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David M. Blass, M.D. Peter V. Rabins, M.D., M.P.H.
Objective: The authors describe mood abnormalities seen in a case series of patients with frontotemporal dementia (FTD). Method: Authors provide a structured review of outpatient and inpatient charts of FTD patients. Results: Three distinct depressive syndromes were identiﬁed: The ﬁrst corresponds to DSM–IV major depression. The second is a syndrome of mood lability with prominent responsiveness to the environment. The third is a syndrome of profound apathy, without other evidence of depression. Conclusion: A variety of mood disorders are seen in FTD, requiring careful attention to differential diagnosis. FTD should be included in the differential diagnosis during the evaluation of older patients with mood abnormalities. (Psychosomatics 2009; 50:239 –247)
rontotemporal dementia (FTD), a progressive neurodegenerative disorder with personality changes, behavioral abnormalities, cognitive decline, and language impairments, is characterized by pathologic and phenotypic heterogeneity.1,2 Symptom presentation is primarily determined by anatomic region of disease involvement rather than speciﬁc molecular pathology.3,4 Clinical and neuropathological investigations have broadened the spectrum of which entities are considered part of FTD.5,6 Patients with FTD exhibit a broad range of psychopathology.7 Most dramatic and characteristic are behavior and personality changes.8 –11 Hyperorality, verbal and behavioral stereotypies, disinhibition, socially inappropriate behavior, and neglect of personal hygiene are highly prevalent early in the FTD course and help distinguish it from Alzheimer’s disease (AD).7,8,12 Personality changes include coldness, passivity, excessive jocularity, poor judgment, decreased empathy, and loss of insight. Some of these have been linked to the anatomic distribution of disease involvement.11,13 Psychotic symptoms are uncommon.5,7,8,14 Disturbances of mood and affective regulation have been described in FTD; these include depression, apathy, mood lability, anxiety, irritability, and euphoria.15 The prevalence of depression in two studies was approximately
Psychosomatics 50:3, May-June 2009
40%.5,14,16 Most studies of mood disturbances in FTD have used instruments such as the Neuropsychiatric Inventory (NPI)17 or the BEHAVE–AD18 that do not generate a clinical diagnosis of a mood disorder and are not depression-speciﬁc, such as the Cornell Scale for Depression in Dementia (CSDD)19 or the Montgomery-Asberg Depression Rating Scale (MADRS).20 One case series, using a descriptive phenomenological approach, noted that FTD patients treated for major depression (MDD) before receiving the diagnosis of FTD primarily suffered from social withdrawal and psychomotor retardation, but not melancholia.21 Another descriptive series noted that depressed mood states in FTD patients were short-lived, but, while present, were intense, producing dysphoria and even suicidal ideations.22 Overall, the mood disturbances of FTD have not yet been fully characterized. In clinical settings, early FTD can be confused with depression.21 Many FTD patients are severely apathetic,
Received January 21, 2007; revised July 2, 2007; accepted July 25, 2007. From Abarbanel Mental Health Center, afﬁliate of the Sackler School of Medicine, Tel Aviv University; Johns Hopkins Medical Institutions, Departments of Psychiatry and Behavioral Sciences, Medicine, and Health Policy and Management. Send correspondence and reprint requests to David M. Blass, M.D., Abarbanel Mental Health Center, 15 Keren Kayemet St., Bat Yam, Israel 59436. e-mail: email@example.com © 2009 The Academy of Psychosomatic Medicine
