cortisol levels in peri-implant sulcus fluid were linearly correlated with probing depth, with evidence suggesting this relationship may be independent of hyperglycemia. Depression emerged as the most significant CPS subtype associated with peri-implantitis. Additionally, CPS may amplify peri-implantitis inflammation by modulating cytokine expression effects. Long-term studies with larger, more diverse patient populations and careful control of confounding variables are needed to establish causality and understand the underlying mechanisms. Including psychological evaluations and stress management techniques in peri-implant care protocols could improve treatment outcomes and patient health.

Key Words: Chronic psychological stress; Cortisol; Peri-implantitis; Periodontitis; Systemic review

Core Tip: The bidirectional oral-brain axis has been recently proposed. Numerous contemporary studies have highlighted the association between psychological distress and periodontitis. However, the relationship between psychological distress and peri-implantitis remains unclear. Although the current evidence is limited, all human studies to date suggest that psychological distress increases the risk of peri-implantitis, similar to its impact on periodontitis.

INTRODUCTION

The human body continuously adapts to internal and external changes to maintain stability, a process known as homeostasis. This dynamic equilibrium relies on a complex interplay of physiological mechanisms, particularly stress response pathways regulated by hormones such as cortisol, adrenaline, and noradrenaline[1]. These hormones activate the autonomic and central nervous systems, enabling the body to respond effectively to stressors in a process called allostasis[1,2]. While allostasis facilitates adaptation to fluctuating environmental conditions[2], chronic activation of stress response pathways can result in "allostatic load", a physiological dysregulation linked to pathological conditions, e.g. cardiovascular dysfunction, metabolic derangements, and impaired glucose homeostasis[3-5]. These adverse outcomes arise through both direct neuroendocrine-autonomic dysregulation and indirect behavioral changes, highlighting the multifaceted health impacts of chronic psychological stress (CPS)[6,7].

CPS has been shown to significantly affect oral health, particularly in the development and progression of periodontal diseases[8,9]. Chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to prolonged glucocorticoid hormone release, result in immune suppression[6,8]. This immunosuppressive state weakens host defenses against oral pathogens, exacerbates inflammatory processes, and accelerates tissue destruction. Clinical and experimental evidence consistently demonstrates that CPS heightens inflammatory processes, delays wound healing, and contributes to periodontal tissue deterioration, underscoring its critical role in periodontal health[6,8-10].

Peri-implantitis, an inflammatory condition characterized by the progressive destruction of peri-implant tissues, shares similar pathophysiological mechanisms with periodontitis but presents unique challenges due to the implant-tissue interface[11]. Despite the well- established link between CPS and periodontitis, the association between stress-induced immune modulation and peri-implantitis remains inadequately explored[12-14]. Investigating this relationship is crucial for understanding the broader impact of CPS on oral health and for developing targeted therapeutic and preventive strategies to mitigate peri-implant tissue destruction. This systematic review aims to bridge this knowledge gap by examining the pathophysiological links between CPS and peri-implantitis in human models, advancing our understanding of how CPS translates into biological effects.

MATERIALS AND METHODS

Protocol and search strategy

This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines[15]. A systemic and comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, MEDLINE, Cochrane Library and the ClinicalTrials.gov, with a focus on English-language publications. Furthermore, reference lists of retrieved articles and relevant reviews were manually screened to identify additional studies. Search terms were constructed using specific keywords combined with Boolean operators, including [(heart rate) OR (blood pressure) OR (cytokines) OR (cortisol) OR (catecholamines) OR (copeptin) OR (salivary amylase) OR (interleukin-6) OR (C-reactive protein)] OR [(psychological health) OR (mental health) OR (psychological stress) OR (mental stress) OR (psychological disorders) OR (mental disorders)] AND [(peri-implant health) OR (peri-implantitis) OR (peri-implant mucositis) OR (osseointegration)]. The final update of the search was performed on December 10, 2024.

Screening method and data extraction

Two independent reviewers (Yen-Lan Chang and Shih-Ying Lin) conducted eligibility assessments and data extraction using standardized forms. Titles and abstracts were initially screened against predefined criteria. Full-text reviews were conducted for studies meeting eligibility requirements, and disagreements were resolved through discussion or consultation with a third reviewer (Kun-Zhe Tsai). The review exclusively included clinical investigations in human samples, such as randomized and non-randomized controlled trials and cohort studies examining the association between CPS and peri-implantitis prevalence. Systematic and narrative reviews, case reports, letters, commentaries, in vitro studies, and animal experiments were excluded.

