Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia.

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.

Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations.

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 (rho = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD.

Psychiatric profile in rubinstein-taybi syndrome. A review and case report.

BACKGROUND: The diagnosis of Rubinstein-Taybi syndrome (RTS) is primarily clinical and based on the characteristic phenotype that is often combined with a variety of somatic anomalies and psychiatric disorders. SAMPLING AND METHODS: In this paper, a review is presented of the psychiatric and behavioural aspects of RTS. This is illustrated with a case report. RESULTS: Behavioural aspects of about 150 patients are described, and include a variable degree of mental retardation, impulsivity, distractibility, instability of mood and stereotypies. In general, patients with RTS are described as sociable and friendly. Information about brain pathology is virtually absent. In about half of the cases, the syndrome is caused by a mutation or deletion of the CREB-binding protein (CBP) gene (16p13.3). The case report deals with an adult male who was referred for impulsivity and temper outbursts. A provisional diagnosis of atypical depression was made, and treatment with citalopram resulted in a remarkable amelioration of his mood and behaviour that persisted for more than 2 years (last observation). CONCLUSION: Patients with undetected genetic syndromes do occur in clinical psychiatry, and the clinician has to consider such disorders in cases with disturbed development, dysmorphias and somatic comorbidity.

[An algorithm for psychotropics for the mentally handicapped: psychiatric diagnosis in three stages]. / Een algoritme voor psychofarmaca bij verstandelijk gehandicapten: psychiatrische diagnostiek in drie stappen.

BACKGROUND: Psychiatric treatment of mentally handicapped patients is still in its infancy because these patients are diagnosed by means of inadequate DSM vignettes that were not developed for such a homogeneous group and that do not have the status of diagnoses based on aetiology and pathophysiology. AIM: To raise awareness that the psychiatrist dealing with this group of patients needs to have a thorough knowledge of the syndromes involved which can be accompanied by psychiatric and somatic comorbidity and also needs to have expertise in linked disciplines such as genetics, epileptology and pharmacology. METHOD: On the basis of the international scientific literature an attempt was made to identify the rationale that underlies the current practice of treating challenging behaviour with a fairly random selection of psychotropics. RESULT: A diagnostic algorithm was formulated which can help the psychiatrist to provide evidence-based specialised advice on treatment and which can also prevent the occurrence of harm or damage. CONCLUSION: The top-down orientation of current diagnostic procedures, which tries to link symptoms to an underlying pathology, should be counterbalanced by a bottom-up approach in which the aetiology is the starting point. If this principle is observed, a well-founded proposal about treatment can sometimes be put forward. In all other cases treatment at present is little more than symptomatic pharmacotherapy involving a few well-documented psychotropics.

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.

Meditation-induced psychosis.

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.

[At the boundaries of self-determination: ethical and juridical dimensions of involuntary abortion and sterilization]. / De grenzen van zelfbeschikking: ethische en juridische dimensies van onvrijwillige abortus en sterilisatie.

A young woman, diagnosed with schizophrenia, was admitted to a psychiatric clinic with an acute relapse of her illness. Two months later, while still at the clinic, she was found to be pregnant. Due to her illness she was not considered competent to decide whether to have an abortion. Treatment was complicated by the chronic nature of her illness, a total lack of family and social support and mild mental retardation. Eventually she gave birth to a healthy baby and then was sterilized with the consent of her guardian. Ethical and juridical aspects are discussed here.

Chromosomal abnormalities in clinical psychiatry: a report of two older patients

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Background and Objectives: In clinical psychiatry genetic anomalies are infrequently part of the differential diagnosis, especially in the elderly. Two case reports are used to illustrate the relevance of a genetic workup for diagnosis, treatment and prognosis. Methods: A female and a male patient, aged 81 and 68 year respectively, were admitted because of psychotic symptoms. Despite their relatively low level of intelligence together with autistic-like behaviour in the female patient and dysmorphias in the male patient, a genetic disorder was previously never considered. Results: In the female patient a balanced translocation between chromosomes X and 19 was found, while in the male patient a mosaic trisomy 8 was demonstrated. Conclusions: Genetic analysis is indicated in patients with autism, lower intelligence, unexplained somatic anomalies and dysmorphias (AU)

Neuropsychiatric aspects of patients with hypothalamic hamartomas.