but not hopeless or suicidal. Mrs. History. motivation. reduced interest in activities. we present a series of patients in whom depressive symptoms initially complicated or delayed the diagnosis of FTD. or interest. PMR – Subject demographic and clinical information. mood improved after ﬁnding employment. There were no psychotic symptoms. She felt and appeared anxious but denied sadness. Her MSE remained unchanged for the next 5 days.21 To date. F” “Mrs. Many subjects had been evaluated by the neurology consultation services in our center as well. ALS: amyotrophic lateral sclerosis. All subjects underwent a comprehensive dementia assessment that included a detailed history. and results of neuroimaging studies. and Neuroimaging Past Psychiatric History – Recurrent MDDa Brief MDDb – – Brief MDDc – – Past Substance Abuse – – – – – – – – Medical History CHF Elevated lipids Back pain ALS. She was pessimistic and self-doubting. E” “Mr. irritability. The family reported mild memory impairment.Depression in Frontotemporal Dementia with profound executive disturbance. b After losing job. A” “Mrs. Mrs. Marital Work years Education Status Residence History “Mrs. RESULTS Case 1: “Mrs. Neurological examination was unremarkable. including medical and past psychiatric histories. poor grooming. We present histories of selected FTD patients from the Johns Hopkins Geriatric Psychiatry and Neuropsychiatry inpatient and outpatient services. a Episodes at age 59 and 66. Although standardized diagnostic instruments were not used. and MADRS was 25/60. CHF – – hypothyroid. based on published diagnostic criteria. and neuroimaging. reported improved mood. She had little energy.25 Similarly. she appeared brighter. diminished motivation. A brief description of the various psychometric tests applied is given in Appendix 1. and denied anhedonia or self-doubt. investigations into the accuracy of the FTD diagnosis. relevant laboratory studies. May-June 2009 . A’s” depressive symptoms of 7 months’ duration included social withdrawal.psychiatryonline. C” “Mr. resolved with hospitalization. Demographics. and diminished conﬁdence. She was discharged to the Age. MDD: major depression.14. Admission mental status exam (MSE) found her to be alert and cooperative. Treatment with sertraline was started. resolved with medication. or phobias. B” “Mr. LT: left temporal lobe. TABLE 1. On Hospital Day 3. At this point. METHOD This study utilizes a descriptive case-series methodology. Mini-Mental State Exam (MMSE) was 26/30.) The review was authorized by the Johns Hopkins Hospital Institutional Review Board. and results of cognitive testing are shown in Table 2.23. G” “Mrs. and may appear depressed while having few symptoms of depression. H” 77 79 68 89 57 62 68 70 9 years University University High school University High school High school High school Independent Independent Independent Independent Independent Independent Independent Independent – – CT/MRI SPECT B/L F. B/L T: bilateral temporal lobes. unless for practical reasons this could not be obtained.26 For the sake of brevity. LT 2RF. B/L T B/L F. 2B/L T 2B/L F. A denied sadness but reported low energy. RF: right frontal lobe. c After being robbed 10 years earlier. B/L T 2B/L F Normal B/L F. in all cases. CT/MRI: computed tomography/magnetic resonance imaging scan. CHF: congestive heart failure. and not from MDD. anxiety. are listed in Table 1. B/L F: bilateral frontal lobe. Such individuals are often diagnosed with and treated for MDD before the deﬁnitive diagnosis of FTD. with some exceptions. Mrs. A was admitted to the hospital for treatment. obsessions. There were no psychotic symptoms or suicidality. In this article.24 have focused primarily on differentiating FTD from other degenerative dementias. 2: hypoperfusion. 2LT General atrophy B/L F. D” “Mr. PMR: polymyalgia rheumatica. On Hospital Day 2. A met DSM–IV criteria for MDD. B/L T 2RF 2B/L F. 2B/L T – – Work History: stable work history before dementia onset. tearfulness. mental status and neurological examination. and somatic preoccupation. anhedonia. in all cases. FTD diagnoses were. only some of the symptoms supporting the diagnosis of FTD have been included in the case vignettes.org Psychosomatics 50:3. SPECT: single photon emission imaging. compulsions. MDD diagnosis was based on DSM–IV criteria. (Names have been altered to protect patient identity. 240 http://psy.
