Demência frontotemporal variante comportamental em pacientes com transtorno mental grave prévio: revisão sistemática e crítica

Gambogi, Leandro Boson; Guimarães, Henrique Cerqueira; De Souza, Leonardo Cruz; Caramelli, Paulo

doi:10.1590/0004-282X20190107

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Arquivos de Neuro-Psiquiatria

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Sumário

View and Review • Arq. Neuro-Psiquiatr. 77 (9) • Set 2019 • https://doi.org/10.1590/0004-282X20190107 copiar

Demência frontotemporal variante comportamental em pacientes com transtorno mental grave prévio: revisão sistemática e crítica

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

Objetivos:

Explorar a relação entre doença mental grave (DMG) e a variante comportamental da demência frontotemporal (DFTvc), uma vez que os padrões de sintomas e de desempenho cognitivo que caracterizam ambos os transtornos compartilham semelhanças.

Métodos:

Revisão sistemática investigando estudos publicados sobre a relação entre DFTvc e DMG. Os estudos foram selecionados nas bases de dados PubMed e LILACS, incluindo aqueles publicados até 12 de fevereiro de 2018. A estratégia de busca incluiu os seguintes termos: “demência frontotemporal” e “bipolar”, OU “demência frontotemporal” e “esquizofrenia” OU “demência frontotemporal” e “esquizoafetivo”. Publicações sem resumos, relatos de casos sem confirmação genética ou histopatológica, revisões e artigos escritos em idiomas que não fossem o inglês não foram selecionados na busca sistemática.

Resultados:

A pesquisa no PubMed encontrou 186 artigos, dos quais 42 alcançaram critérios de elegibilidade. Na base de dados LILACS, nenhum dos nove artigos identificados atendeu aos requisitos. Foram identificados três objetivos de pesquisa principais: buscar anormalidades genéticas associadas à degeneração lobar frontotemporal (DLFT) em pacientes com SMI prévia; comparar o perfil cognitivo entre pacientes acometidos por doenças neurodegenerativos e esquizofrênicos; destacar a associação entre DFTvc e condições psiquiátricas precedentes e/ou distinguir ambos. As mutações investigadas foram encontradas infrequentemente nas amostras estudadas. Os estudos transversais comparando o desempenho cognitivo entre DFTvc e os transtornos psiquiátricos não encontraram diferença, e houve apenas relatos de casos confirmando de DLFT em pacientes com diagnósticos psiquiátricos prévios.

Conclusões:

A evidência disponível demonstra quão frágil é o entendimento atual sobre a associação entre DFTvc e DMG.

Palavras-chave:
Transtorno bipolar; demência frontotemporal; transtornos psicóticos; esquizofrenia

