Case Report: De Clerambault's Syndrome in Dementia With Lewy Bodies

Abstract

Background: Erotomania, also known as de Clerambault's syndrome, is characterized by the delusion that a person has fallen in love with the patient. It occasionally appears secondary to psychiatric disorders and organic brain diseases. However, there have been no reports on cases secondary to dementia with Lewy bodies (DLB).
Case Presentation: The patient was an 83-year-old woman who lived alone. Mild cognitive impairment appeared at the age of 82 years. Soon after, she had the delusional conviction that her family doctor was in love with her. Her symptoms, such as gradually progressive cognitive impairment, cognitive fluctuations, and parkinsonism, indicated DLB. She was treated with a small dose of antipsychotic agents.
Conclusions: This case report suggests the possibility of de Clerambault's syndrome during the early stages of DLB. Further investigations are required to clarify the mechanism and treatment of de Clerambault's syndrome in patients with DLB.

Full text

CASE REPORT
published: 10 June 2021
doi: 10.3389/fpsyt.2021.665868
Frontiers in Psychiatry | www.frontiersin.org 1June 2021 | Volume 12 | Article 665868
Edited by:
Breno Satler Diniz,
University of Connecticut Health
Center, United States
Reviewed by:
Madia Lozupone,
University of Bari Aldo Moro, Italy
Hiroshige Fujishiro,
Nagoya University, Japan
*Correspondence:
Manabu Ikeda
mikeda@psy.med.osaka-u.ac.jp
Specialty section:
This article was submitted to
Aging Psychiatry,
a section of the journal
Frontiers in Psychiatry
Received: 09 February 2021
Accepted: 19 May 2021
Published: 10 June 2021
Citation:
Suehiro T, Satake Y, Hashimoto M and
Ikeda M (2021) Case Report: De
Clerambault’s Syndrome in Dementia
With Lewy Bodies.
Front. Psychiatry 12:665868.
doi: 10.3389/fpsyt.2021.665868
Case Report: De Clerambault’s
Syndrome in Dementia With
Lewy Bodies
Takashi Suehiro, Yuto Satake, Mamoru Hashimoto and Manabu Ikeda*
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan
Background: Erotomania, also known as de Clerambault’s syndrome, is characterized
by the delusion that a person has fallen in love with the patient. It occasionally appears
secondary to psychiatric disorders and organic brain diseases. However, there have been
no reports on cases secondary to dementia with Lewy bodies (DLB).
Case Presentation: The patient was an 83-year-old woman who lived alone. Mild
cognitive impairment appeared at the age of 82 years. Soon after, she had the delusional
conviction that her family doctor was in love with her. Her symptoms, such as gradually
progressive cognitive impairment, cognitive fluctuations, and parkinsonism, indicated
DLB. She was treated with a small dose of antipsychotic agents.
Conclusions: This case report suggests the possibility of de Clerambault’s syndrome
during the early stages of DLB. Further investigations are required to clarify the
mechanism and treatment of de Clerambault’s syndrome in patients with DLB.
Keywords: de Clerambault’s syndrome, erotomania, dementia, dementia with Lewy bodies, delusion
INTRODUCTION
Erotomania (de Clerambault’s syndrome) is a relatively rare disorder, characterized by the delusion
that a person is in love with the patient (1). The object of the delusion commonly has a higher
social status than the patient and usually remains unchanged (1). The epidemiology of the disorder
is unclear (2). The pure form of de Clerambault’s syndrome cannot be explained by any other
psychiatric disorders and a pre-existing psychiatric disorder is associated with the onset of the
syndrome in its secondary form (3). Schizophrenia is reportedly the most frequent psychiatric
comorbidity in the secondary form (4). Moreover, there are few reports on de Clerambault’s
syndrome in the clinical course of dementia (5), such as Alzheimer’s disease (AD) (2,6,7), vascular
dementia (8), and frontotemporal dementia (9).
Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia
after AD (10). While delusions, such as delusion of theft and misidentification, are highly
prevalent in patients with dementia, they are more frequent in patients with DLB (4). In addition,
delusions in such patients are relatively various. For instance, delusional jealousy is observed most
frequently in patients with DLB (11). However, there are no reports on de Clerambault’s syndrome
in patients with DLB. Herein, we report a case of de Clerambault’s syndrome that appeared in the
early stages of DLB.

