The Neuropsychiatry and Neuropsychology Of

The Neuropsychiatry and Neuropsychology Of Lipoid Proteinosis Helena B. Thornton, Ph.D. Daan Nel, Ph.D. Dorothy Thornton, Ph.D. Jack van Honk, Ph.D. Gus A. Baker, Ph.D. Dan J. Stein, M.D., Ph.D.

Lipoid proteinosis is a rare hereditary disease which often results in bilateral calcifications in the medial temporal region. Thirty-four adults living with lipoid proteinosis (⬎10% of the world population) were extensively assessed with standardized neuropsychiatric and neuropsychological measures. Of these, 27 patients representing a homogenous group living in the Northern Cape were matched with 47 controls. Subjects with lipoid proteinosis had a high incidence of neuropsychiatric disorders and performed poorly on facial recognition of positive and negative emotions and on many neuropsychological measures. These findings are consistent with involvement of the medial temporal areas in cognitive and emotive processing. (The Journal of Neuropsychiatry and Clinical Neurosciences 2008; 20:86–92)

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ipoid proteinosis, also known as Hyalinosis cutis et mucosae or Urbach-Wiethe Disease, is a rare hereditary disorder transmitted by an autosomal recessive gene.1–2 From the time Urbach and Wiethe3 gave the first clear description of the disease, a cumulative total of 2501 to 300 cases4–6 have been reported in the literature. The disorder is a systemic illness characterized by depositions of storage material in the mucous membranes.4,7–11 The most classic symptoms are hoarseness of speech, often from birth or infancy,7,12 and skin lesions.12–14 There is considerable clinical variability among lipoid proteinosis subjects2 and lesions may increase in severity and extent with age.15 The most consistent clinical features for a diagnosis have been a hoarse voice and a thickened sublingual frenulum leading to restricted tongue movement.2 Bilateral, circumscribed, and symmetrical calcification in the medial temporal regions are common4,9,16–17 and are associated with neuropsychiatric sequelea including seizure disorder9,16,18 and psychotic symptoms.6,19–20

Received October 8, 2005; revised January 12, 2007; accepted January 18, 2007. Drs. Thornton and Stein are affiliated with the Departments of Psychiatry, University of Stellenbosch and University of Cape Town, South Africa. Dr. Nel is affiliated with the Centre for Statistical Consultation, University of Stellenbosch, South Africa. Dr.Thornton is affiliated with the School of Public Health, University of California, Berkeley, California. Dr. van Honk is affiliated with the Helm Holtz Institute, Utrecht University, The Netherlands. Dr. Baker is affiliated with the Division of Neurosciences, University of Liverpool, United Kingdom. Address correspondence to Dr. Thornton, Department of Psychiatry, University of Cape Town, Private Bag X1, Observatory 7925, Cape Town, South Africa; [email protected] (e-mail). Copyright 䉷 2008 American Psychiatric Publishing, Inc.

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J Neuropsychiatry Clin Neurosci 20:1, Winter 2008

THORNTON et al. Medial temporal regions encompass the amygdala and studies on patients with lipoid proteinosis contributed to our understanding of the role of the amygdala in fear processing and social cognition.17,21–26 The lipoid proteinosis subjects of Adolphs et al.21 and Calder and Young27 showed significant impairment in recognizing fearful expressions, although individual performances ranged from severely impaired to essentially normal. In addition, while most subjects were impaired in recognizing other negative expressions in addition to fear, they were not impaired in recognizing happy expressions. Lipoid proteinosis has been associated with difficulty in coping with emotionally loaded memory28,29 and impaired executive control over social behavior.17 There has, however, been significant variability in neuropsychiatric and neuropsychological findings across studies. In some studies there has been no evidence of psychiatric symptomatology.30–32 Siebert et al.28 studied 10 people with lipoid proteinosis, six with bilateral calcification of the amygdaloid complex, and did not find that lipoid proteinosis necessarily impaired the recognition of basic emotions such as fear and anger. Lipoid proteinosis has been associated with both intact intelligence9,17,20,30,33 and mental retardation.14,16,34–36 While there is true heterogeneity within the lipoid proteinosis population,2 which may represent a variable and slowly progressive degenerative process in the brain,28 some of the variation across the studies may be explicable on the basis of relatively small sample sizes and other methodological problems (e.g., different methods of assessing symptomatology). The current study is, to our knowledge, the largest systematic study of psychiatric diagnosis and neuropsychological measures in lipoid proteinosis. In view of evidence of amygdala pathology and prior findings of associated neuropsychiatric impairment, we hypothesized that this population would be characterized by increased rates of mood and anxiety disorders and impairments in processing emotional expressions.

