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Fluoxetine-responsive depression in a Chinese cerebrotendinous xanthomatosis
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General Hospital Psychiatry 34 (2012) 578.e1 – 578.e4
Case Report
Fluoxetine-responsive depression in a Chinese cerebrotendinous xanthomatosis Qiaozhen Chen, M.D. a , Weibo Liu, M.D. a,⁎, Biao Jiang, M.D. b , Risheng Yu, M.D. b , Xiuzhen Li, M.S. c , Huichun Li, M.S. a a
Department of Psychiatry, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China c Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China Received 15 September 2011; accepted 18 October 2011
b
Abstract Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive, lipid storage disorder which is extremely rare in the Chinese population. It is characterized by progressive neurologic dysfunction and enlargement of tendon xanthomas, and is often accompanied with neuropsychiatric symptoms. Few reports are available regarding depression and antidepressant medication in CTX patients. Here, we report a Chinese case of CTX associated with fluoxetine-responsive major depression. © 2012 Elsevier Inc. All rights reserved. Keywords: Cerebrotendinous xanthomatosis; Major depression; Chinese; Fluoxetine
1. Introduction
2. Case report
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive, lipid storage disease. Patients often exhibit progressive tendon xanthomas, juvenile cataract and neuropsychiatric symptoms due to the accumulation of cholestanol in the tissue of the Achilles tendon and central nervous system [1,2]. Some CTX cases have been described with psychotic symptoms, whereas depression is less reported [1,3,4]. Treatment with chenodeoxycholic acid (CDCA) alone or in combination with 3-hydroxy-methyglutaryl coenzyme A reductase inhibitors has been reported to halt and even reverse disease progression [3,5]. However, few reports have covered antidepressant medication in CTX patients. Here, a brief report on a Chinese case of CTX and major depression was presented to show the effectiveness of therapeutic approach with fluoxetine.
A 39-year-old, married, Han-nationality man was admitted to our inpatient psychiatric service with hopelessness and despondency. History was obtained from the patient and his relatives with reliability. The patient was diagnosed as having CTX by pathological examination and genetic analysis 8 months ago. Surgical excision and reconstruction of right Achilles tendon xanthomatosis were performed by the transfer of the tibialis posterior tendon, while he received ursodeoxycholic acid (UDCA) medication. Since he cannot go on with his work, he had been depressed and worried about losing his job for more than 2 months. He had poor sleep and little appetite with a severe body weight loss, He lost his interest and stopped caring for his personal hygiene and once seriously thought about committing suicide by taking sleeping pills. According to his mother, he displayed normal development until 15 years of age when he began to show learning difficulties. He had worked in a post office for 10 years after graduating from middle school. He was introverted and showed poor sociality ability. At age 37 years, he started to
⁎ Corresponding author. Tel.: +86 571 87784757; fax: +86 571 87784757. E-mail address: [email protected] (W. Liu). 0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2011.10.008
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Q. Chen et al. / General Hospital Psychiatry 34 (2012) 578.e1–578.e4
have progressive gait instability and enlargement of the Achilles tendons. He had no seizures, no manic episode, no psychotic feature and no other remarkable medical history. There is no family history of the same disorder and neuropsychiatric illness. The neurological examination showed bilaterally increased deep tendon reflexes and positive Babinski reflexes. He walked with a shuffling wide-based gait but showed normal motor strength of extremities. He had no cerebellar ataxia, no peripheral neuropathy and no cataracts, but had high myopia. The mental status examination revealed depressed mood, loss of interest and decreased energy. He was especially concerned about losing his job and was very pessimistic about his future, often using such expressions as “my life is ruined” and “no work is more painful than killing me.” He admitted having recurrent suicidal ideation but denied hallucinations and delusional ideas.
