Misidentification syndrome: A narrative review

Abstract

Misidentification syndromes have been described for a long time, but the major developments occurred in the 19^th and 29^th centuries. Many reviews have discussed the various aspects of delusional misidentification syndromes (DMSs). However, there is a lack of updated comprehensive review. This narrative review aims to review the historical aspects, classification, clinical aspects, epidemiology, etiological models, assessment, differential diagnosis, and management of DMS. Multiple internet searches were done to identify the literature on DMSs, and the literature was organized under different headings. DMSs are classified variously and are seen in patients with psychiatric disorders and in those with associated physical diseases, especially those involving the brain. The overall prevalence of DMS has varied from 5.2 to 81.6%. While evaluating DMS, it is important to distinguish it from disorientation, visual problems, memory problems, depersonalization and derealization, and dissociative disorder. There is little information about the management of DMS. DMSs are a rare phenomenon in patients with primary psychiatric disorders and organic conditions. Future studies must attempt to evaluate the efficacy of different antipsychotics in patients with DMS.

Misidentification syndromes (MDSs) or delusional misidentification syndrome (DMSs) are a group of rare psychopathological phenomena characterized by a belief that a person, place, object, or event has been duplicated, reformed, or replaced. Various neuropsychiatric disorders can present with DMS¹. A recurring theme in all cases of DMS is the idea that one person is a replica of another, often known as the sosie or double ¹. The French word ‘Sosie’ originated from an ancient tragic comedy, the ‘Amphitryon,’ by the Roman comedian Plautus, and it was for the first time used in the context of DMS by Capgras and Reboul-Lachaux.[1] Various MDSs are highly overlapping; they do not reflect unique syndromes and cannot be considered an indication of a specific condition. One type of MDS may evolve into another.[1] MDSs described in the literature are given in Table 1.[1,2,3,4,5,6,7,8,9,10,11,12]

Table 1.

Types of MDSs

Syndrome	Clinical features
Capgras syndrome[2]	The patient believes that a physically identical imposter has replaced a familiar person.
Fregoli syndrome[3]	The patient believes that strangers are familiar people in disguise
Intermetamorphosis[4]	The patient believes that familiar people and strangers in the environment have exchanged identities and maintained their original physical appearance
Subjective doubles[5]	The belief that they have a doppelganger who acts independently
Reduplicative Paramnesia[6]	The belief that a place or location has been duplicated, existing in two or more places
Mirror Sign[7]	Misidentification of self in the mirror
Phantom boarder syndrome[8]	Someone uninvited living in their home
Nurturing syndrome[9]	Deceased family member is believed to be living
TV sign misidentification[10]	Events on television are understood to be happening in external space
Clonal Pluralization of Self[11]	The belief that there are many physically and psychologically identical copies of a given original
Reverse Capgras syndrome[1]	The patient believes that they are imposters themselves (famous figure)
Reverse Fregoli[1]	The belief that others do not recognize them
Reverse intermetamorphosis[12]	The person believes that they have changed substantially, both physically and psychologically
Delusional hermaphroditism[12]	Belief that oneself and a familiar person of opposite gender have been incorporated into the same body

In view of the lack of comprehensive reviews assessing different aspects of DMS, the present review aims to evaluate the historical aspects, classification, clinical aspects, epidemiology, etiological models, assessment, differential diagnosis, and management of DMS.

METHODOLOGY

For this review, Internet searches were carried out using the multiple search engines, that is, PUBMED, Google, Google Scholar, Science Direct, and Scopus. The keywords used included, Delusion*, misidentification, history, classification, epidemiology, etiology, assessment, differential diagnosis, and management in different combinations. Independent searches were carried out by NY and SG. All the abstracts of the extracted articles were reviewed, the articles reported from different aspects were selected, and the literature was organized under different headings for this narrative review. The selection of the article was guided by the area covered in the article and year of publications. Recent articles were preferred for the section of epidemiology and management, whereas older articles were included for the historical aspects. The articles reporting single case reports or small case series were excluded if these focused on common DMS. However, for less commonly discussed DMSs, case reports were included.

Historical developments associated with misidentification syndromes

Many authors have reviewed the history of MDS and DMS.[1,5,13,14,15,16] Centuries old medical literature has accounts of individuals who suffered from delusions involving misidentification. These reports were, however, often anecdotal and lacked systematic study. Early 19^th-century psychiatrists mentioned these symptoms in their descriptions of manifestations of insanity.[17] However, during the later part of the 19^th century and the early 20^th century, the study of MDS followed two separate paths, that is, the German and the French path. Historically, the German descriptions of MDS are considered to have appeared before the currently well-understood MDS, which originated from French literature. Three of the most commonly known DMSs have been named by French clinicians.[2]

After the initial description of Capgras syndrome, Fregoli syndrome, and intermetamorphosis by French clinicians, Christodoulou in 1978, described a syndrome of Subjective Doubles.[5] In 1981, Christodoulou lumped together four MDSs, Capgras, Fregoli, Intermetal-morphosis, and Subjective Doubles, and designated them the DMS. Christodoulou believed that all four DMSs should be considered “variants of the same essential condition”.[13,15,16]

Classification of misidentification syndromes

Different classifications have been proposed for MDS/DMS [Table 2]. One of the classifications includes hypoidentification or hypofamiliarity [Capgras syndrome, mirror sign (self-misidentification)] and hyperidentification or hyperfamiliarity (Fregoli, intermetamorphosis, subjective doubles, and reduplicative paramnesia).[18] Similarly, the hypofamiliarity may also involve places (Foreign reduplicative paramnesia, i.e., Capgras for places; disorientation of places), and there could be hyperfamiliarity of places (reduplicative paramnesia).

Table 2.