METHOD Thirty-four adult South African subjects with lipoid proteinosis (ages 17–63 years) participated in this study. Two were patients attending a large state hospital in Cape Town, five were from the greater Johannesburg, South Africa/Pretoria area, and 27 lived in the impoverished and rural Northern Cape. Forty-seven controls


from the Northern Cape (matched for home language, socioeconomic status, age, and matched as closely as possible for years of education and gender) completed the same batteries. Ethics approval was obtained from the University of Stellenbosch, Tygerberg Hospital, and abided by the Helsinki, Finland, declaration guidelines of “good clinical practice.” All subjects gave informed consent. Six participants (two with lipoid proteinosis and four matched controls) were 17 years old and they and their guardians gave consent. Three children with lipoid proteinosis under 16 years were excluded from this study. The diagnosis of lipoid proteinosis was established through genetic and clinical means. Subjects were examined by use of standardized neuropsychiatric and neuropsychological measures. The battery was designed to assess neuropsychiatric symptoms and neuropsychological dysfunction previously reported in the literature in association with lipoid proteinosis (e.g., psychosis, depression, problems with emotional recognition, and memory and executive functioning). Tests were not administered if the subjects were unable to complete them validly (e.g., due to psychosis or illiteracy). Subjects were assessed in their home language on the following neuropsychiatric measures: Mini International Neuropsychiatric Interview (MINIⳭ),37 Positive and Negative Syndrome Scale (PANSS),38 and Montgomery-Asberg Depression Rating Scale (MADRS).39 They were assessed on neuropsychological measures including the Wechsler Abbreviated Scale of Intelligence (WASI) except for the vocabulary subtest.40 This was substituted with the vocabulary subtest from the WAIS-III scaled score, using the Human Sciences Research Council of South Africa’s Afrikaans translation and adaptations for South Africa.41 Two people with lipoid proteinosis had already completed the South African Wechsler Intelligence Scale-Revised (SAWAIS-R) and did not do the WASI.42 Subjects were also assessed with the Benton Facial Recognition (short form)43 and the Ekman Facial Emotional Recognition.44 This test consists of 110 photographs of people displaying either a neutral expression or one of six emotions (happiness, sadness, fear, anger, surprise, or disgust). Subjects must try and match one of the seven options to the expression they see. In addition, subjects were assessed with the Controlled Oral Word Association Test (COWAT); the Rey Auditory Verbal Learning Task (RAVLT); subtests from the Wechsler Memory Scale—Revised,45 including Logical Memory,


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THE NEUROPSYCHIATRY OF LIPOID PROTEINOSIS TABLE 1.

