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Fregoli syndrome

Fregoli syndrome

Fregoli syndrome is a disorder in which a person holds a delusional belief that one or more familiar persons, usually persecutors following the patient, repeatedly change their appearance at different times 1. Fregoli delusion is the mistaken belief that some person currently present in the deluded person’s environment (typically a stranger) is a familiar person in disguise 2. The stranger is believed to be psychologically identical to this known person (who is not present) even though the deluded person perceives the physical appearance of the stranger as being different from the known person’s typical appearance 2. Fregoli syndrome is commonly associated with verbal threats and aggressive behavior. Fregoli syndrome is named after the Italian actor Leopoldo Fregoli, who was renowned for his ability to make quick changes in his appearance during his stage acts 3. It was first reported in a paper by Courbon and Fail in 1927. They discussed the case of a 27-year-old woman who believed she was being persecuted by two actors whom she often went to see at the theatre. She believed that these people “pursued her closely, taking the form of people she knows or meets” 4.

In hospital settings, patients with Fregoli syndrome often misidentify members of the treatment team (e.g., nurses, doctors, trainees, psychiatrist, etc.) who work closely with the patients. This misidentification may result in assaultive behavior towards the staff 5. Fregoli syndrome is considered a rare neuropsychiatric condition commonly linked to schizophrenia, schizoaffective disorder, and other organic illnesses 6. The frequency of violence in Fregoli syndrome is unclear 5. Silva et al. 7 described 144 cases of patients who exhibited violence towards misidentified people; of these, only 6 had Fregoli syndrome, 86 had Capgras syndrome and 22 had other diagnoses. The most common Axis 1 diagnosis in that sample was paranoid schizophrenia (59.8%) 5.

Fregoli syndrome falls into the general category of Delusional Misidentification Syndromes (Capgras syndrome, Fregoli syndrome, Intermetamorphosis syndrome, syndrome of Subjective Doubles) 8. The category of delusional misidentification syndromes is sometimes characterized by paranoia and hostility towards misidentified objects 7 and, subsequently, it can lead to significant danger of physical harm to others. Fregoli syndrome has often been discussed as a variant of the Capgras syndrome in the literature, but these two syndromes have different phenomenological structures and age and sex distributions. Capgras syndrome is the delusion that an impostor has replaced a close friend or relative. It is named after Joseph Capgras (1873–1950), a French psychiatrist who first described the disorder in a paper he co-authored with Reboul-Lachaux in 1923. They used the term l’illusion des sosies (the illusion of doubles) to describe the case of a woman who complained that various “doubles” had taken the place of people she knew 4. Christodoulou 9 suggested that Capgras syndrome is a “hypoidentification” of a person closely related to the patient, whereas Fregoli syndrome is a “hyperidentification” of a person not well known to the patient. The syndrome of intermetamorphosis is characterized by the patient’s conviction that a person has changed both physically and psychologically. It was first described by Courbon and Tusques in 1932 10 and it is exceedingly rare. Further extensions of these core delusional misidentification syndromes have also been described. Somatoparaphrenia is a subtype of asomatosognosia, in which patients also display delusional misidentification and confabulation 11. It also involves orbitofrontal dysfunction, which distinguishes it from asomatosognosia 12. Reduplicative paramnesia is the belief that a place or location has been duplicated or relocated. This is the scenario in the movie The Truman Show, where the protagonist finds that his world is actually a reality TV show set. Similarly, the concept of the physical world as an illusion has been depicted in Vanilla Sky, The Thirteenth Floor and The Matrix. Other extensions of delusional misidentification syndromes have been postulated to include lycanthropy 13, Ekbom syndrome, delusional hermaphroditism 14, delusion of sexual transformation 15 and the antichrist delusion 16.

Delusional Misidentification Syndromes have been repeatedly associated with structural or functional cerebral abnormalities, and an association with impaired facial recognition has been observed in some cases. Feinberg and associates in 1999 17 reported the case of a 61-year-old man who suffered traumatic brain injury resulting in right frontal and left temporoparietal contusions and subsequently developed florid Fregoli-type delusional misidentification syndromes. This patient’s “neuropsychological profile” closely resembled that of patients with Capgras syndrome previously reported in the literature. The authors concluded that a combination of executive and memory deficits may account for delusional misidentification syndromes associated with brain lesions 17.