5/36 ( 1) 4/36 (4) 54 (4) 186 ( 1) D: 70 (75) ND: 69 (77) 27/36 (5) 17/36 (69) 16/75 ( 1) 2/15 ( 1) 42/75 (15) 9/15 (50) Rey-Osterrieth–Copy Rey-Osterrieth–Recall 82 (2) D/C’ed D: 243 (Abnormal) D: 70 (50) D: 59 (85) ND: 220 (Abnormal) ND: 73 (60) ND: 74 (57) 14/36 ( 1) 26/36 (15) 30/36 (31) 2. D: dominant.53 Fluency–Literal. She was instructed to stop driving.org 241 .psychiatryonline.57 D/C’ed: discontinued. She was readmitted to the hospital and treated with therapeutic doses of nortriptyline and lithium without achieving full remission. Adequate trials of mirtazapine. She slept well and did not feel guilty or self-deprecating. In the ensuing months.54 Clock-Drawing. guilt. agnosia. insomnia Psychosomatics 50:3. She spent most days in bed. C 25/30 (3) 25/30 4 ( 1) 20 Normal Normal 3 (2) 9 (21) Mr. A underwent a comprehensive dementia evaluation.59 Rey-Osterrieth. but apathy and diminished interest. thoughts of death or suicide. MMSE was 26/30. TABLE 3. aphasia. Profound apathy Absence of sadness. loneliness. Depressive Syndromes Seen in Frontotemporal Dementia Patients Clinical Description DSM–IV Major Depression Mood reactivity and lability Apathy syndrome 5 symptoms from the following: depressed mood. loss of energy. Highly reactive to immediate environment. Symptoms are present daily for 2 weeks.Blass and Rabins Day Hospital and then to outpatient follow-up with a behavior plan emphasizing increased structure and activity. and lack of initiative. Symptoms during her post-ECT relapse were crying.5/36 ( 1) 13/36 (45) 4/36 (8) A brief description of the neuropsychological tests can be found in Appendix 1. Case 2: “Mrs. ND: non-dominant. venlafaxine. F 30/30 21/30 9 (1) 17 Borderline Borderline 2 (1) 8 (8) Mrs. D 27/30 Mr. B 21/30 21/30 6 11 Deﬁcient Mr. guilt feelings. psychomotor retardation or agitation. Once depressive symptoms had resolved. E 28/30 13 ( 10) Normal Mr. H 60/60 28/30 5 ( 3) 17 BNT MMSE Verbal Fluency-Literal Verbal Fluency–Semantic Clock–Command Clock–Copy HVLT–Delay HVLT–Recognition RAVLT–Total RAVLT–Recall Trails A Trails B Grooved Peg Board 20/30 (7) 26/30 11 (7) 31 Deﬁcient Normal 11 (84) 11 (25–50) 29/75 ( 3) 6/15 ( 20) 163 ( 1) D/C’ed D: 227 (1) ND: 261 (1) 9. decreased concentration. All three of her episodes met DSM–IV criteria for MDD. or impaired visual-spatial perception. Values in parentheses are age-matched percentiles. May-June 2009 http://psy. loss of interest or pleasure. anorexia.58 Grooved Pegboard Test. and a diagnosis of FTD was made. poor concentration. and methylphenidate were unsuccessful. anxiety. change in appetite and sleep. without apraxia. A Mrs.57 Trails A and B. symptoms changed in character.55 HVLT: Hopkins Verbal Learning Test. citalopram.54 Fluency–Semantic. Neuropsychological Test Results Mrs. BNT: Boston Naming Test.56 RAVLT: Rey Auditory Verbal Learning Test.52 MMSE: Mini-Mental State Exam. but could be engaged in activities and enjoy them. pessimism. Rapidly modiﬁable by environmental changes. G 42/60 ( 1) 24/30 5 ( 3) Mrs. Depressive symptoms (including suicidality) may only exist in certain environments or in the presence of certain people. ﬂuoxetine. A course of seven right-unilateral electroconvulsive (ECT) treatments produced short-lived improvement. She refused to change TABLE 2. Mrs. She relapsed again at age 76 and had an unsuccessful high-lethality suicide attempt. sertraline. bupropion. Her predominant mood state was not sadness. Neuropsychological testing performed during this time revealed poor executive functioning (performance in the 2nd percentile). anorexia. guilt. B” was a 79-year-old woman referred for evaluation of treatment-resistant recurrent depression and mild cognitive impairment. insomnia.