Quality assessment and risk of bias

Efforts were made to address missing or unclear data by contacting corresponding authors. In cases of data redundancy across publications, the most comprehensive dataset was extracted. The quality and risk of bias (ROB) were evaluated using a modified Newcastle–Ottawa Scale for cross-sectional studies (Supplementary Table 1), ensuring a rigorous evaluation of study reliability and validity[16,17]. The review focused on human studies directly examining dental implants, specifically excluding pediatric studies and studies centered on natural teeth.

RESULTS

Systemic review following PRISMA guidelines

Figure 1 presents the selection process in a PRISMA flow diagram. A total of 3964 studies were identified after database searches, with 1292 duplicates subsequently excluded. After screening titles and abstracts, 9 studies were retrieved for full-text evaluation. During this stage, 5 studies were excluded for specific reasons detailed in Supplementary Table 2. Ultimately, 4 cross-sectional studies comprising 432 participants fulfilled the stringent inclusion criteria and were comprehensively analyzed.

Figure 1 Flow diagram of the study.

Quality assessment and risk of bias

Table 1 reveals the quality assessment of included studies. Among these four eligible studies, one had a low ROB[18], two showed a moderate ROB[19,20], and one was assessed as having a high ROB[21]. All studies exhibited selection bias due to the non-random selection of participants and small sample sizes. Only one study explicitly excluded individuals with a history of periodontitis[21], while another study excluded those with active periodontal disease[20]. One study noted that participants had no active periodontal disease at the time of implant placement[18], and another did not report whether periodontal conditions were considered during participant selection[19]. Moreover, one study failed to adjust for key confounding factors[19], such as smoking and blood glucose, which may affect cortisol levels in bodily fluids[22,23].

Table 1 Modified Newcastle–Ottawa Scale for included studies.

Ref.	ROB	Selection		Study design				Outcome assessment		Confounding factor assessment		Data analysis		Study results
		Representative sample	Adequate sample size	Accuracy of exposure/risk factors	Data quality control	Definition of cases and controls	Selection of control group	Accuracy of outcome	Timing of outcome assessment	Control of confounding factors	Stratification or multivariate analysis	Appropriateness of statistical methods	Reporting of results	Consistency of results	Openness and reproducibility
Soysal et al[21], 2024	Medium				+	+	+	+	+				+	+	+
Strooker et al[20], 2022	Low			+	+	+	+	+		+	+	+	+	+	+
Ali et al[19], 2022	High							+						+
Alresayes et al[18], 2021	Medium				+	+	+	+				+		+	+

ROB: Risk of bias.

Study characteristics and outcomes

Table 2 illustrates the major characteristics of these four studies. CPS was assessed through cortisol levels in peri-implant sulcular fluid (PISF) in two studies[19,21], via questionnaires in one study[18], and through a combination of questionnaires with measurements of glucocorticoid receptor-α GRα concentration in another[20]. While one study explicitly reported no antipsychotic drug use among participants[20], the remaining three studies did not address medication status, making it uncertain about the potential effect of antipsychotic drugs on the results[18,19,21]. Peri-implantitis definitions varied across the studies. Two studies[19,20] adhered to the 2017 World Workshop consensus criteria, which included probing depth ≥ 6 mm, bleeding on probing/suppuration, and marginal bone loss ≥ 3 mm[11]. One study employed less stringent criteria, defining peri-implantitis as probing depth ≥ 4 mm, bleeding on probing/suppuration, and marginal bone loss ≥ 2 mm[18]. Another study did not provide the definition of peri-implantitis[21].

Table 2 Characteristics of the included studies.

