http://repub.eur.nl/res/aut/17423/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/20498/ 2010-08-01T00:00:00Z Objective: Sanfilippo B is a rare autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by a deficiency of N-acetyl-α-D-glucosaminidase (NAGLU). Method: A mild mentally retarded elderly female patient is described with a slowly progressive dementia who had given birth to a daughter who developed normally. Results: Metabolic screening revealed an enhanced concentration of heparan sulfate in urine. Enzymatic assay demonstrated deficiency of N-acetyl-α-D-glucosaminidase. Mutations in the NAGLU gene were found. One mentally retarded and hospitalized elder brother was also found to have MPS IIIB, whereas a second brother, who had died earlier, is suspected to have had the same metabolic disorder. Prior to the development of dementia, both the patient and her brother showed autistic like features, signs of ideomotor apraxia and weakness in verbal comprehension. Conclusion: Screening for metabolic disorders, in particular MPSes, should always be considered in patients with a history of mental deficit and dementia or progressive functional decline. http://repub.eur.nl/res/pub/23095/ 2010-08-01T00:00:00Z Abstract. OBJECTIVE: Sanfilippo B is a rare autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by a deficiency of N-acetyl-alpha-D-glucosaminidase (NAGLU). METHOD: A mild mentally retarded elderly female patient is described with a slowly progressive dementia who had given birth to a daughter who developed normally. RESULTS: Metabolic screening revealed an enhanced concentration of heparan sulfate in urine. Enzymatic assay demonstrated deficiency of N-acetyl-alpha-D-glucosaminidase. Mutations in the NAGLU gene were found. One mentally retarded and hospitalized elder brother was also found to have MPS IIIB, whereas a second brother, who had died earlier, is suspected to have had the same metabolic disorder. Prior to the development of dementia, both the patient and her brother showed autistic like features, signs of ideomotor apraxia and weakness in verbal comprehension. CONCLUSION: Screening for metabolic disorders, in particular MPSes, should always be considered in patients with a history of mental deficit and dementia or progressive functional decline. http://repub.eur.nl/res/pub/19792/ 2010-03-01T00:00:00Z Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer's disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (ρ = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD. http://repub.eur.nl/res/pub/16073/ 2009-01-01T00:00:00Z A novel duplication of chromosome (13)(q14.1q21.3) in a patient with mental retardation and microcephaly: We report on a mentally retarded female with behavioural problems, microcephaly, mild facial dysmorphisms, short stature and small hands with thin fingers due to a de novo partial duplication within the long arm of chromosome 13(q14.1q21.3). She was primarily referred to the outpatient department of neuropsychiatry because of short lasting psychotic episodes. No formal psychiatric diagnosis was made and the behavioural problems appeared the result of anxieties provoked by novel situations, enhanced by the intellectual disability. To the author's knowledge, this duplication has not been published previously and it is considered causative of the phenotype. http://repub.eur.nl/res/pub/22887/ 2009-01-01T00:00:00Z Objective: Despite the relatively high prevalence of epilepsy, the existing literature is inconclusive with respect to the association between violent or aggressive behaviours and epilepsy related disorders. Method: The present paper describes two male adult siblings with fetal anticonvulsant syndrome and a history of felonies and misdemeanours. In addition, the main epilepsy related conditions that may coincide with aggression, such as postictal psychotic states, hypothalamic hamartoma and use of anti-epileptics, are briefly reviewed. Results: For epilepsy related behaviours, brain disorders, contextual parameters, and the interictal period, as well as the behavioural pharmacology of antiepileptics and their teratogenic effects with prenatal exposure, are much more important than the epileptic fit itself. Conclusions: The clincal neuroscientist should be equipped with specialized knowledge about psychopathology related to epilepsy and anticonvulsants. Of special importance for the clinician is the awareness during the diagnostic process that prenatal exposure to anti-epileptics may be associated with prolonged behavioural disinhibition as a long-term consequence. http://repub.eur.nl/res/pub/22888/ 2009-01-01T00:00:00Z Abstract Metabolic syndrome during clozapine treatment Objective: To assess the prevalence of metabolic syndrome in inpatients with psychotic disorders treated with clozapine for at least one year. Design: Chronically admitted patients were screened on the use of clozapine and the presence of metabolic side effects. Methods: The Third Adult Treatment Panel was used tot assess metabolic syndrome. In addition, patient variables, dosage and plasma concentration of clozapine were recorded. Results: Included were 62 patients with a most prevalent diagnosis of schizophrenia. Mean duration of treatment with clozapine was 9.2 years. Metabolic syndrome was present in 60% of the patients and more frequent in cases with comedication of mood stabilizers. Conclusion: Metabolic syndrome is highly prevalent among patients treated with clozapine for psychotic disorders. Additional factors in the emergence of metabolic syndrome are: unhealthy life style, inactivity and comedication. http://repub.eur.nl/res/pub/16270/ 2008-06-01T00:00:00Z Phenomenology has been the reference point that investigators have used in their efforts to understand schizophrenia. Although symptoms and signs are crucial for the diagnosis of schizophrenia, there is an ongoing debate since Kraepelin attempted to group symptoms to understand the etiology of schizophrenia. Several operational criteria have been developed to establish the diagnosis of schizophrenia, making it obvious that there