Suehiro et al. De Clerambault’s Syndrome in DLB
CASE DESCRIPTION
The patient was an 83-year-old woman. She had been receiving
treatment for hypertension and constipation for more than 20
years. However, she had no other medical history, including
psychiatric disorders. There was no family history of psychiatric
disorders or neurodegenerative disorders. Following graduation
from high school, she began working in a nightclub. She got
married in her twenties and had a daughter. She divorced a
few years later. Following her daughter gaining employment,
she started living alone. She was on public income support
during her visit to our clinic. She gradually felt a lack of
motivation for outdoor activities at the age of 82 years.
Simultaneously, she started facing difficulty with housework
and complained of mild amnesia. A few months later, she
informed her daughter about the delusional thought that
the family doctor drew her blood to kill her. Despite the
delusion of persecution, she continued visiting the clinic. Her
daughter pointed out that her thought was delusional as it was
impossible. Despite all evidence to the contrary, it remained
unchanged. However, the delusion suddenly changed a month
later, without any specific cause. She believed that her family
doctor had fallen in love with her and proposed marriage to
her. The delusional conviction seemingly strengthened with
time. Moreover, she gradually made up her mind to accept
the proposal. Considering the gradual progression of cognitive
impairment and apathy, her daughter proposed living together.
She refused her daughter’s proposal and continued living alone
because she was convinced that she would live with her family
doctor in the near future. Her daughter recommended that she
visit a memory clinic. Although she did not have any insight into
her delusional beliefs, she was aware of her cognitive impairment.
Therefore, she visited our memory clinic and was admitted
to our hospital for examination and treatment at the age of
83 years.
On her first visit to our hospital, we did not observe
any apparent depressive or manic symptoms. Neurological
examinations revealed mild bradykinesia, mild rigidity of the
left upper and lower limbs, and chronic constipation. The
results of her cognitive assessment were as follows: Mini-
Mental State Examination score was 20/30, a Japanese version
of the Alzheimer’s Disease Assessment Scale-cognitive subscale
score was 10/70, the index of subtests of the digit span
of Wechsler Adult Intelligence Scale-III was 5, and Mayo
Fluctuation Questionnaire score was 5 out of 8, which indicated
mild recent memory impairment, attention deficit, and cognitive
fluctuation (Table 1). We conducted the Neuropsychiatric
Inventory 12 to assess her neuropsychiatric symptoms. She
scored 20 points, involving the categories of delusion (12/12)
and apathy (8/12) (Table 1). Blood test results, including
vitamins, thyroid function, and infections, were all normal.
Brain magnetic resonance imaging revealed mild diffuse cortical
atrophy and mild bilateral hippocampal atrophy, compatible with
her age (Figure 1). Perfusion single photon emission computed
tomography revealed mild hypoperfusion in the bilateral parietal
lobe. Myocardial accumulation of metaiodobenzylguanidine
(123I-MIBG) was low (H/M =early: 1.72, delayed: 1.34)
TABLE 1 | The results of neuropsychological tests and the Neuropsychiatric
Inventory (NPI).
Score
Mini-Mental State Examination 20/30
Japanese version of the Alzheimer’s Disease Assessment
Scale-cognitive subscale score
10/70
Digit span of Wechsler Adult Intelligence Scale-III (index) 5
Mayo Fluctuation Questionnaire 5/8
Neuropsychiatric Inventory 12
Delusions 12/12
Hallucinations 0
Agitation/aggression 0
Depression 0
Anxiety 0
Euphoria 0
Apathy 8/12
Disinhibition 0
Irritability/lability 0
Aberrant motor behavior 0
Sleep disturbances 0
Eating abnormalities 0
FIGURE 1 | Brain MRI of the patient showing mild diffuse atrophy, compatible
with her age. (A–C) Axial sections of T1 weighted images; (D) A coronal
section.
(Figure 2). The aforementioned results indicated a probable
diagnosis of DLB (12).
Following the examinations, she was prescribed 3 mg of
donepezil, the dose of which was gradually increased to 10 mg.