Electroencephalogram analysis result was moderately abnormal with the enhancement of theta activity and short runs of irregular delta waves of 2–3 Hz. An abdominal ultrasound revealed cholecystic polypus. His blood test results — including cholesterol and triglycerides levels, and liver, kidney and thyroid function — were all in normal range. Results of X-rays of chest, bone mineral density, electrocardiogram and echocardiogram were also normal. Psychological testing revealed gross deterioration in his intellectual abilities with Wechsler Adult Intelligence ScaleChinese Revision IQ score of 58. Magnetic resonance imaging (MRI) of the brain revealed bilaterally symmetrical hyperintensities in the dentate nucleus of cerebellar hemisphere, posterior limb of the internal capsule and brain stem, but no restriction on diffusion-weighted imaging, no spaceoccupying effect and no shift of cerebral midline (Fig. 1). MRI of the left ankle showed fusiform thickening and heterogeneous signals in the Achilles tendon (Fig. 2).
Fig. 1. Brain MRI: axial T2-weighted image (A) and Fluid Attenuated Inversion Recovery-weighted image (B) show high signal intensity symmetrically in the posterior limb of the internal capsule. Axial T2-weighted image (C) shows high signal intensity symmetrically in the dentate nucleus of cerebellar hemisphere. Midsagittal T2-weighted image (D) shows hyperintense signals in cerebellar hemisphere and mild cerebellar atrophy.
Q. Chen et al. / General Hospital Psychiatry 34 (2012) 578.e1–578.e4
57.e3
Fig. 2. Ankle MRI: axial T1-weighted image (A) and T2-weighted image (B) show long T1 and short T2 signals in the Achilles tendon, anterior and posterior tibial tendon, peroneus brevis tendon and peroneus longus tendon. T2-heterogeneous hyperintense foci are present. Sagittal Proton Density-weighted image (C) show fusiform thickening of the Achilles tendon.
Based on these findings, the patient was diagnosed as having major depression. He was prescribed fluoxetine 20 mg daily to relieve depression in conjunction with supportive individual psychotherapy. Because CDCA is not easily available in drugstores in China, he remained on UDCA. Patient's mood improved gradually after 2 weeks of treatment, and the 17-item Hamilton Rating Scale for Depression score decreased from 22 to 10. He continued fluoxetine 20 mg daily, and his condition remained stable in the following 6 months. No recurrence of major depression or worsen of physical symptoms ever observed. 3. Discussion CTX is considered to be rare, with incidence estimated to be 3 to 5 per 100,000 people worldwide [6], and is extremely rare in the Chinese population [7]. Our case was diagnosed as coexistence of CTX and major depression. To our knowledge, the neurological impairment mainly results from the diffuse replacement of cholesterol by cholestanol in the myelin of the nervous systems; thus, the psychiatric disorder may be related to CTX [3]. However concerned with the manifestations of the patient, we think that his depression may be triggered by two reasons: the neuropathology of CTX and the adjustment problems associated with CTX. Oral CDCA has been reported to be beneficial in some CTX patients who showed a correction of biochemical abnormalities and a reversal of neurological symptoms, and CDCA holds an advantage over UDCA [6,8]. Fortunately, the patient condition was not exacerbated in the 6-month follow-up with the UDCA medication. CDCA can also improve neuropsychiatric symptoms [3,9], and its combination with antipsychotic medication may provide benefits to psychiatric symptoms [2]. However, very few reports are available regarding antidepressant medication. Shapiro [3] reported a CTX case with psychotic depression and dementia, which were moderately improved after 2 months