Ref.	Country	Design	Participants	Study groups and age (mean ± SD)	Smoker	Psychological health assessment	Antipsychotic drugs	Definition of peri-implantitis
Soysal et al[21], 2024	Turkey	Cross-sectional	50 (F 16/M 34)	Healthy implant & high stress: 53.06 ± 11.44 years; Healthy implant & low stress: 52.11 ± 16.70 years; Peri-implantitis & high stress: 56.00 ± 6.71 years; Peri-implantitis & low stress: 59.80 ± 7.24 years	No	HAD and STAI questionnaires; GR-α levels of saliva	No use	PD ≥ 6 mm, BoP/suppuration, and BL ≥ 3 mm
Strooker et al[20], 2022	Netherlands	Cross-sectional	230 (F 137/M 93)	No peri-implantitis: 64.4 ± 11.3 years; Peri-implantitis: 62.9 ± 10.8 years	10%	SCL-90 questionnaire	Not available	PD ≥ 4 mm, BoP/suppuration, and BL ≥ 2 mm
Ali et al[19], 2022	Kuwait	Cross-sectional	64	T2DM with peri-implantitis: 53.8 ± 5.6 years; T2DM without peri-implantitis: 52.5 ± 3.2 years; Non-DM with peri-implantitis: 52.7 ± 1.6 years; Non-DM without peri-implantitis: 52.2 ± 1.2 years	No	Cortisol level in peri-implant sulcular fluid	Not available	Not available
Alresayes et al[18], 2021	Saudi Arabia	Cross-sectional	88 (F 42/M 46)	Peri-implantitis: 65.3 ± 5.6 years; No peri-implantitis: 63.8 ± 4.4 years	No	Cortisol level in peri-implant sulcular fluid	Not available	PD ≥ 6 mm, BoP/suppuration, and BL ≥ 3 mm

HAD: Hospital anxiety and depression scale; STAI: State-trait anxiety inventory; GRα: Glucocorticoid receptor-α; PD: Probing depth; BoP: Bleeding on probing; BL: Bone loss; SCL-90: Symptom checklist-90; T2DM: Type 2 diabetes mellitus.

Three studies[18,20,21] identified a potential association of CPS with peri-implantitis, with one study[21] revealing this relationship persisted independently of hyperglycemia. Notably, although one study similarly identified a positive result, the authors cautioned that while elevated PISF cortisol levels may indicate CPS, the measurements alone could not definitively confirm chronic stress levels in affected patients[19]. Additionally, in absences of controlling for established confounding factors, such as smoking and blood glucose concentrations, a conclusive relationship between CPS and peri-implantitis cannot be established[19]. Since the heterogeneity of the data and the variety of studies included, a further meta-analysis could not be conducted.

DISCUSSION

Cortisol, the primary glucocorticoid synthesized in the adrenal cortex's zona fasciculata, has been extensively studied for its role in systemic stress responses[24,25]. Recent studies have reported significant positive associations between cortisol levels and probing depth in peri-implantitis, with the strongest correlations observed in individuals without Type 2 diabetes (T2DM)[19,21]. Alresayes et al[19] demonstrated linear relationships between cortisol levels, probing depth, and crestal bone loss, while Ali et al[19] additionally observed this association only in participants without T2DM. In contrast to cortisol-focused studies, Strooker et al[18] utilized the Symptom Checklist-90 (SCL-90) to assess psychological distress across eight subdomains, identifying depression as the only psychological variable significantly associated with peri-implantitis in univariate analyses [odds ratio (OR) = 2.150, 95% confidence interval (CI) = 1.147–4.032]. Even after adjusting for confounders such as smoking, medical treatments, and lung conditions during a five-year follow-up, depression remained an independent risk factor (OR = 2.036, 95%CI = 1.067–3.884)[18]. Building upon the evidence presented in previous studies, Soysal et al[20] offer another approach to exploring the relationship between CPS and peri-implantitis by integrating questionnaire-based assessments with biomarker analyses. CPS was evaluated using the Hospital Anxiety and Depression Scale and the State-Trait Anxiety Inventory, alongside measurements of salivary GRα mRNA expression, a stress-related biomarker. Although no significant association was observed between GRα levels and peri-implantitis, their analysis of salivary cytokines suggested that CPS might exacerbate peri-implantitis-related inflammation by influencing cytokine expression[20].

Clinical data linking the psychological stress to peri-implantitis are limited. While CPS has been extensively studied in relation to periodontitis, offering valuable insights, these findings can only serve as a reference due to fundamental differences between the two conditions. Peri-implantitis is an immune-mediated complication driven by bacterial biofilms on implant surfaces, with unique pathophysiological mechanisms distinct from periodontitis[26]. Unlike mineralized hydroxyapatite of teeth, implant surfaces—typically composed of titanium dioxide or other alloys—alter initial bacterial adhesion through differing electrostatic forces and ionic interactions[26]. These differences may lead to distinct biofilm characteristics and expose peri-implant tissues to implant degradation products, which can affect microbiota behavior and immune responses[26]. Further investigation into the relationship between peri-implantitis and CPS should build on the established understanding of periodontitis and stress to uncover both shared and distinct pathways. Nevertheless, the binary oral-brain axis concept, originally proposed in the context of periodontitis, remains a valuable framework for reference.

