Bibliographie de Rutger J. van der Gaag au 1/01/2009

samedi 17 janvier 2009

Il s’agit d’une bibliogaphie indicative, non exhaustive, extraite de la base Pubmed, les articles étant classés du plus récent au plus ancien.

1. Groen WB, van Orsouw L, Huurne NT, Swinkels S, van der Gaag RJ, Buitelaar JK, Zwiers MP. Intact Spectral but Abnormal Temporal Processing of Auditory Stimuli in Autism. J Autism Dev Disord,2009, (Jan 16).

The perceptual pattern in autism has been related to either a specific localized processing deficit or a pathway-independent, complexity-specific anomaly. We examined auditory perception in autism using an auditory disembedding task that required spectral and temporal integration. 23 children with high-functioning-autism and 23 matched controls participated. Participants were presented with two-syllable words embedded in various auditory backgrounds (pink noise, moving ripple, amplitude-modulated pink noise, amplitude-modulated moving ripple) to assess speech-in-noise-reception thresholds. The gain in signal perception of pink noise with temporal dips relative to pink noise without temporal dips was smaller in children with autism (p = 0.008). Thus, the autism group was less able to integrate auditory information present in temporal dips in background sound, supporting the complexity-specific perceptual account.

2. Kan CC, Buitelaar JK, van der Gaag RJ. [Autism spectrum disorders in adults]. Ned Tijdschr Geneeskd,2008 ;152(24), (Jun 14):1365-9.

Early infantile autism’ as defined by Kanner has grown into a spectrum of autistic disorders. The recognition of Asperger’s disorder and of pervasive developmental disorder not otherwise specified (PDD-NOS), has led to increased demand for appropriate diagnostic assessment of autism in adults. The expression ofimpairments in social interaction, communication, imagination and mental flexibility changes during development into adulthood. The diagnostic procedure in adult psychiatry should comprise a collateral developmental interview. Autism spectrum disorders in adults may mimic, or be overshadowed by, other psychiatric disorders. For effective diagnosis, the application of structured interviews, such as the ’Autism diagnostic observation schedule’ (ADOS), ’Autism diagnostic interview-revised’ (ADI-R) or ’Diagnostic interview for social and communication disorders’ (DISCO) is recommended.

3. Groen WB, van Orsouw L, Zwiers M, Swinkels S, van der Gaag RJ, Buitelaar JK. Gender in voice perception in autism. J Autism Dev Disord,2008 ;38(10), (Nov):1819-26.

Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.

4. Groen WB, Zwiers MP, van der Gaag RJ, Buitelaar JK. The phenotype and neural correlates of language in autism : an integrative review. Neurosci Biobehav Rev,2008 ;32(8), (Oct):1416-25.

Although impaired communication is one of the defining criteria in autism, linguistic functioning is highly variable among people with this disorder. Accumulating evidence shows that language impairments in autism are more extensive than commonly assumed and described by formal diagnostic criteria and are apparent at various levels. Phenotypically, most people with autism have semantic, syntactic and pragmatic deficits, a smaller number are known to have phonological deficits. Neurophysiologically, abnormal processing of low-level linguistic information points to perceptual difficulties. Also, abnormal high-level linguistic processing of the frontal and temporal language association cortices indicates more self-reliant and less connected neural subsystems. Early sensory impairments and subsequent atypical neural connectivity are likely to play a part in abnormal language acquisition in autism. This paper aims to review the available data on the phenotype of language in autism as well as a number of structural, electrophysiological and functional brain-imaging studies to provide a more integrated view of the linguistic phenotype and its underlying neural deficits, and to provide new directions for research and therapeutic and experimental applications.

5. Hengeveld MW, van Londen L, van der Gaag RJ. [Recognition of autism spectrum disorders in adults]. Ned Tijdschr Geneeskd,2008 ;152(24), (Jun 14):1353-7.

Autism spectrum disorder was diagnosed in three adults. The first patient, a married man aged 41, was referred to a psychiatrist with ’impending burn-out’. The second was a 32-year-old male student with schizophrenia and a depressive disorder who was referred to a centre for autism because a friend of his mother’s knew someone with Asperger’s syndrome. The third patient was a 25-year-old woman with a ’fixation on food’ who was referred by her general practitioner to a psychiatrist for evaluation of longstanding use of antidepressant medication. Autism used to be thought of as a condition of childhood. Only recently has the diagnosis and treatment of autism spectrum disorders become the focus of attention in adult psychiatry. It is made all the more difficult as during development into adulthood, the expression of disorders of reciprocal social interaction, communication, imagination and repetitive stereotypical thinking and actions, change.

