Exploring the cognitive phenotype of Kabuki (Niikawa-Kuroki) syndrome.

BACKGROUND: Kabuki syndrome (KS) is a Mendelian disorder, characterised by short stature, facial dysmorphisms and developmental delay and/or intellectual disability. Clarification of the neurocognitive profile in KS may provide directions for education and treatment interventions for KS. Previous studies on cognitive functioning in KS are scarce and have mainly focused on the general level of intelligence. The few more extensive studies suggested weaknesses in language skills, visuoconstruction, perceptual reasoning and speed of information processing. Other relevant domains such as memory, executive functioning and social cognition have not been studied yet. METHOD: This is the first study in which cognitive functioning within multiple domains is systematically explored in 29 participants with KS (age range: 5-48 years) and compared to both norm groups (healthy population) and an appropriate control group of 15 individuals with other genetic syndromes (age range: 6-28 years). RESULTS: Compared to the norm groups of the cognitive test manuals, as expected, participants with KS show a weaker performance on all cognitive tests. Comparison with the more appropriate genetic control group indicates weaknesses in visuoconstruction and visual memory and no weaknesses in planning, cognitive flexibility or social cognition. Verbal memory seems to be a relative strength. CONCLUSIONS: Individuals with KS suffer from specific weaknesses in visuoconstruction, in addition to their intellectual disability/developmental delay. These impairments in visuoconstruction plausibly result from problems in visual perceptual processing, which highlight the importance of the use of auditory cues instead of visual cues in targeted educational support and psychosocial interventions.

Inhibition, shifting and updating in relation to psychometric intelligence across ability groups in the psychiatric population.

BACKGROUND: Assessment of intelligence and executive function (EF) is common in complex neuropsychiatric practice. Although previous studies have shown that EF and intelligence are related, it is unknown whether these constructs relate to one another in a similar manner across different ability groups (mild intellectual disability, borderline intellectual disability and normal/high intelligence). This study therefore examines the relation between three EFs (inhibition, shifting and updating) and intelligence in a heterogeneous psychiatric sample. It is hypothesised that the strength of the relation between intelligence and the three EFs decreases when the level of intelligence increases, in accordance with Spearman's Law of Diminishing Returns. METHODS: In a cross-sectional, between and within subject design, one of the three intelligence tests (Kaufman Adolescent and Adult Intelligence Test and Wechsler Adult Intelligence Scale - third and fourth editions) and several EF tests (Stroop Colour-Word Test, Trail Making Test and Spatial Working Memory task) were administered to 250 neuropsychiatric inpatients and outpatients (Mage  = 39.8, standard deviation = 14.3, 52.8% male). Based upon their full-scale IQ score, patients were divided into three ability groups (mild intellectual disability, borderline intellectual disability or normal/high intelligence). The relation between EF and intelligence was assessed through analyses of the correlation pattern; groups were compared using analysis of covariance. RESULTS: Analyses showed significant correlations between the constructs of EF and intelligence. A significant interaction effect was found for shifting, with highest correlations in the normal to high intelligence group, but not for inhibition and updating. CONCLUSIONS: Results support a specific role for shifting in this EF-intelligence relation. The correlational pattern of updating and intelligence, as well as the differential relation of shifting and intelligence across ability groups, suggests that EF tasks may not measure distinct EFs in lower intellectual ability but rely on cognitive primitives such as processing speed. EF tasks can be considered less valid indicators of EF ability. Implications in terms of the need for development of specific tasks to measure cognition in low intellectual ability are discussed.

Executive Dysfunction in Patients With Korsakoff's Syndrome: A Theory-Driven Approach.

AIMS: In addition to amnesia, executive deficits are prominent in Korsakoff's syndrome (KS), yet poorly studied. This study investigates the degree of executive dysfunction in patients with KS for the three main executive subcomponents shifting, updating and inhibition using novel, theory-driven paradigms. SHORT SUMMARY: Compared to healthy controls, patients with KS show impairments on the executive subcomponents shifting and updating, but not on inhibition. METHODS: Executive functions were measured with six carefully designed tasks in 36 abstinent patients with KS (mean age 62.3; 28% woman) and compared with 30 healthy non-alcoholic controls (mean age 61.8; 40% woman). ANOVAs were conducted to examine group differences and effect sizes were calculated. RESULTS: Compared to healthy controls, patients with KS were impaired on the executive subcomponents shifting and updating. No statistically significant group difference was found on the factor inhibition. CONCLUSIONS: Executive dysfunction in long-abstinent patients with alcoholic KS shows a profile in which shifting and updating ability are affected most. It also highlights that executive dysfunction is an important feature of KS and requires more attention in scientific and clinical practice, as these deficits may also affect daily functioning.