Classification of MDSs

•Hypoidentification (Capgras syndrome) and hyperidentifications (the other syndromes)

•Physical alteration (or replacement) of the object in the patient’s mind and object being doubled rather than replaced or transformed

•Relational misidentifications and identical misidentifications

•Environmental reduplication, reduplication of person, and temporal reduplication

•Altered physical identity of self and others and altered psychological identity of self and others

•Delusional versus nondelusional MDS

Roessner[18] classified DMSs into two types, that is, one in which the object of the delusion is physically altered (or replaced) in the patient’s mind and the second in which the object is doubled, rather than replaced or transformed. Weinstein[19] previously described the various MDSs/DMSs based on the reduplication as environmental reduplication, reduplication of person, and temporal reduplication. Environmental reduplication is characterized by the belief that two or more places of the same name exist, although there is only one place with the said name. Reduplication of a person includes phenomena such as Capgras, Fregoli, and Intermetamorphosis. Temporal reduplication is characterized by a current event or period that has occurred. Another proposed classification that uses a developmental and regressive understanding of MDS/DMS includes relational misidentifications (misidentification of human relationships) and identical misidentifications (misidentifications of identity itself, which provides for Capgras and Fregoli) ¹. The identical misidentifications are further subdivided into divided identity type, unionized identity type, and transformed identity type.[1]

Silva[20] suggested a two-category simplification of misidentification syndromes, that is, altered physical identity of the self and others (false attribution or false denial of identity based on a claimed difference between the appearance of a person and who they say they are) and the altered psychological identity of the self and others (the patient acknowledges the physical constancy of the individual but reports changes in attitude, typical responses, and behavior, leading to false recognition or false denial of identity). He also recognized the existence of misidentification of inanimate objects. Although altered identification seems to be a central feature, patients’ explanations are variable, transient, based upon psychotic experiences, and influenced by sociocultural factors. Another classification of MDS includes delusional and nondelusional experiences. The nondelusional MDS is characterized by beliefs, for which the patient has an insight into his beliefs. However, in the setting of paranoid illness, these nondelusional misidentifications may become delusional. Without this paranoid component, nondelusional misidentifications are simply misidentifications that are more neurological conditions rather than psychiatric disorders.[21]

Clinical aspects of misidentification syndromes

DMSs seldom occur independent of comorbid pathology.[22] They have been reported in association with other psychiatric disorders in 60% to 75% of cases and organic illnesses in 25% to 40% of cases. The most common psychiatric diagnoses among patients with DMS include paranoid schizophrenia, schizoaffective psychosis, and bipolar disorder.[1,14,22] However, in recent years, DMS has also been reported in patients with underlying medical illnesses [Table 3].

Table 3.

Conditions in which MDSs have been reported

Psychiatric Disorders[1,7,14,22,23,24]	Medical Illnesses[1,7,14,22,23,24]
Psychiatric disorders	Neurological Diseases
• Schizophrenia	• Cerebrovascular disease
• Schizoaffective psychosis	• Post-traumatic encephalopathy
• Bipolar disorder
• Obsessive-Compulsive	• Temporal lobe epilepsy
Disorder	• Post-encephalitic parkinsonism
• Paranoid Personality
Disorder	• Viral encephalitis
• Pervasive Developmental	• Migraine
Disorder	• Head trauma
• Delirium	• Multiple sclerosis
• Dementia	• Parkinson's Disease
Substance Use Disorders	• Meningioma
• Alcohol use and withdrawal	• Seizure disorders
• Stroke
• Amphetamine use	• Neurocysticercosis
• Phencyclidine use	• Pituitary tumors
• Cocaine or ketamine intoxication states	Endocrinological Diseases
Psychotropic Medication Side effects or Intoxication	• Diabetes mellitus
• Hypoglycemia
• Chronic Intoxication of lithium	• Hypothyroidism
• Pseudohypoparathyroidism
• Intoxication or use of amphetamine	• Thyroid tumours
Cardiovascular
• Amitriptyline	• Hypertension
• Disulfiram	• Myocardial infarction
Somatic Treatments	Infections
• Electroconvulsive therapy	• Pneumonia
	• Tuberculosis
	• AIDS
	Nutritional
	• Vitamin B12 deficiency
	• Anaemia
	• Malnutrition
	Medications
	• Phenytoin
	• Digoxin
	• Metrizamide myelopathy
	Miscellaneous
	• Hepatic encephalopathy
	• Klinefelter syndrome

Epidemiology of misidentification syndromes

DMS is reported to be more common among females (75%) and has been reported to have an age of onset of 12–78 years with a mean of early 40s.[22] However, in more than 4/5 of patients, the onset is after 30. In half of the patients, a family history of psychosis is present. Due to the lower prevalence of family history, there is an emphasis on the acquired organic origins of these syndromes. However, genetic vulnerability for organically induced misidentification psychosis might be an essential etiologic factor.[22]

Though DMSs are considered rare, systematic studies have reported that the prevalence of DMS is higher than previously thought. The overall prevalence has varied from 5.2 to 81.6.[22] One of the reviews identified 260 individual cases of DMS. They categorized DMS into three groups, that is, Group 1, characterized by patients who misidentified others exclusively; Group 2 included patients who felt that their form or identity had been affected; and Group 3 included patients with a misidentification of place. The majority of the subjects were categorized into Group 1 (n = 203 out of 260), followed by Group 2 (n = 33) and Group 3 (n = 24).[23] The most common symptoms among the patients of Group 1 included paranoid symptoms (65%), depressive symptoms (22%), and aggressive behavior (18%), and the most common diagnosis was schizophrenia (52%), followed by mood disorders (13%), organic mental syndromes (13%), dementia (7%), brain trauma (4%), epilepsy (4%), and cerebrovascular disease (CVA) (3%). For patients with Group 2 MDS, the most common associated symptoms were paranoid symptoms (73%), followed by auditory hallucinations (36%), depressive symptoms (30%), and aggressive behavior (21%). The most common diagnosis was schizophrenia (64%), followed by CVA (27%), dementia (12%), mood disorders (9%), brain trauma (9%), epilepsy (6%), and organic medical syndrome (6%). For patients belonging to Group 3, the most common associated symptoms were paranoid symptoms (29%), followed by aggressive behavior (13%). In contrast to the other two groups, the most common diagnoses for patients in Group 3 included schizophrenia (21%) and brain trauma (21%), followed by CVA (13%), and in terms of medical illnesses associated with DMS included pneumonia, tuberculosis, AIDS, neurocysticercosis, hypertension, myocardial infarction, anemia, hypothyroidism, thyroid tumors, pseudohypoparathyroidism, pituitary tumors, diabetes mellitus, hypoglycemia, intoxication or use of amphetamines, phenytoin, digoxin, amitriptyline, disulfiram, metrizamide myelopathy, electroconvulsive therapy, hepatic encephalopathy, Klinefelter syndrome, and malnutrition.[23,24]