6. Lahuis BE, Van Engeland H, Cahn W, Caspers E, Van Der Geest JN, Van Der Gaag RJ, Kemner C. Smooth pursuit eye movement (SPEM) in patients with multiple complex developmental disorder (MCDD), a subtype of the pervasive developmental disorder. World J Biol Psychiatry,2008, (Feb 8):1-8.

Objective. Multiple complex developmental disorder (MCDD) is a well-defined and validated behavioural subtype of pervasive developmental disorder-not otherwise specified (PDD-NOS) and is thought to be associated with a higher risk of developing a schizophrenic spectrum disorder. The question was addressed whether patients with MCDD show the same psychophysiological abnormalities as seen in patients with schizophrenia. Method. Smooth pursuit eye movement (pursuit gain and saccadic parameters) was measured in children with either MCDD (n =18) or autism (n =18), and in age- and IQ-matched controls (n =36), as well as in a group of adult patients with schizophrenia (n =14) and a group of adult controls (n =17). Results. We found the expected effect of lower velocity gain and increased number of saccades in schizophrenic patients. Children with MCDD also showed a lower velocity gain compared to controls children. In contrast, velocity gain was similar in autistic subjects and controls. No differences for velocity gain were found in a direct comparison between MCDD and autism. Saccadic parameters were not significantly different from controls in either MCDD or autistic subjects. Conclusion. Children with MCDD, like schizophrenic adults, show a reduced velocity gain, which could indicate that schizophrenia spectrum disorders and MCDD share (at least to some degree) a common neurobiological background.

7. Groen WB, Swinkels SH, van der Gaag RJ, Buitelaar JK. Finding effective screening instruments for autism using bayes theorem. Arch Pediatr Adolesc Med,2007 ;161(4), (Apr):415-6.

8. Couwenbergh C, van den Brink W, Zwart K, Vreugdenhil C, van Wijngaarden-Cremers P, van der Gaag RJ. Comorbid psychopathology in adolescents and young adults treated for substance use disorders : a review. Eur Child Adolesc Psychiatry,2006 ;15(6), (Sep):319-28.

OBJECTIVE : In a recent review, the prevalence of comorbid psychiatric disorders in non-treated adolescents and young adults with substance use disorders (SUD) in the general population was summarized. This review looks into the prevalence of psychiatric comorbidity in adolescents and young adults treated for SUD. METHOD : A computerized literature search was conducted resulting in ten eligible studies. RESULTS : The prevalence of comorbid psychiatric disorders varied from 61% to 88%. Externalizing disorders, especially Conduct Disorder (CD), were most consistently linked to SUD in treatment seeking adolescents. Girls are distinguished by their high rate of comorbid internalizing disorders. CONCLUSIONS : Comparison with data from community and juvenile justice studies shows an ascending trend of comorbidity rates of externalizing disorders from community to clinical and finally to juvenile justice samples. It seems that young addicts with comorbid disorders are at high risk of ending up in the juvenile justice system.

9. Schlooz WA, Hulstijn W, van den Broek PJ, van der Pijll AC, Gabreels F, van der Gaag RJ, Rotteveel JJ. Fragmented visuospatial processing in children with pervasive developmental disorder. J Autism Dev Disord,2006 ;36(8), (Nov):1025-37.

Children diagnosed with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Asperger Syndrome (AS) may be characterised by a similar perceptual focus on details as children with autistic disorder (AD). This was tested by analysing their performance in a visuoperceptual task [the Children’s Embedded Figure Test (CEFT)] and a graphic reproduction task [the Rey Complex Figure Task (Rey CFT)]. Control groups were children with Tourette Syndrome (TS) and typically developing children. The TS sample performed similarly to the normal control group in both tasks. The CEFT results did not show the expected preference for local processing in children with PDD-NOS. However, the Rey CFT data revealed that the children with this lesser variant of PDD processed visuospatial information in a fragmented way and were deficient in global processing.

10. Kalverdijk LJ, Buitelaar JK, van der Gaag RJ. [Medication for ADHD and the risk of cardiovascular mortality]. Ned Tijdschr Geneeskd,2006 ;150(41), (Oct 14):2283-4 ; author reply 2284.

11. Mercadante MT, Van der Gaag RJ, Schwartzman JS. [Non-autistic pervasive developmental disorders : Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified]. Rev Bras Psiquiatr,2006 ;28 Suppl 1, (May):S12-20.

