Letters to Editor
Bipolar affective disorder in Huntington’s disease: A neuropsychiatric perspective Sir, Huntington’s disease (HD) is inherited autosomal dominant neurodegenerative disorder that results from an unstable expansion of trinucleotide repeat cytosine‑adenine‑guanine (CAG) of the huntingtin gene IT‑15 on chromosome 4p16.3. It is characterized by movement disorders (usually chorea), cognitive impairment (resulting in dementia) and psychiatric disorders. Symptoms typically begin in the fourth decade of life and result in progressive deterioration in functional capacity and independence. The association of mood disorder appears confined in certain families, suggesting genetic heterogeneity within HD.[1,2] Psychiatric changes are often present before the development of chorea or intellectual impairment. In our case, the patient had a positive family history of HD in three successive generations. Here, we report a case of 17‑year‑old male patient who presented to neurology out‑patient department (OPD) with complaints of increased blinking of eyes for 8 months and continuous jerky involuntary movements of left foot for 1 month. Genetic analysis showed CAG repeat expansion – 60 units and thus patient was diagnosed to be suffering from HD. Patient was referred to psychiatry OPD for his behavioral complaints and was subsequently admitted to our psychiatric ward. The members of patient’s family complained that for the last 3 months he was having irritable behavior, frequent fights, remained restless, abstained frequently from school, reduced sleep and gradually started boasting about self, talking more than usual, his speech was loud, interjected with rhyming and punning and sometimes complained that other people make gestures and pass comments on him,
though he denied hearing any voices. One year prior to the current hospitalization, patient complained of sadness of mood, loss of energy, loss of appetite and sleep and had these symptoms lasted for 6 months, but did not consult any specialist and these were resolved gradually. There is a strong family history of HD comprising 11 cases in three successive generations [Figure 1]. Of these 11 cases of HD in the family, five cases had comorbid bipolar affective disorder with one of them committing suicide. Patient was diagnosed as having HD with bipolar affective disorder currently episode manic with psychosis (F31.2). On Young Mania Rating Scale (YMRS), baseline score was 32 and Clinical Global Impression (CGI‑severity score) was 6. Treatment was started with divalproate 1500 mg/day as a mood stabilizer, haloperidol (10 mg/day) for psychotic symptoms and lorazepam 4 mg/day for inducing sleep. After 4 weeks, there was a satisfactory response (with 50% reduction) in psychiatric symptoms as assessed on YMRS scale score of 17 and CGI‑ global improvement score of 2. In addition to pharmacotherapy, patient also received individual supportive psychotherapy. After 4 weeks of treatment, there was improvement in patient’s condition, his mood stabilized, and he was no longer delusional. He was discharged and now remains in outdoor patient treatment with a long‑term follow‑up plan for medical care, psychological, genetic, family counseling and emerging benefit of striatal fetal neurotransplantation. In our 17‑year‑old patient, psychiatric changes have appeared before the usual onset of disease. Patient had strong positive family history of HD and on genetic analysis test; there was a higher number (60) of CAG repeats suggestive
Figure 1: Pedigree chart of Huntington’s disease with bipolar affective disorder Indian Journal of Psychiatry 57(1), Jan-Mar 2015
107
Letters to Editor
of earlier onset of disease. The age of onset inversely correlated with the size of the triplet repeat expansion.[3] The progression of HD is inexorable and usually leads to death within 15 to 20 years of presentation in patients who eventually become immobile and severely demented.[4] However, in future treatment with transplantation of fetal neuronal material to replace the degenerated neurons and cell engineered to secrete neurotrophic factors in HD are emerging to ameliorate the condition but replication of results in human needs further research.[5] The affective disorders may be present 20 years prior to the onset of chorea and dementia in HD. The prevalence of Major affective disorder is found in 41% of patients with HD, 32% being depressive and 9% bipolar.[2] Findings show that the frequency of suicidal ideation doubled from 9.1% in at‑risk persons with a normal neurological examination to 19.8% in at‑risk persons with soft neurological signs and increased to 23.5% in persons with “possible HD.” In persons with a diagnosis of HD, 16.7–21.6% had suicidal ideation,[6] 5.7% of deaths among affected persons resulted from suicide and 27.6% of patients attempted suicide at least once.[7] This case shows that patients of HD can present with symptoms of either depression or mania which can further increase the risk of suicide in these patients. Psychosis is not uncommon in bipolar disorder and in case of HD with chorea, the treatment with haloperidol to ameliorate choreiform movement is dependent on the serum haloperidol concentration.[8] Hence cases such as ours emphasize the need for the psychiatrists to be aware of the psychological symptoms and the suicidal risk associated in patients presenting with organic brain disease.