She was simultaneously prescribed 25 mg of quetiapine (at night)
Frontiers in Psychiatry | www.frontiersin.org 2June 2021 | Volume 12 | Article 665868

Suehiro et al. De Clerambault’s Syndrome in DLB
FIGURE 2 | Myocardial accumulation of metaiodobenzylguanidine
(123I-MIBG) is low [H/M =early: 1.72 (A), delayed: 1.34 (B)]. The circled areas
indicate heart.
for the treatment of delusions. However, we soon discontinued
quetiapine because of its adverse reactions, such as drowsiness
and dizziness. We also prescribed brexpiprazole (1 mg/day) and
risperidone (0.5 mg/day). However, their side effects, such as
drowsiness, were extremely severe, without any amelioration of
her delusion. While she did not refuse the medications, she
still had no insight to her delusion. Moreover, she occasionally
claimed to visit her family doctor following her discharge. We
then prescribed blonanserin (4 mg/day) and continued it, with
extremely mild side effects. After 2 weeks, her attitude to the
delusional beliefs began to change. She gradually lost passion
for her family doctor. Based on our suggestions, she changed
her family doctor and was discharged from our hospital. During
follow-up, she rarely talked about the previous doctor, who had
been the subject of her delusion. She still lives alone, and her
delusion has not recurred. She is currently on donepezil (10
mg/day) and a small amount of an antipsychotic agent, with
coordination of the circumstances (non-pharmacotherapy).
DISCUSSION
De Clerambautlt’s syndrome is based on the concept of
erotomania proposed by de Clerambault in 1942 (13). He
considered erotomania to manifest in the following two forms:
(i) pure type and (ii) secondary type. Ellie et al. proposed the
diagnostic criteria of the secondary form of de Clerambault’s
syndrome in 1985 as follows (14): (a) a delusional conviction
of being in amorous communication with another person, (b)
the other person being of a relatively higher rank, (c) the other
person was the first to fall in love, (d) the other person was the
first to make advances, (e) sudden onset, (f) the object of the
amorous delusion remains unchanged, (g) the patient provides
an explanation for the paradoxical behavior of the loved one, (h)
chronic course, and (i) no hallucinations. The aforementioned
case history and symptoms fulfilled all criteria.
Clinical features of the patient, such as gradually progressive
cognitive deficit, fluctuating cognition, rigidity, hypersensitivity
to antipsychotics, and low uptake in 123I-MIBG myocardial
scintigraphy, indicated probable DLB (12). She experienced mild
cognitive impairment, as revealed by several neuropsychological
tests. Moreover, her activities of daily living were relatively
preserved. Therefore, de Clerambault’s syndrome supposedly
appeared during the early stages of DLB. Psychiatric-onset
DLB has increasingly gained attention in recent years. Some
studies have reported sufficiently severe delusion requiring
hospitalization during the early stages of DLB (15).
Sudden onset is one of the features of de Clerambault’s
syndrome. However, the above-mentioned case was unique in
that the object of the delusion was also that of persecutory
delusion, immediately before the manifestation of de
Clerambault’s syndrome. De Clerambault reported the possible
association between the emotional state, including hypomania
and the occurrence of the pure type of the syndrome. In
addition, cases of the syndrome secondary to affective disorders
were described more frequently in the manic state than in the
depressive state (16). Our examinations failed to detect any
emotional problems in the patient, including the results of NPI
(Table 1). However, an emotional change, such as a very mild
manic episode, might have existed around the emergence of
the delusion. In contrast, the patients with de Clerambault’s
syndrome have been often reported to interpret usual situations,
behaviors, or attitudes as proof of delusional love during the
initial stages of the syndrome (17). The attitude of her family
doctor toward her persecutory delusion might have been
interpreted in the delusional context and become the cue for the
appearance of the erotomanic delusion.
