Frégoli Delusion Syndrome: A Hyper-Identification Disorder Explored Through Cognitive Neuropsychiatry, Neurobiology, and Therapeutic Research

Abstract

Frégoli Delusion Syndrome (FDS) is a rare and complex neuropsychiatric condition classified under the Delusional Misidentification Syndromes (DMS). It is defined by the fixed, paranoid belief that a known individual, typically a persecutor, repeatedly assumes the physical appearance of various strangers encountered by the patient. Fundamentally, FDS is a syndrome of hyper-identification, rooted in the pathological dissociation between accurate visual perception and the pathologically over-stimulated affective recognition system. Neurobiological research consistently implicates functional and structural disruption within the right cerebral hemisphere, specifically involving the anterior fusiform gyrus and a resulting temporolimbic-frontal disconnection. Cognitive neuropsychiatric models, such as the Dual-Route Model and the Two-Factor Theory, explain the delusion's emergence as the brain's attempt to rationalise an aberrant internal signal of familiarity (Factor 1), coupled with frontal lobe dysfunction that impairs the ability to reject this improbable belief (Factor 2). Management requires a meticulous, multidisciplinary approach, combining antipsychotic medication to modulate psychotic salience, alongside tailored psychological interventions, particularly Cognitive Behavioural Therapy (CBT), to address the fixed belief structure and mitigate the associated high risk of aggressive behaviour. Future work should focus on clarifying the underlying neurodevelopmental and genetic vulnerabilities shared with primary psychoses to inform targeted therapeutic strategies.

1. Introduction: Delusional Misidentification Syndromes and the Phenomenon of Frégoli

Frégoli Delusion Syndrome (FDS), also known as Frégoli syndrome, is classified as a rare and complex neuropsychiatric condition belonging to the family of Delusional Misidentification Syndromes (DMS). DMS are psychotic conditions characterised by the pathological misidentification of people, objects, or locations, often unified by the concept of the sosie (double). FDS stands alongside Capgras delusion, Intermetamorphosis, and the syndrome of Subjective Doubles as one of the core subtypes of DMS.

The syndrome was first described in 1927 by Courbon and Fail, who named it after the famous Italian actor Leopoldo Frégoli, renowned for his rapid changes in costume and character. FDS is defined by the patient’s fixed, often persecutory, delusional belief that a known individual, typically perceived as a threat, is consistently and repeatedly changing their physical appearance, masquerading as various strangers whom the patient encounters in their environment. The patient maintains the conviction of the psychological identity of the persecutor, even though they consciously perceive the physical appearance of the encountered stranger as being different from the known person's typical guise. This cognitive contradiction, the dissociation between visual perception and identity recognition, forms the central paradox of the syndrome.

FDS is fundamentally categorised as a 'hyper-identification' syndrome. This designation refers to an aberrant excess of perceived familiarity directed towards unfamiliar individuals. This mechanism is in direct opposition to the characteristic 'hypo-identification' observed in Capgras syndrome, where a familiar person is perceived as psychologically unfamiliar and replaced by an imposter, suggesting a loss of the normal affective link. The presence of hyper-identification suggests a crucial functional breakdown: an overactive or pathologically disinhibited affective identification system, referred to in cognitive models as the Person Identity Node (PIN). When this affective system is pathologically hyper-stimulated by a novel face, the higher-order frontal systems responsible for reality testing must attempt to rationalise the resultant contradictory sensory data. The only internally consistent explanation that preserves the fixed identity is intentional deception and disguise, which explains the pervasive paranoid and persecutory nature of the delusion.

2. Clinical Spectrum, Aetiology, and Forensic Relevance

2.1 Aetiological Pathways and Differential Presentation

The pathogenesis of FDS is complex and heterogenous, rarely existing in isolation (Ellis et al., 1994; Hudson & Grace, 2000). Clinically, FDS presents across a bimodal spectrum: either as a feature of primary psychiatric conditions or as a consequence of organic cerebral dysfunction (Corlett et al., 2010). A review of 119 FDS cases revealed that approximately 52% occur within the context of primary psychoses, such such as schizophrenia or bipolar I disorder (Hudson & Grace, 2000; Ellis et al., 1994; Corlett et al., 2010; Christodoulou et al., 2009; Forstl et al., 1994). Conversely, 42% of cases are secondary, stemming from defined organic brain disorders.