Discovery of epidemiology

Many observational studies have reported an association between periodontitis and CPS, regardless of the source of stress, including financial[27], occupational[28], marital[29], or military-related stress[30-32]. However, the evidences are not entirely consistent, as not all studies have demonstrated a clear link between CPS and periodontal tissue destruction. A systematic review conducted in 2007 assessed stress and psychological factors as potential risk factors for periodontitis, with 57.1% of these studies reporting a positive association, 28.5% observing mixed outcomes (positive for some characteristics and negative for others), and 14.2% finding no association[33].

Among neuropsychiatric disorders, major depression is the most extensively studied for periodontitis. Three systematic reviews with meta-analyses have examined the association[34-36]. Findings from cross-sectional studies alone did not reveal a significant relationship between periodontitis and depression[34-36]. However, analyses incorporating case-control studies demonstrated a significant association between periodontitis and depression. Liu et al[34], conducted a meta-analysis combining cross-sectional and case-control studies, reporting a significant association (OR = 1.61, 95%CI = 1.16–2.23). Similarly, a subgroup analysis in Zheng et al’s study[35] focusing on severe periodontitis showed a higher likelihood of depression (OR = 1.43, 95%CI = 1.05–1.93).

Emerging evidence suggests that the relationship between periodontal health and depression may be bidirectional[37]. A cohort study by Hsu et al[38] examined 12708 patients with newly diagnosed periodontitis and 50832 periodontally healthy matched controls over a follow-up period of 5 to 11 years. After adjusting for sex, age, and comorbidities, individuals with periodontitis exhibited a 1.73-fold increased risk of developing depression compared to controls. Additionally, a three-year longitudinal study of 7656 older adults in Japan found that edentulous individuals had a higher risk of developing depressive symptoms[39]. Regarding to peri-implantitis, Strooker et al[18] reported that individuals with depression have approximately twice the odds of having peri-implantitis compared to those without depression.

Discovery of oral microbiota

Periodontitis is increasingly recognized as a potential contributor to CPS and central nervous system (CNS) dysfunction through diverse mechanistic pathways. Periodontal pathogens such as Porphyromonas gingivalis can access the CNS via hematogenous spread, cranial nerves, or circumventricular organs, compromising the integrity of the blood-brain barrier (BBB) and enabling bacterial invasion[40]. These pathogens activate microglia and trigger immune responses, with lipopolysaccharides (LPS) engaging toll-like receptors (TLRs) and factor nuclear kappa B (NF-κB) signaling to generate reactive oxygen species and pro-inflammatory cytokines[41-44]. These processes disrupt CNS homeostasis and may allow intracellular survival of pathogens via mechanisms like the Trojan horse strategy[45,46]. The neuroinflammation underscores an association between oral dysbiosis and CNS pathology[47].

In addition to vascular and neural routes, evidence suggests a potential lymphatic pathway connecting the oral cavity to the brain. Microorganisms such as oral Treponema have been identified in cerebrospinal fluid and the fourth cerebral ventricle, implicating the lymphatic system in the dissemination of oral bacteria[48,49]. Tooth loss and reduced chewing efficiency may impair venous and lymphatic return, facilitating bacterial entry into lymphatic circulation and subsequent systemic dissemination[48,50,51]. Although regional lymph nodes contain antigen-presenting cells to neutralize pathogens, certain bacteria evade phagosome-lysosome fusion, exploiting host cell migration to reach cerebral sites, including the III and IV ventricles[48].

Systemic inflammation associated with periodontitis further exacerbates neuroinflammation through endothelial NF-κB activation, macrophage recruitment, and sustained microglial activation. The lymphatic system’s drainage into the bloodstream may amplify bacteremia, particularly in the context of weakened BBB integrity[52]. Additionally, exosomes, nanoscale vesicles involved in cellular communication, have been implicated in disease progression. Alterations in salivary exosomal markers and the identification of immune-related proteins linked to severe periodontitis underscore the connection between oral dysbiosis and systemic immune modulation[40,53].