Authors	Sample size	Participants	Type of study	Objectives	Results
Watson A et al.¹⁵15. Watson A, Pribadi M, Chowdari K, Clifton S, Joel Wood, Miller BL, et al. C9orf72 repeat expansions that cause frontotemporal dementia are detectable among patients with psychosis. Psychiatry Res. 2016 Jan;235:200-2. https://doi.org/10.1016/j.psychres.2015.12.007 https://doi.org/10.1016/j.psychres.2015.... , 2016	739	697 with psychosis; 42 base controls	Cohort	To identify C9orf72 expansion	Two pairs of related individuals had C9orf72 expansions.
Xu et al.¹⁶16. Xu X, Xie S, Shi X, Lv J, Tang X, Wang X, et al. Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han. PLoS One. 2015 Dec;10(12):e0145347. https://doi.org/10.1371/journal.pone.0145347 https://doi.org/10.1371/journal.pone.014... , 2015	386	Treatment-resistant schizophrenia	Cohort	To identify C9orf72 expansion	No abnormal hexanucleotide expansion was found.
Boutoleau-Bretonnière et al.¹⁷17. Boutoleau-Bretonnière C, Evrard C, Hardouin JB, Rocher L, Charriau T, Etcharry-Bouyx F, et al. DAPHNE: A New Tool for the Assessment of the Behavioral Variant of Frontotemporal Dementia. Dement Geriatr Cogn Disord Extra. 2015 Dec;5(3):503-16. https://doi.org/10.1159/000440859 https://doi.org/10.1159/000440859... , 2015	89	36 bvFTD; 22 Alzheimer's disease; 15 progressive supranuclear palsy; 16 bipolar disorder	Cohort	To produce a behavioral inventory named DAPHNE. The aim was (1) to assess the validity and reliability of DAPHNE and (2) to evaluate its contribution to differentiating patients.	DAPHNE-6 allowed bvFTD diagnosis (score 4) with a sensitivity of 92%, while DAPHNE-40 (score 15) had a specificity of 92%.
Yoshino et al.¹⁸18. Yoshino Y, Mori Y, Ochi S, Numata S, Ishimaru T, Yamazaki K, et al. No abnormal hexanucleotide repeat expansion of C9ORF72 in Japanese schizophrenia patients. J Neural Transm (Vienna). 2015 May;122(5):731-2. https://doi.org/10.1007/s00702-014-1295-y https://doi.org/10.1007/s00702-014-1295-... , 2015	466	Schizophrenia	Cohort	To identify C9orf72 expansion	No abnormal hexanucleotide expansion was found.
Floris et al.¹⁹19. Floris G, Di Stefano F, Pisanu C, Chillotti C, Murru MR, Congiu D, et al. C9ORF72 repeat expansion and bipolar disorder - is there a link? No mutation detected in a Sardinian cohort of patients with bipolar disorder. Bipolar Disord. 2014 Sep;16(6):667-8. https://doi.org/10.1111/bdi.12210 https://doi.org/10.1111/bdi.12210... , 2014	206	Bipolar disorder	Cohort	To identify C9orf72 expansion	No abnormal hexanucleotide repeat expansion was found.
Galimberti et al.²⁰20. Galimberti D, Reif A, Dell'osso B, Kittel-Schneider S, Leonhard C, Herr A, et al. C9ORF72 hexanucleotide repeat expansion is a rare cause of schizophrenia. Neurobiol Aging. 2014;35(5):1214 e7-10. https://doi.org/10.1016/j.neurobiolaging.2013.12.004 https://doi.org/10.1016/j.neurobiolaging... , 2014	298	Schizophrenia or schizoaffective disorder	Cohort	To identify C9orf72 expansion	The C9orf72 expansion was detected in 2 patients (0.67%).
Nicolas et al.²¹21. Nicolas G, Beherec L, Hannequin D, Opolczynski G, Rothärmel M, Wallon D, et al. Dementia in middle-aged patients with schizophrenia. J Alzheimers Dis. 2014;39(4):809-22. https://doi.org/10.3233/JAD-131688 https://doi.org/10.3233/JAD-131688... , 2014	96	Schizophrenia	Cohort	To accurately diagnose dementia and its type in a cohort of middle-aged patients with SCZ	Fourteen patients fulfilled diagnostic criteria for dementia. Four of them were diagnosed with possible or probable bvFTD.
Huey et al.²²22. Huey ED, Nagy PL, Rodriguez-Murillo L, Manoochehri M, Goldman J, Lieberman J, et al. C9ORF72 repeat expansions not detected in a group of patients with schizophrenia. Neurobiol Aging. 2013;34(4):1309 e9-10. https://doi.org/10.1016/j.neurobiolaging.2012.08.011 https://doi.org/10.1016/j.neurobiolaging... , 2013	192	Schizophrenia	Cohort	To identify C9orf72 expansion	No abnormal hexanucleotide repeat expansion was found.
