**REVIEW Open Access** # From shared mechanisms to treatment gaps: a review of the comorbidity between eating disorders and PTSD Hanlai Ouyang1 , Yating Wang1 and Jue Chen1[\\*](http://orcid.org/0000-0002-9924-2573) # **Abstract** Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge eating disorder, are severe psychiatric illnesses marked by disordered eating patterns and psychological disturbances. Post-traumatic stress disorder (PTSD), a common response to trauma, is characterized by re-experiencing, avoidance, negative alterations in cognition and mood, and hyperarousal. The prevalence of PTSD is significantly higher among individuals with EDs than in the general population. This comorbidity is associated with more severe clinical presentations, greater functional impairment, higher treatment dropout rates, and poorer prognoses. Despite increasing recognition of this co-occurrence, the underlying biological and psychological mechanisms remain inadequately understood. This review explores potential shared pathways from a biopsychological perspective, including dysregulation of the hypothalamic-pituitary-adrenal axis, immune system alterations, gut microbiota imbalances, emotional dysregulation, and dissociation. Current treatment strategies are reviewed, highlighting the lack of specific clinical guidelines for this population. There is an urgent need for integrated, trauma-informed interventions to enhance outcomes for individuals affected by the dual burden of EDs and PTSD. # **Plain English summary** Eating disorders, such as anorexia nervosa, bulimia nervosa, and binge-eating disorder, are serious mental illnesses that harm both physical and psychological health. A substantial proportion of people with eating disorders have experienced trauma, and many go on to develop post-traumatic stress disorder (PTSD). PTSD can cause people to relive the trauma through flashbacks, avoid anything that reminds them of it, and feel constantly on edge. When an eating disorder and PTSD occur together, they make each other worse and recovery much harder. People struggling with both conditions often have more intense symptoms, are more likely to drop out of treatment, and generally have a tougher time getting better. This review explores the possible reasons behind the common co-occurrence of eating disorders and PTSD. We discuss how problems with the HPA axis (hypothalamic-pituitaryadrenal axis, our body's stress-response system), changes in the immune system, imbalances in gut health, and difficulties in managing emotions may contribute to this connection. We also look at the current treatments and point out the lack of clear guidelines for treating both conditions at the same time. Our findings highlight the \*Correspondence: Jue Chen chenjue2088@163.com Full list of author information is available at the end of the article ![](https://assets.reachrx.ai/images/10.1186%E2%98%8Ds40337-025-01454-0/_page_0_Picture_12.jpeg) urgent need for combined, trauma-sensitive treatments to improve recovery and quality of life for this vulnerable population. **Keywords** Eating disorders, Post-traumatic stress disorder, HPA axis dysregulation, Trauma-informed care, Comorbidity # **Introduction** Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), are severe psychiatric conditions characterized by maladaptive eating behaviors and significant psychological distress [[1\]](#page-10-0). The global incidence of EDs has steadily increased, with a lifetime prevalence of up to 4% among women [\[2](#page-10-1)]. Meta-analytic data show that individuals with EDs have a mortality rate more than three times higher than the general population. For AN, the rate exceeds fivefold [[3](#page-10-2)], highlighting the substantial public health burden posed by these disorders. Post-traumatic stress disorder (PTSD) is a common and debilitating psychiatric condition triggered by exposure to traumatic events. It is defined by core symptoms such as intrusive re-experiencing, avoidance, negative alterations in cognition and mood, and hyperarousal [\[4](#page-10-3)]. These symptoms are often chronic and severely impair functioning across social, occupational, and daily life domains [[5](#page-10-4)]. Beyond its direct clinical impact, PTSD significantly increases the risk for other psychiatric comorbidities [[6\]](#page-10-5), further compounding its overall burden on mental health systems. A robust body of epidemiological research has consistently demonstrated a high comorbidity between EDs and PTSD. A U.S. population-based study found lifetime PTSD prevalence rates of 12% in individuals with AN, 45.4% in those with BN, and 26.3% in those with BED. These rates are significantly higher than the 6.7% observed in the general population [\[7](#page-10-6), [8](#page-10-7)]. Similarly, a Swedish cohort study of 843 adults with AN and a history of trauma found a lifetime PTSD prevalence of 24.1% [[9\]](#page-10-8). Beyond these elevated rates of comorbidity, several large-scale clinical studies have demonstrated that ED patients meeting DSM-5 criteria for PTSD often exhibit more severe eating pathology, greater psychosocial impairment, and significantly lower quality of life [[10–](#page-10-9)[12](#page-10-10)]. Moreover, the presence of comorbid PTSD has been linked to diminished treatment response, slower symptom resolution, reduced rates of full remission, and higher treatment dropout, all contributing to poorer long-term outcomes [[13](#page-10-11), [14\]](#page-10-12). While the biological and psychological underpinnings of EDs and PTSD have been widely studied in isolation, emerging research increasingly points to shared pathophysiological and psychosocial mechanisms. Elucidating these overlapping pathways is critical for improving clinical understanding, facilitating early identification, and informing the development of integrated interventions. This knowledge may help prevent PTSD in traumaexposed individuals with EDs, treat ED symptoms in those with PTSD, and improve trauma-informed care models. This review synthesizes current evidence on the converging biological and psychological mechanisms underlying the comorbidity of EDs and PTSD. Key shared biological vulnerabilities include dysregulation of neuroendocrine systems (particularly the hypothalamic-pituitary-adrenal axis), immune-inflammatory dysregulation, and gut-brain axis disruption. In parallel, psychological mechanisms such as emotion dysregulation and dissociative processing have emerged as critical contributors to this comorbidity. Building on these mechanistic insights, we review clinical approaches to comorbid EDs and PTSD. We also identify key gaps in the literature and stress the need for integrated, trauma-informed treatment strategies to improve outcomes for this complex, high-risk population. # **Methods** This study is a narrative review aimed at synthesizing current evidence on the comorbidity