The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger’s syndrome, Rett’s syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett’s syndrome and childhood disintegrative disorder, which are well-defined categories, will be discussed, as well as the not well defined categories that have been included in the Pervasive Developmental Disorder Not Otherwise Specified group. Different proposals of categorization have been created, some of which based on descriptive phenomenological approach, and others based upon other theoretical perspectives, such as neuropsychology. Current proposals are presented and discussed, followed by critical appraisals on the clinical advantages and disadvantages of these concepts.

12. van der Gaag RJ, Caplan R, van Engeland H, Loman F, Buitelaar JK. A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders. J Child Adolesc Psychopharmacol,2005 ;15(3), (Jun):465-76.

Along with well-defined categories in classification systems (e.g., autistic disorders and attention-deficit/hyperactivity disorder (ADHD)), practitioners are confronted with many children showing mixed forms of developmental psychopathology. These clusters of symptoms are on the borderlines of more defined categories. The late Donald Cohen proposed heuristic criteria to study a group defined by impaired social sensitivity, impaired regulation of affect, and thinking disorders under the name multiple complex developmental disorders (MCDD). Although these children meet criteria for pervasive developmental disorder—not otherwise specified (PDD-NOS), they have additional important clinical features, such as thought disorder. After highlighting similarities and differences between MCDD and comparable groups (e.g., multidimensionally impaired children), this paper presents the findings of a study comparing formal thought disorder scores in children with MCDD to children with autism spectrum diagnoses, such as autistic disorder (AD), and to children with nonspectrum diagnoses, such as ADHD and anxiety disorders. METHODS : Videotaped speech samples of four groups of high-functioning, latency-aged children with MCDD, AD, ADHD, and anxiety disorders were compared to a control group of normal children using the Kiddie Formal Thought Disorder Rating Scale (K-FTDS). RESULTS : High formal thought disorder scores were found both in the AD and MCDD groups, low rates in the ADHD groups, and no thought disorder in the anxiety disorder and normal control groups. The severity of formal thought disorder was related to verbal IQ scores within the AD and MCDD groups. CONCLUSION : High formal thought scores in children with complex developmental disorders, such as AD and MCDD, appear to reflect impaired communication skills rather than early signs of psychosis.

13. Jansen LM, Gispen-de Wied CC, van der Gaag RJ, van Engeland H. Differentiation between autism and multiple complex developmental disorder in response to psychosocial stress. Neuropsychopharmacology,2003 ;28(3), (Mar):582-90.

Multiple Complex Developmental Disorder (MCDD) represents a distinct group within the autistic spectrum based on symptomatology. Unlike autistic children, part of MCDD children develop schizophrenia in adult life. Despite the differences, patients of both disorders are mainly characterized by abnormal reactions to their social environment. At the biological level, we showed in a previous study that MCDD children have a reduced cortisol response to psychosocial stress. Given the fact that autistic children clinically show more social impairments, it was hypothesized that they may have even further decreased cortisol responses to psychosocial stress than MCDD patients. Therefore, 10 autistic children were compared to 10 MCDD children and 12 healthy control children in their response to a psychosocial stressor, consisting of a public speaking task. In order to test whether any impairments in the biological stress response are specific for psychosocial stress, the autistic children were compared with 11 MCDD children and 15 control children in their response to a physical stressor, consisting of 10 min of bicycle exercise. Heart rate and salivary cortisol levels were used as indicators of response to the stress tests. Autistic children showed a relatively elevated cortisol response to psychosocial stress, in contrast to MCDD children who showed a reduced cortisol response. No differences in heart rate or cortisol responses to the physical stress test were found. The specific difference between autistic and MCDD children in their cortisol response to psychosocial stress indicates that the disturbed reactions to the social environment observed in these disorders may have different biological backgrounds.

14. Buitelaar JK, van der Gaag RJ, Cohen-Kettenis P, Melman CT. A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. J Clin Psychiatry,2001 ;62(4), (Apr):239-48.