The underlying aetiology correlates directly with the typical age of onset. FDS secondary to organic causes tends to present significantly later in life, showing a median onset age of 60, whereas cases associated with a primary psychiatric diagnosis typically have a median onset age of 33 (Forstl et al., 1994). This disparity suggests two distinct initiation pathways. For younger patients, FDS emerges from an underlying neurodevelopmental vulnerability interacting with the acute stress of a primary psychotic break. For older patients, the syndrome is often a catastrophic symptom of structural brain damage, such as neurodegeneration (e.g., Alzheimer's or Lewy body dementia) or acute vascular compromise. This crucial distinction mandates a bifurcated clinical investigation: early-onset FDS requires a thorough psychiatric evaluation for primary psychotic disorders, while late-onset FDS demands immediate and exhaustive neuroimaging (MRI/PET) to screen for structural lesions, such as the temporal lobe masses that have been reported to induce FDS (Hudson & Grace, 2000; Hentati et al., 2022).

2.2 Secondary (Organic) Risk Factors

The occurrence of FDS secondary to neurological damage is well-documented. Specific insult sites include the right frontoparietal and adjacent regions (Hentati et al., 2022; Feinberg et al., 1999). FDS has been linked to Traumatic Brain Injury (TBI) (Feinberg et al., 1999) , cerebral lesions (such as a right temporal lobe mass with associated oedema suggestive of metastasis) (Hentati et al., 2022) , and cerebrovascular accidents. Beyond physical trauma, FDS has been reported secondary to infectious diseases like typhoid fever (Stanley & Andrew, 2002; Hentati et al., 2022) and systemic failure, demonstrated by a case associated with chronic kidney disease requiring haemodialysis (Papageorgiou et al., 2005). Furthermore, the condition may also be iatrogenic; certain medications, notably Levodopa, have been explicitly linked to the onset of FDS symptoms (Turkiewicz et al., 2009; Courbon & Fail, 1927).

2.3 Forensic and Clinical Behavioural Risks

Due to the fundamental paranoid content of the delusion, the persistent belief that the patient is being actively tracked, monitored, and deceived by an individual disguised as multiple people (Courbon & Fail, 1927; Turkiewicz et al., 2009), patients exhibiting FDS are often considered to be at a particularly high risk for dangerousness, including verbal threats and aggressive behaviour. This is particularly pertinent in forensic populations and clinical settings. Patients in hospital environments frequently misidentify members of the treatment team (e.g., nurses or doctors) as the persecutor, leading to assaultive behaviour towards staff (Silva et al., 2012; Lykouras et al., 2002). Documented risk factors for aggression in DMS patients include male sex, a long-standing history of the delusion, a primary diagnosis of schizophrenia, and co-morbid substance use (Forstl et al., 1994). Recognition and early treatment of this relatively uncommon delusional syndrome are thus essential for mitigating assault risk and ensuring patient safety (Silva et al., 2012).

3. Neurobiological Substrates and Functional Disconnection (Neuroscience)

The scientific investigation into FDS and other DMS has shifted dramatically over the decades, moving from purely psychodynamic explanations to identifying clear neurophysiological and neuroimaging correlates (Hentati et al., 2022). The current understanding firmly roots FDS in a functional and structural breakdown of specific pathways within the right cerebral hemisphere.

3.1 Anatomical Localisation and Structural Damage

Neuroimaging studies consistently report identifiable neurological lesions or functional abnormalities in DMS patients, predominantly lateralised to the right hemisphere (Hentati et al., 2022; Stanley & Andrew, 2002). Specific regions implicated include the right temporal lobe, right fusiform gyrus, and right frontoparietal cortex (Stanley & Andrew, 2002; Hentati et al., 2022; Hudson & Grace, 2000; Christodoulou et al., 2009). In cases of co-occurring FDS and Capgras syndrome, structural MRI findings have revealed periventricular and subcortical white matter hyperintensities concentrated in the right frontotemporal region, alongside bilateral frontotemporal volume loss (Stanley & Andrew, 2002; Silva et al., 2012; Lykouras et al., 2002). Functional studies (SPECT) in patients with misidentification delusions also suggest bilateral hypoperfusion in the superior and inferior temporal lobes, corresponding precisely to the location of the fusiform face area (FFA) (Papageorgiou et al., 2005; Turkiewicz et al., 2009).