Clock-Drawing:55 A test of constructional praxis in which patients draw a clock (placing numbers and hands) from memory and by copying from a ﬁgure.. He had word-ﬁnding difﬁculties for common words. following a pre-speciﬁed strategy of numbers in ascending order (Trails A). a diagnosis of FTD was made. with psychomotor slowing. but was inappropriate and disinhibited. and orientation were impaired. but there was no crying.” She had limited insight into her symptoms. Expressed emotion was blunted. Rey Osterrieth Complex Figure Test:55 A test of visual memory. left-right confusion. At this point. agnosia. exhausting her entire supply if allowed to do so. according to her husband. she asked the examiner numerous personal questions. Case 3: “Mr. cooperative. in which words beginning with a speciﬁc letter are generated. or guilty. hopeless.org Psychosomatics 50:3. He displayed contempt for driving rules by speeding and not wearing a seatbelt. Diagnostics are shown in Table 1 and Table 2. She gained 10 –15 pounds. Case 4: “Mr. MADRS was 5/60. In the recall task. Verbal Fluency:54 A timed test of word list-generation using one of two strategies. 242 http://psy. He appeared sad. or astereognosia. She was seen in the clinic 6 months after the most recent hospital discharge. He frequently APPENDIX 1.psychiatryonline. The patient was apathetic. Speech was of normal volume and rate. Behavior was often silly. he had been diagnosed with MDD and possible dementia and was treated with escitalopram. C developed difﬁculties with shortterm memory and word-ﬁnding. and disheveled. he was referred for evaluation. with a restricted range of emotion. she did not meet DSM–IV criteria for MDD. There were no psychotic symptoms. language. anxiety. Language was somewhat agrammatic. He was otherwise apathetic about nearly all issues. He denied feeling depressed or anxious. Neurological examination was normal except for slowed gait and agraphesthesia. appetite. neglect. He frequently repeated inappropriate stereotyped phrases such as “It is all her fault” (when pointing to the medical student). She denied feeling depressed. or suicidality. In the recognition (HVLT) task. Mr. There was no apraxia. assessing ability to learn a word-list presented verbally. MSE revealed the patient to be alert.56 Rey Auditory Verbal Learning Test (RAVLT):57 Tests of verbal memory. animals) are generated. patients reproduce words from memory. anxious. Mr. Hopkins Verbal Learning Test (HVLT). suicidality. He often repeated the same stereotyped phrases. She often perseverated in her answers. and he reported feeling optimistic. Mini-Mental State Exam (MMSE):53 A brief cognitive screen that includes orientation.Depression in Frontotemporal Dementia clothes and had diminished attention to activities of daily living (ADLs). Psychiatric symp- Boston Naming Test (BNT):52 A test of ability to recognize and name objects. C’s” current symptoms began at age 67. and constructional praxis. immediately after presentation and after a delay. C did not meet DSM–IV criteria for MDD. or change in sleep.27 The patient was diagnosed with FTD and admitted to the geriatric psychiatry service for treatment of behavioral disturbances. assessing ability to reproduce from memory a previously-presented complex ﬁgure. and disheveled. A smiley-face was drawn in the clock after its completion. attention. May-June 2009 . Confrontation naming. In the community. visual-spatial impairment. sadness. praxis. recall. when he became uninterested in hobbies or socializing. B’s current mood syndrome was formulated as having an apathy syndrome. He spent most days watching TV. self-deprecation. His personality turned cold and nasty. would “sit and stare at the walls. Neurological examination was normal except for a prominent grasp reﬂex and bilateral agraphesthesia. but she could brighten. at 57. Mrs. She no longer initiated conversations and. Grooved Pegboard Test:59 A timed test of manual dexterity and ﬁne motor movement. cooperative. There were no psychotic symptoms. guilt. After a comprehensive dementia evaluation. only interrupting for meals. with phonemic paraphasias. and he would yell and curse at his family. without improvement. or semantic. Brief Description of Tests made inappropriate sexual remarks to women. planning. patients are presented a word-list containing some of the original words and have to identify the words from the original list. MSE found the patient to be alert. or alternating letters and numbers in ascending order (Trails B). D” was referred for urgent admission because of depression and suicidality. self-deprecation. attention. She began smoking cigarettes obsessively. There was no guilt. This mood state remained stable over the ensuing year. Trail-Making Test:58 A timed test of ability to connect circled letter and number icons on paper. Amyotrophic lateral sclerosis (ALS) had begun at age 84. or energy. As cognitive impairment and behavioral disturbance progressed. phonemic (literal).g. in which words from a category (e. The patient’s total score on the Frontal Behavior Inventory (the FBI) was greatly elevated. rather than MDD. There was signiﬁcant perseveration in test answers.
