Leo de Sonneville | Leiden University (original) (raw)

Papers by Leo de Sonneville

Objective: This study examines the association between neurocognitive functioning and tobacco smo... more Objective: This study examines the association between neurocognitive functioning and tobacco smoking in adolescence. Method: Data from three measurements of the longitudinal Tracking Adolescents ’ Individual Lives Survey (TRAILS), a large regional population-based cohort study of Dutch adolescents, were used. The first measurement took place in 2001–2002 (T1) when partici-pants were age 11, with two follow-up measurements (2003–2004 and 2005–2007; T2 and T3, respectively). A total of 1,797 adolescents participated in all three waves. At T1, they performed a selection of tasks from the Amsterdam Neuropsychological Tasks program (De Sonneville, 1999), which enabled the assessment of the main aspects of neurocognitive functioning. Smoking was assessed with a self-report questionnaire at T1, T2, and T3. In the multivariate analyses we controlled for gender, age, socioeconomic status (SES) and baseline speed. Results: Multivariate logistic regression analyses showed that poor sustained ...

PLOS ONE

Objectives To explore possible working mechanisms of anxiety reduction in women with anxiety diso... more Objectives To explore possible working mechanisms of anxiety reduction in women with anxiety disorders, treated with art therapy (AT). Methods A RCT comparing AT versus waiting list (WL) condition on aspects of self-regulation. Stress regulation (heart rate and heart rate variability) and executive functioning (daily behavioural and cognitive performance aspects of executive functioning (EF)) were evaluated in a prepost design. Participants were women, aged 18-65 years with moderate to severe anxiety symptoms. Results Effectiveness of AT compared to WL was demonstrated in a higher resting HRV post treatment, improvements in aspects of self-reported daily EF (emotion control, working memory, plan/organize and task monitor), but not in cognitive performance of EF, stress responsiveness and down regulation of stress. The decrease in anxiety level was associated with improvements in self-reported daily EF. Conclusions AT improves resting HRV and aspects of EF, the latter was associated with art therapyrelated anxiety reduction.

Regarding dr. Kleen's review: Major recommendations Ad 1) Although Daunorubicin (an anthracycline... more Regarding dr. Kleen's review: Major recommendations Ad 1) Although Daunorubicin (an anthracycline) is mostly known for its cardiotoxicity, it has been demonstrated to be neurotoxic to laboratory rats by increasing CNS levels of nitric oxide (Joshi P, Vig PJ, Veerisetty V, Cameron JA, Sekhon BS, Desaiah D: Increase in brain nitric oxide synthase activity in daunorubicin-treated rats. Pharmacol Toxicol 1996, Feb;78(2):99-103). But this neurotoxic mechanism does not differ from the mechanism associated with e.g. methotrexate (MTX), which also increases CNS levels of nitric oxide and is well-known for its neurotoxicity (Uzar E, Sahin O, Koyuncuoglu HR, Uz E, Bas O, Kilbas S, Yilmaz HR, Yurekli VA, Kucuker H, Songur A: The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: protective effect of caffeic acid phenethyl ester. Toxicology 2006,Feb 1;218(2-3):125-33). MTX was used in both the CT+CRT group and the CT-only group. We cannot think of any other mechanism through which daunorubicin could interact with CRT in a way that none of the other chemotherapeutic agents could. Ad 2) Smaller head size was not measured directly, but meeting with these patients, it was visible with the naked eye. Also, the average smaller head size was implicated by registration problems we encountered during MRI analyses that were also performed in our project. Of course a reference is in place here and has been added to the manuscript (reference n o 21). Ad 3) The 16 patients mentioned in the Methods were excluded during data analyses due to artefacts in the data. These 16 survivors were free from psychiatric disease or CNS disorders. Survivors with CNS disorders were already excluded in an earlier stage. Among those were 2 CRT treated patients with a meningioma discovered in the MRI part of our research. This information was added to the Subjects-section of the Methods. Two CRT-treated patients and 5 CT-treated patients who did not participate, were diagnosed with a psychiatric disease that we know of. But for most of the non-included survivors psychiatric status was unknown, so we do not know if these numbers are representative.

Journal of Autism and Developmental Disorders

Many students with autism spectrum disorders (ASDs) attending higher education drop out premature... more Many students with autism spectrum disorders (ASDs) attending higher education drop out prematurely. The predictive value of self-reported daily executive functioning (EF) and (cognitive) performance-based EF (mental flexibility and working memory) for academic progress was evaluated in 54 young adults with ASD (Mage = 22.5, SD = 2.4, 72% male). Regression analyses showed that autism symptom severity explained 12% of variance in academic progress, which was raised to 36% by adding self-reported daily EF, and to 25% by adding performance-based EF. It is suggested that EF is a candidate marker for academic progress in higher education students with ASD and a candidate target for early intervention.