3.2 Disruption of Face Recognition Pathways

FDS is understood fundamentally as a failure within the brain's visual processing network. Visual perception is organised into two main pathways: the dorsal (spatial) pathway and the temporal-occipital ventral pathway, which is critical for object and face recognition. The pathology in FDS localises to the ventral stream, particularly involving the anterior part of the right fusiform gyrus (Christodoulou et al., 2009; Forstl et al., 1994). This region is home to the FFA, a highly specialised area dedicated to face identification. Lesions here are thought to result in an inability to attribute perceptual uniqueness to a specific face (Papageorgiou et al., 2005; Langdon et al., 2014).

The visual misidentification phenomena in FDS are explained by the disruption of connections between these highly specialised visual areas (like the FFA) and the anterior, inferior, and medial parts of the right temporal lobe (Christodoulou et al., 2009). This latter region is crucial for storing long-term visual recognition memory and retrieving the information necessary for the recognition of faces. The consequence is a loss of function in the associative nodes, the biological links that connect the perception of a specific familiar face to all stored identity information about that person.

3.3 The Temporolimbic-Frontal Disconnection Hypothesis

The most compelling mechanistic explanation is the right temporolimbic-frontal disconnection hypothesis (Stanley & Andrew, 2002; Silva et al., 2012; Lykouras et al., 2002). This functional disconnection creates an impairment in the high-order nervous system function responsible for identification. In FDS, the sensory/perceptual recognition system registers a novel physical appearance, but the limbic-frontal affective and memory systems pathologically register this input as deeply familiar (Stanley & Andrew, 2002). This disjunction prevents the patient from correctly associating established long-term memories of the familiar person with the contradictory new perceptual information (the stranger’s face). Electrophysiological evidence supports this view, with studies noting abnormal event-related potentials (P300) in DMS patients, indicating underlying working memory dysfunction in the frontal and parietal regions (Turkiewicz et al., 2009; Hentati et al., 2022). The misidentification symptoms are therefore the brain's effort to reconcile conflicting internal signals arising from structural or functional disconnection in this critical circuit.

4. Cognitive Neuropsychiatric Models

Cognitive neuropsychiatry seeks to explain delusions by mapping them onto specific disruptions of normal cognitive processes. FDS is a paradigm case for such models, offering a cognitive error that must then be rationalised as a delusion.

4.1 The Dual-Route Model and Hyper-Identification

Building upon earlier models of face processing, Langdon and colleagues (2014) proposed a dual-route model specifically tailored to explain disorders of person identification. This framework delineates separate routes for overt (conscious) and covert (affective/subconscious) face recognition. FDS is explained within this model as a syndrome of hyper-identification, arising from an impaired cognitive system that possesses a pathological propensity to over-excite certain internal representations known as Person Identity Nodes (PINs) (Feinberg et al., 1999; Turkiewicz et al., 2009).

The model asserts that FDS stems from a breakdown in the identification process leading to an inability to attribute visual uniqueness to a face (Papageorgiou et al., 2005). When any face bearing some level of perceived similarity to the persecutor is encountered, the hyper-vigilant PIN associated with the persecutor is pathologically activated. The brain consequently misidentifies the unfamiliar individual as the known person, leading to the fixed, irrational belief that the familiar person is employing multiple physical disguises (Feinberg et al., 1999; Langdon et al., 2014; Hentati et al., 2022).

4.2 The Two-Factor Theory and Belief Maintenance

The formation and maintenance of monothematic delusions like FDS are often discussed within the framework of the Two-Factor Theory (TFT) (Langdon et al., 2014; Turkiewicz et al., 2009; Christodoulou et al., 2009). TFT posits that two independent neuropsychological impairments are necessary: Factor 1, which generates the aberrant perceptual content, and Factor 2, which ensures the formation and tenacious maintenance of the belief.