she developed difﬁculties with word-ﬁnding. He felt bored but not sad. Case 5: “Mr. Sertraline and quetiapine were prescribed without beneﬁt. irritability. paranoia that his children were stealing his money. depressive symptoms had resolved. By Hospital Day 2. severe inattention. He perseverated on speciﬁc themes. MADRS was 6/60. EEG. decreased emotional responsiveness. compulsive skin picking. E became very withdrawn. G. Trials of ﬂuoxetine. Mr. MADRS was 29/60. and inattention to safety. and mildly agitated. Mr. and impaired judgment were noted. Insight into previous symptoms was limited. the diagnosis of FTD was made. limiting interactions with family. bupropion. E was diagnosed with FTD. Mr. suicidality. intermittently refused medications. After a comprehensive dementia evaluation. hopeless. He denied feeling sad. he developed low mood. unable to perform basic tasks because of disorganization. and anorexia. had an intact self-attitude. He acknowledged feeling like he wanted to die and said that he would stab himself if he could. disheveled. He progressively developed insomnia. Mrs. His mood was extremely labile and very reactive to the environment. and hyperorality. naming. He appeared sad. and decreased concentration. Mr. Orientation. shifting from cheerful to crying and suicidal with the mere mention of the recent robbery. E developed perseverative speech and behavior. E” developed symptoms of depression 14 months before the diagnosis of FTD. Symptoms of depression improved slowly. with a restricted range of expressed emotion. Mr.org 243 . was not anhedonic or pessimistic. Mr. and. rather than recurrent MDD. He appeared cheerful. contrary. He reported sadness and appeared depressed. During the hospital stay. lumbar puncture. anergia. F to be functionally impaired. when personality changes. crying. Neuropsychological testing was interrupted when he became agitated. Mr. Case 7: “Mrs. At age 67. even when inappropriate to the context. He started doubting his wife’s ﬁdelity. He was admitted involuntarily with the diagnosis of MDD with psychotic features. She was diagnosed with FTD after a comprehensive dementia assessment. Neurological examination was unremarkable. impulsivity. and argumentative. He frequently cried. developed a depression syndrome characterized by sustained low mood. quiet. self-deprecation.psychiatryonline. and speaking little. Case 6: “Mr. He was diagnosed with MDD. He was unable to work. keeping track of time. and EEG were negative. and was found by the police wandering the streets in tears. F” was admitted to the psychiatric unit after being robbed. and without spontaneity. On MSE. with the patient becoming impatient. rather than MDD. nefazodone. impersistence. Initial differential diagnosis was adjustment disorder with depressed mood. Neurological examination. F was discharged to a dementia-speciﬁc assisted-living facility. feeling as if she were dying. and restless.” His syndrome at this time was felt to be Psychosomatics 50:3. or guilty and was not observed to be crying or anhedonic.Blass and Rabins toms began at age 86. lumbar puncture. MMSE was 25/30. he was noted to be disheveled and unable to clean himself properly. Activity became limited to watching TV. He said that suicidal ideations began immediately after the robbery. He became despondent. and visuospatial perception were normal. He often looked down and blinked repetitively. and escitalopram were ineffective. F was treated with paroxetine. This mood state persisted over the next year. including verbal ﬂuency and divided attention. and throughout the bathroom after defecation. ultimately. May-June 2009 consistent with an apathy syndrome. Insight into the impropriety of his behavior was limited. showed impairment. F was alert. The patient was diagnosed with FTD-ALS syndrome. This was true even after his mood had improved back to baseline. but brightened easily. Mr. There was no guilt. slow-moving. praxis. E primarily described his mood as “bored. At age 87. and a good appetite. She then developed hyperorality with increased appetite (consumption of large amounts of soda) and excessive foodshopping. At age 66. In the emergency room. with craving for sweets. He was not suicidal and had no delusions. feared he was burdening his family. and http://psy. or psychosis. Speech was slow. Over time. Over the next 8 months. He reported sadness and was noted to have low mood. anhedonia. anxious. and performing household tasks. E was alert. He was neatly dressed and appropriately groomed. and laboratory evaluations were normal. calculation. recall. and often expressed the wish to die. reported feeling happy. Blood tests. stating that he wished to kill himself. his clothes. There were no psychotic symptoms. suicidal ideation with a plan. anhedonia. Fecal matter was found smeared on the patient. poor planning. G’s” symptoms began at age 64 with subtle changes in behavior and personality. He was often anxious and restless. His family described him as apathetic about everything. Tests of executive functioning. An occupational-therapy assessment found Mr. Paroxetine treatment was started.