Vignettes

1 DC was a left-handed 52-year-old single woman from a small village in the Northern Cape. She was a single teen mother (her daughter is now 33) and later married, but divorced later due to domestic violence. At the time of the interview she was raising her ten-year-old granddaughter. Her mother, older sister, and brother had lipoid proteinosis; her mother and sister were deceased. She passed Std 1 (Grade 3) and had been unemployed her whole life. She had epilepsy but was unsure when the seizures began. She complained of anxiety and suffered from depression (she once tried to hang herself and had received ECT) and hypomania. She met the MINIⴐ criteria for bipolar affective disorder (BPAD) and generalized anxiety disorder (GAD). Although DC had panic attacks, she did not meet the MINIⴐ criteria for a panic disorder. 2 AF was a right-handed 35-year-old married man and the father of a toddler. He lived in the greater Johannesburg area. He had no family history of lipoid proteinosis. After completing high school, he went to college where he completed a four-year professional qualification and has been in full-time employ for the last 11 years. He had febrile convulsions and was diagnosed with “temporal lobe” epilepsy at the age of 24. He had about fifty seizures a year but was not on any anti-epileptic medication. He denied any psychiatric or substance abuse history. He was self-conscious at times of having lipoid proteinosis (his skin looked as if it was burned and people put the phone down on him because he “whispered”) and did not like to meet new people, but did not meet the criteria for a social phobia.

translated into Afrikaans with the names changed to local geographical settings (e.g., Okiep instead of Boston); Complex Figure of Rey (Copy and Immediate Incidental Recall); draw a clock; Hooper Visual Organization Task; Trail Making Tests A and B; and the Ruff Figural Fluency Test. Statistical Analysis As exemplified in the Table 1 vignettes, the Northern Cape subjects differed significantly from the non-Northern Cape lipoid proteinosis patients on a number of demographic parameters (i.e., years of education, level of employment). Thus non- Northern Cape lipoid proteinosis subjects were excluded from further neuropsychiatric and neuropsychological analyses. Data from Northern Cape lipoid proteinosis subjects and controls were compared with analysis of variance (ANOVA) when normally distributed and with Mann-Whitney analyses when not normally distributed. Significance was set at p⬍0.05.

RESULTS In the Northern Cape lipoid proteinosis group (N⳱27), there were 12 males (44.4%) and 15 females (55.6%) (Table 2). The mean age was 36.89 years (SD⳱14.0), the mean education was 8.37 years (SD⳱3.2), and less than 12% were in full-time employment. The Northern Cape control group had 20 males (42.6%) and 27 females (57.4%), with a mean age of 36.51 years (SD⳱14.2) and a mean education of 8.94 years (SD⳱2.93), and 10.6% were in full-time employment. Twenty-seven percent (27%) of the Northern Cape lipoid proteinosis group reported seizures. Neuropsychiatric diagnoses were compared in lipoid proteinosis subjects from the Northern Cape (N⳱27)

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and controls (N⳱47). In the Northern Cape lipoid proteinosis group, anxiety disorders (33%), mood disorders (33%), psychosis (22%), and schizophrenia (15%) were common (Table 3), and in all cases significantly more prevalent than in the control group (p⬍0.01). Similarly, the Northern Cape lipoid proteinosis group was significantly more likely to have higher scores on the MADRS and on the negative symptoms scale of the PANSS. There was no significant difference between the groups for alcohol abuse (26% in both); 58% of lipoid proteinosis and 60% of control adult men abused alcohol (MINIⳭ). Adults with lipoid proteinosis were significantly less likely to live with partners or to have children. The mean IQ for both the Northern Cape lipoid proteinosis subjects and the Northern Cape controls (including many educationally deprived participants) was markedly poorer than established norms (Table 4). When comparing the lipoid proteinosis to the control subjects the following was evident: of the three WASI tests and Vocabulary test from the WAIS-III, only Similarities was significantly different between the two

TABLE 2.