with haloperidol and doxepin. Lee et al. [4] presented a CTX case with dysthymic disorder, which was improved with trazodone and psychotherapy. Fluoxetine is the first selective serotonin reuptake inhibitor antidepressant which has replaced tricyclic antidepressants in treating major depression. In our case, concerned with severe depressive symptoms, we chose fluoxetine combined with supportive psychotherapy to treat mood disturbance. During 6 months of follow-up, fluoxetine had shown definite efficacy in treating major depression comorbid with CTX. The association of major depression with a primary neurological illness is a common clinical phenomenon, and poor coping strategies to stress may be predisposing factors of depression. We should be alert to depression associated with CTX and emphasize early detection and intervention of depression for better outcome. Our case shows that, besides UDCA being an acceptable therapy to treat CTX, fluoxetine is an effective drug to treat major depression related to CTX. References [1] Moghadasian MH. Cerebrotendinous xanthomatosis: clinical course, genotypes and metabolic backgrounds. Clin Invest Med 2004;27(1): 42–50. [2] Berginer VM, Foster NL, Sadowsky M, et al. Psychiatric disorders in patients with cerebrotendinous xanthomatosis. Am J Psychiatry 1988;145(3):354–7. [3] Shapiro S. Depression in a patient with dementia secondary to cerebrotendinous xanthomatosis. J Nerv Ment Dis 1983;171(9):568–71. [4] Lee Y, Lin PY, Chiu NM, et al. Cerebrotendinous xanthomatosis with psychiatric disorders: report of three siblings and literature review. Chang Gung Med J 2002;25(5):334–40. [5] Berginer VM, Salen G, Shefer S. Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid. N Engl J Med 1984;311(26):1649–52. [6] Lorincz MT, Rainier S, Thomas D, et al. Cerebrotendinous xanthomatosis: possible higher prevalence than previously recognized. Arch Neurol 2005;62(9):1459–63. [7] Ko KF, Lee KW. Cerebrotendinous xanthomatosis in three siblings from a Chinese family. Singapore Med J 2001;42(1):30–2.
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Q. Chen et al. / General Hospital Psychiatry 34 (2012) 578.e1–578.e4
[8] Koopman BJ, Wolthers BG, van der Molen JC, et al. Capillary gas chromatographic determinations of urinary bile acids and bile alcohols in CTX patients proving the ineffectivity of ursodeoxycholic acid treatment. Clin Chim Acta 1984;142(1):103–11.
[9] Bonnot O, Fraidakis MJ, Lucanto R, et al. Cerebrotendinous xanthomatosis presenting with severe externalized disorder: improvement after one year of treatment with chenodeoxycholic Acid. CNS Spectr 2010;15(4):231–6.
General Hospital Psychiatry 34 (2012) 578.e1 – 578.e4
Case Report
Fluoxetine-responsive depression in a Chinese cerebrotendinous xanthomatosis Qiaozhen Chen, M.D. a , Weibo Liu, M.D. a,⁎, Biao Jiang, M.D. b , Risheng Yu, M.D. b , Xiuzhen Li, M.S. c , Huichun Li, M.S. a a
Department of Psychiatry, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China c Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China Received 15 September 2011; accepted 18 October 2011
b
Abstract Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive, lipid storage disorder which is extremely rare in the Chinese population. It is characterized by progressive neurologic dysfunction and enlargement of tendon xanthomas, and is often accompanied with neuropsychiatric symptoms. Few reports are available regarding depression and antidepressant medication in CTX patients. Here, we report a Chinese case of CTX associated with fluoxetine-responsive major depression. © 2012 Elsevier Inc. All rights reserved. Keywords: Cerebrotendinous xanthomatosis; Major depression; Chinese; Fluoxetine
1. Introduction
2. Case report
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive, lipid storage disease. Patients often exhibit progressive tendon xanthomas, juvenile cataract and neuropsychiatric symptoms due to the accumulation of cholestanol in the tissue of the Achilles tendon and central nervous system [1,2]. Some CTX cases have been described with psychotic symptoms, whereas depression is less reported [1,3,4]. Treatment with chenodeoxycholic acid (CDCA) alone or in combination with 3-hydroxy-methyglutaryl coenzyme A reductase inhibitors has been reported to halt and even reverse disease progression [3,5]. However, few reports have covered antidepressant medication in CTX patients. Here, a brief report on a Chinese case of CTX and major depression was presented to show the effectiveness of therapeutic approach with fluoxetine.