between EDs and PTSD, with a focus on shared psychological and biological mechanisms and treatment implications. A comprehensive literature search was conducted in PubMed and Web of Science in January 2025, with a follow-up search in October 2025 to include the most recent publications. No date limits were applied to capture the full range of relevant literature, and studies published up to the date of the last search (October 2025) were considered. Eligible studies included original empirical research, reviews, and meta-analyses examining the comorbidity between EDs and PTSD. The search targeted articles with the relevant terms in the title or abstract. No language restrictions were applied during the initial search; however, only fulltext, peer-reviewed articles written in English were included in the final analysis. The search strategy used in PubMed was adapted for Web of Science using equivalent keywords. Additional relevant studies were identified through manual screening of reference lists. # **Possible mechanisms for developing ED-PTSD** Although PTSD and Eds are diagnostically distinct, a growing body of evidence suggests that they share core psychological and physiological mechanisms. These shared mechanisms not only contribute to their frequent co-occurrence but also offer a transdiagnostic framework for clinical assessment and intervention. In traumaexposed individuals, persistent emotional dysregulation and chronic dysregulation of stress-response systems may drive both the maintenance of PTSD symptoms and the emergence of disordered eating behaviors. Elucidating these overlapping pathways is essential to understanding the underlying basis of ED–PTSD comorbidity. In the sections that follow, we examine these potential shared mechanisms from both psychological and physiological perspectives. #### **Psychological mechanisms** Emotional dysregulation is widely recognized as the central shared psychological mechanism. Comorbidity often amplifies patients' difficulties in managing affective states [\[15](#page-10-13)]. In a study involving 699 hospitalized female ED patients, those with comorbid PTSD reported significantly higher levels of anxiety, depression, and anxiety sensitivity compared to patients with EDs alone or trauma exposure without PTSD [[11\]](#page-10-14). Individuals with PTSD frequently alternate between emotional hyperactivation (e.g., panic, anger, shame) and emotional numbing, whereas disordered eating behaviors (e.g., bingeing, restricting, purging) often serve as maladaptive coping strategies for regulating these emotional extremes [\[16](#page-10-15), [17\]](#page-10-16). A network analysis by Vanzhula et al. [\[18](#page-11-0)] further identified two potential mechanisms linking PTSD and EDs: the "Binge Eating–Irritability Pathway" and the "Body Dissatisfaction–Disturbing Dreams Pathway." For example, feelings of shame or guilt following binge eating may exacerbate PTSD-related irritability, creating a reinforcing feedback loop. Similarly, traumatic dreams may intensify negative body image (e.g., a desire to be thinner as a means of safety), thereby worsening body dissatisfaction. The most recent large-scale network analysis by Brewerton et al. [[19](#page-11-1)], involving 2,178 hospitalized ED patients, found that comorbidity was sustained through negative emotional dysregulation and depressive symptoms. This highlights the central role of emotional dysregulation in ED–PTSD comorbidity. In addition to emotional dysregulation, dissociation has been proposed as another key psychological mechanism underlying the link between PTSD and EDs. Dissociation refers to a disruption in the normal integration of consciousness, memory, identity, or perception of the self and the external world [[20](#page-11-2)], often marked by reduced awareness of bodily sensations [\[21\]](#page-11-3). This psychological "disconnection" may serve as a protective mechanism when confronting traumatic memories or perceived threats. Dissociative symptoms are prevalent in PTSD populations, with a dissociative subtype of PTSD (PTSD-DS)—characterized by depersonalization and derealization—identified in up to 45% of clinical cases [[22,](#page-11-4) [23](#page-11-5)]. Although direct empirical evidence linking dissociation to ED–PTSD comorbidity remains limited, dissociative experiences are relatively common in individuals with EDs. Higher levels of dissociation have been associated with greater ED symptom severity and increased frequency of maladaptive eating behaviors [[24\]](#page-11-6). These may reflect overlapping features such as post-binge confusion, perceived loss of control, and psychological detachment [[25\]](#page-11-7). Some ED patients report intrusive "internal voices" that promote disordered eating—phenomena thought to reflect dissociative defenses rooted in early trauma [[26\]](#page-11-8). A pilot study of psychedelic-assisted therapy in two women with AN found that addressing dissociative processes led to significant improvements in ED symptoms and weight restoration at follow-up [[27](#page-11-9)], suggesting dissociation as a promising therapeutic target. In summary, dissociation functions as a psychological defense mechanism that helps individuals distance themselves from overwhelming emotions and traumatic memories. However, it may also contribute to the maintenance of symptoms in both PTSD and EDs. In ED populations, dissociative experiences—such as emotional detachment or altered bodily perception during binge eating or restriction—may represent unconscious, adaptive responses that do not reach pathological levels. In contrast, the dissociative subtype of PTSD is marked by more severe distortions in self and environmental perception, exceeding normative stress responses. Given these distinctions, it is essential to differentiate functional or defensive dissociation from pathological dissociation during clinical assessment. This differentiation is critical for accurate diagnosis, individualized treatment planning, and improved therapeutic outcomes in patients with comorbid EDs and PTSD. ### **Underlying biological mechanisms** In recent years, there has been growing recognition that eating disorders and post-traumatic stress disorder cannot be fully understood through psychological frameworks alone. Instead, a comprehensive understanding of their etiology and comorbidity requires the integration of underlying biological mechanisms. Advances in neurobiology, endocrinology, immunology, and microbiome science have increasingly shed light on the complex physiological processes that contribute to the onset, maintenance, and co-occurrence of these disorders. Elucidating these biological underpinnings is essential for informing the development of more effective, targeted, and personalized therapeutic interventions. The following section reviews key biological mechanisms implicated in the comorbidity of PTSD and