BACKGROUND : Risperidone is an atypical antipsychotic drug that blocks dopamine as well as serotonin receptor systems. The present study was designed to examine the efficacy and safety of risperidone in a 6-week double-blind, randomized, parallel-group design in the treatment of aggression in adolescents with a primary diagnosis of DSM-IV disruptive behavior disorders and with subaverage intelligence. METHOD : We randomly assigned 38 adolescents (33 boys ; 10 subjects with slightly subaverage IQ, 14 with borderline IQ, and 14 with mild mental retardation), who were hospitalized for treatment of psychiatric disorders associated with severe aggression, to receive risperidone or placebo. The main efficacy measures were the Clinical Global Impressions-Severity of Illness scale (CGI-S), the modified Overt Aggression Scale (OAS-M), and the Aberrant Behavior Checklist (ABC). Side effects were measured using the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS : The mean daily dose of risperidone at the end of treatment was 2.9 mg (range, 1.5-4 mg). Risperidone, compared with placebo, was associated with significant improvements on the CGI-S (p < .001) and the at-school ABC overall and hyperactivity scales (p < .05). During a 2-week washout following the 6-week trial, a statistically significant worsening was found in the risperidone group on the CGI-S scale, the OAS-M. and the ABC. Extrapyramidal symptoms were absent or very mild during risperidone treatment. Transient tiredness was present in 11 (58%) of 19 drug-treated subjects. Other untoward effects included sialorrhea, nausea, and slight weight gain (mean = 3.5% of body weight in the risperidone group). No clinically relevant changes were found in laboratory parameters, electrocardiogram, heart rate, or blood pressure. CONCLUSION : These results suggest that risperidone may be effective for severe aggression in adolescents with disruptive behavior disorders and subaverage intelligence, and these results are consistent with reports suggesting its effectiveness for treating severe aggression in adolescents in general.

15. Jansen LM, Gispen-de Wied CC, Van der Gaag RJ, ten Hove F, Willemsen-Swinkels SW, Harteveld E, Van Engeland H. Unresponsiveness to psychosocial stress in a subgroup of autistic-like children, multiple complex developmental disorder. Psychoneuroendocrinology,2000 ;25(8), (Nov):753-64.

In this study, we tried to replicate the finding of a diminished cortisol response to stress in autistic-like patients in a more homogenous Multiple Complex Developmental Disorder (MCDD) group. MCDD forms a distinct group within the autistic-like disorders, characterized by impaired regulation of anxiety and affective state, impaired social behavior/sensitivity, and thought disorder. A number of MCDD children develop schizophrenia in adult life.Responses to a psychosocial stressor, consisting of speaking in public while recorded on video, were measured in 10 MCDD children and 12 healthy control children. The public speaking test was imbedded in a two-hour test session, and compared to a control test session. Hypothalamic-pituitary-adrenal (HPA) responses were measured on salivary cortisol at about 20-minute intervals. Heart rate was measured continuously. Delta AUC’s were computed for both heart rate (dAUCHR) and salivary cortisol (dAUCCORT), as a measure of response to the test.The public speaking task resulted in significant responses in heart rate and salivary cortisol in healthy control children, but not in MCDD children. dAUCHR was 3.28+/-2.37 in healthy control children, but -0.09+/-1.73 in MCDD children (t=3.31, P<0.01). dAUCCORT was 3.22+/-3.16 in healthy control children, but 0. 17+/-1.74 in MCDD children (t=2.72, P<0.05).The impaired responses to psychosocial stress found in MCDD children may be the result of their limited abilities to react adequately to their (social) environment. The same impairment in stress processing has been found in schizophrenia, and might be a factor in the vulnerability of these MCDD children to develop schizophrenia.

16. Kemner C, van der Gaag RJ, Verbaten M, van Engeland H. ERP differences among subtypes of pervasive developmental disorders. Biol Psychiatry,1999 ;46(6), (Sep 15):781-9.

BACKGROUND : Children with multiple complex developmental disorder (MCDD) have been distinguished from autistic children on the basis of chart reviews. It was questioned whether it is possible to find other, e.g., event-related potential (ERP), evidence for this assertion. METHODS : ERPs were measured in response to stimuli in a visual oddball task in autistic, MCDD, attention deficit disorder, dyslexic, and normal control children, to study whether ERP peaks can be used to distinguish autistic and MCDD children, and to classify the aforementioned groups. RESULTS : It was found that the P3 at four different leads and the frontal Nc showed differences among the groups, and that the autistic and MCDD groups differed from each other as well as from the other groups. Also, it was found that, using discriminant analyses in which these parameters were included, children were classified above chance level. Especially in the MCDD group, a high percentage of correct classification was seen. CONCLUSIONS : ERP parameters indicate that autistic and MCDD children might differ in underlying pathology and might therefore, better be regarded as two separate diagnostic entities.