Schizophrenia is the most frequent disease that induces the
secondary form of de Clerambault’s syndrome. Nonetheless,
other psychiatric disorders or conditions can also be the
underlying causes. Of those diseases, only a few case reports have
described de Clerambault’s syndrome in patients with dementia
(5). In each such report, cognitive impairment was relatively
mild. Moreover, some studies have reported the association
between a deficit of frontal lobe function and the appearance
of delusions (5). The profile of cognitive impairment in the
aforementioned case was compatible with the features suggested
in previous reports. According to Kraepelin, patients suffering
from erotomania usually have preserved intellectual function
(17). Similarly, the occurrence of de Clerambault’s syndrome
may require relatively preserved cognitive function in patients
with dementia. In addition, the neural correlates of the other
delusions in dementia have been investigated in previous studies,
some of which established the association between delusions and
hypoperfusion or a functional deficit in the frontal lobe (18,19).
The same could be true of de Clerambault’s syndrome in patients
with dementia. This necessitates further investigations of the
neural correlates of de Clerambault’s syndrome.
In patients with dementia, the use of antihypertensives has
been reported to be a risk of delusions. Since the present patient
lived alone for a long time, her detailed medication history
was uncertain. Although she seemed to have been prescribed
medications for hypertension and constipation nearly 20 years
according to information from herself and her daughter, we could
not rule out the possibility that some medication influenced the
appearance of the erotomanic delusion.
Approximately 60% of patients with DLB have delusions
(5). More than 50% of these patients develop delusions in the
mild stages (clinical dementia rating, 0.5) (20). There have been
Frontiers in Psychiatry | www.frontiersin.org 3June 2021 | Volume 12 | Article 665868

Suehiro et al. De Clerambault’s Syndrome in DLB
some reports on patients with DLB and unusual delusions, such
as Othello syndrome (11), delusional parasitosis (21,22) and
delusion of duplication (23). In particular, Othello syndrome,
characterized by delusional beliefs of infidelity of a partner, was
known to be found in as much as 26.3% of DLB (11). Although De
Clerambault’s syndrome and Othello syndrome have a common
“sexual” theme, few reports of De Clerambault’s syndrome have
been reported in DLB. Inappropriate sexual behavior is relatively
common in people with dementia (24,25), and the dysfunction of
frontal lobes, cortico-striatal circuit and dopaminergic pathway
are known to be the bases of inappropriate sexual behavior
(26,27). However, de Clerambault’s syndrome has been more
associated to manic state than to depressive state (16) and
depressive state is known to be more common in patients
with neurodegenerative dementias including DLB (20). On
the other hand, Othello Syndrome has been reported to be
more associated with depression than bipolar disorder (25).
The relevance to mood disturbances may account for the
rare occurrence of de Clerambault’s syndrome in patients with
neurodegenerative dementias including DLB. Further studies
are needed to prospectively investigate the association between
senile onset delusions, particularly unusual delusions and DLB
diagnosis. This can be attributed to previous reports on delusions
being the initial symptoms in the prodromal stage of DLB (15)
and their development during the mild stages of DLB (20,28).
The treatment of de Clerambault’s syndrome is relatively
difficult (17). Most reports on its pharmacological treatment
have suggested the usefulness of antipsychotic agents, including
pimozide (12,18), risperidone (29), and olanzapine (30).
Quetiapine (50 mg/day) failed to remit the delusion in a
patient with AD (6). In this case, quetiapine, risperidone,
and brexpiprazole failed to exert their effectiveness because of
adverse reactions. However, the impact of these agents on de
Clerambault’s syndrome in such patients is unclear, because the
duration of administration was not long enough to judge their
actual usefulness. In this case, blonanserin did not produce
severe side effects and was effective against delusions in low
dosage. Considering the hypersensitivity to antipsychotic drugs
in patients with DLB (13), a small dosage might be recommended
initially and, if necessary, the dose can be gradually increased,
with a careful observation of the side effects. Further studies are
required to investigate the pharmacological treatment of patients
with DLB and de Clerambault’s syndrome.
The aforementioned case report revealed that de
Clerambault’s syndrome could appear during the early stages of
disease in patients with DLB. Previous studies have reported the
occurrence of relatively rare delusions during the early stages of
DLB. This necessitates further accumulation of knowledge about
delusions in patients with DLB for an early diagnosis.
DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
ETHICS STATEMENT
Written informed consent was obtained from the patient and her
family for the publication of any potentially identifiable images
or data included in this study.
AUTHOR CONTRIBUTIONS
TS conducted treated the patient during admission, collected
the data, and wrote the initial draft of this article. MI and YS
conducted the outpatient treatment. MI, MH, and YS offered
advice for the treatment and participated in the discussion of the
results. All authors contributed to the article and approved the
submitted version.
