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.

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.

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.

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.

[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.

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.

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.

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.

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.

[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.

Velo-cardio-facial syndrome: clinical report of a 70-year-old woman.

A clinical report is presented of a 70-year-old female in whom, after more than 40 years residential psychiatric care, the diagnosis of velo-cardio-facial syndrome (VCFS) was ultimately established; the patient has a 46, XX.ish del (22)(q11.2q11.2)(D(22)S(75)-) karyotype. It is advocated that a rather specific psychopathological profile is present in patients with VCFS, for which the term psychopathological phenotype is introduced, that should include data from genetics, neuropathology, development, psychology, and psychiatry.

Duplication of chromosome region (16)(p11.2 --> p12.1) in a mother and daughter with mild mental retardation.

We report a 40-year-old female with mild mental retardation and behavior problems and her 6-year-old daughter. Chromosome analysis showed that both patients had a proximal duplication in the short arm of chromosome 16. The aberration was characterized further with band-specific probes, resulting in a 46,XX,dir dup(16)(pter --> p11.2::p12.1 --> qter) karyotype. The clinical and cytogenetical findings are compared to other patients with partial trisomy 16p reported in the literature.

Dimensional classification and behavioral pharmacology of personality disorders; a review and hypothesis.

Nosological orientation in psychiatry has severely hampered the progress of research in biological psychiatry, especially in the case of personality disorders. Dimensional approaches have redefined the characteristics of these disorders and their possible pathogenetic factors. The significance of arousal and stress, so far relatively neglected in clinical research, and its important function in adaptive and coping strategies has to be included in the study of the behavioral pharmacology of personality disorders. Some preliminary clinical data are available suggesting the potential therapeutic use of serotonin modulating agents in the key symptomatology of certain personality disorders such as disturbed impulsive regulation and increased stress reactivity.

Atypical antipsychotics and the relevance of glutamate and serotonin.

In the present study, including 66 schizophrenic patients and 73 healthy controls, the effect of atypical antipsychotic treatment over a period of 14 weeks on psychotic symptoms and plasma levels of glutamate and monoaminergic metabolites was investigated. Treatment induced a modest reduction of psychotic symptoms in 42% of the patients (response criterion: Brief Psychiatric Rating Scale [BPRS] decrease >/=40%). Poor response was associated with severity of psychopathology, age and duration of disease. Glutamate at baseline was significantly higher in patients as compared to controls (p<0.01). During treatment, a significant further increase of glutamate, not related to response, was observed. Glutamate levels correlated significantly with negative symptom scores at baseline and weeks 3, 6 and 14 (p<0.05). At baseline, serotonin (5-HT) in plasma and 5-HT in platelets were significantly lower in the poor responders as compared to controls (p<0.05) and increased significantly during treatment (p<0.05). In the responders, treatment coincided with a decrease of 5-HT parameters. No differences in plasma levels of HVA, 5-HIAA and their ratio were observed between controls and response groups. The results of this study suggest an effect of atypical antipsychotics on glutamatergic neurotransmission and an association between lower pretreatment peripheral 5-HT parameters and response.

The temperament and character inventory in major depression.

Patients admitted for pharmacological treatment of a non-bipolar major depressive episode completed the Temperament and Character Inventory (TCI) prior to and after at least 6 weeks of treatment. Treatment with various antidepressants resulted in a 43% reduction of symptomatology. Scores on the harm avoidance dimension before and after treatment appeared to be significantly higher as compared to Dutch normative data. TCI scores did not predict response to treatment or show a change during treatment. It is concluded that, in this group of patients, the personality dimension harm avoidance is a trait factor without predictive value for antidepressant responsiveness.

Cerebrospinal fluid 5-hydroxyindolacetic acid and aggression: a critical reappraisal of the clinical data.

Over the past 15 years several clinical studies have been published dealing with the hypothesis that disturbances in central serotonergic functioning could be related to outward directed aggression and impulsivity. Close reading of the 22 relevant reports, however, raises doubt about the unequivocality of the results across diagnostic boundaries and in comparison with normal controls. Only eight of the studies are methodologically acceptable and seem to support the hypothesis. Taking all data together, it is concluded that some relationship exists between decreased serotonin metabolism, as reflected by lowered cerebrospinal fluid 5-hydroxyindolacetic acid, and certain aspects of aggressive behavior in a subgroup of young, male, personality-disordered subjects with seriously deviant behavior.

Citalopram in mentally retarded patients with depression: a long-term clinical investigation.

The effect of citalopram was investigated in 20 mentally retarded patients suffering from a depressive disorder characterized by alterations in the domains of affectivity, motivation, motor activity and vital signs. The study followed a baseline-controlled open design. Citalopram was started in a daily dosage of 20 mg that was kept unchanged for 6 weeks. Thereafter dosage was adjusted to maximally 60 mg per day. Treatment effects were assessed according to the Clinical Global Improvement Scale (CGIS) after at least 6 months. In 12 of the 20 patients a moderate to marked improvement in all domains was observed upon treatment with 20-40 mg citalopram daily. Treatment for one year in the effective dose prevented recurrence of depressive symptomatology. Concomitant use of sedative anticonvulsants reduced responsiveness to treatment. No interactions were observed. It is concluded that citalopram is a well-tolerated, safe and effective antidepressant in mentally retarded subjects with depressive disorders.

Quetiapine in the elderly with parkinsonism and psychosis.

In the present open prospective study the effects of quetiapine were investigated in two elderly patients with parkinsonism and psychosis. Treatment induced a marked antipsychotic effect that coincided with an improvement of general motor functioning. These findings support the idea that quetiapine may be preferentially of use in the elderly with parkinson's disease and psychotic symptoms.

Prader-Willi psychiatric syndrome and Velo-Cardio-Facial psychiatric syndrome.

Prader-Willi psychiatric syndrome and Velo-Cardio-Facial psychiatric syndrome: Similar to the studies on behavioural phenotypes, it is suggested to more rigorously promote the investigation of psychopathological phenotypes. The psychopathological profile in patients with Prader-Willi Syndrome (PWS) or Velo-Cardio-Facial Syndrome (VCFS) appears to be not classifiable within the current nosological systems. On a descriptive level, PWS-psychotic states show similarities with the cycloid psychoses, but VCFS psychosis does not. It is therefore advocated to adopt the notion of a brain-structure phenotype as well as that of a syndrome-specific psychiatric disorder.