PLOS ONE

Background Anxiety disorders are one of the most diagnosed mental health disorders. Common treatm... more Background Anxiety disorders are one of the most diagnosed mental health disorders. Common treatment consists of cognitive behavioral therapy and pharmacotherapy. In clinical practice, also art therapy is additionally provided to patients with anxiety (disorders), among others because treatment as usual is not sufficiently effective for a large group of patients. There is no clarity on the effectiveness of art therapy (AT) on the reduction of anxiety symptoms in adults and there is no overview of the intervention characteristics and working mechanisms. Methods A systematic review of (non-)randomised controlled trials on AT for anxiety in adults to evaluate the effects on anxiety symptom severity and to explore intervention characteristics, benefitting populations and working mechanisms. Thirteen databases and two journals were searched for the period 1997-October 2017. The study was registered at PROS-PERO (CRD42017080733) and performed according to the Cochrane recommendations. PRISMA Guidelines were used for reporting. Results Only three publications out of 776 hits from the search fulfilled the inclusion criteria: three RCTs with 162 patients in total. All studies have a high risk of bias. Study populations were: students with PTSD symptoms, students with exam anxiety and prisoners with prelease anxiety. Visual art techniques varied: trauma-related mandala design, collage making, free painting, clay work, still life drawing and house-tree-person drawing. There is some evidence of effectiveness of AT for pre-exam anxiety in undergraduate students. AT is possibly effective in reducing pre-release anxiety in prisoners. The AT characteristics varied and narrative synthesis led to hypothesized working mechanisms of AT: induce relaxation; gain

American journal of medical genetics. Part A, Jan 9, 2018

47,XXY (KS) occurs in 1:650 male births, though less than 25% are ever identified. We assessed st... more 47,XXY (KS) occurs in 1:650 male births, though less than 25% are ever identified. We assessed stability of neurocognitive features across diverse populations and quantified factors mediating outcome. Forty-four boys from the Netherlands (NL) and 54 boys from the United States (US) participated. The Wechsler Intelligence Scales assessed intellectual functioning; the ANT program evaluated cognitive function; and the CBCL assessed behavioral functioning. ANOVA was used for group comparisons. Hierarchical regressions assessed variance explained by each independent variable: parental education, timing of diagnosis, testosterone, age, and nationality. Parental education, timing of diagnosis, and hormonal treatment all played an important role in neurocognitive performance. The observed higher IQ and better attention regulation in the US group as compared to the NL group was observed with decreased levels of behavioral problems in the US group. Cognitive measures that were different betwe...

Journal of Child Psychology and Psychiatry

Background: Empathy deficits are hypothesized to underlie impairments in social interaction exhib... more Background: Empathy deficits are hypothesized to underlie impairments in social interaction exhibited by those who engage in antisocial behaviour. Social attention is an essential precursor to empathy; however, no studies have yet examined social attention in relation to cognitive and affective empathy in those exhibiting antisocial behaviour. Methods: Participants were 8-12 year-old children at high risk of developing criminal behaviour (N=114, 80.7% boys) and typically developing controls (N=43, 72.1% boys). The high-risk children were recruited through an ongoing early identification and intervention project of the city of Amsterdam, focusing on the underage siblings or children of delinquents and those failing primary school. Video clips with neutral and emotional content (fear, happiness and pain) were shown while heart rate (HR), skin conductance level (SCL) and skin conductance responses (SCRs) were recorded to measure affective empathy. Answers to questions about emotions in the clips were coded to measure cognitive empathy. Eye tracking was used to evaluate visual scanning patterns towards social relevant cues (eyes and face) in the clips. Results: The high-risk group did not differ from the control group in social attention and cognitive empathy, but showed reduced HR to pain and fear, and reduced SCL and SCRs to pain. Conclusions: Children at high risk of developing criminal behaviour show impaired affective empathy but unimpaired social attention and cognitive empathy. The implications for early identification and intervention studies with antisocial children are discussed.

Behavior genetics, Jan 3, 2017

Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylk... more Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylketonuria (PKU) have often been associated with metabolic control and its history. For the present study executive functioning (EF) was assessed in 21 PKU patients during childhood (T1, mean age 10.4 years, SD = 2.0) and again in adulthood (T2, mean age 25.8 years, SD = 2.3). At T2 additional assessments of EF in daily life and mental health were performed. Childhood (i.e. 0-12 years) blood phenylalanine was significantly related to cognitive flexibility, executive motor control, EF in daily life and mental health in adulthood (i.e. at T2). Patients with a greater increase in phenylalanine levels after the age of 12 performed more poorly on EF-tasks at T2. Group-based analyses showed that patients with phenylalanine <360 µmol/L in childhood and phenylalanine ≥360 µmol/L from age 13 onwards (n = 11) had better cognitive flexibility and executive motor control than those who had phenylal...

