Forever chemicals and mental health: A systematic review of per- and polyfluoroalkyl substances-related psychiatric outcomes and mechanistic insights

Abstract

BACKGROUND

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants increasingly associated with adverse health outcomes, including psychiatric disorders. Although most research has focused on physiological toxicities, emerging evidence indicates that PFAS exposure may also disrupt central nervous system function - particularly among vulnerable populations such as children, adolescents, and pregnant women.

AIM

To answer the following two critical questions: What key findings regarding the impacts of PFAS exposure on psychiatric outcomes have emerged in the past five years? What research trends currently prevail in terms of methodologies, targeted populations, and mechanistic investigations?

METHODS

A systematic search guided by the PRISMA framework was conducted using Web of Science and Scopus, covering studies published between July 2021 and July 2025. Nineteen eligible studies were identified and thematically analyzed.

RESULTS

The article found increasing evidence linking PFAS exposure to psychiatric conditions, including depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and cognitive impairments. Proposed mechanisms include thyroid hormone disruption, neuroinflammation, and increased blood-brain barrier permeability. However, inconsistencies in findings - stemming from variability in exposure timing, PFAS compound types, and methodological approaches - remain a significant challenge.

CONCLUSION

Despite growing evidence of PFAS-related neuropsychiatric risks, current research is limited by methodological heterogeneity and incomplete mechanistic understanding. Future research should prioritize longitudinal designs, integrate multi-omics approaches, and refine exposure assessments. Urgent action is needed to incorporate scientific insights into public health policy, particularly for socioeconomically and environmentally vulnerable communities disproportionately exposed to PFAS.

Key Words: Per- and polyfluoroalkyl substances; Mental health; Psychiatric outcomes; Depression and anxiety; Environmental exposure; Vulnerable populations; Neurodevelopmental disorders

Core Tip: This article synthesizes recent evidence linking per- and polyfluoroalkyl substances (PFAS) exposure to psychiatric disorders. It highlights the growing relevance of PFAS in psychiatric research, especially concerning children, pregnant women, and socioeconomically vulnerable populations. By examining epidemiological trends and biological mechanisms, the review underscores the urgent need for interdisciplinary research and policy action to mitigate the mental health risks posed by these persistent environmental contaminants.

INTRODUCTION

Per- and polyfluoroalkyl substances (PFAS) comprise a diverse class of synthetic chemicals defined by strong carbon-fluorine bonds. This group includes thousands of compounds, notably perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and shorter-chain alternatives such as perfluorobutanoic acid and perfluorobutane sulfonate[1]. Their remarkable resistance to water, oil, and heat has led to widespread use in both industrial applications and consumer products such as non-stick cookware, food packaging, firefighting foams, and waterproof fabrics - rendering PFAS indispensable in modern manufacturing[2]. One of the most concerning features of PFAS is their extreme environmental persistence, which has earned them the label “forever chemicals”[3]. Their carbon-fluorine bonds, among the strongest in organic chemistry (up to 116 kcal/mol), render them highly resistant to natural degradation[4]. Studies have shown that PFAS compounds like PFOA can persist in the environment for decades, with biological half-lives in humans ranging from two to eight years[5].

As a result, PFAS are now globally ubiquitous found in water, soil, air, and living organisms, even in remote locations such as Antarctica leading to widespread human exposure at various concentrations[3,6]. Although some developed regions, including the European Union and the United States, have implemented regulations limiting specific PFAS, the lack of a coordinated global framework permits continued environmental release and accumulation[7]. Amid rising global concern over environmental health risks, the psychiatric implications of PFAS exposure have gained renewed attention - particularly as mental health has emerged as a major public health priority in the post-pandemic era.