17. Buitelaar JK, Van der Gaag R, Klin A, Volkmar F. Exploring the boundaries of pervasive developmental disorder not otherwise specified : analyses of data from the DSM-IV Autistic Disorder Field Trial. J Autism Dev Disord,1999 ;29(1), (Feb):33-43.

This study aimed to explore the boundaries between PDD and related disorders and to develop classificatory algorithms for what is currently called Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS). Data collected by means of a standard coding system for the DSM-IV field trial for autistic disorder were used. Information on diagnostic criteria for autistic disorder as listed in ICD-10 and DSM-IV was compared between subjects functioning at least in the mildly retarded range and clinically classified as autistic disorder (n = 205), PDDNOS (n = 80) and other non-PDD disorders (n = 174). Only a limited number of items from the ICD-10 and DSM-IV systems for autistic disorder significantly discriminated the PDDNOS group from other disorders. A scoring rule based on a short set of 7 ICD-10/DSM-IV criteria with a cutoff of 3 items and 1 social interaction item set as mandatory had the best balance between high sensitivity and high specificity in discriminating PDDNOS from non-PDD disorders. These rules yielded a somewhat better prediction than most effective rules based on the full set of 12 criteria for autistic disorder with a cutoff of 4 items and 1 social item as mandatory. Generally accepted and well-validated criteria to identify individuals with PDDNOS should facilitate both research and clinical services.

18. Jansen LM, Gispen-de Wied CC, Jansen MA, van der Gaag RJ, Matthys W, van Engeland H. Pituitary-adrenal reactivity in a child psychiatric population : salivary cortisol response to stressors. Eur Neuropsychopharmacol,1999 ;9(1-2), (Jan):67-75.

The aim of this explorative study was to investigate whether physical and psychological challenges are effective in inducing a cortisol response in psychiatric and control children, and if so whether the cortisol response can discriminate between diagnostic groups and is related to psychiatric symptoms. Fifty-two patients, including children with dysthymia, oppositional defiant disorder/conduct disorder, pervasive developmental disorder, not otherwise specified (PDDNOS) and attention deficit hyperactivity disorder, were compared to 15 healthy control children. Symptomatology was scored using the Child Behaviour Checklist. The response to both psychological and physical challenges was assessed by measuring salivary cortisol and heart rate. Physical challenge, but not psychological challenge, resulted in an overall increase in heart rate and saliva cortisol. Dysthymic and PDDNOS patients showed a diminished cortisol response, in spite of a significant increase in heart rate. These groups scored highest on the symptom factor withdrawal. Withdrawal was negatively correlated with the cortisol response. Thus, physical exercise is effective in inducing a salivary cortisol response in children. Dysthymic and PDDNOS patients have a disturbed pituitary-adrenal function in relation to physical stress, that may be associated with withdrawal.

19. Buitelaar JK, van der Wees M, Swaab-Barneveld H, van der Gaag RJ. Theory of mind and emotion-recognition functioning in autistic spectrum disorders and in psychiatric control and normal children. Dev Psychopathol,1999 ;11(1), (Winter):39-58.

The hypothesis was tested that weak theory of mind (ToM) and/or emotion recognition (ER) abilities are specific to subjects with autism. Differences in ToM and ER performance were examined between autistic (n = 20), pervasive developmental disorder-not otherwise specified (PDD-NOS) (n = 20), psychiatric control (n = 20), and normal children (n = 20). The clinical groups were matched person-to-person on age and verbal IQ. We used tasks for the matching and the context recognition of emotional expressions, and a set of first- and second-order ToM tasks. Autistic and PDD-NOS children could not be significantly differentiated from each other, nor could they be differentiated from the psychiatric controls with a diagnosis of ADHD (n = 9). The psychiatric controls with conduct disorder or dysthymia performed about as well as normal children. The variance in second-order ToM performance contributed most to differences between diagnostic groups.

20. Buitelaar JK, van der Wees M, Swaab-Barneveld H, van der Gaag RJ. Verbal memory and Performance IQ predict theory of mind and emotion recognition ability in children with autistic spectrum disorders and in psychiatric control children. J Child Psychol Psychiatry,1999 ;40(6), (Sep):869-81.