Rajnish Raj, Balwant Singh Sidhu, Eish Dalla
Department of Psychiatry, GMC and Rajindra Hospital, Patiala, Punjab, India. E‑mail: [email protected] REFERENCES 1. 2. 3. 4.
5. 6. 7. 8.
Paulsen JS, Ready RE, Hamilton JM, Mega MS, Cummings JL. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry 2001;71:310‑4. Folstein S, Abbott MH, Chase GA, Jensen BA, Folstein MF. The association of affective disorder with Huntington’s disease in a case series and in families. Psychol Med 1983;13:537‑42. Rosenblatt A. Neuropsychiatry of Huntington’s disease. Dialogues Clin Neurosci 2007;9:191‑7. Lovestone S. Alzheimer’s disease and other dementias (including Pseudodementias). In: David AS, Fleminger S, Kopelman MD, Lovestone S, Mellers JD, editors. Lishman’s Organic Psychiatry: A Textbook of Neuropsychiatry. 4th ed. London: Wiley Blackwell Publishing; 2009. p. 576‑84. Freeman TB, Sanberg PR, Isacson O. Development of the human striatum: Implications for fetal striatal transplantation in the treatment of Huntington’s disease. Cell Transplant 1995;4:539‑45. Paulsen JS, Hoth KF, Nehl C, Stierman L. Critical periods of suicide risk in Huntington’s disease. Am J Psychiatry 2005;162:725‑31. Farrer LA. Suicide and attempted suicide in Huntington disease: Implications for preclinical testing of persons at risk. Am J Med Genet 1986;24:305‑11. Barr AN, Fischer JH, Koller WC, Spunt AL, Singhal A. Serum haloperidol concentration and choreiform movements in Huntington’s disease. Neurology 1988;38:84‑8. Access this article online Quick Response Code
Website: www.indianjpsychiatry.org
DOI: 10.4103/0019-5545.148546
Childhood dissociation as a precursor of mood disorder: A 5 years follow-up case study Sir, Dissociative symptoms are seen in patients with psychiatric problems and exist in a continuum from common normal phenomena like daydreaming and attention lapses through to pathological failure to integrate feelings, thoughts and action.[1] Dissociative symptoms have been well described as part of mood disorder,[2,3] but there is no literature, which mentions dissociative disorder in adolescents presenting later as depressive disorder following a prolonged follow‑up. We hereby report a case of adolescent dissociative disorder, which went to develop clinically significant major depressive disorder (MDD) over 5 years. A 13-year-old Asian, boy, from urban area of East India, with normal birth and developmental history, past history of 108
febrile convulsions till the age of 6 years, medical history of bronchial asthma and ankyloglossia, family history of single manic episode in father and dissociative convulsions in mother, presented in November 2003 to the Outpatient Department (OPD) of Centre for Child and Adolescent Psychiatry, Central Institute of Psychiatry, Ranchi, India with reduced interest in studies, episodes of sudden unarousable “sleep,” lasting as long as 14–16 h and sudden awakening for 2 weeks. Simultaneously, there are periods of unresponsiveness for 16–18 h starting and ending abruptly with no response to noxious stimuli and complete amnesia. An initial impression of hypersomnia unspecified with a possibility of dissociative disorder was made, and he was admitted for investigation and management. He was responsive to behavioral management comprising of the problem behavior extinction and differential reinforcement Indian Journal of Psychiatry 57(1), Jan-Mar 2015
Copyright of Indian Journal of Psychiatry is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Bipolar affective disorder in Huntington’s disease: A neuropsychiatric perspective Sir, Huntington’s disease (HD) is inherited autosomal dominant neurodegenerative disorder that results from an unstable expansion of trinucleotide repeat cytosine‑adenine‑guanine (CAG) of the huntingtin gene IT‑15 on chromosome 4p16.3. It is characterized by movement disorders (usually chorea), cognitive impairment (resulting in dementia) and psychiatric disorders. Symptoms typically begin in the fourth decade of life and result in progressive deterioration in functional capacity and independence. The association of mood disorder appears confined in certain families, suggesting genetic heterogeneity within HD.