Later studies that involved different study groups have evaluated the prevalence of DMS. One study evaluated 195 consecutive admissions with functional psychosis and reported a prevalence of 4.1%.[25] Other studies that evaluated the prevalence of DMS have estimated the prevalence to vary from 1.3% to 28%, depending on the study sample (25 patients admitted to chronic clozapine unit; prevalence: 28%),[26] first-episode psychosis (prevalence of Capgras in 517 patients with schizophreniform, brief psychotic, unspecified psychotic, delusional, and schizoaffective disorders, schizophrenia, bipolar-I disorder, and major depression with psychotic features estimated the prevalence to be 14.1%),[27] and patients admitted to the university psychiatric unit over 5 years (prevalence of Capgras was 1.3%, with prevalence among females to be 1.8% and males to be 0.9%).[28] When the authors evaluated the prevalence of Capgras syndrome among the different types of first-episode psychosis, the prevalence was 50% in patients with schizophreniform psychoses, 34.8% in patients with brief psychoses, 23.9% in patients with unspecified psychoses, 15% in major depression, 11.4% in schizophrenia, 11.1% in delusional disorder, 10.3% in bipolar disorder, and 8.2% in patients with schizoaffective disorders.[27] On the other hand, the study that evaluated the prevalence among patients admitted to a university psychiatric unit reported schizophrenia to be the most common psychiatric diagnosis, seen in 50% of the patients. Only two patients presented with an organic etiology underlying Capgras syndrome.[28] A large sample study that analyzed data from 25,000 case records from South London and the Maudsley Hospital identified 84 cases of Capgras syndrome. Patients with Capgras delusion scored higher at the mini-mental state examination than Alzheimer patients but lower than patients with other psychiatric conditions, adding evidence to the neurological etiopathogenesis of the syndrome.[29] The most common diagnosis of patients with MDS was schizophrenia (n = 23), followed by other or unspecified nonorganic psychotic disorders (n = 7), mental disorders not specified (n = 6), Alzheimer’s dementia (n = 6), and acute and transient psychotic disorders (n = 4). A study from India evaluated 105 mothers with postpartum psychosis and reported DMS in 21.5% of interviewed mothers who believed that their baby belonged to someone else.[30]

The prevalence of DMS in patients with dementias ranges from 10.1% to 56%.[31] The prevalence of DMS was 15.8% in Alzheimer’s disease, 16.6% in Lewy body dementia, and 8.3% in semantic dementia. The most frequent DMS was Capgras delusion, often accompanied by reduplication of place, phantom boarder phenomenon, or both.[32]

In another study, based on the Neuropsychiatric Inventory, DMSs were present in 33.3% of the subjects, whereas according to the Misidentification Delusion Questionnaire, the prevalence was 36%.[31] The prevalence of DMS was 34.2% in patients with Alzheimer’s disease, 52.4% among patients with Lewy body dementia, and 46.1% in vascular dementia and mixed dementia.[31] In patients with Alzheimer’s disease, the most common misidentification syndrome was a misidentification of the house, followed by splitting of people and reduplicative paramnesia, with 26.7% of Alzheimer’s disease patients having one to two MDSs and 7.5% having three to four MDSs. In patients with Lewy body dementia, vascular dementia, and mixed dementia, the most common MDS was a misidentification of the house, followed by Capgras syndrome and reduplicative paramnesia. In Lewy body dementia, one to two MDSs were seen in 23.8% of patients and 19% had three to four MDSs, whereas in patients with vascular dementia and mixed dementia, 15.4% of patients had one to two MDSs and 15.4% had three to four MDSs. Another 15.4% had five to six MDSs.[31]

In 240 patients with dementia, the prevalence of Phantom Boarder Syndrome (PBS) was 23.3%. Compared to those without PBS, those with PBS were older, had a higher age of onset for dementia, and had a higher prevalence of hallucinations and other MDS.[33] In 874 consecutive patients (371 women) admitted to the rehabilitation wards within 2 months of their first stroke, the incidence of DMS was 1.1%, with all the patients manifesting as Fregoli syndrome.[34]

Etiological theories of misidentification syndrome

Different etiological theories have been proposed and evaluated for MDS [Table 4]. Initial theories were primarily based on psychological explanations, but in recent times, authors have tried to assess the biological correlates of the DMS. Initially, Capgras postulated that the syndrome was due to agnosia of identification produced by the conflict between sensory and mnemonic images.[21] However, later on, he considered the syndrome to be a defense mechanism against unconscious prohibited desires.[21] Cargnello and Della Beffa[35] explained the Capgras and Fregoli delusional experience as the encounter of three instances, that is, the ill subject, the alter (a third person well known by the patient), and the Alius (the impostor or disguised). The Alius is intensively present in the psychotic experience and becomes the patient’s Erlebnis (life experience).[35]

Table 4.

