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Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases

  • D. Velakoulis (a1), M. Walterfang (a1), R. Mocellin (a1), C. Pantelis (a2) and C. McLean (a3)...



Few studies have investigated the relationship between schizophrenia and frontotemporal dementia.


To investigate this relationship through a clinicopathological investigation of young-onset frontotemporal dementia and a review of the case literature.


Cases of young-onset frontotemporal dementia were identified within the local brain bank. The clinical course and pathological findings were collated. For the literature review, cases of frontotemporal dementia identified through Medline were selected according to defined criteria. The demographic, clinical, pathological and genetic characteristics of cases presenting with a psychotic illness were identified.


In the case series, 5 of 17 patients with frontotemporal dementia had presented with a psychotic illness (schizophrenia/schizoaffective disorder n=4, bipolar disorder n=1) an average of 5 years prior to the dementia diagnosis. Patients with schizophrenia exhibited changes consistent with TDP-43 and ubiquitin-positive frontotemporal dementia. In the cases review, a third of patients aged 30 years or under and a quarter of those aged 40 years or under had been diagnosed with psychosis at presentation.


Patients with young-onset frontotemporal dementia may be diagnosed with a psychotic illness years before the dementia diagnosis is made. These findings have implications for clinicians and for our further understanding of the neurobiology of psychotic illness.

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Corresponding author

Correspondence: Dr Dennis Velakoulis, Neuropsychiatry Unit, Level 2 John Cade Building, Royal Melbourne Hospital, Parkville, Victoria 3052, Australia. Email:


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1 Lishman, WA. Organic Psychiatry (3rd edn). Blackwell Science, 1998.
2 Lewis, SW. The secondary schizophrenias. In Schizophrenia (eds Hirsch, SR & Weinberger, DR): 324–40. Blackwell Science, 1995.
3 McKenna, PJ. Schizophrenia and Related Syndromes. Oxford University Press, 1994.
4 Davison, K, Bagley, CR. Schizophrenia-like psychoses associated with organic disorders of the central nervous system. Br J Psychiatry 1969; 115 (suppl. 4): s11384.
5 Davison, K. Schizophrenia-like psychoses associated with organic cerebral disorders: a review. Psychiatr Dev 1983; 1: 133.
6 Johnstone, EC, Macmillan, JF, Crow, TJ. The occurrence of organic disease of possible or probable aetiological significance in a population of 268 cases of first episode schizophrenia. Psychol Med 1987; 17: 371–9.
7 Achte, K, Jarho, L, Kyykka, T, Vesterinen, E. Paranoid disorders following war brain damage. Psychopathology 1991; 24: 309–15.
8 Johnstone, EC, Cooling, NJ, Frith, CD, Crow, TJ, Owens, DG. Phenomenology of organic and functional psychoses and the overlap between them. Br J Psychiatry 1988; 153: 770–6.
9 Feinstein, A, Ron, MA. Psychosis associated with demonstrable brain disease. Psychol Med 1990; 20: 793803.
10 Roberts, GW, Done, DJ, Bruton, C, Crow, TJ. A ‘mock up’ of schizophrenia: temporal lobe epilepsy and schizophrenia-like psychosis. Biol Psychiatry 1990; 28: 127–43.
11 Kraepelin, E. Dementia Praecox and Paraphrenia. Livingstone, 1919.
12 Lawrie, SM, Abukmeil, SS. Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry 1998; 172: 110–20.
13 Brewer, WJ, Francey, SM, Wood, SJ, Jackson, HJ, Pantelis, C, Phillips, LJ, et al. Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis. Am J Psychiatry 2005; 162: 71–8.
14 McKhann, GM, Albert, MS, Grossman, M, Miller, B, Dickson, D, Trojanowski, JQ. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch Neurol 2001; 58: 1803–9.
15 Neary, D, Snowden, JS, Gustafson, L, Passant, U, Stuss, D, Black, S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51: 1546–54.
16 Snowden, JS, Neary, D, Mann, DMA. Frontotemporal dementia. Br J Psychiatry 2002; 180: 140–3.
17 Wszolek, ZK, Tsuboi, Y, Ghetti, B, Pickering-Brown, S, Baba, Y, Cheshire, WP. Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Orphanet J Rare Dis 2006; 1: 30.
18 Neary, D, Snowden, J, Mann, D. Frontotemporal dementia. Lancet Neurol 2005; 4: 771–80.
19 Assal, F, Cummings, JL. Neuropsychiatric symptoms in the dementias. Curr Opin Neurol 2002; 15: 445–50.
20 Snowden, JS, Bathgate, D, Varma, A, Blackshaw, A, Gibbons, ZC, Neary, D. Distinct behavioural profiles in frontotemporal dementia and semantic dementia. J Neurol Neurosurg Psychiatry 2001; 70: 323–32.
21 Sumi, SM, Bird, TD, Nochlin, D, Raskind, MA. Familial presenile dementia with psychosis associated with cortical neurofibrillary tangles and degeneration of the amygdala. Neurology 1992; 42: 120–7.
22 Lendon, CL, Lynch, T, Norton, J, McKeel, DW, Busfield, F, Craddock, N, et al. Hereditary dysphasic disinhibition dementia: a frontotemporal dementia linked to 17q21-22. Neurology 1998; 50: 1546–55.
23 Nitrini, R, Rosemberg, S. Psychotic symptoms in dementia associated with motor neuron disease: a pathophysiological hypothesis. J Neuropsychiatry Clin Neurosci 1998; 10: 456–8.
24 Hutton, M, Lendon, CL, Rizzu, P, Baker, M, Froelich, S, Houlden, H, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998; 393: 702–5.
25 Poorkaj, P, Bird, TD, Wijsman, E, Nemens, E, Garruto, RM, Anderson, L, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 1998; 43: 815–25.
26 Baker, M, Mackenzie, IR, Pickering-Brown, SM, Gass, J, Rademakers, R, Lindholm, C, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006; 442: 916–9.
27 Cruts, M, Gijselinck, I, van der Zee, J, Engelborghs, S, Wils, H, Pirici, D, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442: 920–4.
28 Watts, GDJ, Wymer, J, Kovach, MJ, Mehta, SG, Mumm, S, Darvish, D, et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet 2004; 36: 377–81.
29 Skibinski, G, Parkinson, NJ, Brown, JM, Chakrabarti, L, Lloyd, SL, Hummerich, H, et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet 2005; 37: 806–8.
30 Neumann, M, Sampathu, DM, Kwong, LK, Truax, AC, Micsenyi, MC, Chou, TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314: 130–3.
31 McGuffin, P, Farmer, A, Harvey, I. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch Gen Psychiatry 1991; 48: 764–70.
32 Williams, J, Farmer, AE, Ackenheil, M, Kaufmann, CA, McGuffin, P. A multicentre inter-rater reliability study using the OPCRIT computerized diagnostic system. Psychol Med 1996; 26: 775–83.
33 Yase, Y, Matsumoto, N, Azuma, K, Nakai, Y. Amyotrophic lateral sclerosis. Association with schizophrenic symptoms and showing Alzheimer's tangles. Arch Neurol 1972; 27: 118–28.
34 Kato, S, Oda, M, Hayashi, H, Kawata, A, Shimizu, T. Participation of the limbic system and its associated areas in the dementia of amyotrophic lateral sclerosis. J Neurol Sci 1994; 126: 62–9.
35 Kertesz, A, Kawarai, T, Rogaeva, E, St George-Hyslop, P, Poorkaj, P, Bird, TD, et al. Familial frontotemporal dementia with ubiquitin-positive, tau-negative inclusions. Neurology 2000; 54: 818–27.
36 Kimura, N, Inayama, Y, Shigenobu, K, Kakiuchi, Y, Tabushi, K. [MRI findings in schizophrenic patient with frontal lobe atrophy]. Seishin Shinkeigaku Zasshi 2004; 106: 152–60.