Demographics (Matching Gender, Age, and Education) NC LiP Subjects (Nⴔ27)

Subjects Male Female Full time employ Part time employ Full or part time employ Age Education

12 15 3 2 5 Mean 36.9 8.4

44.4% 55.6% 11.1% 7.4% 18.5 SD 14.0 3.2

NC Controls (Nⴔ47) 20 27 5 4 9 Mean 36.5 8.9

42.6% 57.4% 10.6% 8.5% 19.2% SD 14.2 2.9

LiP⳱lipoid proteinosis NC⳱Northern Cape


THORNTON et al. groups (controls significantly better than lipoid proteinosis subjects). Northern Cape lipoid proteinosis subjects were significantly less likely to recognize correctly the emotional expressions—fear, anger, disgust, surprise, sadness, happiness and neutrality—than the matched Northern Cape controls (Table 5). On basic face recognition, there were no significant differences on the Benton Facial Recognition Test, unless presented with less lighting or from a different angle. In terms of neuropsychological testing, there were no significant differences across Northern Cape lipoid proteinosis subjects and controls for the two tests of language (COWAT and Vocabulary, WAIS-III). However, the Northern Cape lipoid proteinosis group scored significantly worse than controls on several tests of memory, including digits forward and backward, auditory new learning on RAVLT, retention after distraction, the recognition task, the number of repetitions in new learning, both immediate and delayed paragraph recall, as well as the percentage of the story that was retained, and delayed recall of the visual reproduction designs. There were no significant differences in either the forewarned or incidental immediate visual recall tasks (Table 4). On selected executive tasks, there were no significant differences on tests of planning (draw a clock, copy of complex figure, WASI Matrices, or block design) between the Northern Cape lipoid proteinosis group and controls, although the Northern Cape lipoid proteinosis

TABLE 3.

group did significantly worse on visual organization (Table 4). However, for tasks of design fluency, switching and dual sequencing, and abstract thinking, the control group performed significantly better. Thus, controls performed significantly better than Northern Cape lipoid proteinosis subjects on memory and specific executive abilities (design initiation, switching, visual organization, and abstract thinking), but language tasks and other executive skills (planning) appeared unaffected by lipoid proteinosis.

DISCUSSION These findings represent the largest report to date of neuropsychiatric and neuropsychological data in people with lipoid proteinosis. Compared with controls, a sample of people with lipoid proteinosis in the Northern Cape had increased rates of mood, anxiety, and psychotic disorders as well as greater symptom severity, a decreased ability to identify both positive and negative emotional expressions, and significant impairment on memory and executive (specifically design fluency, switching, and abstract thinking) functions. The findings here confirm many of the observations made in previous reports on neuropsychiatric symptoms and neuropsychological impairment in smaller groups of lipoid proteinosis subjects.21–27 A larger sample provides us with some additional in-

Neuropsychiatric Diagnosis in Northern Cape Lipoid Proteinosis and Northern Cape Controls According to the MINIⴐ

Group and Disorder Type NC LiP Subjects Psychosis (N⳱6) Anxiety (N⳱9) Mood (N⳱9) Substance (N⳱7) NC Control Subjects Anxiety (N⳱1) Mood (N⳱4) Substance (N⳱12)

Specific Diagnosis Schizophrenia (N⳱3); psychotic disorder NOS (lifetime) (N⳱1); brief psychotic disorder (lifetime) (N⳱1) Generalized anxiety disorder (N⳱2); anxiety disorder with panic attacks (N⳱1); panic disorder (N⳱1); agoraphobia (N⳱2); social phobia (N⳱6); *history of social phobia (N⳱1); specific phobia (N⳱2); hypochondriasis (N⳱1); somatization disorder (N⳱1); body dysmorphic disorder (N⳱1) Bipolar affective disorder (N⳱2); major depressive episode (recurrent) (N⳱4); major depressive episode (current) (N⳱1); major depressive episode (current, with melancholic features) (N⳱1); *history of clinical depression (N⳱1); dysthymia (N⳱1); premenstrual dysphoric disorder (N⳱3) Alcohol abuse (past 12 months) (N⳱4); alcohol abuse (lifetime) (N⳱4); alcohol dependence (lifetime) (N⳱1) Specific phobia (N⳱1) *History of clinical depression (N⳱4) Alcohol abuse (past 12 months) (N⳱5); alcohol abuse (lifetime) (N⳱1); alcohol dependence (past 12 months) (N⳱4); alcohol dependence (lifetime) (N⳱7); substance dependence (lifetime) (N⳱4)