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.

Klinefelter's syndrome and Prader-Willi syndrome: a rare combination.

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.

Plasma amino acids and neopterin in healthy persons with Down's syndrome.

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.

Neuropsychiatry and deletions of 18q; case report and diagnostic considerations.

The 18q deletion syndrome can be caused by several terminal and interstitial deletions of which terminal deletions of the distal part of 18q are the most frequent and known as the DeCroughy syndrome. The neuropsychiatric phenotype is not well documented and includes disorganised and disinhibited behaviours as well as language difficulties. Non development of language seems to be specific for cases with a more proximally located interstitial deletions. In the present paper a 18-year-old severely mentally retarded male with an interstitial deletion of 18q is described (46.XY,del(18)(q12.1q22.1) who was referred for behavioural problems and neuropsychiatric evaluation. No categorical psychiatric diagnosis could be established. Given this and other reports, it is advocated to describe the psychopathological phenotype of 18q deletions in a dimensional way that will result in a clinical picture characterised mainly by symptoms from the motor and motivation domains. Treatment should include primarily behavioural measures, combined if necessary with symptomatic psychopharmacotherapy.

[Psychoses and epilepsy. A case study]. / Psychosen en epilepsie.

Over the last few decades much research has been done into the raised level of psychiatric comorbidity in epilepsy. On the basis of a case study of a patient suffering from post-ictal psychoses we explain the psychiatric differential diagnosis within the framework of epilepsy and we investigate the frequent psychiatric side-effects of anticonvulsants. It is concluded that the links between epilepsy and psychiatric symptoms are complex and that the neuropsychiatry of epilepsy is concerned with syndromes that are unique and do notfit into modern psychiatric classification systems.

Nitric oxide and neopterin in bipolar affective disorder.

BACKGROUND: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. METHODS: In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective patients were compared to those of patients with a major depression and healthy controls. As an index of NO synthesis, the ratio of the amino acids citrulline and arginine (Cit-Arg ratio) was calculated. Neopterin is a bypass product in the synthesis of tetrahydrobiopterin, which is a cofactor of NO synthase. RESULTS: The results indicate that both neopterin and the Cit-Arg ratio are decreased in bipolar affective patients, irrespective of their symptomatic status. In addition, an association between the values of the Cit-Arg ratio and the neopterin level was observed, which is suggestive for a low tetrahydrobiopterin activity. CONCLUSION: NO formation may be endangered in bipolar affective disorder.

Bipolar mania and plasma amino acids: increased levels of glycine.

Previous studies have suggested that the N-methyl-d-aspartate (NMDA) glutamate receptor complex is implicated in the pathophysiology of several neuropsychiatric disorders. Especially the glycine coagonist site of this receptor has been proposed as a therapeutic target. It has been hypothesized that the NMDA receptor and the serotonergic system, which function is compromised in affective disorders, are functionally coupled. Furthermore, several studies suggest that peripheral levels of amino acids are associated with psychotic symptomatology. We therefore measured plasma levels of glutamate, glycine, tryptophan and the tryptophan ratio in 20 bipolar-I patients during the manic phase and at remission of symptomatology. Data were compared to a matched group of healthy controls and a group of euthymic bipolar-I patients. During the manic phase, a significant increase of both glutamate and glycine was found, that persisted at remission. Tryptophan and the tryptophan ratio were decreased in manic patients. Subsequent analysis showed that changes in glutamate, tryptophan and tryptophan ratio could be attributed to the use of anticonvulsants. The increased glycine, however, was not related to the use of mood stabilizers. Although the exact relationship between peripheral measures of amino acids, e.g., glycine is not fully clear, the results of this study suggest an involvement of glycine and/or its coagonist site of the NMDA receptor in a manic relapse of patients with a bipolar-I disorder.

Disturbed serine metabolism and psychosis in a patient with a de novo translocation (2;10)(p23;q22.1).