Discovery in immunology

Under acute psychological stress, the body's initial response is driven by the sympathoadrenal medullary (SAM) system, which activates rapidly to prepare for immediate action—the "fight or flight" response[54]. The SAM system promptly triggers the release of catecholamines, particularly adrenaline and noradrenaline, from the adrenal medulla[55]. Following this immediate SAM system response, the HPA axis is engaged to sustain the stress response over a longer period. When activated, the HPA axis initiates the release of corticotropin-releasing hormone from the hypothalamus, which in turn stimulates the anterior pituitary to secrete adrenocorticotropic hormone (ACTH)[6,8,56]. ACTH then prompts the adrenal cortex to release cortisol, a glucocorticoid that initially enhances immune activity by boosting natural killer (NK) cell function and promoting pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor (TNF)-α[56]. However, chronic cortisol exposure due to CPS could lead to immune dysregulation, reducing T cell proliferation and weakening adaptive immune responses, which may increase susceptibility to infections[57]. In parallel, the sympathetic nervous system activation causes short-term catecholamine release that mobilizes immune cells and enhances innate immunity through NK cells and macrophages. However, chronic exposure to catecholamines might suppress adaptive immunity by downregulating T cell receptors and inhibiting T cell activation[56,58]. In experimental studies on mice, thought acute norepinephrine release boosts macrophage activity, CPS ultimately impairs B cell function and antibody production, thereby compromising humoral immunity[59]. In addition to cortisol, other neuroendocrine mediators—particularly adrenaline and noradrenaline may activate both autonomic and central nervous system responses and are intimately involved in the body’s acute and adaptive mechanisms for managing stress[1]. Their functions are encapsulated within the concept of allostasis, a dynamic process that facilitates physiological stability in the face of environmental challenges. However, chronic activation of these stress pathways may lead to allostatic load, a maladaptive state marked by systemic dysregulation. Allostatic load has been implicated in a range of adverse health outcomes, including cardiovascular disease, metabolic disturbances, and impaired glucose homeostasis[1]. These pathophysiological consequences may stem from both direct neuroendocrine effects and indirect behavioral changes associated with chronic stress, thereby highlighting the complex and multifactorial impact of sustained psychological stress on systemic and oral health.

Upon initial exposure to a stressor, central catecholamine levels surge rapidly that trigger an immediate physiological response, and brain corticosteroid levels rise more gradually that can sustain the response over time. Catecholamines initiate fast-acting effects, while corticosteroids exert a dual action: Rapid non-genomic effects followed by delayed genomic responses[54]. These effects overlap within an early window post-stress onset, with successive waves of stress-related neurotransmitters and hormones affecting diverse brain regions[54]. At the cellular level, catecholamines interact with corticosteroids’ early non-genomic effects, while cortisol’s genomic actions typically emerge approximately 60 minutes after stress initiation[60].

Periodontitis/peri-implantitis, a chronic inflammatory condition, has been increasingly linked to systemic inflammation and the development of non-communicable diseases such as cardiovascular diseases, diabetes, and respiratory disorders[61]. The condition arises from an imbalance between oral microorganisms and host immune defenses, leading to periodontal tissue destruction and systemic effects[62,63]. Systemic chronic low-grade inflammation is increasingly recognized as a shared risk factor for psychiatric conditions, including anxiety disorders, mood disorders, and trauma-related disorders[64-66].

Discovery of behavior

CPS also indirectly contributes to periodontal/peri-implant tissue destruction by promoting maladaptive behaviors and impairing oral hygiene. Stress-related structural and functional changes in the hippocampus, as revealed by imaging, post-mortem, and rodent studies, lead to reduced motivation, disorganization, and poor adherence to personal care routines[67-70]. These behaviors manifest as decreased brushing frequency, poor brushing quality, and reduced compliance with dental maintenance, which elevate the risk of periodontal diseases[71-73]. Patients with severe periodontitis, inadequate plaque control, and irregular post-implant care are particularly vulnerable to peri-implantitis[11]. Additional factors, such as poor nutrition, substance misuse (e.g., alcohol, betel nut, and tobacco), limited access to dental care, and xerostomia from psychotropic medications, further exacerbate oral health issues in stressed individuals[74].

Psychotropic medications

Psychiatric disorders and their associated psychotropic medications present significant challenges to bone health and dental outcomes. Conditions such as schizophrenia, depression, and bipolar disorder, when treated with medications like lithium (Li), antidepressants, and antipsychotics can compromise bone metabolism through multiple complex mechanisms. These pharmacological interventions can induce substantial changes in physiological processes, resulting in reduced bone mineral density and an increased risks of osteoporosis and dental implant failure[75-78].

The underlying pathophysiological mechanisms are multifaceted. Medication-induced hormonal disruptions, including hyperprolactinemia, hypercortisolemia, and hypogonadism, directly impact bone remodeling. Moreover, the interaction of serotonin with bone metabolism accelerates bone resorption and compromises osseointegration[75]. Compounding these pharmaceutical effects, lifestyle factors such as active smoking, malnutrition, and sedentary behavior further amplify the potential for adverse bone and dental implant outcomes[79-84].