EDs. # *HPA axis dysregulation* The hypothalamic-pituitary-adrenal (HPA) axis is a central component of the body's response to chronic stress [[28,](#page-11-10) [29](#page-11-11)]. It consists of three major endocrine structures: the hypothalamus, which secretes corticotropin-releasing hormone (CRH); the pituitary gland, which responds to CRH by releasing adrenocorticotropic hormone (ACTH); and the adrenal glands, which are stimulated by ACTH to produce glucocorticoids, primarily cortisol [[30\]](#page-11-12). Both PTSD and EDs are characterized by chronic stress—originating from traumatic experiences in PTSD and from prolonged disordered eating behaviors in EDs [[31,](#page-11-13) [32](#page-11-14)]. Both conditions are also linked to HPA axis dysregulation, though the patterns of dysfunction differ. A systematic review of ten studies reported significantly elevated cortisol levels in patients with anorexia nervosa compared to healthy controls, with reductions following nutritional rehabilitation in adolescents [[33](#page-11-15)]. Similarly, individuals with bulimia nervosa showed increased salivary cortisol concentrations. Patients with AN commonly exhibit an exaggerated cortisol awakening response (CAR), indicating a heightened and sustained stressreactive state, whereas CAR levels in BN do not significantly differ from those in healthy individuals [\[34](#page-11-16), [35](#page-11-17)]. These findings suggest divergent HPA axis profiles within ED subtypes, despite their shared diagnostic category. In contrast, patients with PTSD often exhibit an opposite pattern. A meta-analysis revealed significantly lower early-morning salivary cortisol levels in PTSD patients relative to healthy controls [[36\]](#page-11-18). Several studies have also reported increased glucocorticoid receptor sensitivity in individuals with PTSD, contributing to a blunted stress response and exaggerated negative feedback inhibition [[37–](#page-11-19)[40](#page-11-20)]. Importantly, early-life trauma—particularly emotional neglect and abuse—has been identified as a key contributor to HPA axis dysregulation. In individuals with AN or BN and a history of trauma, studies have reported a blunted CAR and reduced cortisol reactivity during standardized stress paradigms such as the Trier Social Stress Test (TSST) [\[41](#page-11-21)[–44](#page-11-22)]. Individuals with AN or BN who have experienced emotional abuse commonly exhibit pronounced feelings of ineffectiveness and alexithymia [[45\]](#page-11-23), and this may serve as a psychological manifestation of HPA axis dysregulation. For instance, women with EDs who exhibited high alexithymia showed both elevated basal cortisol and blunted cortisol reactivity following the TSST, indicating impaired HPA sensitivity [\[46](#page-11-24)]. These findings suggest that trauma exposure may impair adaptive stress regulation, further exacerbating HPA dysfunction in ED populations. However, results are not entirely consistent, with some studies reporting no significant HPA alterations in BN patients with early trauma compared to controls [[47\]](#page-11-25). To further elucidate these mechanisms, research has focused on CRH, a pivotal regulator of the HPA axis. Elevated CRH levels have been reported in both PTSD and AN populations [\[48](#page-11-26)[–50\]](#page-11-27). Beyond its endocrine role, CRH also acts centrally on hypothalamic feeding centers to suppress appetite via activation of anorexigenic pathways [[51,](#page-11-28) [52\]](#page-11-29). Thus, chronic stress-induced elevations in CRH may exacerbate anorexic symptoms in individuals with comorbid PTSD and AN. CRH secretion is tightly regulated by limbic brain regions such as the hippocampus and amygdala, which are both implicated in PTSD and ED pathophysiology. Amygdala hyperactivation [[53,](#page-11-30) [54](#page-11-31)] and hippocampal dysfunction [\[32,](#page-11-14) [55](#page-11-32)] may promote excessive CRH release, thereby contributing to persistent HPA axis dysregulation through shared neural circuits involved in stress and emotion regulation. Recent preclinical research further supports this link; for example, a mouse study showed that AgRP neurons (key promoters of feeding) modulate the HPA axis by disinhibiting CRH neurons, which enhances CRH activity [[56\]](#page-11-33). This bidirectional interaction between appetite-regulatory and stress-response systems offers a neurobiological framework for understanding the behavioral cycles in PTSD–ED comorbidity. These cycles can include, for example, stress-triggered binge eating, which is then followed by guilt and subsequent compensatory behaviors. Despite these insights, the precise relationship between CRH signaling and HPA axis dysregulation in comorbid PTSD and ED remains poorly defined. Further research is needed to delineate how trauma-induced alterations in CRH activity interact with disordered eating patterns across different ED subtypes and stages of illness. # *The transdiagnostic role of neuroinflammation in ED-PTSD* Both eating disorders and post-traumatic stress disorder are associated with underlying immune system dysregulation [[57\]](#page-11-34). Increasing evidence shows that individuals with PTSD exhibit significantly elevated levels of inflammatory markers—such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP)—compared to healthy controls [[58–](#page-11-35)[60](#page-11-36)]. Similarly, patients with EDs display heightened levels of TNF-α, IL-6, and IL-1β [\[61,](#page-11-37) [62](#page-11-38)]. These pro-inflammatory cytokines can cross the blood-brain barrier (BBB) [[63\]](#page-11-39), activating astrocytes and microglia—the brain's resident immune cells—and triggering neuroinflammation [[64,](#page-11-40) [65](#page-11-41)]. This neuroinflammatory cascade accelerates neurotransmitter turnover, promotes the accumulation of neurotoxic metabolites, and disrupts the function of key brain regions [[66](#page-11-42)[–68](#page-11-43)]. In murine models, elevated IL-6 and IL-10 have been shown to increase susceptibility to PTSD-like symptoms [[69\]](#page-11-44), while clinical studies have linked heightened neuroinflammation with core PTSD symptoms such as intrusive flashbacks [\[70](#page-12-0), [71\]](#page-12-1). Notably, individuals with comorbid PTSD and major depressive disorder—and higher levels of systemic inflammation—exhibit abnormal functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). This abnormal connectivity is closely tied to their symptom severity [\[72](#page-12-2)]. Other studies suggest that the combined impact of low-grade inflammation (elevated IL-6, IL-1β, TNF-α) and chronic stress may alter connectivity within higherorder cognitive networks, including the salience network (SN), default mode network (DMN), and central executive network (CEN), thereby increasing PTSD risk. In anorexia nervosa mouse models, increased levels of TNF-α, IL-1β, and