Etiological theories of MDS

Psychological/Psychodynamic Theories

• A defense against unconscious prohibited desires

• Splitting of parental figures into good and evil and regression to archaic modes of thought

• The outcome of a combination of the ill subject, the alter (a third person well known by the patient), and the Alius (the impostor or disguised). The Alius is intensively present in the psychotic experience and becomes the patient’s Erlebnis (life experience)

• Deep regression reactivates a developmental stage before the establishment of object constancy, where there is a splitting of objects into all good or all bad and an absence of self-object differentiation (Kleinien paranoid-schizoid position)

• Regression theory: Capgras’ syndrome is a psychological solution to the love-hate conflict

• Ambivalence theory

• Depersonalization/derealization theories

Biological Theories

Lesional findings

• Right hemisphere lesions

• Lesions affecting limbic structures and also involving the frontal and parietal lobes

• Atrophy of the bilateral frontal and temporal lobe

• Right hemispheric lesions superimposed either on diffuse cortical atrophy or on bifrontal lesions

• Lesions in the right temporo-parieto-occipital lesion

• Bilateral subcortical lesions in the occipitotemporal and frontal regions

• Disconnection syndrome

Neurobiological Theories

• Disturbance in the judgment of identity or uniqueness

• Aberrant information processing

• Reduplicative phenomena: Memory Disturbance

• Cognitive and Behavioural Disorder theory

• Impaired Face recognition theory

• MDS as Identification Disorder

• Two-factor theory

• Interactionist theory

Todd[36] proposed an explanatory theory based on the splitting of parental figures into excellent and evil objects and suggested that psychotic illness causes regression to archaic modes of thought, as in thinking in terms of doubles.[36] He maintained that the concept of doubles is very prominent in mythology and primitive religions. A compromise of higher cerebral functioning results in a reactivation of primitive modes of thinking, which are characterized by the theme of doubles and dualisms also found in myths, primitive religion, and literature. Other variants of this theory propose that deep regression reactivates a developmental stage before the establishment of object constancy, where objects are split into all good or bad and an absence of self-object differentiation (Kleinien paranoid-schizoid position). Enoch[37] proposed the regression theory, according to which Capgras’ syndrome is considered to be a psychological solution to the love–hate conflict. Love and hate for a familiar person exist simultaneously. The patient “imagines” the existence of a double who becomes the “bad” object, while the original remains the “ideal.” Ambivalence theory proposes that ambivalent feelings toward the person who is believed to have been replaced by an impostor lead to a psychotic solution through denial and displacement. The double can be treated with hostility without guilt, mainly because of the projection of a bad attitude toward the double. At the same time, positive feelings are expressed for the imaginary original, who is idealized.[22]

The role of depersonalization/derealization experiences in the development of the DMS has also been implicated, and it is argued that under certain circumstances (presence of a paranoid element, cerebral dysfunction, and a charged emotional relationship with the principal misidentified person), depersonalization/derealization symptoms may evolve into a DMS. The depersonalization/derealization theory is based on the presumption that these patients perceive the environment and their body in an unusual way, which is experienced far more strongly about persons or objects with whom patients have strong affective ties. This sense of strangeness has been projected to others and delusionally elaborated as “projected depersonalization”.[22] A connection between depersonalization/derealization and Capgras experience and a progressive loss of insight by the patient leading to Capgras delusions has been suggested.[38] Three pre-existing conditions, a psychotic state and paranoia, the splitting of an internalized object, and a change in some significant relationships, may lead to Capgras delusion.[39] The emotional attitude of the patient toward the principal misidentified person is not always negative or ambivalent. Many cases of doubles involve a range of inanimate objects with which the emotional bond was understandably weak or even absent. Thus, psychodynamic theories may help understand individual cases, but they fail to account for all types of MDS.[21]

Emerging neuropsychological, cognitive, and neuroanatomic findings converge and support the hypothesis that MDS/DMS symptoms are produced at least in part by a damaged or dysfunctional brain, predominantly in the right hemisphere. MDS/DMS is associated specifically with organic lesions affecting limbic structures and involving the frontal and parietal lobes.[40] Patients with MDS/DMS have atrophy of the bilateral frontal and temporal lobe, with right hemispheric lesions superimposed either on diffuse cortical atrophy or on bifrontal lesions or lesions in the right temporo-parieto-occipital lesion.[40,41,42] Magnetic resonance imaging studies suggest the presence of bilateral subcortical lesions in the occipitotemporal and frontal regions.[22]

Recent studies involving stroke patients with Fregoli Syndrome have shown lesions in the right hemisphere.[34] DMSs are described as an outcome of disconnection, and are referred as disconnection syndromes. It is suggested that disconnection between the right and left hemispheres, which decode afferent sensory information and maintain the normal functions of orientation to person, place, time, and object relationship that we describe as ‘orientation,’ may result from organic causes. There is a lack of a cohesive portrayal of the external environment, and two distinct but physically identical objects are adopted. As a result, the patient would recognize two distinct, physically similar individuals, locations, and so on.[41] However, experimental evidence refutes this theory.[43] Neuropsychological assessment studies suggest that DMS is a disturbance in the judgment of identity or uniqueness and is considered a measure of individuality. Others suggest that DMS may be an outcome of aberrant information processing.[40,44]