* denotes MINIⳭ criteria that have been met for the disorder, but were not present in the last twelve months. One NC LiP subject had schizophrenia and was always too psychotic to be assessed on the MINIⳭ (unable to give informed consent and refused to be interviewed). Diagnosis was met via interviews with family and clinic folder notes. One control who did not complete the MINIⳭ, due to intoxication, probably met the criteria for alcohol abuse or alcohol dependence. Specific diagnosis may add up to more than total group N because of comorbidity.



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THE NEUROPSYCHIATRY OF LIPOID PROTEINOSIS formation; for example, we were able to demonstrate that there is impairment not only in processing of negative emotions, but also in processing of positive emotions in lipoid proteinosis. It can be hypothesized that such deficits have a significant impact on functioning in TABLE 4.

Northern Cape Neuropsychology Tests: LiP versus Controls

Neuropsychology Tests

LiP (Nⴔ22–26) Mean SD

Intelligence VIQ PIQ FSIQ Memory RAVLT I RAVLT V RAVLT VI (Recall after Interference) RAVLT VII (Delayed Recall) RAVLT B (Interference trial) RAVLT total (Trials I to V) RAVLT V-VI RAVLT V-VII RAVLT V-I RAVLT VI/V % retention RAVLT VII/V % retention RAVLT VII/VI % retention RAVLT Recognition True Positives (TP) RAVLT Recognition False Positives (FP) RAVLT Adjusted Recognition (TP-FP) RAVLT Errors (Trials I to V) RAVLT Repetitions (Trials I to V) LMI WMS-R LMII WMS-R LMII/LMI % retention VRI WMS-R VRII WMS-R VRII/VRI WMS-R % retention Executive HVOT RCF Copy (/36) Matrices, WASI Block Design, WASI RFFT 1 Unique designs TMTA (seconds) TMTB (seconds) TMTA-B (seconds) Similarities, WASI

TABLE 5.

lipoid proteinosis. Nevertheless, we noted that the people with lipoid proteinosis were able to interact appropriately with us, possibly suggesting the presence of compensatory mechanisms.28 However, the negative impact of impaired cognitive and affective processing

Controls (Nⴔ31–46) Mean SD

p

76.81 76.23 74.38

9.73 10.85 9.82

82.39 79.63 79.86

8.00 10.90 8.99

0.0129 0.2178 0.0254

5.46 10.27 8.08 7.77 5.12 42.42 2.19 2.50 4.81 76.29 72.17 92.76 13.19 5.81 7.38 1.12 6.77 17.85 13.54 72.87 30.16 23.32 74.20

1.90 2.41 3.21 3.61 2.29 10.56 1.88 2.14 1.70 21.25 26.65 30.10 2.42 6.16 6.20 1.90 4.89 6.55 6.20 20.64 7.02 9.61 22.30

6.68 11.46 10.49 9.76 6.07 48.98 0.98 1.71 4.78 90.72 84.57 93.80 14.02 2.88 11.15 0.61 4.54 26.56 23.60 86.29 33.29 28.00 82.27

2.21 2.45 2.93 2.93 2.45 10.48 1.29 1.58 2.14 12.19 13.90 13.65 1.31 3.98 3.98 1.30 4.05 7.69 7.33 11.53 5.46 8.47 20.08

0.0232 0.0285 0.0024 0.0408 0.1149 0.0155 0.0025 0.1638 0.9565 0.0020 0.0627 0.3534 0.2966 0.0348 0.0073 0.4020 0.0336 0.0000 0.0000 0.0024 0.0686 0.0292 0.0731