This study was designed to examine the developmental and cognitive correlates of theory of mind (ToM) and emotion recognition ability in children with autism (N = 20), with pervasive developmental disorder-not otherwise specified (PDD-NOS) (N = 20), and in psychiatric control children (N = 20). The diagnostic groups were person-to-person matched on age and verbal IQ. The age of the children was between 8 and 18 years ; their Full Scale IQ was at least 65. The test battery included tasks for the matching and the context recognition of emotional expressions, and a set of first- and second-order ToM tasks. The relationships between composite domain scores and the subjects’ age, Verbal IQ, Performance IQ, verbal memory, visual memory, and gender were examined in bivariate and multivariate analyses. Further, the subjects who reliably and consistently passed the tasks of a domain and those who could not were compared on developmental and cognitive characteristics. Overall, the results of the various analyses converged and indicated that verbal memory, Performance IQ, age and gender were the best predictors of social cognitive ability.

21. Buitelaar JK, van der Gaag RJ, van der Hoeven J. Buspirone in the management of anxiety and irritability in children with pervasive developmental disorders : results of an open-label study. J Clin Psychiatry,1998 ;59(2), (Feb):56-9.

BACKGROUND : We evaluated the efficacy and safety of buspirone in the management of anxiety and irritability in children with pervasive developmental disorders (PDD). METHOD : Twenty-two subjects, 6 to 17 years old, with DSM-III-R diagnosed PDD-NOS (N = 20) or autistic disorder (N = 2), were included. They were treated with buspirone in dosages ranging from 15 to 45 mg/day in an open-label trial lasting 6 to 8 weeks. Responders continued buspirone treatment and were followed up for up to 12 months. RESULTS : Nine subjects had a marked therapeutic response and 7 subjects a moderate response on the Clinical Global Impressions (CGI) scale after 6 to 8 weeks of treatment. Side effects were minimal, except for 1 patient who developed abnormal involuntary movements. CONCLUSION : These results suggest that buspirone may be useful for treating symptoms of anxiety and irritability in children with PDD.

22. Buitelaar JK, van der Gaag RJ. Diagnostic rules for children with PDD-NOS and multiple complex developmental disorder. J Child Psychol Psychiatry,1998 ;39(6), (Sep):911-9.

This study was designed to examine the classification performance of diagnostic rules for pervasive developmental disorder not otherwise specified (PDD-NOS) and multiple complex developmental disorder (McDD), with clinical diagnosis as the gold standard. McDD is an heuristic concept of a developmental disorder characterised by social impairments, affective dysregulation, and thought disturbance. Detailed information on the symptoms, reliably extracted from the charts of 103 children with PDD-NOS and McDD, 32 with autistic disorder, and 96 with non-PDD disorders, was used to determine the presence of the DSM-IV criteria of autistic disorder and the criteria of McDD. A scoring rule for PDD-NOS based on a short set of seven DSM-IV criteria with a cut-off point of three items and one social interaction item set as mandatory had the best balance between high sensitivity and high specificity. The most effective and simple rule based on McDD criteria had a cut-off of three items, out of six items of anxieties and thought disturbance.

23. Gispen-de Wied CC, Jansen LM, Wynne HJ, Matthys W, van der Gaag RJ, Thijssen JH, van Engeland H. Differential effects of hydrocortisone and dexamethasone on cortisol suppression in a child psychiatric population. Psychoneuroendocrinology,1998 ;23(3), 295-306.

The suppressive effect of hydrocortisone and dexamethasone on salivary cortisol was investigated in a 2-year study of pituitary-adrenal function in a variety of child psychiatric patients and healthy controls. Symptomatology was assessed using the Child Behavioral Checklist (CBCL). Cortisol day profiles were assessed at 2-h intervals from 0800 to 2000 h on three occasions. Dexamethasone and hydrocortisone were administered orally twice at 2000 h, the doses being adjusted for bodyweight according to the standard dexamethasone suppression test. Fifty-one patients, including patients with dysthymia, oppositional defiant disorder, pervasive developmental disorder, and attention deficit hyperactivity disorder, and ten age and sex matched controls participated. Basal cortisol levels in patients were generally lower than in controls. Both dexamethasone and hydrocortisone were effective in suppressing salivary cortisol, although dexamethasone was somewhat more potent and its effect lasted longer. Hyporesponsiveness to hydrocortisone, but not to dexamethasone, distinguished patients with dysthymia and oppositional defiant disorder from controls. Responsiveness to hydrocortisone was correlated with the symptom clusters social problems and anxious/depressed. The data support the idea that there exist syndrome aspecific disturbances in feedback activity beyond the level of the pituitary, i.e. at the hypothalamic level, at an early age. From this perspective, hydrocortisone suppression is a useful tool for studying pituitary-adrenal function in children. Behavioral correlates of these disturbances of pituitary-adrenal function should be determined.