Neuropsychology, Jan 20, 2017

Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive funct... more Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive functions compared to healthy controls. Cognitive problems in phenylketonuria have often been associated with phenylalanine levels. The present study examined the cognitive profile and mental health in adult phenylketonuria, in relation to phenylalanine levels and tetrahydrobiopterin treatment. Fifty-seven early treated adult patients with phenylketonuria and 57 healthy matched controls (18-40 years) performed IQ subtests and executive function tests from the Amsterdam Neuropsychological Tasks. They also completed the Adult Self-Report on mental health problems. Analyses of variance were performed to examine group differences. Patients with phenylketonuria had normal IQs although lower than controls. They performed poorer on working memory, inhibitory control, and sustained attention tasks. Patients reported Depressive and Avoidant Personality problems more frequently. Specifically, patients ...

Child Neuropsychology, 2016

Children with 22q11.2 deletion syndrome (22q11DS; velo-cardiofacial-syndrome) are at risk for the... more Children with 22q11.2 deletion syndrome (22q11DS; velo-cardiofacial-syndrome) are at risk for the developmental disorders, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In this study, the relation between executive functioning (EF) and the severity of ADHD and ASD symptoms is examined, since EF is known to be important in relation to emotional and behavioral problems. The participants consist of 58 children (38 females) with a mean age of 13.5 years (SD 2.6). Standardized assessment was used to evaluate the severity of ASD and ADHD symptomatology. The major aspects of EF, i.e., cognitive flexibility, inhibition, sustained attention, distractibility, working memory and reaction speed, were evaluated. The profile of EF in 22q11DS was found to be characterized by weaker performance compared to the norms on all subdomains of EF. Poor cognitive flexibility and inhibition, as well as high distractibility, were found to be related to more severe ASD symptoms, while poor quality of sustained attention and high distractibility were found to be related to more severe ADHD symptoms. It is concluded that children with 22q11DS experience impairments in EF, and that the degree of impairment on specific EF subdomains is related to the severity of ASD and/or ADHD symptomatology. These results may help in defining the mediating role of neurocognitive dysfunctions in the development of social and behavioral problems in 22q11DS.

Clinical genetics, Jan 26, 2016

This paper examines how COMT(158) genotypes and plasma proline levels are associated with variabl... more This paper examines how COMT(158) genotypes and plasma proline levels are associated with variable penetrance of social behavioural and social-cognitive problems in 22q11.2 deletion syndrome (22q11DS). Severity of autistic spectrum symptoms of 45 participants with 22q11DS was assessed using the Autism Diagnostic Interview Revised. Face and facial emotion recognition was evaluated using standardized computer-based test-paradigms. Associations with COMT(158) genotypes and proline levels were examined. High proline levels and poor face recognition in individuals with the COMT(MET) allele, and poor facial emotion recognition, explained almost 50% of the variance in severity of autism symptomatology in individuals with 22q11DS. High proline levels and a decreased capacity to break down dopamine as a result of the COMT(MET) variant are both relevant in the expression of the social phenotype in patients. This epistatic interaction effect between the COMT(158) genotype and proline on the ex...

Journal of inherited metabolic disease, Jan 25, 2016

Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still ... more Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills. Ninety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4, N = 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined. PKU-patients showed poorer social-cognitive functioning and reportedly had poorer social...

European Journal of Paediatric Neurology, 2015

BACKGROUND AND AIMS Besides motor function the cerebellum subserves frontal lobe functions. Thus,... more BACKGROUND AND AIMS Besides motor function the cerebellum subserves frontal lobe functions. Thus, we investigated executive functions in pediatric posterior fossa tumor survivors. METHODS We tested information processing, aspects of attention, planning and intelligence in 42 pediatric posterior fossa tumor survivors (mean age 14.63 yrs, SD 5.03). Seventeen low-grade tumor patients (LGCT) were treated with surgery only and 25 high-grade tumors patients (HGCT) received postsurgical adjuvant treatment. We evaluated simple reaction time, executive functioning, i.e. visuospatial memory, inhibition, and mental flexibility using the Amsterdam Neuropsychological Tasks program, whereas forward thinking was assessed with the Tower of London-test. Intelligence was determined using the Wechsler Intelligence Scale. Ataxia was assessed with the International Cooperative Ataxia Rating Scale. RESULTS About one third of each patient group showed forward thinking scores below one standard deviation of the norm. Impaired forward thinking correlated significantly with degree of ataxia (r = -0.39, p = 0.03) but not with fluid intelligence. Both patient groups exhibited executive function deficits in accuracy and reaction speed in more difficult tasks involving information speed and attention flexibility. Still, HGCT patients were significantly slower and committed more errors. Working memory was inferior in HGCT patients. CONCLUSION Pediatric cerebellar tumor survivors with different disease and treatment related brain damage exhibit similar patterns of impairment in executive functioning, concerning forward thinking, inhibition and mental flexibility. The deficits are larger in high-grade tumor patients. The pattern of function loss seen in both groups is most probably due to comparable lesions to cerebro-cerebellar circuits that are known to modulate critical executive functions.