are no precise symptomatological boundaries. There is little clear indication which of the systems is valid for genetic and other biological research. Despite the enormous effort to find a linkage between schizophrenia and one or more loci, the results are far from conclusive. Another approach is the search for candidate genes of which DISCI and 22q11 deletion syndrome are examples. In all studies into the genetic underpinnings of schizophrenia, however, the clinical vantage point is neglected in that a broad clinical phenotype with respect to, e.g., developmental issues, symptoms and comorbidity is narrowed down to one categorical diagnosis. This is illustrated by the lack of exclusion criteria in genetic studies and by the occurrence of schizophrenia-like psychoses in a broad array of genetic syndromes. In case of 22q11 deletion syndrome, the psy chotic symptoms emerge in the context of brain anomalies, a plethora of somatic abnormalities and specific neurocognitive deficits. Prader Willi syndrome is a hypothalamic disorder in which psychotic symptoms may occur that resemble schizophrenia. It is concluded that not only schizophrenia is a highly variable disease but that the genetic samples are even much more heterogenous. http://repub.eur.nl/res/pub/30398/ 2008-01-15T00:00:00Z Although Noonan syndrome (NS) is a disorder with a relatively high prevalence, virtually no information in adult patients is available about the psychological and psychopathological profile. In the present clinical report the first series of 10 NS patients from an ongoing project is presented. The purpose of the study is to investigate the psychopathology, social cognition and adaptation as well as the quality of life in NS patients aged 16 years or more. PTPN11 mutations were present in six patients and KRAS and SOS1 in one patient, respectively. In two patients no known mutation was found. The results demonstrate a variable level of intelligence and suggest moderately impaired social cognition in terms of emotion recognition and alexithymia. In some patients mild signs of anxiety and lowered mood are found that, however, do not meet the criteria for a specific psychiatric disorder. It is concluded that NS in adults is associated with a behavioral phenotype in which deficiencies in social and emotional recognition and expression may be key elements. http://repub.eur.nl/res/pub/15396/ 2008-01-01T00:00:00Z Background and Objectives: Testosterone deficiency has been implicated in the etiology of depression although there is an ongoing debate on the nature of this association. There is a paucity of data about the psychological impact of hypogonadism in genetic disorders associated with testosterone deficiency. Methods:A 57-year-old male is described who was referred for treatment resistant depression. His history showed infertility and lowered testosterone. A selective literature review is given to clarify the patient's clinical condition. Results: Cytogenetic analysis demonstrated a Robertsonian translocation between chromosomes 13 and 14 that accounted for his infertility. The psychopathological picture did not meet the criteria for a major depressive disorder but was characterized by symptoms of apathy or avolition. These symptoms were most probably aggravated by previous long lasting treatment with antidepressants. Conclusions: Testosterone deficiency may be related to motivational deficits that should not be misunderstood for depressive illness. Apathy is probably an underestimated side effect of antidepressants. http://repub.eur.nl/res/pub/15961/ 2008-01-01T00:00:00Z Object: The Remission in Schizophrenia Working Group proposed in 2005 criteria for remission in patients with schizophrenia. This composite criterion consists of eight PANSS items and is reached when none of those has a score of more than 3 during a period of 6 months. The present study was done to elucidate the clinical relevance of this concept. Method: A group of 65 patients with schizophrenia was treated with atypical antipsychotics for 14 weeks. At baseline and endpoint, severity of symptoms was assessed with the PANSS, the BPRS, a cognitive subscale derived from the PANSS, and the CGI. A reduction of at least 50% on the BPRS total score was considered to be clinically relevant. Results: At endpoint, 18 patients (28%) had a reduction of 50% or more on the BPRS and 25 patients (39%) reached the severity criterion of remission. No correlation was found between the summed scores of the remission items and those of the cognitive subscale. Remitters and non-remitters did not differ with respect to the total score on the cognitive subscale. Predictors for remission were the PANSS positive and negative sum scores and age. Remission was reached by an only marginal symptomatic improvement. Conclusions: In this patient group, remitters are still symptomatically (e.g. cognitively) impaired and definitely not recovered, which implies that the term remission should be better replaced by partial symptomatic remission. http://repub.eur.nl/res/pub/35915/ 2007-09-01T00:00:00Z Background: Meditation is a self-regulatory psychological strategy that is frequently applied in Western as well as non-Western countries for different purposes; little is known about adverse events. Sampling and Methods: A male patient is described who developed an acute and transient psychosis with polymorphic symptomatology after meditating. A literature search for psychotic states related to meditation was carried out on PubMed, Embase and PsycInfo. Results: In the case presented a diagnosis of acute polymorphic psychotic disorder was made. Other case reports dealt with either a relapse of a pre-existent psychotic disorder or with a brief psychotic reaction in patients without a psychiatric history. Conclusion: Meditation can act as a stressor in vulnerable patients who may develop a transient psychosis with polymorphic symptomatology. The syndrome is not culture bound but sometimes classified in culture-bound taxonomies like Qi-gong Psychotic Reaction. Copyright http://repub.eur.nl/res/pub/36979/ 