Meisler et al.²³23. Meisler MH, Grant AE, Jones JM, Lenk GM, He F, Todd PK, et al. C9ORF72 expansion in a family with bipolar disorder. Bipolar Disord. 2013 May;15(3):326-32. https://doi.org/10.1111/bdi.12063 https://doi.org/10.1111/bdi.12063... , 2013	89	Bipolar disorder	Cohort	To identify C9orf72 expansion	The expansion frequency in this BD cohort was 1%.
de Vries et al.²⁴24. de Vries PJ, Honer WG, Kemp PM, McKenna PJ. Dementia as a complication of schizophrenia. J Neurol Neurosurg Psychiatry. 2001 May;70(5):588-96. https://doi.org/10.1136/jnnp.70.5.588 https://doi.org/10.1136/jnnp.70.5.588... , 2001	8	Schizophrenia patients with disorientation	Cohort	To describe the identification of dementia following SCZ, not better attributed to the psychiatric disorder itself.	Objective evidence of dementia was found in all patients, with a neuropsychological signature and SPECT findings similar to bvFTD.
Fahey et al.²⁵25. Fahey C, Byrne S, McLaughlin R, Kenna K, Shatunov A, Donohoe G, et al. Analysis of the hexanucleotide repeat expansion and founder haplotype at C9ORF72 in an Irish psychosis case-control sample. Neurobiol Aging. 2014;35(6):1510 e1-5. https://doi.org/10.1016/j.neurobiolaging.2013.12.003 https://doi.org/10.1016/j.neurobiolaging... , 2014	2477 controls: 1234; cases: 1243)	Psychosis	Case-control	To compare the prevalence of C9orf72 expansion between psychosis patients and controls	No expansion > 30 repeats was found. Expansions > 22 repeats were similarly prevalent among patients and controls.
Bosia et al.²⁶26. Bosia M, Buonocore M, Guglielmino C, Pirovano A, Lorenzi C, Marcone A, et al. Saitohin polymorphism and executive dysfunction in schizophrenia. Neurol Sci. 2012;33(5):1051-6. https://doi.org/10.1007/s10072-011-0893-9 https://doi.org/10.1007/s10072-011-0893-... , 2012	315	220 schizophrenia; 48 bvFTD; 47 controls	Case-control	To evaluate the possible role of the Saitohin (Tau gene) polymorphism as a concurring factor of cognitive decline in SCZ	No significant difference in allelic distribution between the healthy controls and all other groups. Saitohin polymorphism predicted executive test performance in both patient groups.
Evin et al.²⁷27. Evin G, Smith MJ, Tziotis A, McLean C, Canterford L, Sharples RA, et al. Alternative transcripts of presenilin-1 associated with frontotemporal dementia. Neuroreport. 2002 May;13(6):917-21. https://doi.org/10.1097/00001756-200205070-00036 https://doi.org/10.1097/00001756-2002050... , 2002	46	Various neurodegenerative disorders	Case-control	To analyze the expression of AD-associated presenilin 1 (PS1) in various neurodegenerative disorders	Identified PS1 N- and C-terminal fragments similarly in the cortex of controls, Parkinson's, Huntington's and SCZ individuals.
Rubino et al.²⁸28. Rubino E, Vacca A, Gallone S, Govone F, Zucca M, Gai A, et al. Late onset bipolar disorder and frontotemporal dementia with mutation in progranulin gene: a case report. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Nov;18(7-8):624-6. https://doi.org/10.1080/21678421.2017.1339716 https://doi.org/10.1080/21678421.2017.13... , 2017	1	An Italian male presenting with late-onset bipolar disorder	Case report	To report a case suggesting a possible link between BD, FTD and GRN mutations	In addition to FTD, progranulin may be involved in the neurobiology of BD type 1. Suggestion to screen patients with late-onset BD for GRN mutations.