IL-6 create a pro-inflammatory brain environment, enhancing microglial density in regions involved in feeding motivation and cognitive control [[73–](#page-12-3)[75](#page-12-4)]. Additionally, hypothalamic inflammation has been implicated in the onset of binge-eating behavior [[76\]](#page-12-5). Clinical studies further support the role of inflammation in AN, with elevated cytokine levels correlating with lower BMI and symptom severity, and declining as patients recover. These levels also appear positively associated with hypothalamic autoantibodies [\[77](#page-12-6)]. While direct research into neuroimmune mechanisms underlying ED-PTSD comorbidity is still limited, findings from other psychiatric disorders lend compelling support for the role of immune-brain interactions. In schizophrenia, persistently elevated IL-6 and TNF-α have been proposed as trait markers and are associated with structural brain alterations such as reduced hippocampal volume [[78,](#page-12-7) [79\]](#page-12-8). In mouse models of anxiety, peripheral cytokines directly modulate neural excitability: IL-17 enhances the excitability of basolateral amygdala neurons, while IL-10 has an inhibitory effect, acting as a "molecular switch" for anxiety-related behaviors [[80](#page-12-9)]. These findings suggest that immune dysregulation influences central nervous system function beyond peripheral inflammation, offering a conceptual framework for exploring shared neuroimmune mechanisms in ED-PTSD comorbidity. Anti-inflammatory interventions have shown promise in treating major depressive disorder and schizophrenia [[81,](#page-12-10) [82](#page-12-11)]. In depression, agents such as celecoxib, pioglitazone, and statins have demonstrated efficacy by reducing pro-inflammatory cytokines and restoring neural homeostasis [[83\]](#page-12-12). In PTSD, selective serotonin reuptake inhibitors may exert partial anti-inflammatory effects, though their clinical effectiveness remains inconsistent [[84,](#page-12-13) [85\]](#page-12-14). For EDs, however, evidence is scarce, and the use of anti-inflammatory drugs—particularly in patients with AN—raises safety concerns due to increased infection risk [[86](#page-12-15)]. Future research should investigate whether targeted immunomodulatory strategies can alleviate both ED and PTSD symptoms and reduce chronic inflammation in affected individuals. # *Shared gut microbiota dysregulation in eds and PTSD* The gut–brain axis plays a central role in regulating emotion and eating behavior, positioning the gut microbiota as a critical focus in unraveling the biological underpinnings of psychiatric comorbidities. Accumulating evidence indicates that both eating disorders and post-traumatic stress disorder are associated with gut microbial dysbiosis [[87,](#page-12-16) [88](#page-12-17)]. A common feature of both conditions is reduced α-diversity [[89–](#page-12-18)[91\]](#page-12-19), reflecting diminished microbial complexity, compromised ecological resilience, and increased susceptibility to metabolic dysregulation and chronic inflammation. Shared alterations in major bacterial phyla—particularly Firmicutes and Actinobacteria—have been observed in both disorders, with key taxa such as *Bifidobacterium*, *Lachnospiraceae*, and *Ruminococcaceae* frequently implicated [\[92–](#page-12-20)[95\]](#page-12-21). These taxa are primary producers of shortchain fatty acids (SCFAs), which are integral to energy metabolism, gut barrier integrity, and immune modulation. Although a distinct microbial signature for ED– PTSD comorbidity has not yet been established, impaired SCFA production may represent a shared pathogenic mechanism. SCFAs, especially butyrate, exert diverse effects beyond metabolic regulation. They enhance satiety by stimulating peptide YY (PYY) secretion [[96](#page-12-22)] and function as histone deacetylase (HDAC) inhibitors, influencing transcriptional programs involved in neuroprotection and immune homeostasis [\[97](#page-12-23)]. SCFAs also maintain gut barrier function, suppress lipopolysaccharide translocation, and downregulate pro-inflammatory cytokines such as TNF-α and IL-6, thereby modulating the stress response [[98\]](#page-12-24). In anorexia nervosa, SCFA levels are significantly reduced [[99\]](#page-12-25), with reductions persisting after weight restoration [\[100](#page-12-26)] and positively correlating with BMI [[101](#page-12-27), [102](#page-12-28)]. In binge-spectrum EDs, impaired SCFA signaling may dysregulate neuropeptides (e.g., NPY/PYY), contributing to binge urges and hedonic eating [\[103\]](#page-12-29). Similarly, PTSD is marked by decreased *Lachnospiraceae* abundance, potentially limiting SCFA synthesis and exacerbating systemic inflammation, despite heterogeneous changes in genera such as *Blautia* and *Coprococcus* [[89](#page-12-18), [104](#page-12-30)]. Together, SCFA deficits may constitute a convergent mechanism underlying energy imbalance, neuroinflammation, and impaired stress resilience in both disorders. Microbiota-targeted interventions offer a promising but underexplored avenue for treating ED–PTSD comorbidity. Preclinical studies suggest that prebiotics can boost SCFA production, reduce inflammation, and mitigate stress-induced anxiety and depressive behaviors [[105](#page-12-31)]. Probiotics have been shown to restore gut barrier function and alleviate PTSD-like behaviors in animal models [[106](#page-12-32)], while early clinical trials report improved nutritional status in AN [\[107\]](#page-12-33) and reduced binge episodes in binge eating disorder [[108\]](#page-12-34). One randomized trial also found partial symptom improvement in PTSD following probiotic supplementation [[109](#page-12-35)]. However, evidence remains preliminary and inconsistent, highlighting the need for large-scale trials to evaluate strain-specific effects and differential efficacy across ED subtypes. Fecal microbiota transplantation (FMT) has emerged as a potential adjunctive strategy. Case reports suggest that FMT is well tolerated in AN recovery [[110](#page-12-36), [111](#page-12-37)], and preclinical data indicate its ability to restore gut–brain communication and suppress binge-like behaviors [[112](#page-12-38)]. Although clinical data on FMT in PTSD are lacking, rodent studies demonstrate that stress-induced dysbiosis can be transferred via FMT, inducing anxiety- and fear-related behaviors in recipient animals [[113](#page-12-39), [114](#page-13-0)]. These findings provide compelling evidence for a causal role of the gut microbiota in trauma-related psychopathology. Despite these promising developments, nearly all microbiota-based interventions have been studied in ED or PTSD populations separately, with no research directly addressing their comorbidity. This represents a critical knowledge gap, particularly given their high co-occurrence and likely shared gut–brain mechanisms. Future