16.81 32.04 4.50 6.15 8.92 50.28 121.05 76.68 4.88

4.75 4.93 2.96 2.36 3.51 24.95 65.61 55.14 2.64

20.67 32.77 5.23 6.58 12.02 34.29 72.95 39.34 6.54

4.69 5.33 3.03 2.21 4.07 11.93 28.38 25.82 2.32

0.0028 0.2623 0.3314 0.4654 0.0021 0.0007 0.0010 0.0071 0.0091

Emotional Recognition LiP subjects (Mean Educationⴔ8.37 Years) (Nⴔ24–26)

Controls (Mean Educationⴔ8.94 Years) (Nⴔ47)

Test

Mean

SD

Mean

SD

p

Total Fear Total Disgust Total Surprise Total Sad Total Angry Total Neutral Total Happy Total Emotion

47.44 49.76 54.67 56.25 59.95 62.36 87.18 59.30

22.89 28.09 35.05 22.64 24.96 36.95 13.31 18.08

61.28 74.34 75.84 69.15 77.60 82.67 93.85 75.67

23.62 23.14 19.51 20.91 18.01 20.08 6.47 12.97

0.0179 0.0001 0.0251 0.0167 0.0021 0.0329 0.0349 0.0001

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THORNTON et al. may help explain why lipoid proteinosis patients were less likely to be living with partners and had fewer children than controls. There are only occasional inconsistencies between our data and those reported previously. One report did not find memory or executive difficulties in lipoid proteinosis.28 This may well reflect restriction of that sample to subjects with IQ predominantly in the average to above average ranges. Indeed, the overall picture of lipoid proteinosis described here is also consistent with previous findings of marked inter-individual variability within the lipoid proteinosis population, perhaps reflecting differences in extent of intracranial calcification in this condition7 or in the extent of comorbid seizures (although we did not find significant differences in those with and without seizures). It is also worth considering psychosocial contributors to variance in the data here. We noted significant difference in intelligence and education between lipoid proteinosis subjects living in the relatively impoverished Northern Cape and a smaller group who lived else-

where. Indeed, notable findings here included the high prevalence of alcohol abuse and low neuropsychological performance of normal controls living in the Northern Cape. Much remains to be done in this setting in order to reverse current psychosocial circumstances and their negative impact on mental health. The amygdala plays a key role in mediating emotional responses,17,19,21,27 particularly those related to possible danger and threat.23–26 The amygdala is also important in the modulation of attention, perception, learning, and memory,46,47 as well as in a number of different psychopathologies.48–53 The data here on neuropsychological dysfunction, as well as increased psychotic, mood, and anxiety disorders, is consistent with temporal involvement and with the known high prevalence of temporal calcifications in lipoid proteinosis.9,16,19,28,31 Patients in the current study live in remote rural areas and brain imaging was not available; such work could in the future shed more light on the findings here. This research was supported by the Medical Research Council of South Africa.