For the past two decades, PFAS research has largely concentrated on their physiological toxicities, particularly their impacts on the liver, kidneys, and immune system[3,5,8]. A growing body of toxicological and epidemiological evidence has linked PFAS exposure to a range of systemic health impairments, including liver dysfunction, kidney damage, immune suppression, endocrine disruption particularly thyroid hormone imbalances and reproductive abnormalities[2,4,9]. Notably, PFAS possess strong bioaccumulative properties, allowing them to magnify through food chains and create chronic exposure risks - now recognized as a serious global public health concern[6,10]. Accordingly, the International Agency for Research on Cancer has classified PFOA as a group 2B carcinogen, meaning it is “possibly carcinogenic to humans”[11]. Importantly, the potential harms of PFAS extend well beyond their physiological impacts, prompting growing concern about their neurological and psychiatric effects.

As scientific understanding deepens, increasing attention has been directed toward the potential neurotoxic effects of PFAS on the central nervous system[12]. Emerging evidences suggest that PFAS exposure is associated with elevated risks of neuropsychiatric and neurodevelopmental disorders, including depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). These associations are particularly pronounced among children and adolescents, who are especially susceptible during key neurodevelopmental windows[13]. Such findings have broadened the scope of PFAS-related health research and underscore the importance of incorporating psychiatric outcomes into future risk assessment frameworks.

Recent investigations into the mechanisms underlying PFAS-related psychiatric outcomes have proposed several key biological pathways: First, PFAS exposure has been shown to disrupt thyroid hormone synthesis and regulation processes that are critical for brain development during fetal and early childhood stages potentially impairing cognitive functions[14]. Second, PFAS-induced systemic inflammation and alterations in neurotransmitter systems particularly in serotonin and dopamine pathways critical for mood regulation may increase the risk of developing depression and anxiety disorders[15]. Third, prenatal PFAS exposure may allow these substances to cross the placental barrier, potentially disrupting central nervous system development and contributing to cognitive and behavioral impairments in early childhood[16]. Furthermore, the timing of PFAS exposure plays a crucial role in shaping psychiatric outcomes. Fetal and early childhood periods represent sensitive windows of brain development, marked by heightened plasticity and vulnerability to environmental insults[17]. Exposure during these critical windows may lead to irreversible alterations in neural structure and function, manifesting as persistent psychological and behavioral disorders extending into adolescence and adulthood[11,16]. In summary, the existing body of evidence supports the potential role of PFAS exposure in increasing the risk of psychiatric disorders.

Against this backdrop, the psychiatric impacts of PFAS exposure have emerged as a growing focus within psychiatric outcomes research. An increasing volume of empirical research suggests potential associations between PFAS exposure and a range of psychiatric outcomes particularly among vulnerable populations including children, adolescents, and pregnant women[11,13,14,18]. However, as previously noted, this remains a relatively nascent field of study, with many critical questions yet to be explored and validated. Therefore, a comprehensive synthesis of current evidence is essential not only to chart the existing research landscape and identify promising avenues, but also to inform future psychiatric research and support the formulation of robust, evidence-based environmental health policies.

This review addresses two central research questions: (1) What key findings regarding the impacts of PFAS exposure on psychiatric outcomes have emerged in the past five years; and (2) What research trends currently prevail in terms of methodologies, targeted populations, and mechanistic investigations?

By addressing these questions, this review aims to provide a structured synthesis to inform future psychiatric research, enhance understanding of PFAS-related psychiatric outcomes, and support translational efforts linking environmental exposure to psychiatric outcomes.

MATERIALS AND METHODS

Search strategies

To establish a clear methodological framework, this review followed the PRISMA guidelines and employed a Boolean search strategy across two major databases: Web of Science and Scopus. The search query was designed to capture literature at the intersection of PFAS exposure and psychiatric outcomes, using the following terms: (“PFAS” OR “Per- and Polyfluoroalkyl Substances” OR “PFOA” OR “Perfluorooctanoic acid” OR “PFOS” OR “Perfluorooctane sulfonate” OR “PFNA” OR “Perfluorononanoic acid” OR “PFHxS” OR “Perfluorohexane sulfonic acid”) AND (“mental health” OR “mental disorder” OR “mental conditions” OR “psychiatry”)[19]. The search covered publications from July 2021 to July 2025.