studies should aim to: (1) identify microbiota and metabolomic profiles unique to ED–PTSD comorbidity; (2) test whether restoring SCFA levels or modulating microbial composition alleviates shared symptoms; and (3) evaluate personalized approaches such as strain-specific probiotics or targeted FMT—in large, longitudinal clinical trials. Lastly, the causal direction between gut dysbiosis and ED–PTSD remains unresolved. Evidence suggests a bidirectional relationship: microbial alterations may precede trauma exposure and heighten vulnerability to PTSD [[115](#page-13-1)], while trauma itself may disrupt antiinflammatory taxa, impair gut–brain signaling, and amplify stress sensitivity [[116](#page-13-2)]. Given the high prevalence of early-life trauma in ED populations [\[117\]](#page-13-3), persistent dysbiosis may act as a key susceptibility factor for comorbid PTSD, positioning microbiota-targeted interventions as viable therapeutic or preventive strategies. However, robust human data are scarce. To advance this field, future research must integrate longitudinal cohort studies, multi-omics analyses, and interventional trials to elucidate causal pathways and assess the translational potential of gut microbiota modulation in ED–PTSD comorbidity (Table [1\)](#page-6-0). # **The asymmetric bidirectional relationship between ED and PTSD** The preceding sections underscore the substantial overlap in psychological and biological mechanisms underlying PTSD and eating disorders (Fig. [1\)](#page-7-0). The figure illustrates shared psychological and physiological pathways contributing to ED-PTSD comorbidity. Psychological mechanisms include emotion dysregulation and dissociation. Physiological mechanisms involve HPA axis dysregulation, neuroinflammation, and alterations in gut microbiota. These shared pathways not only elucidate their frequent comorbidity but also suggest a persistent, mutually reinforcing bidirectional relationship. Mechanistic intersections facilitate symptom maintenance and exacerbation: PTSD or trauma-related symptoms (e.g., re-experiencing, hypervigilance) may intensify ED severity and emotional dysregulation via psychological and physiological routes. Conversely, certain ED behaviors or physiological states can reactivate traumatic memories, triggering or worsening PTSD symptoms, thus perpetuating a vicious cycle [[19\]](#page-11-1). Despite these bidirectional effects, evidence suggests an asymmetric relationship, with PTSD typically preceding ED onset and acting as both a risk factor and maintenance mechanism. Trauma—especially childhood abuse, encompassing sexual, physical, and emotional neglect—is a well-established risk factor for EDs [[118–](#page-13-4) [120](#page-13-5)]. Childhood abuse prevalence among ED populations ranges from 21% to 59%, markedly exceeding rates observed in healthy controls (1%–35%) and other psychiatric groups (5%–46%) [\[121\]](#page-13-6). This pattern implies that trauma exposure often predates disordered eating, with PTSD mediating this progression. Longitudinal data reinforce this asymmetry: a 16-year study linked adult PTSD symptoms—particularly intrusive re-experiencing—to greater ED severity, whereas trauma-ED associations were evident only during childhood [\[122](#page-13-7)]. Furthermore, childhood trauma's detrimental impact on ED treatment outcomes primarily manifests in individuals with a PTSD history [[14](#page-10-12)]. Those developing EDs post-sexual trauma frequently exhibit PTSD symptomatology [\[123](#page-13-8)], and military sexual assault has been shown to indirectly increase purging behaviors via PTSD symptoms [\[124](#page-13-9)]. Collectively, these findings support the hypothesis that PTSD sustains ED pathology more strongly than trauma exposure per se [\[125](#page-13-10)], highlighting the importance of directly addressing PTSD symptoms in trauma-related ED interventions. This asymmetry carries critical clinical implications. Trauma-related EDs may respond better to treatments targeting PTSD. However, many patients remain unaware of or reluctant to disclose trauma symptoms during ED treatment, potentially undermining therapeutic **Table 1** Psychological and biological mechanisms | Table 1 Psychological and biological mechanisms
Mechanism | Study | Location | Participants | Outcomes | Main Findings | |--------------------------------------------------------------|-------------------------------------|----------|--------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Emotional
dysregulation | Scharff
et al.
2021 [11] | USA | 699 female inpatients
with EDs: AN (44.9%),
BN (26.5%), OSFED
(22.3%) | EDE-Q, DSM-IV,
OASIS, ASI | ED patients with any history of trauma experienced
greater anxiety and depressive symptoms, experiential
avoidance, anxiety sensitivity relative to patients who
did not report trauma history. Among patients reporting
trauma, those with current PTSD experienced even greater
symptom severity. | | | Lev-ari
et al.
2021 [17] | Israel | 233 participants (40,
17.2% males): 80 com
munity volunteers,
153 students | EDE-Q, LEC, DES
II, DERS | Traumatic events predicted ED symptoms indirectly
through dissociation, emotional dysregulation and BMI. | | | Vanzhula
et al.
2019 [18] | USA | 158 ED patients: 84.8%
AN or atypical AN | EDDS, EDE-Q,
PTSD Checklist | Pathways between binge eating and irritability, body
dissatisfaction and trauma reminders, and concentration
difficulties may be the mechanisms by which comorbidity
is maintained. | | | Brewerton
et al.
2025 [19] | USA | 2178 ED patients:
AN-R (668), AN-BP
(456), BN (399), OSFED
(498), BED (71), ARFID
(63); 46% with comor
bid PTSD | EDE-Q, EDI, PHQ
9, STAI, EDQOL,
LEC-5, PTSD
Checklist | Comorbid symptoms of depression, anxiety and QOL
do in fact play major roles in bridging ED and PTSD
symptoms | | | Moulton
et al.
2015 [25] | UK | 142 female under
graduate students | CTQ, DES-II,
DERS, EDE-Q | Both emotion dysregulation and dissociation were found
to be significant mediators between childhood trauma
and eating psychopathology. | | HPA axis | Montele
one et al.
2015 [42] | Italy | 23 female with AN (8
AN-BP, 15 AN-R), 21
with BN | CTQ, CAR was as
sessed by saliva
samples | There is a dysregulation of HPA-axis activity in symptom
atic patients with EDs and the childhood trauma exposure
may contribute to such dysregulation. | | | Montele
one et al.
2018 [43] | Italy | 41 female with AN, 36
with BN, 41 healthy | CTQ, CAR was as
sessed by saliva
samples | Childhood trauma is associated with an impaired CAR in
adult AN and BN patients and there is a negative dose-de
pendent effect of the traumatic load on HPA axis activity. | | | Connan
et al.
2007 [48] | UK | 12 female with AN-R,
6 with AN-BP | CIS-R, EDE-Q, BDI,
BAI, The com
bined DXM/CRH
challenge test | In AN, HPA axis overactivity is mainly caused by a dysfunc
tional hypothalamus that overproduces CRH. | | Neuro
inflammation | Dani et al.