In FDS, Factor 1 is clearly the perceptual anomaly resulting from the disconnection between the visual processing area (FFA) and the limbic system, leading to the hyper-familiarity signal (Turkiewicz et al., 2009; Christodoulou et al., 2009). This signal provides the initial bizarre content, the stranger feels like the familiar person. Factor 2, the failure to evaluate and reject this highly improbable belief, is associated with dysfunction in the right dorsolateral prefrontal cortex (rDLPFC) and potentially the ventromedial prefrontal cortex (vmPFC) (Hentati et al., 2022; Langdon et al., 2014; Turkiewicz et al., 2009; Christodoulou et al., 2009). This frontal pathology prevents the patient from appropriately weighing the objective visual evidence against the internal feeling of recognition, thereby locking the persecutory, bizarre delusion of disguise into place (Hentati et al., 2022; Turkiewicz et al., 2009).

While TFT remains a strong explanatory tool, recent neurocognitive findings challenge the strict modularity of the two factors. Studies show that neurological lesions frequently span multiple regions, affecting both perceptual and evaluative circuits simultaneously. This suggests that the impairments contributing to the delusion may not be strictly independent processes, but rather integrated components of a single, structurally or functionally disconnected circuit (Langdon et al., 2014; Turkiewicz et al., 2009; Christodoulou et al., 2009).

4.3 Computational Models: Aberrant Prediction Error

Beyond structural models, computational psychiatry offers a sophisticated mechanism for delusion formation based on prediction error (Corlett et al., 2010). Delusions are seen as resulting from aberrations in how brain circuits specify hierarchical predictions and how they compute the prediction error, the mismatch between expectation and sensory experience.

In the context of FDS, the pathological hyper-activation of the PIN generates a powerful internal expectation ("Person X is here and is persecuting me"). However, external sensory data (the stranger's physical appearance) generates a significant prediction error (Corlett et al., 2010). Normal cognitive function would use this high error signal to update and reject the initial expectation. Dysfunction in the frontostriatal circuits, however, compromises the patient's ability to process or correctly respond to this prediction error, leading to a failure to update the belief (Corlett et al., 2010). Consequently, the brain defaults to the least likely, yet internally satisfying, conclusion: that the visual discrepancy is the result of an external, elaborate plot of disguise and deception, thus maintaining the fixed delusion (Corlett et al., 2010; Hentati et al., 2022).

5. Evidence-Based Management and Therapeutic Outcomes (Treatment Research)

The complexity and heterogeneity of FDS, coupled with its relatively low prevalence, mean that no standardised, single-pronged treatment regimen exists (Courbon & Fail, 1927). Effective management requires an individualised, multidisciplinary approach that targets both the psychotic and behavioural symptoms.

5.1 Pharmacological Strategies

Antipsychotic medication forms the cornerstone of pharmacological treatment, supplemented sometimes by antidepressants or antiseizure medications, especially when there is evidence of structural brain injury or organic aetiology. However, robust, syndrome-specific clinical trials comparing drug efficacy in FDS are scarce (Papageorgiou et al., 2005). Treatment protocols are often extrapolated from research on general delusional disorders (DD) and co-morbid primary psychoses.

Systematic reviews covering DD indicate that antipsychotics, as a class, are effective, but show no clear superiority for any one specific agent. Tentative evidence suggests that First-Generation Antipsychotics (FGAs) may show a slight advantage over Second-Generation Antipsychotics (SGAs), with good response rates reported at 39% versus 28%, respectively, in general delusional disorder cohorts. Dosage typically requires careful titration, often over several weeks, to manage persistent symptoms. In one case involving a patient treated with Risperidone, the dose had to be escalated from 2 mg to 6 mg daily to achieve a partial decrease in delusional activity and reactivity (Silva et al., 2012). Critically, while the patient achieved remission in hallucinatory activity, the core delusional belief remained partially present but no longer influenced their behaviour.

Given the high associated risk for aggressive behaviour, clinicians must employ intensive monitoring, particularly regarding medication adherence and potential drug abuse history (Silva et al., 2012; Lykouras et al., 2002). Furthermore, adjusting medication, such as changing levodopa if it is identified as a trigger, may be necessary in secondary cases (Courbon & Fail, 1927).

Clinical insight:

Levodopa, while essential for managing motor symptoms, can trigger dopamine dysregulation syndrome, delusions, and psychiatric effects in some patients.