During the screening process, we strictly adhered to PRISMA procedures, clearly outlining inclusion and exclusion criteria to ensure transparency and reproducibility. Studies were included if they met the following criteria: Peer-reviewed original empirical research; published in English; directly examined associations between PFAS exposure and psychological or neurobehavioral outcomes. Exclusion criteria comprised review articles, commentaries, and studies not involving human participants. The selection process is summarized in Figure 1. While a formal risk-of-bias assessment tool was not employed due to the qualitative approach nature of this review, potential sources of bias were mitigated through independent screening by multiple reviewers and consensus resolution of discrepancies. We acknowledge the possibility of publication bias and language bias, and highlight this as a limitation in the discussion.

Figure 1  Inclusion and exclusion criteria.

Statistical analysis

A thematic analysis approach was employed to synthesize findings across studies. Following Braun and Clarke’s (2006) framework, the process involved six steps: (1) Familiarization with the data through repeated reading; (2) Generating initial codes by identifying patterns related to PFAS exposure and psychiatric effects; (3) Searching for themes across coded data, such as “depression risk”, “prenatal exposure effects”, “endocrine disruption”, and “neuroinflammation”; (4) Reviewing themes for coherence and consistency; (5) Defining and naming themes to reflect key questions; and (6) Producing the report by integrating themes into a coherent narrative supported by representative study findings[20]. This approach allowed for the identification of recurring patterns, conceptual linkages, and emerging areas of consensus or controversy in the current literature. The analysis prioritized both the epidemiological associations and the underlying mechanistic explanations proposed in the studies.

RESULTS

After rigorous screening, a total of 19 studies were included in the analysis of this study, as shown in Table 1[21-39]. In terms of research design, the majority of studies (n = 13, 68.4%) employed a longitudinal cohort approach. These studies primarily investigated the long-term effects of PFAS exposure on various neurodevelopmental and psychiatric conditions, including ASD, ADHD, depression, dementia, and overall cognitive development. The use of longitudinal designs reflects a strong emphasis on establishing temporal relationships and potential causality.

Table 1 Summary of studies on per- and polyfluoroalkyl substances exposure and psychiatric outcomes.

Ref.	Research design	Sample size	Outcomes focus
Ahrens et al[21], 2024	Longitudinal cohort study	16440	ASD
Carrizosa et al[22], 2021	Longitudinal cohort study	1240	Neuropsychological development
Tang et al[23], 2024	Cross-sectional observational study	7301	Depression
Dalsager et al[24], 2021	Longitudinal cohort study	1138	ADHD
England-Mason et al[25], 2025	Retrospective machine learning analysis	406	Neurodevelopment
Hong et al[26], 2024	Cross-sectional study with paired subjects	59	Cognitive impairment
Hu et al[27], 2024	Longitudinal cohort study	50	Depression
Itoh et al[28], 2022	Longitudinal cohort study	770	ADHD
Itoh et al[29], 2025	Longitudinal cohort study	15131	Neuropsychological development
Kim et al[30], 2023	Longitudinal cohort study	221	Postpartum depression, Infant neurodevelopment
Kim et al[31], 2023	Longitudinal cohort study	521	ADHD
Lefèvre-Arbogast et al[32], 2024	Longitudinal cohort study	1288	Dementia
Oh et al[33], 2021	Longitudinal cohort study	173	ASD
Ogundare and Obeng-Gyasi[34], 2025	Cross-sectional observational study	181	Depression
Sun et al[35], 2024	Cross-sectional observational study	7700	Depression
Tillaut et al[36], 2023	Longitudinal cohort study	444	ADHD, depression, anxiety
Yao et al[37], 2022	Longitudinal cohort study	274	Neuropsychological development
Wu et al[38], 2024	Experimental in vitro study	3-6 biological replicates	Alzheimer’s disease
Zhang et al[39], 2025	Longitudinal cohort study	1779	Neurodevelopment

ASD: Autism spectrum disorder; ADHD: Attention-deficit/hyperactivity disorder.

Cross-sectional observational studies comprised 4 out of 19 studies (21.1%), generally focusing on depressive symptoms or cognitive outcomes assessed at a single point in time. While these studies provided valuable insights into population-level associations, they lacked the ability to assess changes over time.