FUNDING
This study was supported by a health and labor sciences research
grant (no. 20GB01001) for MI.
ACKNOWLEDGMENTS
The authors would like to thank Dr. Masao Iwase, Kenji
Yoshiyama, Tamiki Wada, Hideki Kanemoto, Kyosuke Kakeda,
Sumiyo Umeda, Hirotaka Nakatani, Fuyuki Koizumi, and Maki
Yamakawa for their useful comments on the study data.
REFERENCES
1. Rudden M, Sweeny J, Frances A. Diagnosis and clinical course of
erotomanic and other delusional patients. Am J Psychiatry. (1995) 147:625–
8. doi: 10.1176/ajp.147.5.625
2. Carrier L. Erotomania and senile dementia. Am J Psychiatry. (1987)
147:1092. doi: 10.1176/ajp.147.8.1092a
3. Munro A. Delusional Disorder – Paranoia and Related Illness. Cambridge:
Cambridge University Press (1999). doi: 10.1017/CBO9780511544095
4. Gillet T, Emison SR, Hassayeh F. Primary and secondary erotomania:
clinical characteristics and follow-up. Acta Psychiatr Scand. (1990) 82:65–
9. doi: 10.1111/j.1600-0447.1990.tb01357.x
5. Cipriani G, Danti S, Vedovello M, Nuti A, Lucetti C. Understanding
delusion in dementia: a review. Geriatr Gerontol Int. (2014) 14:32–
9. doi: 10.1111/ggi.12105
6. Brüne M, Schröder SG. Erotomania variants in dementia. J Geriatr Psychiatry
Neurol. (2003) 16:232–4. doi: 10.1177/0891988703258323
7. Cobb JP, Marks IM. Morbid jealousy featuring as obsessive–compulsive
neurosis: treatment by behavioural psychotherapy. Br J Psychiatry. (1979)
134:301–5. doi: 10.1192/bjp.134.3.301
8. Heinik J, Aharon-Peretz J, Hes JP. De Clérambault’s syndrome in multi-infarct
dementia. Psychiatr Fenn. (1991) 22:23–6.
9. Olojugba C, de Silva R, Kartsounis LD, Royan L, Carter J. De Clerambault’s
syndrome (erotomania) as a presenting feature of fronto-temporal dementia
and motor neuron disease (FTD-MND). Behav Neurol. (2007) 18:193–
5. doi: 10.1155/2007/274156
10. Vann Jones SA, O’Brien JT. The prevalence and incidence of dementia
with Lewy bodies: a systematic review of population and clinical
studies. Psychol Med. (2014) 44:673–83. doi: 10.1017/S00332917130
00494
Frontiers in Psychiatry | www.frontiersin.org 4June 2021 | Volume 12 | Article 665868

Suehiro et al. De Clerambault’s Syndrome in DLB
11. Hashimoto M. Sakamoto S, Ikeda M. Clinical features of delusional
jealousy in elderly patients with dementia. J Clin Psychiatry. (2015) 76:691–
5. doi: 10.4088/JCP.14m09018
12. McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub
D, et al. Diagnosis and management of dementia with Lewy bodies:
fourth consensus report of the DLB Consortium. Neurology. (2017) 89:88–
100. doi: 10.1212/WNL.0000000000004058
13. de Clérambault GG. Les psychoses passionnelles [Psychoses of passion]. In:
Fretet J, editor. Oewve Pshiatrique. Paris: Presses Universitaires de France.
(1942). Vol. 1. p. 311–451.
14. Drevets WC, Rubin EH. Erotomania and senile dementia of Alzheimer type.
Br J Psychiatry. (1987) 151:400–2. doi: 10.1192/bjp.151.3.400
15. McKeith IG, Ferman TJ, Thomas AJ, Blank F, Boeve BF, Fujishiro H, et al.
Research criteria for the diagnosis of prodromal dementia with Lewy bodies.
Neurology. (2020) 94:743–55. doi: 10.1212/WNL.0000000000009323
16. Stephen FS. “Les psychoses passionnelles” reconsidered: a review of de
Clérambault’s cases and syndrome with respe ct tomood disorders. J Psychiatry
Neurosci. (1991) 16:81–90.