Case 8: Mrs. She had frequent “Yes/No” substitutions. and hopeless. Posture was inappropriately casual. and paroxetine were ineffective. She described her mood as sad. She was diagnosed with MDD. without inﬂection. In these cases. 4. She acknowledged feeling guilty. and 7. initiative. 5. Symptoms progressed to include agitation. and she appeared as such. easily frustrated. and wishing for death. However. but she formed complete. her mood was good. She remained on escitalopram for the next year. grammatically correct sentences. At age 70. which she would correct herself. She felt abandoned by her friends. She was overweight and disheveled. and sleep were impaired. By Hospital Day 4. Speech was hesitant. she was diagnosed with primary progressive aphasia. or psychosis. naming. The patient was diagnosed with DSM–IV MDD. There. Symptoms were generally persistent over a signiﬁcant period of time. or compulsions. Despite trials of trazodone. threatened her husband. the development of MDD may have heralded the onset of FTD. and with a metallic quality. and she consistently denied concerns about her husband’s ﬁdelity. lacking energy. and she developed difﬁculty playing the piano. this belief was absolutely ﬁxed. but. calm. and high doses of SSRIs.27 DISCUSSION FTD is a syndrome with protean neuropsychiatric manifestations. and anhedonic. 4. interest in activities. she would become irritable. After neurological evaluation. quetiapine. H became sad. she was no longer suicidal. 6. venlafaxine with quetiapine augmentation. and became delusional about inﬁdelity. 2. MDD is highly prevalent in the early Psychosomatics 50:3. when she would visit with her children. hopeless and anergic. unmotivated. suicidality. obsessions. energy. MSE revealed Mrs. with yelling. and energy. When present. and she had difﬁculty falling asleep. and 8.org Other cognitive functions were initially intact. olanzapine. Within an hour of leaving the hospital. Initially. She appeared sad and tearful. MSE at age 68 revealed Mrs. and commands were followed inconsistently. The ﬁrst pattern of depressive symptomatology is the classic syndrome of MDD. repetition. Mrs. these symptoms disappeared almost immediately if her husband was not present. handwriting and spelling deteriorated. Appetite. G to be alert and cooperative. her mood improved. MADRS was 4/60. new learning. in the setting of more rapid speech deterioration. Speech was monotonic. sad. they had been present for weeks or months in a pattern typical for MDD before the hospitalization. Depressive symptoms did not recur. Escitalopram was started. meeting DSM–IV criteria. When her husband visited.25 This pattern was seen at some point in time in the histories of Patients 1. and pessimistic. Speech was halting. There were no cortico-sensory deﬁcits. This case series illustrates three patterns of depressed mood found among FTD patients. at other times. with word-ﬁnding difﬁculties and intact comprehension. psychotic symptoms. at 30. 7. but with no sustained sadness or tearfulness. There were no psychomotor abnormalities. May-June 2009 . and cooperative. an FTD-spectrum condition. and praxis. She was meticulously groomed and well-dressed. H’s language difﬁculties began at age 64. She cried. There was no guilt. She was frequently tearful throughout the interview. with word-ﬁnding difﬁculties and frequent semantic and phonemic paraphasic errors. with impairments of orientation. G was admitted to the psychiatry service with an initial diagnosis of recurrent MDD. writing. and began sleeping and eating well. MMSE was 12/30. with a return of optimism. whereas her FBI score remained elevated. Neurological examination was normal. tearful. Mrs. The patient was discharged home with her husband after a 10-day hospitalization. and she moved into an assisted-living facility. Over the next 5 years. Mrs. her mood was stable. Mrs. throwing objects at her husband. self-deprecating. and not letting him out of her sight. By Hospital Day 3. which was not otherwise detectable at that time.Depression in Frontotemporal Dementia suicidality. and sometimes delusional. with instantaneous crying upon mention of the death (many decades earlier) of a close relative. Although the mood symptoms resolved rapidly upon hospitalization in Patients 1. 244 http://psy. Sertraline. She became tearful as soon as her FTD illness was discussed. although she laughed loudly and inappropriately at times. H to be alert. She perseverated on certain themes and phrases. Within 1 month. There were no suicidal ideations. Comprehension was impaired. although she did develop symptoms of pseudobulbar palsy. the belief was absent.psychiatryonline. G could not remain living with her husband because of agitation in his presence. Symptoms were present most of the time. she remained sad. These symptoms would resolve with his departure. Once depression resolved. and delusions were not present. She wished she were dead and thought about riding a bicycle into trafﬁc. G again became depressed. her CSDD score was only 6. She became intermittently suspicious that her husband was having an extramarital affair.