Only one study (5.3%) utilized an in vitro experimental design, contributing mechanistic insights by exploring molecular and cellular changes induced by PFAS exposure under controlled laboratory conditions.

Similarly, one study (5.3%) applied a retrospective machine learning approach, using predictive modeling techniques to examine the relationship between PFAS exposure and neurodevelopmental outcomes. This computational method represents an emerging trend in environmental health research, offering new possibilities for analyzing complex exposure-outcome relationships.

Overall, the dominance of longitudinal designs indicates a growing interest in developmental trajectories and delayed effects, while the inclusion of experimental and computational studies highlights the importance of mechanistic exploration and data-driven modeling in this evolving field. The key findings regarding the impacts of PFAS exposure on psychiatric outcomes which have emerged in the past five years are as follows.

Depression and mood disorders

Recent studies examining the impacts of PFAS exposure on depression and mood disorders have presented mixed results. A study analyzing the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018 suggested that higher exposure to specific PFAS compounds, such asPFOA, perfluorohexane sulfonic acid (PFHxS), perfluoroundecanoic acid was associated with a lower risk of depressive symptoms; however, the cross-sectional design limited causal interpretation[35]. In contrast, another NHANES-based study identified cadmium as a significant factor contributing to depression, finding that PFAS demonstrated antagonistic interactions when co-exposed with heavy metals, reducing their combined depressive effects[23]. Additionally, research on postpartum depression (PPD) in women carrying twins indicated that prenatal exposure to PFAS mixtures significantly increased the risk of PPD, particularly at 1 month and 6 months postpartum[27].

Neurodevelopmental and bvehavioral outcomes

Findings on PFAS exposure and neurodevelopmental outcomes also vary. Exposure to PFAS during early childhood (at around 2 years of age) was linked to increased ADHD symptoms at age 8, particularly at lower to moderate exposure levels[30]. However, several other studies found no significant associations between prenatal or early-childhood PFAS exposure and ADHD symptoms, highlighting inconsistencies in this area[24,28]. Further, prenatal exposure to PFOA and PFNA was associated with heightened ASD risk in specific high-risk cohorts, whereas PFHxS exhibited an inverse relationship[33]. Additionally, prenatal PFAS exposure correlated with reduced gross motor development in infants, notably when mothers experienced elevated psychological distress[39]. Exposure to perfluorobutane sulfonate and PFHxS was similarly linked to decreased neurodevelopmental scores in infants, partly mediated by disruptions in thyroid hormone regulation[37].

Mechanistic insights

Mechanistic studies have identified potential biological pathways through which PFAS may influence psychiatric outcomes. Thyroid hormone disruption emerged as a significant mediator, with prenatal PFAS exposure altering hormone levels and consequently impacting neurodevelopment[28,29,37]. Neurotoxic effects were also observed; for example, PFOA exposure in human-derived cortical neurons triggered pathways analogous to Alzheimer’s disease, including tau protein phosphorylation and related transcriptomic changes[38]. Additionally, increased permeability of the blood-brain barrier to PFOS, leading to cognitive impairments, underscored the direct neurotoxic potential of PFAS[26].

Mixture effects and modifiers

Emerging evidence highlights the complex interactions between PFAS and other environmental or social determinants. Co-exposure to cadmium and PFOS demonstrated antagonistic interactions affecting depression-related biological pathways, suggesting intricate effects dependent on environmental contaminant mixtures[23]. Dietary patterns, specifically high-fat diets, intensified the neurotoxic effects of PFAS, emphasizing the importance of dietary context in PFAS-related health outcomes[32]. Socioeconomic factors also played a modifying role, with lower educational attainment and income levels exacerbating depressive symptoms among populations exposed to combined environmental contaminants, including PFAS and heavy metals[34].

Inconsistent findings

Despite accumulating evidence, some studies reported no significant relationships between PFAS exposure and neurodevelopmental outcomes, reflecting ongoing uncertainties. For instance, investigations into prenatal or childhood PFAS exposure sometimes showed no correlation with ADHD or other neurodevelopmental indicators[22,29]. These inconsistencies underscore critical gaps in understanding, emphasizing the need for further research on the timing of exposure, individual susceptibility, and the complex interplay of contaminant mixtures. Research trends currently prevailing in terms of methodologies, targeted populations, and mechanistic investigations are as follows.