Studies involving patients with brain injury suggest that DMS may be an outcome of a memory disturbance, that is, reduplicative paramnesia. The findings of the co-occurrence of DMS and reduplicative paramnesia support this. Reduplicative paramnesia has been described in patients suffering from central nervous system disease. In many cases, it co-occurs with reduplication for places, time, or events, while in the neurologic literature, reduplicative paramnesia patients also demonstrate reduplication for people.[45] The involvement of frontal lobes in many patients with DMS supports the role of impaired executive, theory of mind, decision and prediction making, time estimation and sequencing, meta-memory, and working memory functions.[46] Frontal dysfunction impairs the ability to monitor the self and to recognize and correct inaccurate memories and familiarity assessments. The resistance of delusions to change despite clear evidence that they are wrong likely reflects frontal dysfunction. The right frontal lobe likely monitors the appropriateness of familiarity decisions, consistent with right frontal lesions in almost all DMSs. In contrast, the right temporal lobe creates the glow of emotional familiarity. The anterior para-hippocampal cortex (perirhinal cortex, Brodmann areas 35 and 36) is activated by familiarity. The hippocampus and posterior para-hippocampal cortex mediate recollection. Lesions that destroy or isolate stimuli from the right perirhinal cortex may lead to loss of familiarity (e.g., Capgras syndrome). Hyperfamiliarity [i.e., misidentifying strange people as familiar (Fregoli syndrome)] may result from overactivity in the right perirhinal cortex from stimulation or disinhibition. The right hemisphere dominates awareness and images of the self, relating perceptual and emotional self to external and internal environments. Thus, right hemisphere lesions may cause delusions by disrupting the relation between and the monitoring of psychic, emotional, and physical self to people, places, and even body parts. This explains why content-specific delusions involve people, places, or things of personal significance and distort their relation to the self. Right frontal injury impairs the monitoring of feedback from others and the self, leading to false memories and delusions that resist erasure despite evidence that they are incorrect. Left hemisphere hyperactivity may play a critical role in the pathogenesis of delusions. Jackson[47] recognized many dramatic positive symptoms that result from intact brain areas being released from control by damaged areas. Lesions outside the right temporal lobe may cause nondelusional hyperfamiliarity syndromes by disinhibiting emotional familiarity; release of the left hemisphere’s creative narrator from the monitoring of self, memory, and familiarity by the right frontal lobe may lead to excessive or false explanations. A left hemisphere released from the right may be overbiased in categorizing but without the right hemisphere’s gestalt and emotional familiarity. This combination may explain the bizarre invention of an impostor or duplicate. The left hemisphere recognizes “she is my wife” but fails to receive other information (sparkle of familiarity, global gestalt, and relation to self) and concludes that “she is not my wife.” The conflict is resolved with a fabrication, a dual category, that is, a duplicate or impostor (“She looks like my wife, but she isn’t my wife”).[46]

According to the Face Recognition theory, there are two routes to face recognition, that is, a ventral route, which is responsible for conscious recognition and runs from the visual cortex to the temporal lobes via the inferior longitudinal fasciculus, and the dorsal route, which is responsible for recognition and runs between the visual cortex and the limbic system via the inferior parietal lobule. When the ventral route is damaged, prosopagnosia occurs. On the other hand, damage to the dorsal route results in Capgras’ syndrome. The patient receives the appropriate semantic information but needs the affective confirmation of this information. As a result, they make some rationalizations and create a double to explain the discrepancy between the absence of emotional familiarity and recognition without familiarity.[48] This hypothesis is criticized on several accounts. This theory does not explain the co-occurrence of the subtypes (on many occasions, the misidentification involves objects, places, and events together with the misidentification of people in different subtype variations). The patient recognizes the person they misidentify and does not mistake the person; that is, the patient knows the name and, for example, the person’s role but needs to identify the person properly.[40] Further, the hypotheses that are based solely on face recognition theories do not explain a frequently met feature of the DMS, that is, the presence of multiple doubles of the misidentified person. If a patient creates a double to explain the discrepancy between the absence of emotional familiarity and recognition without familiarity, it is difficult to find a logical reason for a patient to create multiple doubles as one double should be enough.[40]

Given the criticism of the face recognition hypothesis, the alternate proposed hypothesis is that of identification disorder. Identity encompasses the notion of uniqueness by definition. Accordingly, the identification disorder hypothesis assumes that in DMS patients, there is a total breakdown of the identification process and an inability to attribute uniqueness to specific surrounding objects or even to the self. It is proposed that perceptual, personal, and affective information regarding surrounding objects is implemented on the ground of uniqueness, which compensates for a certain degree of discrepancy between recent and stored information, serving identification constantly and successfully. A disorder at that level is believed to result in a breakdown of the identification process by allowing even a slight discrepant input, as in the case of psychotic perceptual or emotional experiences, to misdirect identification through a denial of the true identity and reidentification as a double.[49]

A two-factor theory has also been proposed to understand the phenomenon of MDS. According to this theory, for monothematic delusions such as Capgras’ syndrome and the rest of the DMS to occur, two abnormalities must be present. The first abnormality initially prompts the delusional belief and is responsible for the content of the delusion (in the case of Capgras’ syndrome, it is considered to be the failure of autonomic responsivity to familiar faces). This abnormality is supposed to be different for each type of monothematic delusion. The second abnormality prevents the person from rejecting the belief in light of the strong evidence against it. This abnormality is hypothesized to be expected in all varieties of monothematic delusions. It is speculated to arise due to damage to a belief evaluation system associated with the right frontal cortex. This theory is claimed to explain most of the DMS.[50] Another theory used to understand the DMS is the interactionist theory. According to this theory, delusional belief constitutes an attempt on the part of the patient to explain their initially odd and somewhat disturbed phenomenal content. The delusion then structures the patient’s experience in such a way that what they perceive is an impostor. This explains the resistance to revision of the delusional belief.[51]

Assessment of patients presenting with DMS

Assessment requires a thorough evaluation focusing on properly identifying the phenomenon and other associated issues and ruling out other differential diagnoses, especially in the presence of neurological and cognitive diseases. History taking in a patient with DMS should focus on the evaluation of other type of psychopathology (other delusions, hallucinations, negative symptoms, affective symptoms, cognitive symptoms), including the presence of more than one DMS, and establishing whether the belief is delusional or not. While evaluating the belief, the cultural factors must also be taken into account before labeling anything as delusional.