References

1. Hamada T, McLean WH, Ramsay M, et al: Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (EMC1). Hum Mol Genet 2002; 11:833–840 2. Van Hougenhouck-Tulleken W, Chan I, Hamada T, et al: Clinical and molecular characterization of lipoid proteinosis in Namaqualand, South Africa. Br J Dermatol 2004; 151:413–423 3. Urbach E, Wiethe C: Lipidosis cutis et mucosae. Virchows Arch Pathol Anat Physiol Klin Med 1929; 273:285–319 4. Aroni K, Lazaris AC, Papadimitriou K, et al: Lipoid proteinosis of the oral mucosa: case report and review of the literature. Pathol Res Pract 1998; 194:844–859 5. Botha MC, Beighton P: Inherited disorders in the Afrikaner population in southern Africa, part II: skeletal, dermal and hematological conditions; the Afrikaners of Gamkaskloof; demographic considerations. S Afr Med J 1983; 64:664–667 6. Cote DN: Head and neck manifestations of lipoid proteinosis. Otolaryngol Head Neck Surg 1998; 119:144–145 7. Hofer P: Urbach-Wiethe disease (lipoglycoproteinosis; lipoid proteinosis; hyalinosis cutis et mucosae): a clinco-genetic study of 14 families from northern Sweden. Hereditas 1974; 77:209–218 8. Costagliola C, Verolino M, Landolfo P, et al: Lipoid proteinosis (Urbach-Wiethe disease). Ophthalmologica 1999; 213:392–396 9. Newton H, Rosenberg RN, Lampert PW, et al: Neurological involvement in Urbach-Wiethe’s disease (lipoid proteinosis). Neurology 1971; 21:1205–1213 10. Caccamo D, Jaen A, Telenta M, et al: Lipoid proteinosis of the small bowel. Arch Pathol Lab Med 1994; 118:572–574 11. Bazopoulou-Kyrkanidou E, Tosios KI, Zabelis G, et al: Case report: hyalinosis cutis et mucosae: gingival involvement. J Oral Pathol Med 1998; 27:233–237 12. Desmet S, Devos SA, Chan I, et al: Clinical and molecular abnormalities in lipoid proteinosis. Eur J Dermatol 2005; 15:344– 346


13. Chan I: The role of extracellular matrix protein 1 in human skin. Clin Exp Dermatol 2004; 29:52–56 14. Teive HA, Pereira ER, Zavala JA, et al: Generalized dystonia and striatal calcifications with lipoid proteinosis. Neurology 2004; 63:2168–2169 15. Feiler-Ofry V, Lewy A, Regenbogen L, et al: Lipoid proteinosis (Urbach-Wiethe syndrome). Br J Ophthalmol 1979; 63:694–698 16. Hofer PA: Urbach-Wiethe disease (lipoglycoproteinosis); lipoid proteinosis; hyalinosis et mucosae: a review. Acta Derm Venerol 1973; 53(suppl 71):1–52 17. Tranel D, Hyman BT: Neuropsychological correlates of bilateral amygdala damage. Arch Neurol 1990; 47:349–355 18. Heyl T: Lipoid proteinosis: the clinical picture. Br J Dermatol 1963; 75:465–472 19. Emsley R, Pastor L: Lipoid proteinosis presenting with neuropsychiatric manifestations. J Neurol Neurosurg Psychiatry 1985; 48:1290–1292 20. Kleinert R, Cervos-Navarro J, Kleinert G, et al: Predominantly cerebral manifestation in Urbach-Wiethe’s syndrome (lipoid proteinosis cutis et mucosae): a clinical and pathomorphological study. Clin Neuropathol 1987; 6:43–45 21. Adolphs R, Tranel D, Hamann S, et al: Recognition of facial emotion in nine individuals with bilateral amygdala damage. Neuropsychologia 1999; 37:1111–1117 22. Bechara A, Tranel D, Damasio H, et al: Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science 1995; 269:1115–1118 23. Adolphs R, Damasio H, Tranel D, et al: Cortical systems for the recognition of emotion in facial expressions. J Neurosci 1996; 16:7678–7687 24. Adolphs R, Tranel D, Damasio H, et al: Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature 1994; 372:669–672