Watanabe et al.²⁹29. Watanabe R, Kawakami I, Onaya M, Higashi S, Arai N, Akiyama H, et al. Frontotemporal dementia with trans-activation response DNA-binding protein 43 presenting with catatonic syndrome. Neuropathology. 2018 Jun;38(3):281-287. https://doi.org/10.1111/neup.12442 https://doi.org/10.1111/neup.12442... , 2017	1	A 58-year-old patient who had a sudden onset of disorganized behavior and meaningless speech. Psychotropic drugs were effective for catatonic symptoms	Case report	To report on a FTD patient who showed catatonia after the first episode of brief psychotic disorder	FTD with trans-activation response DNA-binding protein 43 presenting with a catatonic syndrome.
Gramaglia et al.³⁰30. Gramaglia C, Cantello R, Terazzi E, Carecchio M, D'Alfonso S, Chieppa N, et al. Early onset frontotemporal dementia with psychiatric presentation due to the C9ORF72 hexanucleotide repeat expansion: a case report. BMC Neurol. 2014 Nov;14(1):228. https://doi.org/10.1186/s12883-014-0228-6 https://doi.org/10.1186/s12883-014-0228-... , 2014	1	A 57-year-old Caucasian woman with a recent onset of bizarre behavior and mystic delusions	Case report	To describe a patient with bvFTD with a primary psychiatric presentation and a normal neurological examination	The C9orf72 expansion was detected.
Holm³¹31. Holm AC. Neurodegenerative and psychiatric overlap in frontotemporal lobar degeneration: a case of familial frontotemporal dementia presenting with catatonia. Int Psychogeriatr. 2014 Feb;26(2):345-7. https://doi.org/10.1017/S1041610213001403 https://doi.org/10.1017/S104161021300140... , 2014	1	A patient with traumatic brain injury with subsequent depression and catatonia	Case report	To describe a patient with familial FTD with a primary psychiatric presentation, and typical response to standard treatment (lorazepam + electroconvulsive therapy) at the beginning	The C9orf72 expansion was detected.
Floris et al.³²32. Floris G, Borghero G, Cannas A, Stefano FD, Murru MR, Corongiu D, et al. Bipolar affective disorder preceding frontotemporal dementia in a patient with C9ORF72 mutation: is there a genetic link between these two disorders? J Neurol. 2013 Apr;260(4):1155-7. https://doi.org/10.1007/s00415-013-6833-2 https://doi.org/10.1007/s00415-013-6833-... , 2013	1	A man who, from the age of 42 years, developed an affective disorder characterized by repeated manic and hypomanic episodes	Case report	To report on a patient suggesting a possible link between BD and FTLD	The C9orf72 expansion was detected.
Gourzis et al.³³33. Gourzis P, Skokou M, Polychronopoulos P, Soubasi E, Triantaphyllidou IE, Aravidis C, et al. Frontotemporal dementia, manifested as schizophrenia, with decreased heterochromatin on chromosome 1. Case Rep Psychiatry. 2012;2012:937518. https://doi.org/10.1155/2012/937518 https://doi.org/10.1155/2012/937518... , 2012	1	A 29-year-old female patient previously diagnosed as having schizophrenia	Case report	To describe a young patient suffering from FTD, misdiagnosed as SCZ, suggesting the association between this clinical phenotype with a genetic defect on chromosome 1	The diagnosis of FTD was made clinically. Chromosomal analysis was conducted and revealed decrease in length of heterochromatin on the long arm of chromosome 1 (46, XX, 1qh-).
Khan et al.³⁴34. Khan BK, Woolley JD, Chao S, See T, Karydas AM, Miller BL, et al. Schizophrenia or neurodegenerative disease prodrome? Outcome of a first psychotic episode in a 35-year-old woman. Psychosomatics. 2012 May-Jun;53(3):280-4. https://doi.org/10.1016/j.psym.2011.04.005 https://doi.org/10.1016/j.psym.2011.04.0... , 2012	1	A 35-year old woman who presented with new-onset of bizarre behavior and delusions	Case report	To make physicians aware of the potential overlapping symptoms and age at onset between some forms of bvFTD and SCZ	The patient was found to have a MAPT tau S356T mutation and a focal pattern of brain atrophy consistent with FTD.