17. Sampogna G, Zinno F, Giallonardo V, Luciano M, Vecchio VD, Fiorillo A.
The de Clérambault syndrome: more than just a delusional disorder? Int Rev
Psychiatry. (2020) 32:385–90. doi: 10.1080/09540261.2020.1744536
18. Nagahama Y, Okina T, Suzuki N, Matsuda M. Neural correlates of
psychotic symptoms in dementia with Lewy bodies. Brain. (2010) 133:557–
67. doi: 10.1093/brain/awp295
19. Reeves SJ, Gould RL, Powell JF, Howard RJ. Origins of delusions
in Alzheimer’s disease. Neurosci Biobehav Rev. (2012) 36:2274–
87. doi: 10.1016/j.neubiorev.2012.08.001
20. Kazui H, Yoshiyama K, Kanemoto H, Suzuki Y, Sato S, Hashimoto
M, et al. Differences of behavioral and psychological symptoms of
dementia in disease severity in four major dementias. PLoS ONE. (2016)
11:e0161092. doi: 10.1371/journal.pone.0161092
21. Magierski R, Magierska J, Kloszewska I, Sobow T. Dementia with Lewy bodies
manifested as delusional parasitosis (Ekbom’s syndrome). Alzheimers Dement.
(2015) 11:781–2. doi: 10.1016/j.jalz.2015.06.1746
22. Ochiai S, Sugawara H, Kajio Y, Tanaka H, Ishikawa T, Fukuhara R, et al.
Delusional parasitosis in dementia with Lewy bodies: a case report. Ann Gen
Psychiatry. (2019) 18:29. doi: 10.1186/s12991-019-0253-3
23. Solla P, Mura G, Cannas A, Floris G, Fonti D, Orofino G, et al. An unusual
delusion of duplication in a patient affected by Dementia with Lewy bodies.
BMC Neurol. (2017) 17:78. doi: 10.1186/s12883-017-0842-1
24. Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s
disease. IV: disorders of behaviour. Brit J Psychol. (1990) 157:86–
94. doi: 10.1192/bjp.157.1.86
25. Szasz G. Sexual incidents in an extended care unit for aged men. J Am Geriatr
Soc. (1983) 31:407–11. doi: 10.1111/j.1532-5415.1983.tb03715.x
26. Black B, Muralee S, Tampi RR. Inappropriate sexual behaviors in dementia. J
Geriatr Psychiatry Neurol. (2005) 18:155–62. doi: 10.1177/0891988705277541
27. Santa Rosa Malcher CM, Roberto da Silva Gonçalves Oliveira K, Fernandes
Caldato MC, Lopes Dos Santos Lobato B, da Silva Pedroso J, de Tubino
Scanavino M. Sexual disorders and quality of life in Parkinson’s disease. Sex
Med. (2021) 9:100280. doi: 10.1016/j.esxm.2020.10.008
28. Hashimoto M, Yatabe Y, Ishikawa T, Fukuhara R, Kaneda K, Honda K, et al.
Relationship between dementia severity and behavioral and psychological
symptoms of dementia in dementia with Lewy bodies and Alzheimer’s
disease patients. Geriatr Cogn Dis Extra. (2015) 5:244–52. doi: 10.1159/0003
81800
29. Kelly BD, Kennedy N, Shanley D. Delusion and desire:
erotomania revisited. Acta Psychiatr Scand. (2000) 102:74–
5. doi: 10.1034/j.1600-0447.2000.102001074.x
30. Alao AO, Armenta W, Yolles JC. de Clerambault syndrome
successfully treated with olanzapine. Ann Pharmacother. (2000)
34:266–9. doi: 10.1345/aph.19123
Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Copyright © 2021 Suehiro, Satake, Hashimoto and Ikeda. This is an open-access
article distributed under the terms of the Creative Commons Attribution License (CC
BY). The use, distribution or reproduction in other forums is permitted, provided
the original author(s) and the copyright owner(s) are credited and that the original
publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these
terms.
Frontiers in Psychiatry | www.frontiersin.org 5June 2021 | Volume 12 | Article 665868