[Simple is not always easy: genetics in general psychiatry]. / Drie patiënten met langdurig onopgehelderde psychiatrische klachten waarbij genetische diagnostiek uitkomst bracht.

Many of the patients who attend the outpatient mental health clinics already have a long history of psychiatric problems. Their symptoms seem easy to classify, but the misdiagnosis of the patients' underlying problems can lead to a long series of costly referrals as inpatients or to an ineffective treatment outcome. In this article we focus on three patients whose history and background circumstances had been analysed in detail and who had also been subjected to a genetic analysis. The analyses pointed to an etiology-based diagnosis which had important implications for their future treatment and its outcome.

[Alcohol-related cognitive impairment and the DSM-5]. / Alcoholgerelateerde cognitieve stoornissen in de DSM-5.

BACKGROUND: It is evident from the dsm-iv-tr that alcohol-related impairment is extremely difficult to classify accurately. As a result, cognitive deficits can easily be overlooked. The dsm-5, however, incorporates a new category, namely 'neurocognitive disorders', which may lead to significant improvements in clinical practice. AIM: To compare the classification of alcohol-related cognitive dysfunction in dsm-iv-tr and dsm-5 and to discuss the clinical relevance of the revised classification in the dsm-5. METHOD: We compare the chapters of the dsm-iv-tr and the dsm-5 concerning alcohol-related cognitive impairment and describe the changes that have been made. RESULTS: The dsm-5 puts greater emphasis on alcohol-related neurocognitive impairment. Not only does dsm-5 distinguish between the degree of severity (major or minor neurocognitive disorder), it also distinguishes between the type of impairment (non-amnestic-type versus confabulating-amnestic type). It also makes a distinction between the durations of impairment (behavioural and/or persistent disorders). CONCLUSION: The dsm-5 gives a clearer description of alcohol-related neurocognitive dysfunction than does dsm-iv-tr and it stresses the essential role of neuropsychological assessment in the classification, diagnosis, and treatment of neurocognitive disorders.

[Could you please reduce your seclusion rates? To structure patient care by the methodical work approach]. / 'Kunnen de separatiecijfers omlaag?' Structuur geven aan behandelbeleid met methodisch werken.

BACKGROUND: Creating a safe treatment environment with a minimum use of seclusion at a ward for intensive psychiatric care is a complex process involving many actors. Although s/he is accountable for the use of seclusion, the psychiatrist's influence on actual seclusion practices is limited. The methodical work approach (MWA) to patient care is designed to improve multidisciplinary care delivery. AIM: To investigate ways in which the psychiatrist can structure the treatment and reduce seclusion rates by introducing the MWA. METHOD: We performed a quantitative analysis of the effects that the implementation of the MWA on an intervention ward had on the use of seclusion, comparing the intervention ward to control wards. We also conducted a qualitative analysis of the changes that occurred in the work process and in the roles of the various professionals involved. RESULTS: The use of seclusion had reduced significantly more at the intervention ward than it had at the control wards. The reduced seclusion rates were associated with an increase in interdisciplinary collaboration and professionalisation. CONCLUSION: By helping to limit the use of seclusion, possibly due to enhanced interdisciplinary collaboration and professionalisation, the MWA offers new horizons for mental health care professionals and their patients.

Neuropsychological phenotype and psychopathology in seven adult patients with Phelan-McDermid syndrome: implications for treatment strategy.

Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by a variable degree of intellectual disability, impaired speech and language as well as social communicative skills and mild dysmorphic features. The SHANK3 gene is thought to be a major contributor to the phenotype. Apart from the syndrome-associated autistic features, symptoms from the bipolar spectrum can be discerned, in particular behavior instability and fluctuating mood culminating in a (hypo)manic state. In case of coincident major somatic events, a deteriorating course may occur. This study comprises seven adult patients (four females and three males; aged 21-44 years) with genetically proven PMS. Data from medical records were collected and extensive assessment of neuropsychological variables was performed to identify cognitive characteristics and their relation with psychopathology and treatment. All patients showed profound communication deficits and their developmental functioning ranged from 1.0 to 6.3 years. In addition, they had slow speed of information processing, impairment of attentional and executive functions and cognitive alexithymia. As to psychopathology, features from the affective and anxiety domains were prominent findings in these seven patients suggesting the presence of a bipolar spectrum disorder that could be effectively moderated with mood-stabilizing agents. Results are discussed in terms of the putative involvement of structural brain abnormalities, in particular cerebellar vermis hypoplasia and corpus callosum thinning and their cognitive and emotional sequelae. It is concluded that the treatment of 22q13.3-associated psychopathology should include prescription of mood-stabilizing agents in combination with individually tailored contextual neuropsychological measures.