Psychiatric diagnosing in mentally retarded patients is notoriously difficult and routine application of current taxonomies is of very limited use. Although psychotic disorders in general can be satisfactory grouped on a descriptive level, the aetiology is most probably very heterogeneous. In this case report a female patient is described who presented with mild mental retardation and recurrent affective psychotic episodes. Chromosome analysis showed a female karyotype with a de novo translocation (2;10)(p23;q22.1). Biochemical evaluation demonstrated a persistently increased taurine and decreased methionine in plasma, suggesting a disturbed one-carbon metabolism. Treatment with risperidone in combination with valproic acid resulted in prevention of further relapses and stabilisation of mood. An imbalance of chromosomes 2 and 10 was excluded by array CGH. A disruption of the PCBD gene could not be demonstrated by FISH.

The enigmatic phenotype: relevant signs and symptoms in schizophrenia

Ever since schizophrenia was conceptualized by Kraepelin and Bleuler,attempts have been made to rearrange signs and symptoms in order to achieve an useful disease concept with consequences for outcome, prognosis, treatment response and etiology. Several procedures were used to describe relevant phenotypes of the disease. In the beginning, famous psychiatrists conceptualized definitions of schizophrenia which was followed by a consensus about the operational criteria of schizophrenia. Later, more emphasis was placed on the statistical analyses of symptoms present in patients with psychotic disorders which resulted in a great variety of symptom clusters. In another approach, investigators try to deconstruct psychiatric diagnoses in search for so called end phenotypes of which covert symptoms like cognitive deficits in schizophrenia, are an example. The value of all these endeavours ultimately depends on the external validity which means that a relationship has to be established with the etiology, treatment response and outcome. The premises of all these research efforts is, however, the idea that the pathogenic agent of schizophrenia or a subtype will be found. In this paper an outline of the literature about the ordering of overt and covert symptoms in schizophrenia is presented. It is concluded that the different approaches are essential analogue and that research into the delineation of cognitive deficits and their treatment is at present most promising (AU)

Catatonia: disappeared or under-diagnosed?

BACKGROUND: Over the last century, especially during the latter half, the prevalence of the diagnosis of catatonic schizophrenia decreased considerably. Several explanations for this phenomenon have been put forward. SAMPLING AND METHODS: The present study investigated the frequency of the diagnosis of catatonic schizophrenia in a large sample of admitted psychiatric patients (n = 19,309). In addition, the presence of catatonic symptoms was studied in a sample of patients with schizophrenia (n = 701) and in a group of consecutively admitted psychotic patients (n = 139). In these two groups the effect of the diagnostic procedures on the recognition of catatonia was examined. RESULTS: The diagnosis of catatonic schizophrenia dropped from 7.8% in 1980-1989 to 1.3% in 1990-2001 (p < 0.001). In addition, a possible under-diagnosis of catatonic schizophrenia was found in an independent sample of patients with schizophrenia. Application of a systematic catatonia rating scale in patients admitted with acute psychosis identified a bimodally distributed catatonic dimension. At least 18% of these patients fulfilled the criteria for catatonia. Interestingly, the catatonic subgroup used atypical antipsychotic compounds more frequently (p < 0.05). CONCLUSIONS: The results suggest that changes in diagnostic criteria and the diagnostic procedure itself are responsible for the under-recognition of catatonia.

Amino acids in schizophrenia: evidence for lower tryptophan availability during treatment with atypical antipsychotics?

Amino acids play a role in neurotransmitter availability in the central nervous system, in that e.g. the synthesis of brain serotonin depends on the concentration of its precursor tryptophan. Disturbances in amino acid metabolism have been implicated in the pathophysiology of schizophrenia.In the present study the effect of a 14 week treatment with atypical antipsychotics on the plasma levels of amino acids was investigated in patients with schizophrenia and compared to normal controls.Non-responders (< or =20% decrease in BPRS at endpoint) demonstrated lower baseline values of methionine as compared to good responders (> or =50% decrease in BPRS at endpoint; p<.05) and controls (p<.01). The ratio between tryptophan and the other large neutral amino acids (Trp/LNAA ratio) in poor-responders (<40%) decreased during treatment as compared to responders (> or =40%; p<.05). It is concluded that poor or non-response to atypical antipsychotics may be associated with an impaired synthesis of serotonin in the central nervous system.