Cerami et al.³⁵35. Cerami C, Marcone A, Galimberti D, Villa C, Scarpini E, Cappa SF. From genotype to phenotype: two cases of genetic frontotemporal lobar degeneration with premorbid bipolar disorder. J Alzheimers Dis. 2011;27(4):791-7. https://doi.org/10.3233/JAD-2011-110788 https://doi.org/10.3233/JAD-2011-110788... , 2011	2	Two apparently-sporadic FTLD patients, with a premorbid bipolar disorder	Case report	To report two patients of definite FTLD with premorbid psychiatric symptoms	Medical history and genetic investigation revealed the presence of bipolar spectrum disorders and mutations in the GRN gene.
Momeni et al.³⁶36. Momeni P, DeTucci K, Straub RE, Weinberger DR, Davies P, Grafman J, et al. Progranulin (GRN) in two siblings of a Latino family and in other patients with schizophrenia. Neurocase. 2010 Jun;16(3):273-9. https://doi.org/10.1080/13554790903456209 https://doi.org/10.1080/1355479090345620... , 2010	2	A Latino family in which two siblings were diagnosed as having either schizophrenia or frontotemporal dementia	Case report	To characterize GRN mutations in the affected individuals	The siblings both have loss-of-function GRN mutations.
Momeni et al.³⁷37. Momeni P, Wickremaratchi MM, Bell J, Arnold R, Beer R, Hardy J, et al. Familial early onset frontotemporal dementia caused by a novel S356T MAPT mutation, initially diagnosed as schizophrenia. Clin Neurol Neurosurg. 2010 Dec;112(10):917-20. https://doi.org/10.1016/j.clineuro.2010.07.015 https://doi.org/10.1016/j.clineuro.2010.... , 2010	2	Familial FTD with an exceptionally early age at onset. Both the proband and the proband's father were initially diagnosed as having schizophrenia	Case report	To report a novel exon 12 mutation in MAPT (S356T) causing familial bvFTD	Pathological examination showed FTLD with extensive neuronal and glial tau deposition.
Stone et al.³⁸38. Stone J, Griffiths TD, Rastogi S, Perry RH, Cleland PG. Non-Picks frontotemporal dementia imitating schizophrenia in a 22-year-old man. J Neurol. 2003 Mar;250(3):369-70. https://doi.org/10.1007/s00415-003-0989-0 https://doi.org/10.1007/s00415-003-0989-... , 2003	1	A 22-year-old man who had presented six years previously with symptoms that were initially attributed to schizophrenia	Case report	To report on a patient and to raise awareness that FTD should be considered in patients in their early 20s with SCZ and negative symptoms, who display frontotemporal dysfunction and have a relentlessly progressive course	Magnetic resonance imaging and neuropathology obtained at brain biopsy suggest a diagnosis of non-Pick's FTD.
Waddington et al.³⁹39. Waddington JL, Youssef HA, Farrell MA, Toland J. Initial ‘schizophrenia-like’ psychosis in Pick's disease: case study with neuroimaging and neuropathology, and implications for frontotemporal dysfunction in schizophrenia. Schizophr Res. 1995 Dec;18(1):79-82. https://doi.org/10.1016/0920-9964(95)00064-X https://doi.org/10.1016/0920-9964(95)000... , 1995	1	A woman with a consistent clinical diagnosis of typical schizophrenia	Case report	To report on a patient and to report ‘schizophrenia-like’ psychosis as a prodrome of Pick's disease	The neuropathological hallmarks of Pick's disease were present.
Baez et al.⁴⁰40. man. J Neurol. 2003 Mar;250(3):369-70. https://doi.org/10.1007/s00415-003-0989-0 https://doi.org/10.1007/s00415-003-0989-... , 2019	51	16 bvFTD/ 13 Bipolar disorder/ 22 controls	Cross sectional	The compare the executive functions (EF) and social cognition profiles as well as the structural neuroimaging of bvFTD and elderly patients with BD.	bvFTD patients showed deficits in working memory, abstraction capacity, inhibitory control, cognitive flexibility, verbal fluency and theory of mind (ToM). Patients with BD showed lower performance than controls in terms of abstraction capacity and verbal inhibitory control. In bvFTD patients, atrophy of frontal, temporal and insular cortices was related to EF deficits. Atrophy of the amygdala, the hippocampus, the parahippocampal gyrus, the putamen, the insula, the precuneus, the right temporo-parietal junction and superior temporal pole was associated to ToM impairments. No significant associations between atrophy and EF performance were observed in BD patients. BvFTD patients showed greater EF and ToM deficits than BD patients. Moreover, compared to BD, bvFTD patients exhibited a significant decrease in GM volume in frontal, temporal and parietal regions