Fregoli syndrome causes

Neurobiological research on Delusional Misidentification Syndromes (Capgras syndrome, Fregoli syndrome, Intermetamorphosis syndrome, syndrome of Subjective Doubles) points to lesions in both frontal lobes and/or right hemispheres 5. Right hemispheric lesions have particularly been associated with Fregoli syndrome. Underactivity in the perirhinal cortex seems to be responsible for loss of familiarity in Capgras syndrome, whereas overactivity seems to account for hyperfamiliarity seen in the Fregoli syndrome, intermetamorphosis syndrome and Subjective Doubles syndrome 18. Impaired connectivity between the right fusiform and right parahippocampal areas has also been implicated in deficits in visual memory recall, face recognition, and identification processes in these patients 19.

Christodoulou 20 described patients diagnosed with paranoid schizophrenia who developed Fregoli delusions many years after their diagnosis and only after organic brain damage. Others 21 have also documented the association between delusional misidentification syndromes and organic brain disease.

Levodopa (L-DOPA), is the precursor to several catecholamines, specifically of dopamine, epinephrine and norepinephrine. It is clinically used to treat Parkinson’s disease and dopamine-responsive dystonia. Clinical studies have shown that the use of levodopa can lead to visual hallucinations and delusions. In most patients, delusions were more salient than hallucinations. With prolonged use of levodopa, the delusions occupy almost all of a patient’s attention. In experimental studies, when the concentration of levodopa decreases, the number of reported delusions decreases as well. It has been concluded that delusions related to antiparkinsonian medications are one of the leading causes of Fregoli syndrome 22.

Fregoli delusion symptoms

Fregoli delusion is the mistaken belief that some person currently present in the deluded person’s environment (typically a stranger) is a familiar person in disguise. The stranger is believed to be psychologically identical to this known person (who is not present) even though the deluded person perceives the physical appearance of the stranger as being different from the known person’s typical appearance.

Fregoli delusion is considered a rare neuropsychiatric condition commonly linked to schizophrenia, schizoaffective disorder, and other organic illnesses 23. The frequency of violence in Fregoli syndrome is unclear. Silva et al. 7 described 144 cases of patients who exhibited violence towards misidentified people; of these, only 6 had Fregoli syndrome, 86 had Capgras syndrome, and 22 had other diagnoses. The most common Axis 1 diagnosis in that sample was paranoid schizophrenia (59.8%).

Fregoli syndrome diagnosis

Theo Manschreck 24 outlined 3 steps in the initial evaluation of patients who present with delusions.

First, establish whether psychopathology is present. This represents a clinical judgment that is sometimes difficult to make. Some comments that appear delusional may be in fact true. In contrast, some reports that initially seem believable may later be identified as delusions as the symptoms worsen, the delusions become less encapsulated (i.e., begin to extend to more people or situations), and more information comes to light. The clinical judgment that delusions are present should be made after taking into account the degree of plausibility, systemization, and the possible presence of culturally sanctioned beliefs that are different from the examiner’s own beliefs. Making the distinction between a true observation, a firm belief, an overvalued idea, and a delusion is sometimes a challenging task. Often, the extremeness and inappropriateness of the patient’s behaviors associated with a given belief, rather than the simple truth or falsity of the belief itself, indicate its delusional nature 25.

The second step is determining the presence or absence of important characteristics and symptoms often associated with delusions, such as confusion, agitation, perceptual disturbances, physical symptoms, and prominent mood abnormalities 24. Studies have shown that the most common symptoms reported were self-reference (40%), irritability (30%), depressed mood (20%), and aggressiveness (15%) 26.