While evaluating the DMS, clinicians should focus on selectivity, coexistent types, duality and dissociation, depersonalization and derealization, and symbolic and adaptive aspects of the phenomenon. This may provide important clues to confirm the phenomenon and rule out other differential diagnoses. Selectivity refers to the evaluation of the fact that only one or a few persons, places, objects, events, or body parts are involved, or it is generalized. Generalized misidentification indicates the phenomenon of DMS. The misidentified person is apt to be the one with whom the patient has an emotional relationship and who is closely associated with the patient as a spouse, child, parent, or doctor. In terms of place, the misidentified places may include a home or hospital. In terms of possession, only one possession may be considered to have been replaced. Reduplication of a body part involves only a member whose function has been impaired, for example, an arm on the hemiplegic side.[19] It is also important to understand that MDS/DMS often occurs in clusters. Hence, evaluating for more than one MDS/DMS in a patient presenting with one MDS/DMS is important. The misidentification delusion questionnaire (MDQ) investigates misidentification of house, Capgras people, Capgras animals and objects, Fregoli, reduplicative paramnesia, intermetamorphosis, syndrome of subjective doubles, mirrored self-misidentification, splitting of people, television, and Cotard syndrome.[52] This can be used to evaluate the range of MDS.[31]

Further, it is also essential to focus on the duality (i.e., the patient can identify the original person as such) and dissociation aspects of the phenomenon. Although a patient misidentifies a person, they often have implicit knowledge of the other’s identity; for example, even though a patient during the interview may say that the nurse is an old high-school classmate, he will relate to her strictly in her professional role. Patients with MDS may also report a loss of a sense of familiarity or of a feeling of the reality of an experience (Capgras believed that the delusions served to combat the threat of depersonalization), which may be more akin to depersonalization and derealization. Further, while evaluating the patient’s relationship with the misidentified person, clinicians should assess the symbolic and adaptive aspects that the symptoms serve the patient. The ‘original’ and the ‘other’ person, place, event, object, body part, or self are not identical but almost always differ in some respect, germane to the patient’s experience, feelings, or problems.[19]

It is essential to understand that the appearance of DMS in popular and traditional cultural expressions is extensive. Science fiction has been especially fruitful for the emergence of modern stories related to imposters masquerading as humans. This can be seen most readily in stories about robots or androids. Understanding these can help distinguish delusions from other beliefs.[53] As done for any other patient with mental disorder, the patients should also be evaluated for risk to harm to the self and others. It is also essential to suspect the presence of an underlying medical condition. Some of the authors suggest that patients with Capgras or Fregoli syndrome may be violent toward the delusionally misidentified person. Fregoli syndrome is often associated with verbal threats or aggressive behaviors toward the misidentified person and may frequently lead to assaults or aggressions in the therapeutic setting.[14] In terms of risk factors for violence, evidence suggests that having a significant history of physical aggression, independent of their delusional misidentification, is a predictor of violence. Increased risk of violence in DMSs may be derived from their high-risk triad of highly valued beliefs, negative affect, and identified targets (often a close relative or attachment figure). In terms of affect and emotional response, anger due to delusion is a critical factor that explains the relationship between violence and DMS. The risk factors for violence include men with long-standing delusions, a history of aggressive behavior, a diagnosis of schizophrenia, and comorbid substance use.[1]

A thorough physical examination, especially the neurological examination, is paramount. Clinicians should look for evidence of underlying neurological conditions, such as cerebrovascular disorders (complicated migraine, stroke), Central nervous system infections (such as AIDS, neurocysticercosis), degenerative disorders (Alzheimer’s disease, Parkinson’s disease), developmental and genetic disorders (chromosome abnormality, Huntington’s disease, intellectual disability), neoplasms (meningioma), seizure disorders, and head trauma. Clinicians should also focus on other conditions such as metabolic disturbances (i.e., hepatic encephalopathy), endocrinopathies (diabetes mellitus, hypothyroidism, pseudohypoparathyroidism), infections (pneumonia), use of alcohol, other illicit drugs and medications, and nutritional deficiencies. While doing the neurological examination, clinicians should focus on evaluation for prosopagnosia, which is understood as an inability to recognize familiar persons from their faces. It is important to note that a person with prosopagnosia will also have difficulties learning new faces. They can recognize the person using other modalities such as voice or name preserved. One of the characteristics of persons with prosopagnosia is that they have good skills at using extrafacial visual cues, such as a specific haircut or distinctive trait, gait, or posture, further highlighting that it is facial features that they cannot process.[54] In terms of investigations, all patients should undergo routine investigations. The physical examination findings and the elicited history should guide additional investigations. A neuroimaging and electroencephalogram may be helpful in patients with suspected neurological ailments.

Differential diagnosis

Many conditions (both organic and psychiatric) need to be considered while evaluating a person presenting with DMS. The first distinction is to consider the possibility of an underlying medical condition. The presence of associated psychopathology such as visual hallucination and other tell-tale signs of various physical illnesses may provide clues for the same. Patients with primary psychotic illnesses would usually have paranoid delusions before the development of features of DMS. In terms of types of DMS, misidentification of person is more common in patients with primary psychotic illnesses, whereas misidentification of place should be more indicative of an organic etiology, especially involving the right hemisphere.[55] Similarly, reduplicative paramnesia is more often reported in patients with head trauma or cerebral infractions, with lesions involving the right hemisphere.[23] Whenever in doubt, the patient should be investigated appropriately to rule out the various medical conditions.

The cultural beliefs of the patient including an assessment of familial beliefs, belief systems, religious beliefs, spiritual beliefs, and an evaluation of history related to migration should be considered. Patients’ explanatory models of the illness or the phenomenon, patients’ environmental factors such as sociopolitical factors, understanding of mythology, science and technology, science fiction, and knowledge about certain movies may be important in understanding the narrative of the patient and establishing the phenomenon of DMS.[56]

Further, while evaluating the DMS, the clinicians should also evaluate the association of DMS with other phenomena, especially when they have persecutory delusions against their family members and other close people. In such a situation, the person may just accuse the family members of being not their real parents and being persecutors. However, when interviewed properly, these people often explain that they voice that they are not their parents because they feel that they want to harm them with no imposter phenomenon being involved. At times, the patient may attribute the belief that “they are not their family members” to hallucinations. In such a scenario, it is important to establish whether the patient believes that their family members are imposters, or they say the same because this was told to them by the voices.