91

THE NEUROPSYCHIATRY OF LIPOID PROTEINOSIS 25. Adolphs R, Tranel D, Damasio H, et al: Fear and the human amygdala. J Neurosci 1995; 15:5879–5891 26. Adolphs R, Tranel D: Amygdala damage impairs emotion recognition from scenes only when they contain facial expressions. Neuropsychologia 2003; 41:1281–1289 27. Calder AJ, Young AW: Facial emotion recognition after bilateral amygdala damage: differently severe impairment of fear. Cogn Neuropsychology 1996; 13:699–745 28. Siebert M, Markowitsch HJ, Bartel P: Amygdala, affect and cognition: evidence from 10 patients with Urbach-Wiethe disease. Brain 2003; 126:1–11 29. Cahill L, Babinsky R, Markowitsch HJ, et al: The amygdala and emotional memory. Nature 1995; 377:295–296 30. Van Rooy CH, Swart JG, Pietrzak JT: Lipoidproteinosis: a report of four cases. S Afr Med J 1991; 79:160–162 (Afrikaans) 31. Hofer PA: Urbach-Wiethe disease (lipoglycoproteinosis; lipoid proteinosis; hyalinosis cutis et mucosae): a clinical-genetic study of 14 families from northern Sweden. Hereditas 1974; 7:209–218 32. Botha P: Oral lipoid proteinosis. SADJ 1999; 54:371–373 ¨ zbek SS, Akyar S, Turgay M: Case report: computed tomog33. O raphy findings in lipoid proteinosis: report of two cases. Br J Radiol 1994; 67:207–209 34. Bo¨hme M, Wahlgren CF: Lipoid proteinosis in three children. Acta Paediatr 1996; 85:1003–1005 35. Izaki M, Horiuchi T, Hozaki H: Lipoidosis cutis et mucosae (lipoid proteinosis Urbach-Wiethe): report of a case. Keio J Med 1954; 3:163–177 36. Grosfeld JCM, Spaas J, Van de Staak WJBM, et al: Hyalinosis cutis et mucosae. Dermatologica (Basel) 1965; 130:239–266 37. Sheehan D, Janavs J, Baker RM, et al: Mini International Neuropsychiatric Inventory Plus. Tampa, University of South Florida, 2003 38. Kay SR, Opler LA, Lindenmayer JP: The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiatry 1989; 155:59–65 39. Montgomery SA, Asberg M: A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134:382–389

92


40. The Psychological Corporation: Wechsler Abbreviated Scale of Intelligence: Manual. San Antonio, TX, Harcourt Brace Jovanovich, 1999 41. Claasen NCW, Krynauw AH, Paterson H, et al: A Standardisation of the WAIS-III for English-Speaking South Africans. Pretoria, South Africa, Human Sciences Research Council, 2001 42. Human Sciences Research Council: South African Wechsler Adult Intelligence Scale. Johannesburg, South Africa, Human Sciences Research Council, 1983 43. Benton AL, Sivan AB, Hamsher K de S, et al: Facial Recognition: Stimulus and Multiple Choice Pictures. Oxford, Oxford University Press, 1983 44. Ekman P, Friesen WV: Pictures of Facial Affect. Palo Alto, Calif, Consulting Psychologists Press, 1976 45. Wechsler D: Wechsler Memory Scale–Revised: Manual. San Antonio, TX, Psychological Corp., 1987 46. Aggleton JP (ed): The Amygdala: A Functional Analysis, 2nd ed. Oxford, Oxford University Press, 2001 47. Baxter MG, Murray EA: The amygdala and reward. Neuroscience 2002; 3:563–573 48. Baron-Cohen S: Mindblindness: An Essay on Autism and Theory of Mind. Cambridge, MA, MIT Press, 1995 49. Baron-Cohen S, Ring HA, Bullmore ET, et al: The amygdala theory of autism. Neurosci Behav Rev 2000; 24:355–364 50. Fudge JL, Powers JM, Habner SN, et al: Considering the role of the amygdala in psychotic illness: a clinicopathological correlation. J Neuropsychiatry Clin Neurosci 1998; 10:383–394 51. Evangeli M, Broks P: Face processing in schizophrenia: parallels with the effects of amygdala damage. Cogn Neuropsychiatry 2000; 5:81–105 52. Sachdev P, Brodaty H, Cheang D: Hippocampus and amygdala volumes in elderly schizophrenic patients as assessed by magnetic resonance imaging. Psychiatry Clin Neurosci 2000; 54:105– 113 53. Haber SN, Fudge JL: The interface between dopamine neurones and the amygdala: implications for schizophrenia. Schizophr Bull 1997; 23:471–482