24. Kemner C, Verbaten M, Koelega HS, Buitelaar J, van der Gaag RJ, Camfferman G, Van Engeland H. Event-related brain potentials in children with attention-deficit and hyperactivity disorder : effects of stimulus deviancy and task relevance in the visual and auditory modality. Biological psychiatry 1996 ;40(6), 522-34.

It has frequently been reported that in so-called oddball tasks, children with attention-deficit and hyperactivity disorder (ADDH) show small P3 peaks of the event-related potential (ERP) in response to "targets" (task-relevant deviant stimuli) than normal children. It is not clear, however, whether this smaller P3 is due to abnormal processing of infrequent stimuli per se and/or of task-relevant stimuli and whether it is preceded by abnormalities in earlier peaks, especially those thought to be related to automatic deviancy detection [mismatch negativity (MMN) in the auditory modality and P2N2 in the visual modality]. ERPs of ADDH and normal children in response to visual and auditory stimuli were studied in a condition without task relevance as well as in a task-relevant condition. ADDH children showed smaller P3 amplitudes and (marginally) smaller MMN to auditory deviant stimuli, irrespective of task relevance, so smaller P3s in ADDH children are due to stimulus deviancy per se. In the visual modality the P3 effect failed to reach significance. Because the smaller P3s were also found in a condition not requiring task-related motivation, recent motivational interpretations of differences with normal children are not supported. ADDH children also showed smaller P1 amplitudes than normal children to all stimuli except visual novels. The ERP differences were unrelated to performance, since both groups performed equally well.

25. Buitelaar JK, Swaab H, van der Wees M, Wildschut M, van der Gaag RJ. Neuropsychological impairments and deficits in theory of mind and emotion recognition in a non-autistic boy. Eur Child Adolesc Psychiatry,1996 ;5(1), (Apr):44-51.

A 9-year-old non-autistic boy revealed marked deficits in visuo-spatial and visuo-motor skills, in planning and organizational capacities and in impulse inhibition. Particular strengths were his verbal comprehension and reasoning abilities. This neuropsychological pattern of assets and deficits fitted the nonverbal learning disability syndrome as described by Rourke (1989). On a battery of Theory of Mind (TOM) and emotion recognition tests he performed rather poor on several first-order TOM tasks and on all second-order TOM and emotion-matching tasks, compared to samples of autistic and normal subjects. It is suggested that his visuo-spatial and cognitive shifting deficits account for his social cognitive failures, while his superior verbal skills protect him from severe social handicaps.

26. Buitelaar J, van der Gaag RJ, Swaab-Barneveld H, Kuiper M. Pindolol and methylphenidate in children with attention-deficit hyperactivity disorder. Clinical efficacy and side-effects. Journal of child psychology and psychiatry,1996 ;37(5), 587-95.

The purpose of this study was to examine the efficacy and side-effects of pindolol, a beta-blocker, in children with attention-deficit hyperactivity disorder (ADHD). Fifty-two ADHD children, 7-13 years old, participated in a prospective double-blind placebo-controlled comparison of pindolol and methylphenidate (MPH). Active treatment was pindolol and MPH : pindolol 20 mg b.i.d. or MPH 10 mg b.i.d. for 4 weeks. The outcome was assessed on the basis of the Abbreviated Conners Rating Scales (ACRS) completed by parents, teachers, and by a psychologist during psychological testing. Pindolol treatment was associated with a higher incidence of paraesthesias and with more intense nightmares and hallucinations than MPH or placebo treatment. These side-effects led to an interim change in design by ending pindolol treatment after 32 participants. Pindolol proved to be just as effective as MPH in decreasing hyperactivity and conduct problems at home, and hyperactivity problems at school. Pindolol, however, had less therapeutic effects than MPH during psychological testing, and failed to affect conduct problems in school. In sum, pindolol was modestly effective in the treatment of ADHD. Safety concerns on troubling side-effects clearly limit the use of it.

27. Van der Gaag RJ, Buitelaar J, Van den Ban E, Bezemer M, Njio L, Van Engeland H. A controlled multivariate chart review of multiple complex developmental disorder. J Am Acad Child Adolesc Psychiatry,1995 ;34(8), (Aug):1096-106.