A 2025 case report documented a patient developing Frégoli syndrome alongside drug dependence and hallucinations after prolonged levodopa/carbidopa use and self-adjusted dosing (Springer, 2025). When the levodopa dosage was reduced or discontinued, delusional symptoms including misidentification diminished.

📌 Implication for clinicians:

If Frégoli symptoms appear, especially in Parkinson’s patients, reviewing and adjusting levodopa dosing is not just advisable, it may be essential. This is not just about psychiatric overlay, it is about dopaminergic overload and its distortion of identity perception.

5.2 Psychological and Non-Pharmacological Interventions

Pharmacological intervention, even when successful, often manages the severity and reactivity of the delusion, rather than eradicating the fixed belief entirely. Therefore, psychological therapy is essential to address the distorted thoughts and associated behaviour patterns.

Cognitive Behavioural Therapy (CBT) is considered crucial for FDS, particularly when comorbid with schizophrenia, where the combination of CBT and antipsychotics proves significantly more effective than medication alone (Lykouras et al., 2002). CBT aims to help the patient evaluate the non-bizarre elements of their thoughts, challenge the persecutory inferences derived from the misidentification error, and restructure their response to the belief (Courbon & Fail, 1927).

For patients with complex clinical histories, including trauma or chronic non-adherence, personalised interventions, such as trauma-focused care, are necessary (Lykouras et al., 2002; Schmitt et al., 2023). Additionally, some case reports suggest that adjunctive treatments such as hypnosis may be helpful alongside traditional pharmaceutical and cognitive therapies (Courbon & Fail, 1927). The ultimate measure of therapeutic success is often redefined from complete delusion eradication to substantial reduction in patient reactivity, functional impairment, and associated violence risk.

6. Conclusion and Future Directions

Frégoli Delusion Syndrome is a striking example of a monothematic delusion, classified as a hyper-identification DMS, rooted in a fundamental disruption of the cerebral circuits responsible for face recognition and identity processing. The current evidence overwhelmingly points to a critical functional and structural failure within the right hemisphere, specifically involving the fusiform gyrus and its connections to the right temporolimbic and frontal structures. This disconnection prevents the integration of visual discrepancy with identity confirmation, resulting in the brain's rationalisation of the fixed identity through a bizarre, persecutory narrative of disguise.

The clinical heterogeneity of FDS, arising either from primary neurodevelopmental vulnerabilities (schizophrenia/bipolar disorder) or secondary organic insults (TBI/neurodegeneration), necessitates a stringent differential diagnostic protocol tailored by age of onset. Management must be multidisciplinary, relying on antipsychotics to modulate the salience of the delusion (likely by reducing prediction error signalling) and robust psychological intervention, chiefly CBT, to manage the fixed belief structure and mitigate high risks of aggressive behaviour.

Summary of Aetiological and Therapeutic Concepts

Domain	Aetiology/Model	Primary Correlates	Therapeutic Implication
Neuroanatomy	Right Hemisphere Dysfunction	Lesions in Fusiform Gyrus; Temporolimbic-frontal disconnection	Mandatory neuroimaging (MRI) to rule out structural causes (e.g., mass lesions).
Cognitive Model	Dual-Route / Hyper-PIN Activation	Over-excitation of Person Identity Nodes; Failure to attribute visual uniqueness	Cognitive Behavioural Therapy (CBT) to challenge and restructure the fixed belief.
Pharmacological	Psychotic Vulnerability / Prediction Error	Dopaminergic dysregulation; Schizophrenia comorbidity	Antipsychotic medication (FGAs or SGAs) to modulate delusional salience and reactivity.

Directions for Prospective Research

To advance the understanding and treatment of FDS, future efforts should be concentrated on three key areas. Firstly, further investigation into the familial genetic risk shared between DMS and core psychotic disorders (such as Schizophrenia and Bipolar Disorder) is required to clarify the underlying neurodevelopmental vulnerability. Secondly, specific, controlled clinical trials are necessary to compare the efficacy of modern antipsychotics (SGAs) against FGAs and adjunctive agents in homogenous DMS cohorts, moving beyond reliance on general delusional disorder data. Finally, the continued application of computational psychiatry, utilising advanced neuroimaging techniques, holds promise for refining the understanding of aberrant prediction error mechanisms, thereby offering clearer neurobiological targets for future pharmacological and neuromodulatory interventions.

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