A 39-year-old, married, Han-nationality man was admitted to our inpatient psychiatric service with hopelessness and despondency. History was obtained from the patient and his relatives with reliability. The patient was diagnosed as having CTX by pathological examination and genetic analysis 8 months ago. Surgical excision and reconstruction of right Achilles tendon xanthomatosis were performed by the transfer of the tibialis posterior tendon, while he received ursodeoxycholic acid (UDCA) medication. Since he cannot go on with his work, he had been depressed and worried about losing his job for more than 2 months. He had poor sleep and little appetite with a severe body weight loss, He lost his interest and stopped caring for his personal hygiene and once seriously thought about committing suicide by taking sleeping pills. According to his mother, he displayed normal development until 15 years of age when he began to show learning difficulties. He had worked in a post office for 10 years after graduating from middle school. He was introverted and showed poor sociality ability. At age 37 years, he started to
⁎ Corresponding author. Tel.: +86 571 87784757; fax: +86 571 87784757. E-mail address: [email protected] (W. Liu). 0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.genhosppsych.2011.10.008
578.e2
Q. Chen et al. / General Hospital Psychiatry 34 (2012) 578.e1–578.e4
have progressive gait instability and enlargement of the Achilles tendons. He had no seizures, no manic episode, no psychotic feature and no other remarkable medical history. There is no family history of the same disorder and neuropsychiatric illness. The neurological examination showed bilaterally increased deep tendon reflexes and positive Babinski reflexes. He walked with a shuffling wide-based gait but showed normal motor strength of extremities. He had no cerebellar ataxia, no peripheral neuropathy and no cataracts, but had high myopia. The mental status examination revealed depressed mood, loss of interest and decreased energy. He was especially concerned about losing his job and was very pessimistic about his future, often using such expressions as “my life is ruined” and “no work is more painful than killing me.” He admitted having recurrent suicidal ideation but denied hallucinations and delusional ideas.
Electroencephalogram analysis result was moderately abnormal with the enhancement of theta activity and short runs of irregular delta waves of 2–3 Hz. An abdominal ultrasound revealed cholecystic polypus. His blood test results — including cholesterol and triglycerides levels, and liver, kidney and thyroid function — were all in normal range. Results of X-rays of chest, bone mineral density, electrocardiogram and echocardiogram were also normal. Psychological testing revealed gross deterioration in his intellectual abilities with Wechsler Adult Intelligence ScaleChinese Revision IQ score of 58. Magnetic resonance imaging (MRI) of the brain revealed bilaterally symmetrical hyperintensities in the dentate nucleus of cerebellar hemisphere, posterior limb of the internal capsule and brain stem, but no restriction on diffusion-weighted imaging, no spaceoccupying effect and no shift of cerebral midline (Fig. 1). MRI of the left ankle showed fusiform thickening and heterogeneous signals in the Achilles tendon (Fig. 2).
Fig. 1. Brain MRI: axial T2-weighted image (A) and Fluid Attenuated Inversion Recovery-weighted image (B) show high signal intensity symmetrically in the posterior limb of the internal capsule. Axial T2-weighted image (C) shows high signal intensity symmetrically in the dentate nucleus of cerebellar hemisphere. Midsagittal T2-weighted image (D) shows hyperintense signals in cerebellar hemisphere and mild cerebellar atrophy.
Q. Chen et al. / General Hospital Psychiatry 34 (2012) 578.e1–578.e4
57.e3
Fig. 2. Ankle MRI: axial T1-weighted image (A) and T2-weighted image (B) show long T1 and short T2 signals in the Achilles tendon, anterior and posterior tibial tendon, peroneus brevis tendon and peroneus longus tendon. T2-heterogeneous hyperintense foci are present. Sagittal Proton Density-weighted image (C) show fusiform thickening of the Achilles tendon.
