Skip to main content
To the Editor: Dementia is generally considered to have a low risk of suicide, but several reports have highlighted suicide in dementia, and the exact predictors are still poorly known (1). Here we show that a suicide attempt can be the first manifestation of early dementia due to the recently identified C9orf72 expansion (2, 3). This novel type of dementia can be easily missed in elderly patients with dementia or misdiagnosed as Alzheimer’s disease (4).
A 72-year-old German man without significant previous medical or psychiatric illnesses was admitted after trying to hang himself. An adjustment disorder was assumed at first, but psychiatric examination revealed a striking lack of concern about the suicide attempt, frequent irrelevant answers, and inappropriate jocularity without any signs of depression. His wife reported a 2-year history of subtle behavioral disinhibition (short episodes of socially inappropriate behavior and impulsive reactions) and deficits in short-term memory and face recognition in her husband, but history and observation did not reveal additional symptoms necessary for a diagnosis of possible behavioral frontotemporal dementia (5). (For details of the diagnostic workup, see the data supplement that accompanies the online edition of this letter.) Neuropsychological testing results revealed mild deficits in the domains of verbal episodic memory and visuospatial abilities but not in executive functions such as strategic thinking and executive flexibility (see the online data supplement). MRI and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) revealed several abnormalities, including temporal atrophy with hippocampal degeneration and biparietal and temporomesial hypometabolism, but no frontal atrophy or hypometabolism (Figure 1). Although behavioral frontotemporal dementia can present with anterior temporal atrophy without frontal atrophy or hypometabolism (5), this imaging pattern was considered to be atypical for behavioral frontotemporal dementia or, at least, to be unspecific. The patient’s sister died by suicide at age 50, and his mother began to show late-onset progressive nonfluent aphasia at age 85. Based on this family history, C9orf72 genotyping was initiated, revealing a pathogenic expansion of more than 50 repeats (2, 3). A written informed consent was obtained from the patient after the procedures and the publication had been fully explained to him and his family.
FIGURE 1. Cerebral MRI and [18F]-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in the C9orf72 Index Patienta
a The coronal T2-weighted MRI scan in panel A shows substantial bilateral temporal atrophy with temporomesial predominance, including hippocampal atrophy (arrows) and concomitant (panel B) mild cerebellar atrophy (arrows). Horizontal fluid-attenuated inversion recovery-weighted MRI shows absence of frontal atrophy (panels C and D). The FDG-PET images in panel E show hypometabolism in the biparietal cortex, including adjacent parts of the cuneate and in the temporomesial cortex. No frontal hypometabolism was observed. FDG-PET images were stereotactically normalized and, after Gaussian smoothing, compared with age-matched comparison subjects to obtain z scores (blue clusters).
This case of a suicide attempt as the presenting symptom of early dementia due to a C9orf72 expansion suggests that C9orf72 dementia and associated behavioral disturbances (e.g., disturbed impulse inhibition) may present a risk factor for suicide in the elderly. As shown here, suicidal ideation and attempts might become apparent even before the criteria for behavioral frontotemporal dementia are fulfilled. Death by suicide may be unappreciated or unreported in the family history (especially if not accompanied by clear-cut dementia), and this might explain—at least in part—the high rate of apparently “sporadic” patients with C9orf72 dementia (6).
Our case demonstrates that identifying the underlying C9orf72 dementia can be complicated by the fact that results of neuropsychological testing and imaging studies can be more suggestive of Alzheimer’s disease (pronounced hippocampal atrophy, biparietal and temporomesial hypometabolism, and early deficits in episodic verbal memory and visuospatial abilities) than of frontotemporal dementia. Thus, while frontal hypoperfusion or atrophy with relative sparing of the temporal lobes has been described as a predominant pattern in several patients with C9orf72 dementia (7, 8), neurodegenerative dysfunction might be much more variable in others: C9orf72 dementia might present as “mixed dementia” with features of both frontotemporal dementia and Alzheimer’s disease. This explains why C9orf72 dementia can easily be misdiagnosed as Alzheimer’s disease (4).

Acknowledgments

The authors thank the Department of Psychiatry, Hertie-Institute for Clinical Brain Research, and the German Research Center for Neurodegenerative Diseases (DZNE) for their support of this work.