Methodological advancements

Recent studies on PFAS and psychiatric outcomes have embraced increasingly sophisticated methodologies to better understand complex exposure-outcome relationships. One prominent advancement involves the use of mixture analysis and multi-pollutant models. Techniques such as Bayesian Kernel Machine Regression and quantile g-computation are now commonly used to assess the combined effects of PFAS mixtures, often in the context of co-exposure to metals and sociodemographic modifiers[23,35]. Furthermore, machine learning approaches are emerging as powerful tools for modeling the intricate interactions among PFAS, other contaminants, and individual- or population-level risk factors[25].

In terms of study design, there has been a clear trend toward longitudinal and cohort-based methodologies. Large-scale birth cohorts, such as the INfancia y Medio Ambiente Project, Hokkaido Study, and Shanghai Birth Cohort, have allowed researchers to track prenatal PFAS exposure and subsequent neurodevelopmental outcomes across several years[22,28,39]. While cross-sectional studies like NHANES remain widely used, they are increasingly complemented by designs incorporating retrospective exposure assessment or repeat sampling over time[35].

The integration of biomarkers and multi-omics data has also enhanced mechanistic understanding. Analyses of cord blood, serum, and cerebrospinal fluid have facilitated the quantification of PFAS penetration into neurological tissues[26]. In parallel, transcriptomic and metabolomic analyses have elucidated molecular mechanisms - such as tau phosphorylation in Alzheimer’s-like neurodegeneration - associated with PFAS toxicity[38].

Targeted populations

Research has increasingly focused on populations that are especially susceptible to the psychiatric outcomes of PFAS exposure. Prenatal and early-life exposure remains a key area of concern, with numerous studies examining pregnant women and infants due to their heightened vulnerability to hormonal and neurodevelopmental disruptions[27,37]. High-risk cohorts such as MARBLES (for autism risk) and the Odense Child Cohort (for ADHD) have been instrumental in identifying specific neurodevelopmental impacts of early PFAS exposure[24,33].

Vulnerable subgroups have also been prioritized in recent research. For instance, stronger associations between PFAS exposure and PPD have been reported in women with twin pregnancies[27]. Populations with low socioeconomic status or high-fat dietary intake appear more susceptible to PFAS-related neurotoxic effects, likely due to both higher exposure levels and reduced physiological or social resilience[32,34].

Adult and aging populations are increasingly represented in epidemiological studies as well. Data from NHANES and other national surveys have helped identify associations between PFAS exposure and depression in adults[23,35]. Research is also extending into geriatric contexts, with some studies examining dietary PFAS exposure and its potential link to dementia risk in older adults[32].

Mechanistic investigations

Mechanistic research has provided critical insights into how PFAS exposure may lead to mental health impairments. One prominent pathway involves thyroid hormone disruption: Prenatal exposure to PFAS has been shown to alter levels of free thyroxine, free triiodothyronine, and thyroid-stimulating hormone, which in turn are associated with developmental deficits[28,37].

In addition to endocrine disruption, PFAS compounds have been implicated in neuroinflammatory and neurodegenerative processes. For instance, exposure to PFOA in human pluripotent stem cell-derived cortical neurons has been shown to induce Alzheimer’s-like pathology, including tau aggregation and calcium signaling dysregulation[38]. PFOS has been found in cerebrospinal fluid and is linked to impaired cognitive function, highlighting its potential to cross the blood-brain barrier and affect brain health directly[26].

Emerging research also suggests that PFAS may exert epigenetic and multi-generational effects. Animal and in vitro models have indicated that PFAS exposure may disrupt the hypothalamic-pituitary-adrenal axis and impair synaptic plasticity[38]. Furthermore, maternal stress appears to interact synergistically with PFAS exposure, compounding neurodevelopmental risks in infants[39].