Of particular concern are selective serotonin reuptake inhibitors (SSRIs), especially sertraline, which demonstrate a notable correlation with increased implant failure rates[76,77]. However, the existing research landscape is nuanced. Current studies exhibit methodological limitations, including inconsistent drug standardization and variable research protocols[76,78]. Consequently, while preliminary evidence suggests a potential risk of SSRIs, the scientific community has not yet established a definitive, unequivocal association between antidepressant use and dental implant complications.

Nevertheless, a materials science investigation uncovered intriguing insights into the interactions between lithium and bone regeneration in dental implant surfaces. When Li was incorporated into a sandblasted, large-grit, acid-etched (SLA) surface, it showed significant inhibitory effects on osteoclastogenesis—the process of bone cell breakdown[85]. The researchers found that the SLA-Li surface activated the wingless-related integration site (Wnt)/β-catenin signaling pathway and modulated the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) signaling axis, which are critical molecular mechanisms in bone metabolism[85-91]. Notably, in vivo experiments revealed that the SLA-Li surface substantially enhanced bone formation and osseointegration during the crucial early stages of dental implant surgery, suggesting promising therapeutic potential for improving implant success rates[85].

Sex differences

Sex-specific considerations warrant greater attention. In particular, the male-to-female ratios reported in the studies and the influence of hormonal changes associated with menopause should be carefully evaluated. Postmenopausal women may be especially susceptible to the effects of CPS, and recent evidence suggests that depression—a prevalent and severe subtype of chronic stress—may be significantly associated with peri-implantitis in this population[8]. This finding underscores the complex and bidirectional relationship between mental health and peri-implant disease, and reinforces the importance of adopting an integrative framework that accounts for psychological, physiological, and demographic factors in future research.

Limitations

This systematic review is subject to several noteworthy limitations that constrain the interpretability and generalizability of its findings. First, all four included studies employed cross-sectional designs, which inherently limit the ability to draw causal inferences. Second, the relatively small total sample size, coupled with the absence of randomization in participant selection, introduces the potential for selection bias and undermines the internal validity of the findings. Third, considerable methodological heterogeneity across studies may weaken the strength of the conclusions. CPS was assessed by diverse modalities —including cortisol concentrations in peri-implant sulcular fluid, self-reported questionnaires, and glucocorticoid receptor expression—while the diagnostic criteria for peri-implantitis varied substantially. Only a subset of the studies adhered to the standardized 2017 World Workshop consensus, thereby limiting comparability and the consistency of pooled results. Fourth, although some studies excluded individuals with active periodontal disease or a history of periodontitis, others did not adequately control for critical confounders, e.g., smoking and hyperglycemia—both of which are independently associated with peri-implant disease and stress biomarkers. The failure to account for these factors may lead to a bias into the observed associations. Furthermore, the potential influence of antipsychotic medications—known to modulate HPA axis function and, consequently, affect both cortisol levels and peri-implant tissue health—was largely overlooked, with three of the four studies failing to consider or report medication use. Fifth, given the paucity of research in this area, interpretations for the mechanisms linking CPS to peri-implantitis should be made with caution, underscoring the need for rigorous, longitudinal cohort studies. Future investigations should incorporate larger, more diverse populations; adopt standardized diagnostic criteria and validated stress assessment tools; and employ robust analytical approaches that comprehensively control for confounding factors. Such methodological rigor is essential for elucidating the complex interplay between chronic psychological stress and peri-implant disease pathogenesis.

CONCLUSION

Previous research has identified a link between chronic CPS and periodontitis, introducing the concept of a bilateral oral-brain axis. Even current evidence also suggests a potential association between CPS and peri-implantitis in the general population, and this relationship may be independent of the effects of hyperglycemia. Additionally, CPS may amplify peri-implantitis inflammation through its modulating effects on cytokine expression. However, the existing evidence remains weak, constrained by small sample sizes, high heterogeneity, and failure to account for key confounding variables. These limitations preclude definitive conclusions regarding causality or even a robust association. Future research should focus on well-designed longitudinal cohort studies with larger, more diverse populations to strengthen the evidence base. Such studies should also consider potential confounding factors, such as psychotropic medication use or therapeutic interventions, and provide comprehensive assessments of peri-implant tissue health, including bleeding on probing, probing depth, and clinical attachment levels, before and after CPS interventions.