OBJECTIVE : The primary aim of the study was to ascertain the usefulness and the validity of the set of criteria proposed to define a subgroup within the DSM-III-R category of pervasive developmental disorder-not otherwise specified under the name of multiple complex developmental disorder (MCDD). METHOD : A multivariate analysis (cluster and principal-components analysis) was performed on the characteristics, reliably extracted from the charts of 105 children with MCDD, 32 with autistic disorder, 51 with externalizing disorders, and 56 with internalizing disorders, all with an IQ greater than 70, fully assessed in our department between 1984 and 1991. RESULTS : The main finding was a strong correspondence between the classification of the cases by DSM-III-R categories and the subdivision by means of a multivariate cluster analysis. The cluster analysis did not discriminate between children with emotional and disruptive disorders. Furthermore, children with MCDD and autistic disorder were significantly different both on symptom factors ("psychotic thinking/anxiety," "aggression," "deficient interaction / communication," "stereotyped and rigid behavior," and "suspiciousness/odd interaction") and on factors that reflected developmental and environmental background variables. CONCLUSION : The results of this study add to the nosology of autistic spectrum disorders and lend additional support to the need for a separate subcategory of MCDD within DSM-V. Further corroboration of these results in independent (multicenter) samples will be required.

28. Buitelaar J, Van der Gaag RJ, Swaab-Barneveld H, Kuiper M. Prediction of clinical response to methylphenidate in children with attention-deficit hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry,1995 ;34(8), 1025-32.

OBJECTIVE : To examine the pattern of individual responses to to methylphenidate (MPH) in children with attention-deficit hyperactivity disorder and to examine factors that predict drug response. METHOD : Individual drug response was defined on the basis of changes on the Abbreviated Conners Rating Scales completed by parents and teachers. These scales were the main outcome measures in a double-blind, placebo-controlled trial of MPH. Response prediction was examined in stepwise discriminant analyses, in which baseline variables and the response to a single, 10-mg dose of MPH were entered. RESULTS : Predictors of a strong MPH response were a high IQ, considerable inattentiveness, young age, low severity of disorder, and low rates of anxiety. A positive response to a single dose of MPH significantly improved the prediction of less stringently defined levels of MPH response. CONCLUSION : Only strong levels of response could be predicted by baseline characteristics. Severity of disorder based on clinical judgment and improvement after a single dose of MPH are found to be important contributors to response prediction.

29. Buitelaar J, Swinkels S, de Vries H, van der Gaag RJ, van Hooff J. An ethological study on behavioural differences between hyperactive, aggressive, combined hyperactive/aggressive and control children. Journal of child psychology and psychiatry,1994 ;35(8), 1437-46.

Frequencies and sequential patterns of behaviour elements in pure hyperactive (N = 12), pure aggressive (N = 13), combined hyperactive/aggressive (N = 15) and control children (N = 10) were recorded in a semistructured playroom session and subsequently compared. The samples were age- and IQ-matched. In an overall MANOVA a significant main effect for hyperactivity but not for aggression was found. The hyperactive children were characterized particularly by differences in squirming and changes in sitting. The sequential patterning of their behaviour revealed weaker temporal contingencies between their behaviour and the conversational speech of the experimenter than in the case of the nonhyperactive (aggressive and control) children. This may be explained by deficits in social attention in the hyperactive groups.

30. Verbaten M, Overtoom CC, Koelega HS, Swaab-Barneveld H, van der Gaag RJ, Buitelaar J, van Engeland H. Methylphenidate influences on both early and late ERP waves of ADHD children in a continuous performance test. Journal of abnormal child psychology,1994 ;22(5), 561-78.

Although it has frequently been reported that hyperactive children have abnormally small P3 amplitudes of the event-related potential (ERP), which are normalized by the stimulant drug methylphenidate (MPH), the literature is inconsistent concerning earlier ERP waves. The aim of the present study was to investigate whether the normalizing effect of a 10-mg dose of MPH was also apparent on earlier waves, such as the N1, the P2, and the N2, besides the P3. Twelve attention deficit with hyperactivity disorder (ADHD) children performed a Continuous Performance Test involving a button-press response to the letter X (CPT-X) under the influence of MPH in a double-blind placebo controlled acute dosage design. ERPs were recorded at Oz, Pz, Cz, and Fz. The expected increase of the parietal P3, both to targets and nontargets, was apparent, as well as a significant increase in percentage of hits. There also was a significant increase of an earlier, negative going, wave, the N2, with a frontal maximum, under the influence of MPH. This wave was probably a manifestation of an increase in processing negativity for target stimuli only, after the intake of the stimulant drug. No effect of MPH was found on the N1 or the P2.


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