37 Ferrara, M, Freda, F, Massa, R, Carratelli, TJ. Frontal lobe syndrome or adolescent-onset schizophrenia? A case report. Acta Psychiatr Scand 2006; 114: 375–7.
38 Van Swieten, JC, Stevens, M, Rosso, SM, Rizzu, P, Joosse, M, de Koning, I, et al. Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Ann Neurol 1999; 46: 617–26.
39 Sim, M, Bale, RN. Familial pre-senile dementia: the revelance of a histological diagnosis of Pick's disease. Br J Psychiatry 1973; 122: 671–3.
40 Guyant-Marechal, L, Laquerriere, A, Duyckaerts, C, Dumanchin, C, Bou, J, Dugny, F, et al. Valosin-containing protein gene mutations: clinical and neuropathologic features. Neurology 2006; 67: 644–51.
41 Kovach, MJ, Waggoner, B, Leal, SM, Gelber, D, Khardori, R, Levenstien, MA, et al. Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Mol Genet Metab 2001; 74: 458–75.
42 Ibach, B, Poljansky, S, Barta, W, Koller, M, Wittmann, M, Hajak, G. Patterns of referring of patients with frontotemporal lobar degeneration to psychiatric in- and out-patient services. Results from a prospective multicentre study. Dement Geriatr Cogn Disord 2004; 17: 269–73.
43 Piguet, O, Brooks, WS, Halliday, GM, Schofield, PR, Stanford, PM, Kwok, JBJ, et al. Similar early clinical presentations in familial and non-familial frontotemporal dementia. J Neurol Neurosurg Psychiatry 2004; 75: 1743–5.
44 Lindau, M, Almkvist, O, Kushi, J, Boone, K, Johansson, SE, Wahlund, LO, et al. First symptoms–frontotemporal dementia versus Alzheimer's disease. Dement Geriatr Cogn Disord 2000; 11: 286–93.
45 Seeley, WW, Bauer, AM, Miller, BL, Gorno-Tempini, ML, Kramer, JH, Weiner, M, et al. The natural history of temporal variant frontotemporal dementia. Neurology 2005; 64: 1384–90.
46 American Psychiatric Association. Quick Reference to the Diagnostic Criteria for DSM–IV. APA, 1994.
47 Hyde, MD, Ziegler, JC, Weinberger, DR. Psychiatric disturbances in metachromatic leukodystrophy. Arch Neurol 1992; 49: 401–6.
48 Walterfang, M, Wood, SJ, Velakoulis, D, Copolov, D, Pantelis, C. Diseases of white matter and schizophrenia-like psychosis. Aust N Z J Psychiatry 2005; 39: 746–56.
49 Walterfang, M, Fietz, M, Fahey, M, Sullivan, D, Leane, P, Lubman, DI, et al. The neuropsychiatry of Niemann-Pick type C disease in adulthood. J Neuropsychiatry Clin Neurosci 2006; 18: 158–70.
50 Benes, FM. Why does psychosis develop during adolescence and early adulthood? Curr Opin Psychiatry 2003; 16: 317–9.
51 Kirkpatrick, B, Messias, E, Harvey, PD, Fernandez-Egaz, E, Bowie, CR. Is schizophrenia a syndrome of accelerated aging? Schizophr Bull 2007; 34: 1024–32.
52 Pantelis, C, Barnes, TRE, Nelson, HE, Tanner, S, Weatherley, L, Owen, AM, et al. Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain 1997; 120: 1823–43.
53 Shamay-Tsoory, SG, Aharon-Peretz, J, Levkovitz, Y. The neuroanatomical basis of affective mentalizing in schizophrenia: comparison of patients with schizophrenia and patients with localized prefrontal lesions. Schizophr Res 2007; 90: 274–83.
54 Kessels, RPC, Gerritsen, L, Montagne, B, Ackl, N, Diehl, J, Danek, A. Recognition of facial expressions of different emotional intensities in patients with frontotemporal lobar degeneration. Behav Neurol 2007; 18: 31–6.
55 Geschwind, DH, Robidoux, J, Alarcon, M, Miller, BL, Wilhelmsen, KC, Cummings, JL, et al. Dementia and neurodevelopmental predisposition: cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia. Ann Neurol 2001; 50: 741–6.
56 Velakoulis, D, Wood, SJ, Wong, MTH, McGorry, PD, Yung, A, Phillips, L, et al. Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Arch Gen Psychiatry 2006; 63: 139–49.
57 Kaufer, DI, Miller, BL, Itti, L, Fairbanks, LA, Li, J, Fishman, J, et al. Midline cerebral morphometry distinguishes frontotemporal dementia and Alzheimer's disease. Neurology 1997; 48: 978–85.
58 Walterfang, M, Wood, AG, Reutens, DC, Wood, SJ, Chen, J, Velakoulis, D, et al. Morphology of the corpus callosum at different stages of schizophrenia: cross-sectional study in first-episode and chronic illness. Br J Psychiatry 2008; 192: 429–34.
59 Laakso, MP, Frisoni, GB, Kononen, M, Mikkonen, M, Beltramello, A, Geroldi, C, et al. Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer's disease: a morphometric MRI study. Biol Psychiatry 2000; 47: 1056–63.
60 Velakoulis, D, Stuart, GW, Wood, SJ, Smith, DJ, Brewer, WJ, Desmond, P, et al. Selective bilateral hippocampal volume loss in chronic schizophrenia. Biol Psychiatry 2001; 50: 531–9.
61 Velakoulis, D, Pantelis, C. What have we learned from functional imaging studies in schizophrenia? The role of frontal, striatal and temporal areas. Aust N Z J Psychiatry 1996; 30: 195209.
62 Arnold, SE, Trojanowski, JQ, Gur, RE, Blackwell, P, Han, LY, Choi, C. Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Arch Gen Psychiatry 1998; 55: 225–32.
63 Horton, K, Forsyth, CS, Sibtain, N, Ball, S, Bruton, CJ, Royston, MC, et al. Ubiquitination as a probe for neurodegeneration in the brain in schizophrenia: the prefrontal cortex. Psychiatry Res 1993; 48: 145–52.

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Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases

  • D. Velakoulis (a1), M. Walterfang (a1), R. Mocellin (a1), C. Pantelis (a2) and C. McLean (a3)...


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Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases

  • D. Velakoulis (a1), M. Walterfang (a1), R. Mocellin (a1), C. Pantelis (a2) and C. McLean (a3)...
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