References

1.
Purandare N, Voshaar RC, Rodway C, Bickley H, Burns A, Kapur N: Suicide in dementia: 9-year national clinical survey in England and Wales. Br J Psychiatry 2009; 194:175–180
2.
DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R: Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011; 72:245–256
3.
Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Hölttä-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chiò A, Restagno G, Borghero G, Sabatelli M, Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJITALSGEN Consortium: A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011; 72:257–268
4.
Majounie E, Abramzon Y, Renton AE, Perry R, Bassett SS, Pletnikova O, Troncoso JC, Hardy J, Singleton AB, Traynor BJ: Repeat expansion in C9ORF72 in Alzheimer’s disease. N Engl J Med 2012; 366:283–284
5.
Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL: Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134:2456–2477
6.
Majounie E, Renton AE, Mok K, Dopper EG, Waite A, Rollinson S, Chiò A, Restagno G, Nicolaou N, Simon-Sanchez J, van Swieten JC, Abramzon Y, Johnson JO, Sendtner M, Pamphlett R, Orrell RW, Mead S, Sidle KC, Houlden H, Rohrer JD, Morrison KE, Pall H, Talbot K, Ansorge O, Hernandez DG, Arepalli S, Sabatelli M, Mora G, Corbo M, Giannini F, Calvo A, Englund E, Borghero G, Floris GL, Remes AM, Laaksovirta H, McCluskey L, Trojanowski JQ, Van Deerlin VM, Schellenberg GD, Nalls MA, Drory VE, Lu CS, Yeh TH, Ishiura H, Takahashi Y, Tsuji S, Le Ber I, Brice A, Drepper C, Williams N, Kirby J, Shaw P, Hardy J, Tienari PJ, Heutink P, Morris HR, Pickering-Brown S, Traynor BJChromosome 9-ALS/FTD Consortium; French Research Network on FTLD/FTLD/ALS; ITALSGEN Consortium: Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 2012; 11:323–330
7.
Boeve BF, Boylan KB, Graff-Radford NR, DeJesus-Hernandez M, Knopman DS, Pedraza O, Vemuri P, Jones D, Lowe V, Murray ME, Dickson DW, Josephs KA, Rush BK, Machulda MM, Fields JA, Ferman TJ, Baker M, Rutherford NJ, Adamson J, Wszolek ZK, Adeli A, Savica R, Boot B, Kuntz KM, Gavrilova R, Reeves A, Whitwell J, Kantarci K, Jack CR, Parisi JE, Lucas JA, Petersen RC, Rademakers R: Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 2012; 135:765–783
8.
Hsiung GY, DeJesus-Hernandez M, Feldman HH, Sengdy P, Bouchard-Kerr P, Dwosh E, Butler R, Leung B, Fok A, Rutherford NJ, Baker M, Rademakers R, Mackenzie IR: Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain 2012; 135:709–722

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1211 - 1213
PubMed: 23128926

History

Accepted: August 2012
Published online: 1 November 2012
Published in print: November 2012

Authors

Details

Matthis Synofzik, M.D.
Department of Psychiatry and Hertie-Institute for Clinical Brain Research, Tübingen, Germany
Saskia Biskup, M.D., Ph.D.
Department of Psychiatry and Hertie-Institute for Clinical Brain Research, Tübingen, Germany
Thomas Leyhe, M.D.
Department of Psychiatry and Hertie-Institute for Clinical Brain Research, Tübingen, Germany
Matthias Reimold, M.D.
Department of Psychiatry and Hertie-Institute for Clinical Brain Research, Tübingen, Germany
Andreas J. Fallgatter, M.D.
Department of Psychiatry and Hertie-Institute for Clinical Brain Research, Tübingen, Germany
Florian Metzger, M.D.
Department of Psychiatry and Hertie-Institute for Clinical Brain Research, Tübingen, Germany

Competing Interests

The authors report no financial relationships with commercial interests.

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard

View Options

View options

PDF/EPUB

View PDF/EPUB

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Purchase Options

Purchase this article to access the full text.

PPV Articles - American Journal of Psychiatry

PPV Articles - American Journal of Psychiatry

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share