Other factors to be considered include evaluation of orientation, visual problems, memory problems, depersonalization and derealization, dissociative identity disorder, and delusion of nihilism, depending on the type of DMS.

Clinicians should focus on the content of the DMS, that is, whether the duplication phenomenon involves the self, others, or the environment. However, it is important to remember that a patient can have involvement in more than one of these.

In persons presenting with DMS involving others, the first and foremost thing to evaluate is the orientation and memory of the patients presenting with the DMS. Evaluation of orientation will provide information about the fact, whether the person misidentifies one or a few people or places or it is a generalized phenomenon, indicative of disorientation. Additionally, a patient presenting with disorientation may name the same person as more than one person on different occasions. For example, over multiple assessments, a disoriented person may identify a person as his uncle on one occasion and brother on another occasion. In contrast to this, a person with DMS will identify the same person as someone else, and this misidentification would be specific, that is, would always misidentify the same person and only that person and would identify everyone else correctly, over multiple assessments. Disorientation usually follows a pattern; that is, the person first gets disoriented to time, followed by place and person. A person with disorientation will also have impairment in other cognitive functions. Next, the issue to consider is the problem of vision. One of the important issues to consider here is metamorphopsia, which is an outcome of pathology involving the retina or macula, in which the patient sees the straight lines as distorted or bent. Due to this, the patient can have micropsia or macropsia. Another visual problem to consider is the prosopagnosia. In this, the person is not able to recognize the familiar faces or at times own face. This occurs in the absence of other visual and intellectual difficulties. However, they can recognize the person by other stimuli, such as auditory stimulus, that is, voice. The prosopagnosia can be developmental (i.e., present since the birth) or acquired. Acquired prosopagnosia is usually seen in patients with head trauma, stroke, degenerative diseases of the brain (dementia), or encephalitis.[57] Patients with acquired prosopagnosia are aware of their deficit and may have associated distress and embarrassment. Another condition to evaluate is the person agnosia, which is characterized by loss of semantic knowledge about people. As a result of this, the person cannot recognize others through any modality (such as face, voice, or name). Another important issue to be considered as a differential diagnosis is memory disturbances. One of the important differentials to consider is prosopamnesia, which is characterized by impaired learning in the face-selective memory. The person cannot learn/remember new faces after a brain lesion. However, the person can identify people correctly, known to them before the lesion[57,58,59] [Table 5]. Grief reaction should be considered while evaluating a person presenting with nurturing syndrome.[61] Phantom boarder syndrome is usually seen in the background of dementia, and the person may have associated cognitive symptoms and other psychotic symptoms.[33]

Table 5.

Differential diagnosis for DMS

Differential Diagnosis of DMSs	Characteristic Features pointing towards DMSs
Disorientation	DMS - Involving Others
• Misrecognition is nonselective and the same person would be misrecognised as different persons across multiple assessments	• Misidentification is specific; a particular person or a few persons are misidentified • The same person is misrecognised across different time frames • Disorientation usually follows a pattern, i.e., the person first gets disoriented to time, followed by place and person.
Metamorphopsia	DMS - Involving Others
• Visual Problem • Faces or things appear distorted • The findings are generalized and not specific to one or a few persons	• Misidentification is specific- a particular person or a few persons are misidentified
Prosopagnosia	DMS - Involving Others
• Visual Problem, also known as face blindness • Inability to recognise familiar faces or at times own face • Able to recognize the person by voice and other cues • This will also lead to difficulty in recognizing the emotions of other people • In the pure form other objects, such as tools and animals, are recognized commonly; however, in some cases may have difficulty in finding a path, difficulty in recognizing other things such as Cars, or animals	• Misidentification is specific; a particular person or a few persons are misidentified • Misidentification not affected by voice • Misidentification outside the DMS is absent
Person agnosia	DMS - Involving Others
• Loss of semantic knowledge about people. As a result of this, the person cannot recognize others through any modality (such as face, voice, or name • There is no deficit in the senses	• Misidentification is specific; a particular person or a few persons are misidentified
Prosopamnesia	DMS- Involving others
• Disorder of learning • Inability to learn/remember new faces after a brain lesion • However, the person can identify people correctly, known to them before the lesion • May have insight into their deficits	• No difficulty in learning to remember new faces
Dissociative Identity Disorder (DID)	DMS involving self
• It is characterized by a person assuming two or more distinct identities or personalities	• These are delusional beliefs, rather than the same person assuming two different identities
Cotard Syndrome (delusion of Nihilism)	DMS involving self
A person has a delusional belief that they don't exist.	• The delusional belief of the existence of more than one person representing self.
Alice Hand Syndrome	DMS involving self
• A person is considered to have Alien hand syndrome when the hand or arm of a person seems to have its own life	• Sometimes persons manifesting subjective doubles may consider there is a duplicate of their self, or part of their body that acts independently
Autoscopy	DMS- Involving self
• Autoscopy is a visual phenomenon that is characterized into three subcategories: autoscopic hallucinations, heautoscopic hallucinations, and out-of-body experience • Persons experiencing autoscopic hallucinations see a vivid, varied, and three-dimensional replica of their own body in extra-personal space generally when they are awake. The image appears as a mirror reversal. • In heautoscopy, the persons see self as a doppelganger and the double appears as colorless, foggy, pale, through a veil. The doppelganger may behave autonomously, or may mirror the person's appearance, and can maintain sidedness • These phenomena can persist for seconds, or hours, and may even persist as a constant companion to the patient • In out-of-body experiences, the second body is visualized from an elevated perspective and location associated with disembodiment.	• DMSs are not hallucinatory experiences
Derealization	DMS Involving Environment
• It is a sense of detachment from the external world • Sees the external environment as foggy, dreamlike, or visually distorted • Associated with significant distress and patient has insight	• In reduplicative paramnesia, the person usually believes that there is illusory relocation to a place familiar to them (such as to their home or town, with which they are very familiar) • Lacks insight • In TV sign misidentification the person feels that the events on television are understood to be happening in an external space
Palinopsia	DMS - Involving environment
• Characterized by seeing the same thing, even after the stimulus has gone away • This is usually limited to the vicinity	• In reduplicative paramnesia, the person usually believes that there is illusory relocation to a place familiar to them (such as to their home or town, with which they are very familiar)