[1,2] Psychiatric changes are often present before the development of chorea or intellectual impairment. In our case, the patient had a positive family history of HD in three successive generations. Here, we report a case of 17‑year‑old male patient who presented to neurology out‑patient department (OPD) with complaints of increased blinking of eyes for 8 months and continuous jerky involuntary movements of left foot for 1 month. Genetic analysis showed CAG repeat expansion – 60 units and thus patient was diagnosed to be suffering from HD. Patient was referred to psychiatry OPD for his behavioral complaints and was subsequently admitted to our psychiatric ward. The members of patient’s family complained that for the last 3 months he was having irritable behavior, frequent fights, remained restless, abstained frequently from school, reduced sleep and gradually started boasting about self, talking more than usual, his speech was loud, interjected with rhyming and punning and sometimes complained that other people make gestures and pass comments on him,
though he denied hearing any voices. One year prior to the current hospitalization, patient complained of sadness of mood, loss of energy, loss of appetite and sleep and had these symptoms lasted for 6 months, but did not consult any specialist and these were resolved gradually. There is a strong family history of HD comprising 11 cases in three successive generations [Figure 1]. Of these 11 cases of HD in the family, five cases had comorbid bipolar affective disorder with one of them committing suicide. Patient was diagnosed as having HD with bipolar affective disorder currently episode manic with psychosis (F31.2). On Young Mania Rating Scale (YMRS), baseline score was 32 and Clinical Global Impression (CGI‑severity score) was 6. Treatment was started with divalproate 1500 mg/day as a mood stabilizer, haloperidol (10 mg/day) for psychotic symptoms and lorazepam 4 mg/day for inducing sleep. After 4 weeks, there was a satisfactory response (with 50% reduction) in psychiatric symptoms as assessed on YMRS scale score of 17 and CGI‑ global improvement score of 2. In addition to pharmacotherapy, patient also received individual supportive psychotherapy. After 4 weeks of treatment, there was improvement in patient’s condition, his mood stabilized, and he was no longer delusional. He was discharged and now remains in outdoor patient treatment with a long‑term follow‑up plan for medical care, psychological, genetic, family counseling and emerging benefit of striatal fetal neurotransplantation. In our 17‑year‑old patient, psychiatric changes have appeared before the usual onset of disease. Patient had strong positive family history of HD and on genetic analysis test; there was a higher number (60) of CAG repeats suggestive
Figure 1: Pedigree chart of Huntington’s disease with bipolar affective disorder Indian Journal of Psychiatry 57(1), Jan-Mar 2015
107
Letters to Editor
of earlier onset of disease. The age of onset inversely correlated with the size of the triplet repeat expansion.[3] The progression of HD is inexorable and usually leads to death within 15 to 20 years of presentation in patients who eventually become immobile and severely demented.[4] However, in future treatment with transplantation of fetal neuronal material to replace the degenerated neurons and cell engineered to secrete neurotrophic factors in HD are emerging to ameliorate the condition but replication of results in human needs further research.[5] The affective disorders may be present 20 years prior to the onset of chorea and dementia in HD. The prevalence of Major affective disorder is found in 41% of patients with HD, 32% being depressive and 9% bipolar.[2] Findings show that the frequency of suicidal ideation doubled from 9.1% in at‑risk persons with a normal neurological examination to 19.8% in at‑risk persons with soft neurological signs and increased to 23.5% in persons with “possible HD.” In persons with a diagnosis of HD, 16.7–21.6% had suicidal ideation,[6] 5.7% of deaths among affected persons resulted from suicide and 27.6% of patients attempted suicide at least once.[7] This case shows that patients of HD can present with symptoms of either depression or mania which can further increase the risk of suicide in these patients. Psychosis is not uncommon in bipolar disorder and in case of HD with chorea, the treatment with haloperidol to ameliorate choreiform movement is dependent on the serum haloperidol concentration.[8] Hence cases such as ours emphasize the need for the psychiatrists to be aware of the psychological symptoms and the suicidal risk associated in patients presenting with organic brain disease.