2024 [62] | / | 51 studies | Meta-analysis | Patients with eating disorders showed significantly el
evated levels of TNF-α and IL-1β than healthy controls. | | | Otsuka
et al.
2021 [70] | Japan | 57 female with PTSD,
73 non-trauma
exposed healthy
controls | PDS, CTQ, Blood
samples for the
measurement of
hsCRP, hsTNF-α,
and IL-6. | CRP genetic variation with circulating proinflammatory
markers, PTSD symptom severity, and cognitive dysfunc
tion in a sample of women with PTSD | | | Amerio
et al.
2023 [77] | Italy | 17 female with AN-R,
6 with AN-BP | Blood samples
for the measure
ment of IL-1β,
IL-6, TNF-α and
TGF-β | Increased pro-inflammatory phenotype in patients
affected by AN correlates with the concentration of auto
antibody specific for hypothalamic antigens. | | Gut Microbiota | Bajaj et al.
2019 [89] | USA | 93 combat-exposed
male veterans, 31%
combat-PTSD | DSM-V for PTSD,
stool sample | In male cirrhotic veterans, combat-related PTSD is associ
ated with lower microbial diversity (lower Lachnospirace
aeae and Ruminococcaceae) | | | Breton et al.
2016 [92] | USA | 29 healthy female
participants, 24 with
AN-R, 29 with BN, 13
with BED | EDI, blood
sample for ClpB | The gut bacterial protein ClpB, which shows elevated
concentrations in patients ED, contributing to ED patho
physiology by mimicking the anorexigenic neuropeptide
α-MSH in the brain. | | | Prochazkova
et al.
2021 [101] | Czechia | 59 female with AN-R,
67 healthy female
participants | EDE-Q, blood
samples | Fecal concentrations of the short-chain fatty acids butyr
ate and acetate were significantly lower in patients with
AN compared to healthy control. | AN-BP, anorexia nervosa binge-purging subtype; AN-R, anorexia nervosa restrictive subtype; LEC, Life Events Checklist; EDE-Q-IV, The Eating Disorder Examination Questionnaire – IV; PHQ-9, Patient Health Questionnaire; CTQ, Childhood Trauma Questionnaire; DES-II, Dissociative Experiences Scale-II; CAR, cortisol awakening response; BDI, Beck Depression Inventory; BAI, Beck Anxiety Inventory; CIS-R, clinical interview schedule; PDS, Posttraumatic Diagnostic Scale; EDI, Eating Disorder Inventory; DERS, Difficulties in Emotion Regulation Scale; OASIS, The Overall Anxiety Severity and Impairment Scale; ASI, Anxiety Sensitivity Index; EDDS, Eating Disorder Diagnostic Scale ![](https://assets.reachrx.ai/images/10.1186%E2%98%8Ds40337-025-01454-0/_page_7_Figure_3.jpeg) **Fig. 1** Overlapping mechanisms underlying comorbidity of EDs and PTSD efficacy [\[117](#page-13-3), [126\]](#page-13-11). For example, trauma symptoms in BED patients have been shown to attenuate the effectiveness of cognitive behavioral therapy (CBT) at sixmonth follow-up [\[127](#page-13-12)]. Similarly, in a cohort of 112 BED patients, lifetime PTSD was significantly associated with higher binge frequency at treatment endpoint [\[128](#page-13-13)]. These data emphasize that identifying and prioritizing trauma-related PTSD symptoms—particularly intrusive memories and emotional avoidance—may provide a more effective therapeutic entry point for improving ED outcomes. # **Current treatment strategies for ED-PTSD** Patients with comorbid eating disorders (EDs) and posttraumatic stress disorder (PTSD) consistently demonstrate poorer treatment outcomes [[12,](#page-10-10) [129](#page-13-14), [130](#page-13-15)]. Trauma-related symptoms represent a significant barrier to ED recovery, as PTSD features such as emotional dysregulation and intrusive memories interfere with foundational treatment goals like establishing regular eating patterns, thereby increasing dropout risk [[120\]](#page-13-5). A systematic review examining PTSD's impact on ED treatment dropout identified seven studies, three of higher methodological quality, all reporting a consistent association between PTSD and elevated dropout rates [\[11–](#page-10-14)[13\]](#page-10-11). Currently, psychological interventions for ED-PTSD comorbidity lack standardized treatment models. Cognitive-behavioral therapy (CBT) remains the cornerstone for EDs; however, trauma history predicts poorer CBT response in binge eating disorder (BED), underscoring the necessity to address trauma and dissociation in this population [[127](#page-13-12)]. Emerging research increasingly focuses on adapting or integrating treatments to target overlapping mechanisms such as cognitive distortions, emotional dysregulation, and dissociation. Cognitive processing therapy (CPT), a trauma-focused CBT modality with strong evidence for PTSD symptom reduction [[131](#page-13-16), [132](#page-13-17)], has been applied to address shared symptoms in ED patients [[133\]](#page-13-18). Recent advances propose an integrated CBT-CPT approach, combining CPT's trauma-processing elements within a framework targeting ED behaviors to enhance emotion regulation and trauma resolution [\[134](#page-13-19)]. A randomized controlled trial demonstrated that CBT-CPT outperformed standard ED-focused CBT in reducing PTSD, depression, and anxiety symptoms at six-month follow-up [[135](#page-13-20)]. Other promising interventions include comprehensive inpatient care [\[136\]](#page-13-21), the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) [\[137](#page-13-22), [138\]](#page-13-23), and imagery rescripting, which has shown efficacy and safety in ED populations [\[139](#page-13-24)]. Eye Movement Desensitization and Reprocessing (EMDR)—which integrates brief imaginal exposure with bilateral stimulation—also shows potential for ED patients with trauma histories. When combined with enhanced CBT (CBT-E), EMDR may particularly benefit those with moderate-to-severe childhood abuse, with improvements in ED symptoms partially mediated by reductions in dissociation [\[140\]](#page-13-25). Conversely, prolonged exposure (PE) therapy, despite its efficacy in PTSD, has demonstrated limited effectiveness for ED outcomes [[141\]](#page-13-26). Failure to address core PTSD symptoms adequately may impede ED recovery and increase relapse risk, often necessitating intensified levels of care [\[142\]](#page-13-27). Notably, current ED treatment guidelines rarely offer specific recommendations for PTSD screening or intervention, focusing instead on optimal timing for trauma-focused treatment initiation [\[143](#page-13-28)[–145\]](#page-13-29). Given the complex interplay of trauma history, ED psychopathology, and PTSD symptoms, there is an urgent need for integrative treatment frameworks that simultaneously address these domains to optimize outcomes for patients with comorbid ED-PTSD. # **Discussion** # **Limitations of neurobiological evidence** While this review integrates current findings on the psychological and biological mechanisms underlying PTSD– ED comorbidity, the