DISCUSSION

This discussion synthesizes current findings on the psychiatric implications of PFAS exposure, critically evaluates methodological and conceptual trends in the literature, and outlines directions for future research and policy development.

Current methodological approaches rely heavily on observational designs, which constrain causal inference and limit temporal resolution. Most studies investigating PFAS and psychiatric outcomes employ cross-sectional surveys or prospective birth cohorts. While these approaches offer initial insights into associations, they are often hampered by residual confounding, misclassification of exposure, and limited capacity to capture long-term effects. Advanced statistical models - such as Bayesian kernel machine regression, quantile g-computation, and machine learning - have been introduced to manage complex mixture exposures[23,25]. However, methodological challenges persist, particularly the reliance on single-timepoint serum measurements and inconsistent biomarker use, which obscure cumulative exposures and critical developmental windows.

The current research agenda focuses narrowly on selected psychiatric endpoints and underrepresents both vulnerable populations and dimensional symptomatology. Most studies concentrate on clinically defined outcomes such as ADHD, ASD, and depression, often overlooking intermediate cognitive and affective features such as executive dysfunction, irritability, or social cognition deficits[27,33,35]. This diagnostic approach, while pragmatic, may not fully capture the spectrum of neurobehavioral effects associated with PFAS exposure. Additionally, while children, pregnant women, and adolescents receive appropriate attention, other vulnerable groups - including the elderly, occupationally exposed individuals, and socioeconomically marginalized communities - remain insufficiently studied despite evidence of heightened susceptibility to PFAS-related cognitive decline and psychiatric symptoms[26,32,34].

Future research must adopt integrative, developmentally sensitive, and mechanistically grounded frameworks. Longitudinal cohort designs with multi-wave follow-ups and repeated biomarker assessments are needed to trace the neurobehavioral trajectories associated with PFAS from prenatal stages through adolescence and adulthood. Transitioning from categorical diagnoses to dimensional models, such as the National Institute of Mental Health’s Research Domain Criteria, would enable a more precise mapping of PFAS effects onto fundamental mental processes, such as attention regulation, emotional response, and cognitive flexibility[39]. At the mechanistic level, integrating multi-omics (e.g., epigenomics, metabolomics), neuroimaging, and toxicokinetic modeling will help uncover the molecular pathways and brain network disruptions underlying psychiatric risk. Equally important, future research must address PFAS mixtures in the context of co-exposures (e.g., heavy metals, endocrine disruptors) and psychosocial stressors - factors likely to interact in shaping psychiatric vulnerability.

Environmental justice and translational impact should guide the evolving research agenda. Studies must proactively include diverse global populations and stratify results by social determinants such as income, occupation, and geographic vulnerability. Importantly, research must move beyond exposure characterization toward testing interventions. Clinical and community-based trials evaluating whether reducing PFAS exposure - via dietary interventions, water filtration, or pharmacological modulation of hormonal and inflammatory pathways - can improve psychiatric outcomes are critically needed. These efforts will bridge environmental science with psychiatric care and yield actionable insights for at-risk populations.

The potential psychiatric burden of PFAS exposure calls for a reevaluation of current regulatory and public health strategies. Current safety thresholds predominantly emphasize hepatic, reproductive, and immunological endpoints, frequently overlooking critical neurobehavioral effects. Our findings highlight that PFAS exposure, particularly involving PFHxS and PFOS, is linked to early-life motor delays detectable as early as 14 months, and sex-specific impairments in working memory evident by ages 4-5 both representing essential neurodevelopmental domains during sensitive developmental windows[26,28,35,37,39]. These cognitive and motor domains serve as significant predictors of later psychiatric outcomes, including ADHD, mood disorders, and executive dysfunction. However, major regulatory agencies, such as the United States Environmental Protection Agency and the European Food Safety Authority still largely neglect these neurobehavioral endpoints in their risk assessments[40]. Moreover, vulnerable groups such as pregnant women, young children, and the elderly warrant heightened consideration[1,29,38]. Given the consistent evidence of neurodevelopmental vulnerabilities tied to early-life PFAS exposure, incorporating psychiatric and cognitive outcomes particularly those involving attention, memory, and affect regulation into regulatory frameworks would enhance the comprehensiveness and public-health relevance of PFAS toxicity evaluations. Our analysis thus strongly supports revising current safety thresholds and prioritizing mental health endpoints in environmental health surveillance and regulatory policies.