2007-09-01T00:00:00Z Hypothalamic hamartomas (HH) are developmental malformations that are associated with gelastic seizures, other types of seizures, cognitive decline, and symptoms related to hypothalamic dysfunction. Although aggressive behavior is frequently described, data on the neuropsychiatric profile are limited. In this article, five patients with HH are described who displayed a wide variety of psychiatric symptoms that, dependent on the time frame, met the criteria for several categorical diagnoses. Major neuropsychiatric symptoms comprised aggression that is only partial context dependent, compulsive behavior, psychotic symptoms not responding to treatment, and organic mood instability. HH should therefore be considered a neuropsychiatric syndrome with a highly variable expression that can be best captured by a thorough description of behaviors, symptoms, sequelae of epilepsy, and hypothalamic dysfunction. http://repub.eur.nl/res/pub/35923/ 2007-08-01T00:00:00Z In this paper a review is presented of the rare combination of Klinefelter's syndrome and Prader-Willi syndrome (PWS) and a second case of this combination with a uniparental disomy (UPD) etiology of PWS is described. Patients outlined in all other 8 reports and the present case have a PWS phenotype. Virtually no information is available on the behavioral and psychopathological phenotype in this combination. The latter may be explained by the observation that psychiatric syndromes are especially prevalent in PWS patients with a UPD. It is concluded that instability in mood and behavior in this and other syndromes should be preferentially treated with mood stabilizing agents. Copyright http://repub.eur.nl/res/pub/36052/ 2007-08-01T00:00:00Z In persons with Down's syndrome (DS) immunological abnormalities as well as hypothyroidism and Alzheimer type dementia are frequently observed. In addition, the activity of the enzyme cystathionine beta-synthase (CBS) is over-expressed which results in an altered homocysteine metabolism. In the present study, 48 older healthy DS persons without signs of dementia, psychiatric or somatic comorbidity and free of medication were analyzed for plasma levels of amino acids, neopterin and monoaminergic metabolites. Data were compared with those obtained from age and sex matched healthy controls. It was found that the spectrum of amino acids showed widespread differences in that levels of nearly all essential amino acids were lower in DS patients as compared to healthy controls. In addition, a significantly lower methionine and higher taurine concentration were observed which is in accordance with a disturbed homocysteine metabolism. With respect to the monoamine metabolites, the concentration of 5-hydroxyindoleacetic acid was not altered whereas that of homovanillic acid was significantly increased. Finally, the concentration of the immune activation marker neopterin was increased in persons with DS. It is concluded that healthy DS persons of older age show extensive biochemical abnormalities suggesting a compromised homocysteine metabolism, an activated cell-mediated immune response and an enhanced turnover of dopamine. http://repub.eur.nl/res/pub/36426/ 2007-08-01T00:00:00Z Background: In both Prader-Willi syndrome (PWS) and 22q11 deletion syndrome [velo-cardio-facial syndrome (VCFS)], an increased risk for psychotic disorders is reported, which are as a rule not included in the behavioural phenotype of these two syndromes. For the description of a behavioural phenotype, the complete spectrum of physical, developmental, neuropsychological and psychiatric aspects is generally not taken into account. Moreover, psychiatric signs and symptoms often do not meet the criteria for a categorical diagnosis. Objective: In this study, a further specification of psychotic symptoms in PWS and VCFS is shown as well as a proposal for a new model to ascertain predictors, including behavioural, for a genetic syndrome. Methods: Over the past years, 27 patients with PWS and 19 with VCFS were referred for neuropsychiatric evaluation because of psychotic symptoms. In all the patients, a standardised psychiatric examination was performed; seven of the patients with VCFS were evaluated by means of an extensive neuropsychological battery. Results: In both patient groups, a rather specific psychopathological profile seemed to be present, which in the case of patients with PWS showed some resemblance with bipolar affective disorder. In patients with VCFS, no formal psychiatric diagnosis could be established. Because the psychopathological profiles were rather aspecific, they are not sufficient to predict membership of a certain syndrome. Conclusions: A quantitative probabilistic approach toward the description of a (behavioural) phenotype is suggested. For such a procedure, large data sets and international collaboration are required. http://repub.eur.nl/res/pub/14916/ 2007-01-01T00:00:00Z Object: In this paper an overview is presented of the enduring efforts of physicians to control aggressive and disinhibited behaviors irrespective of the nosological context. Compounds that are thought to have a specific antiaggressive effect are called serenics. Method: First, a selective review of the historical concepts is outlined together with the treatment modalities. Second, the pharmacological approaches are described that have been developed since the introduction of psychotropics. Results: From ancients times on several herbal sedatives and containment strategies have been used to control manifestations of aggression. In the second half of the past century, all psychotropics have been advanced as a potential treatment. The results, however, are only aspecific. During the past decade, animal experiments have shown that systemic administration of specific serotonin receptor antagonists may exert behavioral specific effects. Conclusions: So far no specific pharmacological treatment is available for aggressive behaviors. Modern research suggests that aggressive behavior should be studied as a separate functional disorder across diagnostic boundaries.