field remains nascent, with most mechanistic models lacking rigorous empirical validation. For instance, the specific nature of HPA axis dysfunction in this context remains poorly defined. Although corticotropin-releasing hormone plays a recognized role in both PTSD and anorexia nervosa, its precise contribution as a comorbidity mechanism requires systematic investigation, particularly considering moderating factors such as sex and age, which may generate heterogeneous physiological responses [[146,](#page-13-30) [147](#page-13-31)]. Notably, females generally demonstrate heightened stress sensitivity relative to males, reflected in altered HPA axis negative feedback, fluctuating cortisol levels, and sustained CRH elevation [[148\]](#page-13-32). Estrogen further modulates this system by promoting CRH secretion and cortisol release, with menstrual cycle phases potentially influencing HPA axis activity [[149\]](#page-13-33). Supporting this, a small CBT study involving AN and bulimia nervosa patients revealed that individuals with abuse histories exhibited pronounced HPA axis dysregulation and persistently elevated cortisol levels [\[150](#page-13-34)]. Future treatment research should prioritize interventions aimed at restoring HPA axis function, especially among ED patients with early trauma exposure or established PTSD–ED comorbidity, to enhance clinical outcomes. Increasing evidence links elevated inflammatory markers in psychiatric disorders to alterations in brain structure and function, as well as symptom severity. For example, major depressive disorder associates with elevated pro-inflammatory cytokines and disrupted neural networks, whereas schizophrenia is characterized by cortical thinning in prefrontal and parieto-occipital areas, with inflammation implicated in these changes [[151\]](#page-13-35). Although neuroinflammation likely contributes to the chronicity of PTSD and ED, research specifically addressing neuroimmune mechanisms in ED populations remains sparse. Critical questions remain regarding the precise brain regions and neural circuits affected by inflammation in PTSD–ED comorbidity, underscoring the need for targeted human studies. Similarly, gut microbiota alterations have emerged as a promising yet underexplored mechanism. However, reproducibility challenges—stemming from methodological heterogeneity, small sample sizes, and inconsistent taxonomic classification—limit current interpretations. It remains uncertain whether and how gut microbiota modulates brain inflammatory pathways and food reward signaling to influence symptomatology in ED–PTSD [[152\]](#page-13-36). Overall, while these biological mechanisms provide promising therapeutic targets, their specific pathways and causal roles require further rigorous investigation. # **Clinical intervention challenges** *Screening difficulties* Although some experts have advocated for integrating trauma-informed care (TIC) into clinical practice for ED patients [[153](#page-13-37)], current ED treatment guidelines provide limited practical recommendations on addressing trauma-related issues within standard care frameworks [[154,](#page-13-38) [155\]](#page-13-39). To date, the only PTSD guideline explicitly addressing comorbidity with EDs is that of the American Psychiatric Association, which recommends routine screening for trauma history and PTSD symptoms among patients suspected of having ED, and emphasizes psychotherapy targeting co-occurring psychological difficulties, internal conflicts, and symptom functionality [[156\]](#page-13-40). Brewerton [[157\]](#page-13-41) further highlights that, although some guidelines recognize that comorbidity should not preclude treatment, trauma specialists are often insufficiently equipped to manage PTSD patients presenting with ED symptoms. Consequently, individuals with ED-PTSD frequently receive treatment focused solely on the "primary" disorder within specialized programs, resulting in undertreatment and suboptimal outcomes. Sexual trauma, for example, may intensify ED symptomatology by exacerbating body dissatisfaction and psychological distress [[158](#page-13-42)]. However, pervasive feelings of shame often lead patients to conceal such histories, contributing to clinical underrecognition [\[159,](#page-13-43) [160\]](#page-13-44). Given that EDs disproportionately affect women—who also experience higher rates of sexual violence [\[161](#page-14-0), [162](#page-14-1)] the potential for unreported trauma in this population underscores the critical importance of trauma identification. Importantly, trauma screening should prioritize assessing the impact of trauma on functioning rather than eliciting detailed trauma narratives, thereby minimizing patient distress and enhancing disclosure [\[163](#page-14-2)]. Trauma-Informed Care and Trauma-Informed Approaches (TIA) offer essential frameworks for supporting patients with ED-PTSD comorbidity. TIC focuses on trauma-sensitive clinical interactions, emphasizing safety, respect for patient autonomy, and avoidance of retraumatizing language or practices [[164\]](#page-14-3). In contrast, TIA operates at the organizational level, embedding trauma awareness within institutional policies, procedures, and culture to foster trauma-sensitive care environments [\[165\]](#page-14-4). Implementation of TIA in ED treatment settings necessitates training multidisciplinary teams including psychologists, nurses, and physicians—to recognize trauma-related symptoms and effectively address the complex interplay between ED and PTSD. Such integrated trauma-informed frameworks are critical for improving identification, engagement, and therapeutic outcomes in this high-risk population. ### *Impact of trauma heterogeneity and onset sequence on treatment* Clinical interventions may benefit from tailoring treatment focus according to trauma type. Emotional abuse—such as neglect, belittlement, or emotional unavailability—has been more strongly associated with impaired emotion regulation and restrictive eating behaviors than physical or sexual abuse [[166\]](#page-14-5). Chronic and often ambiguous emotional trauma frequently goes unrecognized yet profoundly impacts emotion regulation systems, thereby necessitating targeted therapeutic approaches. In contrast, PTSD resulting from sexual or physical abuse may require an emphasis on body-focused interventions, such as addressing hypervigilance or avoidance related to bodily sensations [\[167](#page-14-6)]. Although PTSD is traditionally conceptualized as a categorical diagnosis, it exists along a spectrum. The ICD-11 introduced complex post-traumatic stress disorder (CPTSD), distinguished by prolonged interpersonal trauma rather than discrete