Metin et al.⁴¹41. Baez S, Pinasco C, Roca M, Ferrari J, Couto B, Garcia-Cordero I, et al. Brain structural correlates of executive and social cognition profiles in behavioral variant frontotemporal dementia and elderly bipolar disorder. Neuropsychologia. 2019 Mar;126:159-69., 2018	38	18 bvFTD/ 20 late-life Bipolar disorder	Cross sectional	To compare differential diagnosis ability of electrophysiological and neuroimaging findings in BD and bvFTD, aimed to show their classification power using an artificial neural network and genetic algorithm based approach	The artificial neural network method classified BD from bvFTD with 76% overall accuracy only by using on EEG power values. The radiological diagnosis classified BD from bvFTD with 79% overall accuracy. The radiological diagnosis added to the EEG analysis, classifiied with 87% overall accuracy.
Vijverberg et al.⁴²42. Metin SZ, Erguzel TT, Ertan G, Salcini C, Kocarslan B, Cebi M, et al. The use of quantitative EEG for differentiating frontotemporal dementia from late-onset bipolar disorder. Clin EEG Neurosci. 2018 May;49(3):171-6. https://doi.org/10.1177/1550059417750914 https://doi.org/10.1177/1550059417750914... , 2017	381	42 major depression/ 41 Bipolar disorder/ 47 schizophrenia/ 173 bvFTD/ 78 controls	Cross sectional	To compare neuropsychological profiles in bvFTD with its most common primarypsychiatric differential diagnoses.	Cognitive deficits in bvFTD are less severe than in primary psychiatric disorders with active symptoms.
Devenney et al.⁴³43. Vijverberg EG, Schouws S, Meesters PD, Verwijk E, Comijs H, Koene T, et al. Cognitive Deficits in Patients With Neuropsychiatric Symptoms: A Comparative Study Between Behavioral Variant Frontotemporal Dementia and Primary Psychiatric Disorders. J Clin Psychiatry. 2017 Sep/Oct;78(8):e940-6. https://doi.org/10.4088/JCP.16m11019 https://doi.org/10.4088/JCP.16m11019... , 2016	79	56 bvFTD/ 23 healthy controls	Cross sectional	To address the gap in the literature regarding the severity and underlying neural correlates of psychotic symptoms in frontotemporal dementia with and without the C9orf72 gene expansion	34% of bvFTD showed psychotic features. C9orf72 expansion cases were more likely to exhibit psychotic symptoms than non-carriers (64% vs. 26%; p = 0.006). Increased psychotic symptoms in C9orf72 expansion carriers correlated with atrophy in a distributed cortical and subcortical network that included discrete regions of the frontal, temporal and occipital cortices, as well as the thalamus, striatum and cerebellum.
Chan et al.⁴⁴44. Devenney EM, Landin-Romero R, Irish M, Hornberger M, Mioshi E, Halliday GM, et al. The neural correlates and clinical characteristics of psychosis in the frontotemporal dementia continuum and the C9orf72expansion. Neuroimage Clin. 2016 Dec;13:439-45. https://doi.org/10.1016/j.nicl.2016.11.028 https://doi.org/10.1016/j.nicl.2016.11.0... , 2015	50	7 inpatients with schizophrenia/ 13 community-dwelling outpatients with /12 bvFTD/ 18 healthy controls	Cross sectional	To compare neurocognitive performance across groups in 16 cognitive domains	Their findings revealed a similar cognitive profile among schizophrenia inpatients and bvFTD groups, compared with schizophrenia outpatients' group, which outperformed the former two groups.