22q11.2 deletion syndrome: atypical antipsychotics and relapsing psychoses.

In their letter to the editor, Boot and colleagues comment on the results of treatment with atypical antipsychotics in patients with 22q11.2 deletion syndrome and relapsing psychoses. They identify 3 issues (i. e., description of study rationale and assessments, the importance of endocrine dysfunctions and possible effects of sample bias) and conclude that "until strong evidence to the contrary [is available], standard pharmacological management of psychotic illness in 22q11DS remains recommended." In our reply, we will illustrate the erroneous nature of their conjectures.

Atypical Antipsychotics and Relapsing Psychoses in 22q11.2 Deletion Syndrome: A Long-term Evaluation of 28 Patients.

INTRODUCTION: This study includes 28 patients with genetically proven 22q11.2 deletion syndrome referred for treatment-resistant psychoses and aims at the identification of a suitable pharmacological treatment strategy. METHODS: Based on standardized diagnostic procedures, key psychiatric symptoms and cognitive status were assessed. Also, data about previous diagnostic vignettes as well as the history of psychotropic medication and medical conditions were collected. Finally, the effect of the subsequent treatment regimen was periodically re-assessed. RESULTS: Since psychotic symptoms had been shown to be non-responsive to conventional antipsychotics including risperidone, treatment with either clozapine or quetiapine was started. In 21 patients, a substantial reduction of psychotic symptoms was achieved with either one, and in 3-quarters of this group remission was attained over a longer follow-up period. In a significant number of patients, valproic acid was added either for mood stabilizing purposes or to avoid epileptic side effects of clozapine. DISCUSSION: Treatment of psychotic symptoms in patients with 22q11DS with the atypical antipsychotic quetiapine or clozapine in combination with the mood-stabilizing anticonvulsant valproic acid, appears likely to be more effective than with other psychotropic compounds.

Monitoring in language perception in high-functioning adults with autism spectrum disorder: evidence from event-related potentials.

OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impaired global language processing, whereas local language processing often appears intact. Recent psycholinguistic research suggests that the quality of language perception relies on monitoring, an aspect of executive control. The aim of the study was to examine monitoring in people with ASD of (a) local, orthographic violations, and (b) global, syntactic violations, when provided with single level versus dual level task instructions. METHODS: We recorded event-related potentials and compared P600 effects to the linguistic violations relative to correct words in 14 adults with ASD and 14 matched controls. RESULTS: In control participants, local errors elicited a monitoring response as tapped by the P600 effect in both conditions. For global errors, the P600 effect was present only at one centroposterior site in the single level condition, whereas in the dual level condition a broadly distributed effect was obtained. People with ASD, however, showed a monitoring response to local and global errors both in the single and dual level condition. CONCLUSIONS: The main ERP finding suggests that when instructed people with ASD monitor global aspects of language already under simple circumstances, whereas people without ASD mainly do so under more complex circumstances. SIGNIFICANCE: Results suggest that language problems in ASD should not be studied in terms of a linguistic dysfunction as such, but in light of the use of executive resources during language comprehension.

[Neuropsychiatry as practised in a highly specialised department of a psychiatric teaching hospital: a successful interdisciplinary approach]. / Topklinische neuropsychiatrie: een succesvolle interdisciplinaire benadering.