The third step is to present a systematic differential diagnosis. A thorough history, mental status examination, and laboratory/radiologic evaluation should be performed to rule out other systemic medical and psychiatric conditions that are commonly present with delusions. Other, non-psychiatric central nervous system (CNS) illnesses are high on the differential diagnosis of any psychotic disorder, especially so in the onset of delusional disorder in patients older than the typical age of onset of schizophrenia. Delusional disorder in this sense should be seen as a diagnosis of exclusion 24.

Delusional disorder diagnostic criteria (DSM-5)

The specific DSM-5 criteria for delusional disorder are as follows 27:

  • Presence of one or more delusions with a duration of one month or longer.
  • The diagnostic criteria for schizophrenia has never been met. Note: Hallucinations, if present, are not prominent and are clearly thematically related to the delusional theme (e.g., the sensation of being infected with insects is associated with the delusions of infestation).
  • Apart from the impact of the delusion(s) or its ramifications, patient functioning is not markedly impaired, and behavior is not obviously bizarre or odd.
  • If manic or major depressive episodes have occurred, these have been brief relative to the duration of the delusional symptoms.
  • The disturbance is not better explained by another mental disorder such as obsessive-compulsive disorder, and is not attributable to the physiological effects of a substance or medication or another systemic medical condition.

Subtypes include erotomanic, grandiose, jealous, persecutory, somatic, mixed, and unspecified. The diagnosis is further specified “with bizarre content” when delusions are clearly implausible, not understandable, and not derived from ordinary life experiences.

The following duration specifiers apply after 1-year duration of the delusional disorder:

  • First episode, currently in acute episode
  • First episode, currently in partial remission
  • First episode, currently in full remission
  • Multiple episodes, currently in acute episode
  • Multiple episodes, currently in partial remission
  • Multiple episodes, currently in full remission
  • Continuous

Fregoli syndrome treatment

A review of literature of the past 20 years dealing with treatment of delusional misidentification syndromes reveals that there are very few publications and no controlled studies that address the issue of effective treatment 3. In a paper by Zanker 28, the author states the symptoms of delusional misidentification syndromes are very refractory to treatment despite various neuroleptic therapies, but the literature indicates that they are sometimes responsive to typical and atypical antipsychotics such as olanzapine 29, risperidone 30, quetiapine 31, sulpiride and trifluoperazine 32 and pimozide 33. Two reports on the possible effectiveness of pimozide, one in a patient who had failed to improve on haloperidol 34, 35, suggest that delusional misidentification syndromes may often be refractory to the commonly used neuroleptics. Roane et al 36 proposed clozapine, an antipsychotic with specificity for mesolimbic dopamine receptors, as generally effective and well tolerated in patients with Parkinson’s disease dementia plus delusional misidentification syndromes, confirming previous findings 37. There is very little in the published literature regarding the effectiveness of atypical neuroleptics or SSRIs in the treatment of delusional misidentification syndromes.

In a study published before the advent of atypical neuroleptics and SSRIs, delusional misidentification syndromes was reported to respond to various biological treatment methods. In the setting of depression, it may respond to tricyclic antidepressants 38. In the setting of schizophrenia or “organic psychosis,” it may respond to anti-psychotics. Specifically, in schizophrenic patients, delusional misidentification syndromes has a greater chance of responding to trifluoroperazine either given alone or in association with other psychotropics 38. Treating the co-existing “organic dysfunction,” if there is one, is equally important according to Christodolou 38.

A study showed a positive outcome in a patient with Capgras syndrome after treatment with mirtazapine 39. This antidepressant drug is also a serotonin 2A receptor antagonist, which could potentially afford its antipsychotic effects resulting in alleviation delusional misidentification syndromes 39. Such a conclusion, however, is only speculative without controlled clinical studies to demonstrate a potential antipsychotic action of mirtazapine. Spiegel et al 40, however, confirm the efficacy of mirtazapine in significantly decreasing the symptoms in a case of Capgras syndrome. With patients who have progressive dementia, such as Lewy body dementia, in which delusional misidentification syndromes is common, cholinesterase inhibitors have demonstrated some ability to reduce psychiatric symptoms 41.

References
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