Rajnish Raj, Balwant Singh Sidhu, Eish Dalla
Department of Psychiatry, GMC and Rajindra Hospital, Patiala, Punjab, India. E‑mail: [email protected] REFERENCES 1. 2. 3. 4.
5. 6. 7. 8.
Paulsen JS, Ready RE, Hamilton JM, Mega MS, Cummings JL. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry 2001;71:310‑4. Folstein S, Abbott MH, Chase GA, Jensen BA, Folstein MF. The association of affective disorder with Huntington’s disease in a case series and in families. Psychol Med 1983;13:537‑42. Rosenblatt A. Neuropsychiatry of Huntington’s disease. Dialogues Clin Neurosci 2007;9:191‑7. Lovestone S. Alzheimer’s disease and other dementias (including Pseudodementias). In: David AS, Fleminger S, Kopelman MD, Lovestone S, Mellers JD, editors. Lishman’s Organic Psychiatry: A Textbook of Neuropsychiatry. 4th ed. London: Wiley Blackwell Publishing; 2009. p. 576‑84. Freeman TB, Sanberg PR, Isacson O. Development of the human striatum: Implications for fetal striatal transplantation in the treatment of Huntington’s disease. Cell Transplant 1995;4:539‑45. Paulsen JS, Hoth KF, Nehl C, Stierman L. Critical periods of suicide risk in Huntington’s disease. Am J Psychiatry 2005;162:725‑31. Farrer LA. Suicide and attempted suicide in Huntington disease: Implications for preclinical testing of persons at risk. Am J Med Genet 1986;24:305‑11. Barr AN, Fischer JH, Koller WC, Spunt AL, Singhal A. Serum haloperidol concentration and choreiform movements in Huntington’s disease. Neurology 1988;38:84‑8. Access this article online Quick Response Code
Website: www.indianjpsychiatry.org
DOI: 10.4103/0019-5545.148546
Childhood dissociation as a precursor of mood disorder: A 5 years follow-up case study Sir, Dissociative symptoms are seen in patients with psychiatric problems and exist in a continuum from common normal phenomena like daydreaming and attention lapses through to pathological failure to integrate feelings, thoughts and action.[1] Dissociative symptoms have been well described as part of mood disorder,[2,3] but there is no literature, which mentions dissociative disorder in adolescents presenting later as depressive disorder following a prolonged follow‑up. We hereby report a case of adolescent dissociative disorder, which went to develop clinically significant major depressive disorder (MDD) over 5 years. A 13-year-old Asian, boy, from urban area of East India, with normal birth and developmental history, past history of 108
febrile convulsions till the age of 6 years, medical history of bronchial asthma and ankyloglossia, family history of single manic episode in father and dissociative convulsions in mother, presented in November 2003 to the Outpatient Department (OPD) of Centre for Child and Adolescent Psychiatry, Central Institute of Psychiatry, Ranchi, India with reduced interest in studies, episodes of sudden unarousable “sleep,” lasting as long as 14–16 h and sudden awakening for 2 weeks. Simultaneously, there are periods of unresponsiveness for 16–18 h starting and ending abruptly with no response to noxious stimuli and complete amnesia. An initial impression of hypersomnia unspecified with a possibility of dissociative disorder was made, and he was admitted for investigation and management. He was responsive to behavioral management comprising of the problem behavior extinction and differential reinforcement Indian Journal of Psychiatry 57(1), Jan-Mar 2015
Copyright of Indian Journal of Psychiatry is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