BACKGROUND: Psychiatric disorders can be interpreted as a general dysregulation of the interplay between brain and behaviour. This is why, since the late 1990’s, the terms biological psychiatry and behavioural neurology have been gradually replaced by the term neuropsychiatry. Neuropsychiatry, when practiced in combination with clinical neuropsychology, have given rise to a paradigm that is not based solely on the usual classification models but is directed primarily towards diagnosis and treatment that are based on a functional-dimensional approach. AIM: To discuss the daily practice and organisation in a specialised department for neuro-psychiatry located in a psychiatric teaching hospital. METHOD: The interdisciplinary approach is explained and analysed on the basis of 10 case studies. RESULTS: Most of the patients referred to the specialised department already had a long history of visits to the health care facilities where they had been treated by a variety of specialists in single disciplines. Often, however, this trajectory did not involve periodical re-evaluation and updating of the original diagnosis. If this strategy had been adopted, then a clear diagnosis with simplified treatment programme might have been devised which could have resulted in a patient’s successful reintegration into society. CONCLUSION: It is essential that the interdisciplinary approach is adopted in specialised centres for neuropsychiatry because it can make an important contribution to individual patient care and to the spread of specialised knowledge that can benefit the entire field of psychiatry.

[The neuropsychology of cognitive functions in alcohol abstinence]. / Neuropsychologische diagnostiek en cognitieve functies bij alcoholabstinentie.

BACKGROUND: There is a vast amount of scientific evidence for the negative effects of alcohol on the functioning of the whole human body and particularly of the brain. The literature, however, is unclear about whether these functions can fully recover and about how long the abstinence period must be before patients with alcohol use disorder (AUD) can be reliably assessed for cognitive and emotional functioning. AIM: To review current findings on the length of the abstinence period required before a reliable neuropsychological assessment of the cognitive and emotional functioning of AUD patients can be carried out. METHOD: Using PubMed, PsycINFO and Medline, we consulted the literature for the period from 1975 to October 2011 relating to the effects of alcohol abstinence on the brain. RESULTS: The longer the period of abstinence, the greater the improvement in a patient's neuropsychological functioning. In the case of AUD patients, it takes at least six weeks for neuropsychological functioning to return to a fairly stable level. CONCLUSION: An abstinence period of at least six weeks is needed before a reliable neuropsychological assessment can be carried out. This time period minimises the disturbance caused by earlier alcohol abuse. A neuropsychological standard of this kind, involving a six week period of abstinence, is needed for AUD patients if they are to receive an appropriate and individualised neuropsychological assessment.

X-linked Aarskog syndrome: report on a novel FGD1 gene mutation. Executive dysfunction as part of the behavioural phenotype.

Aarskog-Scott syndrome [OMIM 100050] is a predominantly X-linked disorder that is phenotypically characterized by short stature, craniofacial dysmorphisms, brachydactyly and urogenital abnormalities. The level of intelligence shows a great variability and no specific behavioural phenotype has been described so far. In about 20 percent ofAarskog families, a mutation in the FGD1 gene located in Xp11.21 can be identified. In the present study, four affected males from the fourth generation of a large Dutch family (published in 1983 by Van de Vooren et al. (41)) are described. A novel FGD1 missense mutation (R402W) at position 1204 (1204C>T) was demonstrated. In the patients, the level of intelligence varied between normal and severely disabled. Their behavioural profile showed, among others, elements of attention deficit hyperactivity disorder, primarily reflected by impaired executive attentional processes that may be sensitive to systematic training.

Cognitive functioning of adults with Noonan syndrome: a case-control study.

Noonan syndrome (NS) is a genetic disorder characterised by short stature, facial dysmorphia, congenital heart defects and mildly lowered intellectual abilities. Research has mainly focused on genetic and somatic aspects, while intellectual and cognitive functioning has been documented scarcely. Also, to date studies have been primarily performed in children. This is the first study in which functioning within the major cognitive domains is systematically evaluated in a group of adults with NS and compared with a control group. Extensive neuropsychological assessment, including the domains intelligence, speed of information processing, memory (working memory, immediate recall and delayed recall), executive function and visuoconstruction, was performed in a sample of 42 patients with NS and 42 healthy controls, matched on age, sex and education level. In addition, subjective cognitive complaints were assessed with self-report questionnaires. On the domain speed of information processing patients performed worse than controls (P < 0.05). Furthermore, except for slightly better results on delayed recall in the patients with NS (P < 0.05), none of the other cognitive domains showed between-group differences. On the questionnaires, patients reported substantially more complaints about their own cognitive abilities than controls (P < 0.05). A lowered speed of information processing and relatively intact functioning in other cognitive domains characterises the cognitive profile of adult patients, in contrast to previous findings in children with NS, who seem to have more generalised cognitive deficits.

Affective functioning and social cognition in Noonan syndrome.