Chan et al.⁴⁵45. Chan HM, Stolwyk R, Neath J, Kelso W, Walterfang M, Mocellin R, et al. Neurocognitive similarities between severe chronic schizophrenia and behavioural variant frontotemporal dementia. Psychiatry Res. 2015 Feb;225(3):658-66. https://doi.org/10.1016/j.psychres.2014.11.029 https://doi.org/10.1016/j.psychres.2014.... , 2014	60	26 schizophrenia/ 34 bvFTD	Cross sectional	To compare retrospectively the neuropsychological performance of schizophrenia and frontotemporal dementia patients.	Cognitive impairment was similar in degree and pattern between groups.
Nishida et al.⁴⁶46. Chan HM, Stolwyk R, Kelso W, Neath J, Walterfang M, Mocellin R, et al. Comparing neurocognition in severe chronic schizophrenia and frontotemporal dementia. Aust N Z J Psychiatry. 2014 Sep;48(9):828-37. https://doi.org/10.1177/0004867414529477 https://doi.org/10.1177/0004867414529477... , 2013	93	18 mild FTD/ 20 schizophrenia/ 18 mild Alzheimer's disease/ 37 age matched controls	Cross sectional	To compare resting EEG patterns, related to resting-state fMRI networks, among groups.	The duration of class C was significantly shorter in FTD than in controls and AD, and the duration of class D was significantly shorter in schizophrenia than in controls, FTD and AD
Weickert et al.⁴⁷47. Nishida K, Morishima Y, Yoshimura M, Isotani T, Irisawa S, Jann K, et al. EEG microstates associated with salience and frontoparietal networks in frontotemporal dementia, schizophrenia and Alzheimer's disease. Clin Neurophysiol. 2013 Jun;124(6):1106-14. https://doi.org/10.1016/j.clinph.2013.01.005 https://doi.org/10.1016/j.clinph.2013.01... , 2013	70	20 FTLD/24 schizophrenia/ 26 controls	Cross sectional	To investigate and compare probabilistic association learning between schizophrenia and FTLD patients.	There was no difference in performance between FTLD and schizophrenia groups.
Bediou et al.⁴⁸48. Weickert TW, Leslie F, Rushby JA, Hodges JR, Hornberger M. Probabilistic association learning in frontotemporal dementia and schizophrenia. Cortex. 2013 Jan;49(1):101-6. https://doi.org/10.1016/j.cortex.2011.09.011 https://doi.org/10.1016/j.cortex.2011.09... , 2012	214	Several neurodegerative disorders and schizophrenia patients	Cross sectional	To compare Facial Emotion Recognition test performance acrros several groups, and invetsigate the influece of dopaminergic drugs on these findings.	FTD patients presented the worst performance across all groups. Symtpomatic schizophrenia patients standed between FTD and AD groups, and as simililar as Parkinson's disease patients.
Woolley et al.⁷7. Woolley JD, Khan BK, Murthy NK, Miller BL, Rankin KP. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry. 2011 Feb;72(2):126-33. https://doi.org/10.4088/JCP.10m06382oli https://doi.org/10.4088/JCP.10m06382oli... , 2011	252	Several neurodegenerative disorders	Cross sectional	To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease, retrospectively by chart review.	bvFTD patients received a prior psychiatric diagnosis significantly more often than other dementia types and were also more likely to receive a diagnosis of bipolar disorder or schizophrenia.
Ziauddeen et al.⁴⁹49. Bediou B, Brunelin J, d'Amato T, Fecteau S, Saoud M, Hénaff MA, et al. A comparison of facial emotion processing in neurological and psychiatric conditions. Front Psychol. 2012 Apr;3:98. https://doi.org/10.3389/fpsyg.2012.00098 https://doi.org/10.3389/fpsyg.2012.00098... , 2011	23	12 schizophrenia/ 11 bvFTD	Cross sectional	To compare clinical and neuropsychological features between schizophrenia patients with predominant negative symtoms and bvFTD.	Negative and frontal lobe symptoms were similarly present in both groups. Negative scores were higher in schizophrenia and frontal lobe behaviors were more pronounced in bvFTD.
