0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letters to the Editor   |    
Suicide Attempt as the Presenting Symptom of C9orf72 Dementia
Matthis Synofzik, M.D.; Saskia Biskup, M.D., Ph.D.; Thomas Leyhe, M.D.; Matthias Reimold, M.D.; Andreas J. Fallgatter, M.D.; Florian Metzger, M.D.
Am J Psychiatry 2012;169:1211-1213. doi:10.1176/appi.ajp.2012.12060733
View Author and Article Information

The authors report no financial relationships with commercial interests.

Department of Psychiatry and Hertie-Institute for Clinical Brain Research, Tübingen, Germany

Accepted August , 2012.

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.

 
Anchor for JumpAnchor for Jump
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).

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.

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
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
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  BJ;  ITALSGEN Consortium:  A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.  Neuron 2011; 72:257–268
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
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  BJ;  Chromosome 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
[CrossRef] | [PubMed]
 
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  Jr;  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
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
References Container

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).

+

References

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
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
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  BJ;  ITALSGEN Consortium:  A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.  Neuron 2011; 72:257–268
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
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  BJ;  Chromosome 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
[CrossRef] | [PubMed]
 
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  Jr;  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
[CrossRef] | [PubMed]
 
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
[CrossRef] | [PubMed]
 
References Container
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 6

Related Content
Books
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 9.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 62.  >
Textbook of Traumatic Brain Injury, 2nd Edition > Chapter 3.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 44.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 53.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
APA Guidelines