In these patients. Second. Mood lability had the character of being highly reactive to the immediate environment and was rapidly modiﬁable by an environmental change. among others. without signiﬁcant consideration having been given to the possibility of FTD. In Patient 7.42 First. In contrast.38.org 245 .45 The cases presented in this series illustrate the importance of considering the FTD diagnosis in patients with atypical or treatment-resistant depressive symptoms. and traumatic brain injury. May-June 2009 able from MDD. is common in MDD.31 and there is evidence that. and 7. One reason is diagnostic accuracy. Arguing against the diagnosis of MDD is the absence of sadness. In Patients 1 and 4.39 as well as the interruption in frontal–subcortical functional circuits that occurs in FTD.40 A third affective syndrome. Moreover. one of the central impairments seen in FTD. in some patients. pessimism. easily misdiagnosed as MDD.psychiatryonline.37 This mechanism may be relevant in FTD. clinically.30. seen in Patients 1. Pathologic crying or laughing is deﬁned as the sudden and insuppressible outburst of crying or laughing that may or may not occur in socially appropriate settings. mood lability (including inducing passive death wishes and suicidal ideations) was triggered by changing the topic of discussion. Likewise. In Patient 6. http://psy. apathy and dysfunction of the anterior cingulate circuit. in FTD. as MDD is associated with signiﬁcant morbidity.28. the diagnosis of MDD may stand in the way of an accurate diagnosis of FTD. in particular. MDD has a much higher prevalence than FTD. and sadness and anhedonia with dysfunction of the medial orbitofrontal cortex. this differentiation remains a challenge. 4. given that executive dysfunction. low mood may be associated with involvement of the right temporal lobe. although this differentiation can also be challenging.46. the diagnosis of AD is often considered in geriatric patients who are depressed and have mild memory or language difﬁculties. stroke. which is relatively insensitive to the deﬁcits of early FTD.Blass and Rabins stages of neurodegenerative disorders such as AD or Huntington’s disease (HD). accurate characterization of depressive symptoms may facilitate identiﬁcation of neuroanatomic correlations. it is important to identify MDD in FTD patients who develop it. this syndrome followed the resolution of a full MDD episode. Many patients with this syndrome also are diagnosed with MDD or dysthymia. but. Mood lability and reactivity may have a different anatomic substrate than MDD with or without psychosis. As outlined above. mood abnormalities were seen only in the presence of her husband and disappeared promptly when he departed.47 Precise characterization of the mood abnormalities of FTD is important for several reasons. 6. 3. multiple sclerosis.44. seen in Patients 2. The apathy syndrome is distinguishPsychosomatics 50:3. Second. anxiety. in Patient 7. guilt. and. particularly if cognition is initially assessed with a screening instrument such as the MMSE. FTD patients with severe apathy may be so functionally impaired and uninterested in their environment that the initial diagnosis is MDD. for a few reasons.29 Some authors have suggested that depression seen in neurodegenerative disorders is a consequence of damage to subcortical structures. anorexia.43 Finally. Third. clinicians may naturally avoid making a diagnosis of an irreversible neurodegenerative condition when the possibility of a treatable and reversible condition such as MDD exists. Current evidence suggests a link between mood lability and dysfunction of the lateral orbitofrontal cortex.32 Thus.48 Indiscriminately grouping all of these syndromes together in the category “depression” misses the opportunity for better understanding. since the typical age at onset of FTD is relatively young (in the 6th decade). cognitive abnormalities that are identiﬁed may initially be attributed to presumed MDD. mild cognitive abnormalities of early FTD can be obscured by the more prominent psychopathology. despite her having been consistently asymptomatic in the hospital. or insomnia. dementia may not initially be suspected. The second mood syndrome is that of affective reactivity and lability. given the abnormalities of serotonergic transmission believed to be present in FTD.41. many FTD patients were initially referred for evaluation of what was thought to be treatment-resistant depression. and 5. A number of forms of pathologic emotional reactivity have been previously described. MDD may be the earliest manifestation of the underlying FTD neuropathologic process. In our experience in a geriatric psychiatry clinic specializing in mood disorders in elderly patients. longstanding depressive symptoms resolved rapidly upon hospitalization. These syndromes have been described in patients with AD. is profound apathy. and may precede the development of dementia in AD or movement disorder in HD. This differentiation can be especially challenging.33–36 Such pathological displays of emotion are thought to be mediated by interruptions of ascending serotonergic projections from the raphe nuclei as they project from the brainstem through the subcortical structures and to the frontal cortex.15. there may be therapeutic implications of accurate differentiation among different mood syndromes. the symptoms returned promptly after hospital discharge. Finally. possibly biasing clinicians toward the diagnosis of MDD.
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