Schoder et al.⁵⁰50. Ziauddeen H, Dibben C, Kipps C, Hodges JR, McKenna PJ. Negative schizophrenic symptoms and the frontal lobe syndrome: one and the same? Eur Arch Psychiatry Clin Neurosci. 2011 Feb;261(1):59-67. https://doi.org/10.1007/s00406-010-0133-y https://doi.org/10.1007/s00406-010-0133-... , 2010	200	100 first-degree relatives of bvFTD patients/ 100 first-degree relatives of AD patients	Cross sectional	To calculate de morbid risk of schizophrenia in first-degree relatives	The morbid risk for schizophrenia was significantly higher in relatives of frontotemporal dementia probands
Foley et al.⁵¹51. Schoder D, Hannequin D, Martinaud O, Opolczynski G, Guyant-Maréchal L, Le Ber I, et al. Morbid risk for schizophrenia in first-degree relatives of people with frontotemporal dementia. Br J Psychiatry. 2010 Jul;197(1):28-35. https://doi.org/10.1192/bjp.bp.109.068981 https://doi.org/10.1192/bjp.bp.109.06898... , 2009	185	37 geriatric schizophrenia-spectrum disorders (SSD) / 41 bvFTD / 107 controls	Cross sectional	To address whether measures for assessing premorbid intellectual functioning are adequate for geriatric schizophrenia	Analysis showed unique patterns of spared function in when compared to FTD and controls
Velakoulis et al.⁶6. Velakoulis D, Walterfang M, Mocellin R, Pantelis C, McLean C. Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases. Br J Psychiatry. 2009 Apr;194(4):298-305. https://doi.org/10.1192/bjp.bp.108.057034 https://doi.org/10.1192/bjp.bp.108.05703... , 2009	17	Patients with bvFTD who had symptoms onset before 60 years.	Cross sectional	To investigate the relationship between early age at onset and psychotic presentations in pathologically verified definiter bvFTD patients.	Five out of 17 patients had presented psychotic symptoms.
Velakoulis et al.⁵²52. Foley J, Golden C, Simco E, Schneider B, McCue R, Shaw L. Corollary-and discrepancy-based approaches for examining the appropriateness of premorbid cognitive estimation in geriatric schizophrenia. Int J Neurosci. 2009;119(10):1810-29. https://doi.org/10.1080/00207450903192878 https://doi.org/10.1080/0020745090319287... , 2009	23	12 Schizphrenia/ 3 Bipolar disorder/ 11 controls	Cross sectional	To determine whether FTD-like abnormalities in TARDNA binding protein (TDP-43) and ubiquitin are detectable in hippocampal dentate gyrus of patients with schizophrenia and bipolar disorder	The regular nuclear expression of TDP-43 was not detected in 3 patients.
Foley et al.⁵³53. Velakoulis D, Walterfang M, Mocellin R, Pantelis C, Dean B, McLean C. Abnormal hippocampal distribution of TDP-43 in patients with-late onset psychosis. Aust N Z J Psychiatry. 2009 Aug;43(8):739-45. https://doi.org/10.1080/00048670903001984 https://doi.org/10.1080/0004867090300198... , 2008	185	37 geriatric schizophrenia-spectrum disorders / 41 bvFTD / 107 controls	Cross sectional	To investigate pattern of memory deficits across groups.	Failed to find differences between groups on pattern of memory impairment.
Kosmidis et al.⁵⁴54. Foley J, Golden C, Simco E, Schneider B, McCue R, Shaw L. Pattern of memory compromise in chronic geriatric schizophrenia, frontotemporal dementia and normal geriatric controls. Acta Neuropsychiatr. 2008 Feb;20(1):9-19. https://doi.org/10.1111/j.1601-5215.2007.00244.x https://doi.org/10.1111/j.1601-5215.2007... , 2008	63	28 schizophrenia plus 26 age-matched controls / 9 bvFTD plus 10 age-matched controls	Cross sectional	To investigate social cognition and theory of mind across groups using videotaped scenarios of social interactions.	Both groups displayed generalized impairments in comprehension of social interactions. Schizophrenia patients were not impaired in evaluating sincere remarks. bvFTD patients were markedly impaired in recognizing sarcasm, specially when non-verbal cues were minimal.

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[1] Correspondence: Paulo Caramelli; Departamento de Clínica Médica - Faculdade de Medicina da UFMG; Avenida Alfredo Balena, 190 / Sala 246; 30130-100 Belo Horizonte MG, Brasil; E-mail: caramelli@ufmg.br