Reference[5,7,23,33,54,55,56,57,58,59,60,61,62,63,65,66]

In person with DMS involving self, it is also important to distinguish DMS from the phenomenon of depersonalization and derealization. Most of these DMSs are again seen in patients with degenerative diseases of the brain. In misidentification of the self in the mirror, they misidentify themselves but can identify others correctly when they are asked to identify others’ images in the mirror. Patients usually relate to their image in the mirror as a separate person and almost always have a strong emotion, mostly that of paranoia. However, in some cases, this may be friendly or affiliative.[7] In the DMS of subjective doubles, the patient believes that there is a double of themselves. The delusion of clonal pluralization of the self is a further extension of subjective doubles and is a further extension of the belief in which the patient believes that they appear in pleural numbers who are both psychologically and physically completely identical to them.[5] A variant of this may also involve clonal pluralization of others.[62] In reverse intermetamorphosis, the affected patients believe that they have changed substantially in both their physical and psychological conditions. However, at times, this may be limited to psychological change only.[63] It is important to remember that in all these phenomena involving the self, the person may also have the comorbid phenomenon of depersonalization. Similarly, reverse Capgras will involve the self, rather than others, and the person considers themselves to be replaced by an imposter.[64] In reverse Fregoli, the person believes that they have assumed the psychological identity of others, although they are physically the same.[65] However, it is important to remember that in contrast to various DMSs, in depersonalization, the person considers himself as an outside observer of the self, remains aware of his/her identity, and has insight. Another phenomenon to consider while evaluating DMS involving self includes autoscopic hallucinations, in which patients see their replica.[66,67] Other phenomena to consider as differential diagnoses include dissociative identity disorder, Alice hand syndrome, and Cotard syndrome.[53]

While evaluating DMS involving the environment, a visual issue to be considered is palinopsia, which is characterized by seeing the same thing, even after the stimulus has gone away. It is caused by multiple systemic causes including medications. It is further characterized by hallucinatory (characterized by the creation of a formed visual stimulus where none exists in the form of perseveration of the formed images, scene, and patterned visual spread) or illusionary (it is characterized by prolonged indistinct afterimages, light streaking, visual trailing, and perseveration of momentary formed image) palinopsia. The illusionary palinopsia is usually seen during the morning or at the time of adaptation to light.[58] In contrast, in reduplicative paramnesia, the person usually believes that there is illusory relocation to a place familiar to them (such as to their home or town, with which they are very familiar). As mentioned earlier too, reduplicative paramnesia is usually seen in patients with organic conditions.[59] Derealization should also be considered as a differential phenomenon in persons presenting the DMS involving the environment [Table 5].

Management of MDS

There is a lack of controlled trials for the management of DMS. In general, it is believed that symptoms of DMS are very refractory to psychopharmacological treatment. A meta-analysis included data from 104 DMS cases published in the literature from 1957 to 1994 for whom information regarding treatment with antipsychotic medications was available, which reported that 70 cases showed improvement with antipsychotics, while 34 cases did not improve with antipsychotics.[68] Isolated case reports suggest that patients with DMSs with an underlying organic etiology often show remission on most occasions.[1] A review of 84 clinical cases of DMSs obtained from medical records of 25,000 patients found that antipsychotic drugs have been primarily used (66 patients/84) in these patients; olanzapine (n = 40) was the most commonly used antipsychotic medication, and this was followed by risperidone (n = 37), aripiprazole (n = 24), quetiapine (n = 15), and haloperidol (n = 13).[29] In one study, hypnosis was used for the management of Fregoli delusion.[69] There are limited data on the beneficial effect of electroconvulsive therapy (ECT). Some of these reports have shown beneficial effects, whereas others have failed to show the same. ECT is useful in the treatment of Capgras syndrome, especially in mood disorders with postpartum onset and those with treatment resistance.[70] Considering that there are limited data, it is difficult to make any specific antipsychotic recommendations for the management of MDS. Accordingly, the selection of antipsychotics should be guided by the underlying psychiatric disorder, the course of the illness, and the treatment history. Psychotherapeutic interventions can help patients and their families cope with the stress of misidentifications.[54]

Course of MDS

There are limited data on the course and outcome of MDS/DMS. Available data among the patients of psychosis suggest that DMS follows the overall course of the psychotic disorder.[71]

CONCLUSIONS

MDSs/DMSs are rare syndromes that are associated with various psychiatric disorders and associated underlying medical illnesses. Although four classical DMSs are described in the literature, the exhaustive lists of DMS look beyond these four syndromes. In routine clinical practice, clinicians often miss out on many of these phenomena because of a need for more knowledge about these syndromes. A thorough assessment is required for patients exhibiting one DMS for the presence of other DMS, associated psychiatric disorders, and medical disorders. Efforts also must be made to rule out a possible differential diagnosis. The management of DMS requires the use of antipsychotics. However, there needs to be more evidence to make any specific recommendation. Psychotherapeutic interventions can help patients and their families cope with the stress of misidentifications.

Authors’ contributions

SG: Concept, Carrying out the Internet searches, Review of the available literature, Drafting of the manuscript, Final Approval of the manuscript. NY: Concept, Carrying out the Internet searches, Review of the available literature, Drafting of the manuscript, Final Approval of the manuscript. YS: SG: Concept, Review of the available literature, Drafting of the manuscript, Final Approval of the manuscript. NS: SG: Concept, Review of the available literature, Drafting of the manuscript, Final Approval of the manuscript.

Data availability statement

The review is based on the available published literature.

Ethical statement

None.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.