BACKGROUND: Noonan syndrome (NS) is a common genetic disorder, characterized by short stature, facial dysmorphia, congenital heart defects and a mildly lowered IQ. Impairments in psychosocial functioning have often been suggested, without, however, systematic investigation in a clinical group. In this study, different aspects of affective processing, social cognition and behaviour, in addition to personal well-being, were assessed in a large group of patients with NS. METHOD: Forty adult patients with NS were compared with 40 healthy controls, matched with respect to age, sex, intelligence and education level. Facial emotion recognition was measured with the Emotion Recognition Task (ERT), alexithymia with both the 20-item Toronto Alexithymia Scale (TAS-20) and the Bermond-Vorst Alexithymia Questionnaire (BVAQ), and mentalizing with the Theory of Mind (ToM) test. The Symptom Checklist-90 Revised (SCL-90-R) and the Scale for Interpersonal Behaviour (SIB) were used to record aspects of psychological well-being and social interaction. RESULTS: Patients showed higher levels of cognitive alexithymia than controls. They also experienced more social distress, but the frequency of engaging in social situations did not differ. Facial emotion recognition was only slightly impaired. CONCLUSIONS: Higher levels of alexithymia and social discomfort are part of the behavioural phenotype of NS. However, patients with NS have relatively intact perception of emotions in others and unimpaired mentalizing. These results provide insight into the underlying mechanisms of social daily life functioning in this patient group.

Nurses' decision on seclusion: patient characteristics, contextual factors and reflexivity in teams.

While many characteristics of patients, professionals and facilities with relevance to seclusion rates have been investigated, their relative importance is unclear. Virtually no attention has been paid to team processes and reflexivity in relation to decision making on seclusion. The aim of this paper is to estimate the effects of these factors on nurse decision making on seclusion. Sixty Dutch psychiatric nurses of four closed wards reported team reflexivity and their tendency to seclude a theoretical patient. Approachability (whether there was a good or hardly any possibility to communicate with the patient), staffing level and confidence within the team had the greatest impact on the decision to seclude. Intra class correlation was 0.30. There was a large interaction effect of reflexivity with team 4, and team reflexivity was highly correlated with team tendency to avoid seclusion. In nurses' decision on seclusion, the effects of 'pure' patient characteristics are small as compared with the effects of interpersonal and contextual factors, and nurses vary widely in their judgement. Team reflexivity is related to the tendency to prevent seclusion.

Comparability of scores on the MMPI-2-RF scales generated with the MMPI-2 and MMPI-2-RF booklets.

In most validity studies on the recently released 338-item MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008; Tellegen & Ben-Porath, 2008), scale scores were derived from the 567-item MMPI-2 booklet. In this study, we evaluated the comparability of the MMPI-2-RF scale scores derived from the original 567-item MMPI-2 booklet with MMPI-2-RF scale scores derived from the 338-item MMPI-2-RF booklet in a Dutch student sample (N = 107). We used a counterbalanced (ABBA) design. We compared results with those previously reported by Tellegen and Ben-Porath (2008). Our findings support the comparability of the scores of the 338-item version and the 567-item version of the 50 MMPI-2-RF scales. We discuss clinical implications and directions for further research.

[Compulsive buying or oniomania: an overview]. / Koopverslaving of oniomanie.

BACKGROUND: Compulsive buyers feel a continual urge to buy things, irrespective of their financial means. Interest in compulsive buying has increased in the last 30 to 40 years. Since excessive buying is a regularly occurring feature of various illnesses encountered in clinical practice, one wonders whether it should be regarded as a sign of the times, as a symptom of a psychiatric illness or as a distinct psychiatric syndrome. AIM: To gain insight into the concept of compulsive buying. METHOD: We searched the literature via Medline, PubMed and PsycInfo for the period from 1966 to August 2008. results Compulsive buying is a relatively unknown and poorly defined phenomenon, despite its high incidence and high comorbidity. It is characterised by chronic, repetetive behaviour; it occurs mainly among women and should be classified as an impulsive-control disorder nos. Current aetiological models lack explanatory power and, so far, the most successful treatment results seem to have been achieved with behavioural therapy. CONCLUSION: Compulsive buying should be considered from a neuroscientific perspective. Future research needs to have a neuropsychiatric focus and a contextual psychological and behavioural analytical approach in which inhibition, self-control and rule-governed behaviour play a central role.

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.

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.