Based on these findings, the patient was diagnosed as having major depression. He was prescribed fluoxetine 20 mg daily to relieve depression in conjunction with supportive individual psychotherapy. Because CDCA is not easily available in drugstores in China, he remained on UDCA. Patient's mood improved gradually after 2 weeks of treatment, and the 17-item Hamilton Rating Scale for Depression score decreased from 22 to 10. He continued fluoxetine 20 mg daily, and his condition remained stable in the following 6 months. No recurrence of major depression or worsen of physical symptoms ever observed. 3. Discussion CTX is considered to be rare, with incidence estimated to be 3 to 5 per 100,000 people worldwide [6], and is extremely rare in the Chinese population [7]. Our case was diagnosed as coexistence of CTX and major depression. To our knowledge, the neurological impairment mainly results from the diffuse replacement of cholesterol by cholestanol in the myelin of the nervous systems; thus, the psychiatric disorder may be related to CTX [3]. However concerned with the manifestations of the patient, we think that his depression may be triggered by two reasons: the neuropathology of CTX and the adjustment problems associated with CTX. Oral CDCA has been reported to be beneficial in some CTX patients who showed a correction of biochemical abnormalities and a reversal of neurological symptoms, and CDCA holds an advantage over UDCA [6,8]. Fortunately, the patient condition was not exacerbated in the 6-month follow-up with the UDCA medication. CDCA can also improve neuropsychiatric symptoms [3,9], and its combination with antipsychotic medication may provide benefits to psychiatric symptoms [2]. However, very few reports are available regarding antidepressant medication. Shapiro [3] reported a CTX case with psychotic depression and dementia, which were moderately improved after 2 months
with haloperidol and doxepin. Lee et al. [4] presented a CTX case with dysthymic disorder, which was improved with trazodone and psychotherapy. Fluoxetine is the first selective serotonin reuptake inhibitor antidepressant which has replaced tricyclic antidepressants in treating major depression. In our case, concerned with severe depressive symptoms, we chose fluoxetine combined with supportive psychotherapy to treat mood disturbance. During 6 months of follow-up, fluoxetine had shown definite efficacy in treating major depression comorbid with CTX. The association of major depression with a primary neurological illness is a common clinical phenomenon, and poor coping strategies to stress may be predisposing factors of depression. We should be alert to depression associated with CTX and emphasize early detection and intervention of depression for better outcome. Our case shows that, besides UDCA being an acceptable therapy to treat CTX, fluoxetine is an effective drug to treat major depression related to CTX. References [1] Moghadasian MH. Cerebrotendinous xanthomatosis: clinical course, genotypes and metabolic backgrounds. Clin Invest Med 2004;27(1): 42–50. [2] Berginer VM, Foster NL, Sadowsky M, et al. Psychiatric disorders in patients with cerebrotendinous xanthomatosis. Am J Psychiatry 1988;145(3):354–7. [3] Shapiro S. Depression in a patient with dementia secondary to cerebrotendinous xanthomatosis. J Nerv Ment Dis 1983;171(9):568–71. [4] Lee Y, Lin PY, Chiu NM, et al. Cerebrotendinous xanthomatosis with psychiatric disorders: report of three siblings and literature review. Chang Gung Med J 2002;25(5):334–40. [5] Berginer VM, Salen G, Shefer S. Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid. N Engl J Med 1984;311(26):1649–52. [6] Lorincz MT, Rainier S, Thomas D, et al. Cerebrotendinous xanthomatosis: possible higher prevalence than previously recognized. Arch Neurol 2005;62(9):1459–63. [7] Ko KF, Lee KW. Cerebrotendinous xanthomatosis in three siblings from a Chinese family. Singapore Med J 2001;42(1):30–2.
578.e4
Q. Chen et al. / General Hospital Psychiatry 34 (2012) 578.e1–578.e4
[8] Koopman BJ, Wolthers BG, van der Molen JC, et al. Capillary gas chromatographic determinations of urinary bile acids and bile alcohols in CTX patients proving the ineffectivity of ursodeoxycholic acid treatment. Clin Chim Acta 1984;142(1):103–11.
[9] Bonnot O, Fraidakis MJ, Lucanto R, et al. Cerebrotendinous xanthomatosis presenting with severe externalized disorder: improvement after one year of treatment with chenodeoxycholic Acid. CNS Spectr 2010;15(4):231–6.