events [[168\]](#page-14-7). Compared to PTSD, CPTSD is characterized by more frequent and enduring trauma exposure and greater functional impairment [[169\]](#page-14-8). CPTSD includes "disturbances in selforganization" (DSO), encompassing symptoms such as emotion dysregulation, negative self-concept, and interpersonal difficulties. Notably, ED patients exhibit higher CPTSD prevalence than PTSD [\[170\]](#page-14-9). DSO symptoms alone account for approximately 12.4% and 12.3% of the variance in psychopathology and functional impairment, respectively, suggesting a unique influence of these symptoms on eating behaviors and psychological functioning. Despite this, no treatments specifically targeting CPTSD in ED populations have been developed. While trauma exposure is common among individuals with EDs [[126](#page-13-11)], not all develop PTSD [\[171](#page-14-10)], indicating that trauma alone may not fully account for ED symptomatology. Greater research attention is warranted on subthreshold trauma-related symptoms and their clinical significance [\[172\]](#page-14-11). The temporal sequence of symptom onset al.so has treatment implications. Shared early risk factors—such as childhood emotional abuse, neglect, and family conflict—may predispose individuals to both ED and PTSD via emotion dysregulation pathways, justifying traumafocused interventions. Conversely, some individuals may develop PTSD secondary to trauma related to their ED experience, including interpersonal violence or medical trauma. Given that ED patients often exhibit heightened anxiety and threat sensitivity [[173](#page-14-12)], these factors may exacerbate trauma-related symptoms. However, existing research on this secondary PTSD onset is limited, and clear clinical guidelines are lacking. Further studies are needed to clarify how trauma timing, perceived impact, and cumulative exposure affect differential ED trajectories and outcomes [[13](#page-10-11)]. The heterogeneity of trauma types and symptom onset sequences underscores the clinical variability seen in patients with comorbid PTSD and ED. If ED functions primarily as a trauma coping mechanism, prioritizing trauma-focused treatment is likely appropriate. However, if ED reflects a more complex dysregulation of adaptive systems—incorporating chronic emotional suppression, familial relational stress, and sociocultural gender expectations—trauma-focused interventions alone may be insufficient. In these cases, treatment should emphasize eating behavior management, nutritional rehabilitation, and family involvement to address multifaceted clinical needs. # **Conclusion** This review synthesizes recent advances in understanding the psychological and biological mechanisms underlying PTSD and eating disorder (ED) comorbidity, highlighting their complex and often asymmetric interplay. While mechanisms such as HPA axis dysfunction, neuroinflammation, and gut microbiota dysregulation show promise as shared pathways, current findings are limited by methodological heterogeneity, small sample sizes, and insufficient validation. Moreover, individual differences including gender, trauma type, and symptom onset sequence—contribute to substantial heterogeneity in both biological and psychological profiles among comorbid patients, underscoring the need for more nuanced, stratified research approaches. Clinically, the high rates of trauma exposure among ED patients, combined with the frequently covert presentation of PTSD symptoms, present significant barriers to accurate identification and effective treatment. Conventional approaches often marginalize trauma, focusing primarily on the "primary" disorder, which may lead to suboptimal outcomes. Trauma-Informed Care (TIC) and Trauma-Informed Approaches (TIA) offer comprehensive, integrated frameworks better suited to addressing the complex needs of patients with trauma histories. Furthermore, the elevated prevalence of complex PTSD (CPTSD) in ED populations—characterized by disturbances in self-organization such as emotional dysregulation and negative self-concept—calls for clinical pathways that encompass the full trauma spectrum. Ultimately, advancing understanding of ED-PTSD comorbidity requires transcending simple comorbidity rates or isolated mechanistic models. A transdisciplinary framework integrating biological, psychological, and sociocultural dimensions is crucial for developing personalized, precision medicine strategies that optimize prevention, assessment, and intervention for this challenging clinical population. #### **Abbreviations** ACTH Adrenocorticotropic hormone AN Anorexia nervosa BED Binge eating disorder BN Bulimia nervosa CAR Cortisol awakening response CBT Cognitive-behavioral therapy CBT-CPT Cognitive processing therapy combined with ED-focused CBT CBT-E Enhanced cognitive-behavioral therapy CEN Central executive network CPTSD Complex post-traumatic stress disorder CPT Cognitive processing therapy CRP C-reactive protein CRH Corticotropin-releasing hormone DMN Default mode network EDs Eating disorders EMDR Eye Movement Desensitization and Reprocessing FMT Fecal microbiota transplantation HDAC Histone deacetylase HPA axis Hypothalamic-pituitary-adrenal axis IL-1β Interleukin-1 beta IL-6 Interleukin-6 PE Prolonged exposure therapy PTSD Post-traumatic stress disorder PTSD-DS Dissociative subtype of PTSD PYY Peptide YY SAN Salience network SCFA Short-chain fatty acids TIA Trauma-Informed Approaches TIC Trauma-informed care TNF-α Tumor necrosis factor-alpha TSST Trier Social Stress Test UTM Unified Protocol for Transdiagnostic Treatment of Emotional Disorders vmPFC Ventromedial prefrontal cortex #### **Acknowledgements** Not applicable. #### **Author contributions** Hanlai Ouyang: Conceptualization, Writing – original draft– review & editingYating Wang: Conceptualization, review & editingJue Chen: Supervision, review & editing. #### **Funding** This work was supported by the Clinical Science and Technology Innovation Project of Shanghai Hospital Development Center (SHDC12023122), the Chinese Medicine Education Association (2022KTM033), the Integrated Innovation Team of Shanghai Mental Health Center, and the National Natural Science Foundation of China (82471573). # **Data availability** Not applicable. # **Declarations** #### **Ethics approval and consent to participate** Not applicable. #### **Consent for publication** Not applicable. #### **Competing interests** The authors declare no competing interests. ### **Author details** Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine and School of Psychology, Shanghai, China Received: 18 August 2025 / Accepted: 30 October 2025 #### **References** - 1. 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