Policy action must prioritize precautionary regulation, transparency, and equitable exposure reduction. A global phase-out of long-chain PFAS should be accelerated, while stricter evaluation of short-chain alternatives is urgently required. Mandated labeling of PFAS-containing products and public disclosure of industrial emissions would enhance consumer awareness and community oversight. Concurrently, integrating PFAS monitoring into maternal and child health programs and linking this to mental health surveillance systems would support early detection and prevention. Community-centered interventions and environmental justice initiatives are essential to mitigate exposure in high-risk populations[41]. Educational campaigns, behavioral nudges, and provision of PFAS-free alternatives must be tailored for communities with limited resources. Special attention should be given to coastal, industrial, and low-income regions where cumulative exposures are high and mitigation resources scarce. Long-term policy solutions require cross-sector collaboration among governments, industry, academia, and local stakeholders to ensure sustainable reductions in PFAS-related psychiatric risk.

Notably, this systematic review still has several limitations that should be acknowledged. First, although we followed the PRISMA framework to guide search and selection procedures, we restricted our search to two databases (Web of Science and Scopus) and included only peer-reviewed English-language publications. This may have excluded relevant studies from non-English literature or grey literature sources such as governmental reports, dissertations, or conference proceedings potentially introducing publication bias. Second, as this is a qualitative systematic review, formal quality appraisal tools such as the Newcastle-Ottawa Scale or the Risk Of Bias In Non-randomized Studies of Interventions were not employed to assess the methodological rigor or risk of bias of the included studies. Consequently, the synthesis reflects reported findings without a standardized evaluation of study quality, which limits the strength of any causal interpretations. Third, while the thematic analysis allowed us to identify conceptual patterns and mechanistic insights, the interpretation of themes is inherently subjective and may vary with researcher perspective. Fourth, although several included studies reported sex-stratified results, this review did not systematically examine sex-based differences. This is a notable omission given established sex-related variability in both PFAS toxicokinetics and psychiatric susceptibility.

CONCLUSION

This article underscores the emerging significance of PFAS exposure as a potential environmental risk factor for psychiatric disorders. Over the past five years, a growing body of evidence has linked PFAS exposure to various mental health outcomes, including depression, anxiety, ADHD, ASD, and cognitive impairments. These associations are particularly evident in vulnerable groups such as pregnant women, children, and communities with socioeconomic or environmental disadvantages.

However, inconsistencies across studies stemming from differences in exposure timing, PFAS compound variability, and methodological approaches highlight the complex and multifactorial nature of PFAS-related psychiatric outcomes. While several biological pathways have been proposed to explain PFAS-related neuropsychiatric effects, including disruptions in endocrine signaling and neuroimmune function, their validation in human populations remains limited and warrants further mechanistic investigation.

To address these gaps, future research must prioritize longitudinal, developmentally sensitive cohort studies, integrate multi-omics and neuroimaging technologies, and enhance exposure assessment protocols. Equally important, studies should reflect environmental justice considerations by including underrepresented populations and exploring the psychosocial and structural factors that modulate PFAS vulnerability.

Beyond scientific inquiry, urgent policy and public health actions are needed to mitigate PFAS exposure and its psychiatric consequences. Regulatory frameworks should incorporate neurodevelopmental and psychiatric endpoints into safety thresholds, while public health systems must adopt proactive surveillance and intervention strategies. Community-led education, access to PFAS-free alternatives, and equitable environmental protections are critical for safeguarding mental health especially in regions burdened by cumulative environmental risks.

Ultimately, addressing PFAS-related psychiatric risks will require sustained interdisciplinary collaboration across environmental science, psychiatry, and public policy. Integrating rigorous evidence with actionable solutions will be essential to protect brain health and promote equity in a world increasingly challenged by persistent environmental contaminants.