Journal of the International Neuropsychological Society : JINS, 2015

The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are... more The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are now aging into adulthood, and concerns are growing about the development of radiotherapy-induced cognitive deficits in the aging brain. These deficits are hypothesized to increase over time. Their impact on daily functioning of older survivors, and the accompanying need for interventions, should be anticipated. By describing a detailed profile of executive function deficits and their associations with age, specific targets for neuropsychological intervention can be identified. Fifty survivors of childhood lymphoid malignancies and 58 related controls were assessed with the Amsterdam Neuropsychological Tasks program. The survivors were on average 31.1 (4.9) years old, treated with 22.5 (6.8) Gy cranial irradiation, and examined on average 25.5 (3.1) years after diagnosis. The survivors showed significantly decreased response speed, irrespective of the task at hand. Furthermore, we found ...

Autism Research, 2014

Autism spectrum disorders (ASD) are associated with early disturbances in brain maturation proces... more Autism spectrum disorders (ASD) are associated with early disturbances in brain maturation processes and these interferences presumably have their consequences for the progressive emergence of cognitive deficits later in life, as expressed in intelligence profiles. In this study, we addressed the impact of age on cognitive functioning of 6- to 15-year-old children and adolescents with ASD. Intelligence profiles were measured by the Wechsler Intelligence Scale for Children and compared among four consecutive age cohorts (children aged 6.17-8.03 years, 8.04-9.61 years, and 9.68-11.50 years and adolescents aged 11.54-15.85 years) of 237 high-functioning boys with ASD. The results clearly demonstrated that the global intelligence level was lower in children aged 8 years and older, when compared with 6- and 7-year-old children with ASD. This is mostly due to the Freedom From Distractibility factor, suggesting that older children were less able to sustain their attention, they were more distractible, or had more graph motor difficulties. Moreover, an effect of age was also found with respect to the relatively poor performance on the subtest Comprehension when compared with other verbal comprehension subtests, indicating that specifically the impairments in verbal comprehension and social reasoning abilities were more profound in older children when compared with 6- and 7-year-old children with ASD. Findings of this cross-sectional study showed that it is relevant to take age into account when evaluating the impact of cognitive impairments on intelligence in children with ASD, because the impact of these developmental disorders might be different at different ages.

Schizophrenia Research, 2011

This study addresses the unraveling of the relationship between autism spectrum and schizophrenia... more This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well.

Molecular Genetics and Metabolism, 2014

Schizophrenia Research, 2014

Background: Medication nonadherence in patients with schizophrenia presents a serious clinical pr... more Background: Medication nonadherence in patients with schizophrenia presents a serious clinical problem. Research on interventions incorporating motivational interviewing (MI) to improve adherence have shown mixed results. Primary aim is to determine the effectiveness of a MI intervention on adherence and hospitalization rates in patients, with multiepisode schizophrenia or schizoaffective disorder, who have experienced a psychotic relapse following medication nonadherence. Secondary aim is to evaluate whether MI is more effective in specific subgroups. Methods: We performed a randomized controlled study including 114 patients who experienced a psychotic relapse due to medication nonadherence in the past year. Participants received an adapted form of MI or an active control intervention, health education (HE). Both interventions consisted of 5-8 sessions, which patients received in adjunction to the care as usual. Patients were assessed at baseline and at 6 and 12 months follow-up. Results: Our results show that MI did not improve medication adherence in previously nonadherent patients who experienced a psychotic relapse. Neither were there significant differences in hospitalization rates at follow-up between MI and HE (27% vs 40%, P=0.187). However, MI resulted in reduced hospitalization rates for female patients (9% vs 63%, P=0.041), non-cannabis users (20% vs 53%, P=0.041), younger patients (14% vs 50%, P=0.012), and patients with shorter illness duration (14% vs 42%, P=0.040). Discussion: Targeted use of MI may be of benefit for improving medication adherence in certain groups of patients, although this needs further examination. References: [1] Barkhof E, Meijer CJ, de Sonneville LM, Linszen DH, de Haan L. The effect of motivational interviewing on medication adherence and hospitalization rates in nonadherent patients with multi-episode schizophrenia.

Schizophrenia Research, 2010

These results imply that sex hormone changes during fetal period might play some roles in the dev... more These results imply that sex hormone changes during fetal period might play some roles in the development of schizophrenia.

Objective: This study examines the association between neurocognitive functioning and tobacco smo... more Objective: This study examines the association between neurocognitive functioning and tobacco smoking in adolescence. Method: Data from three measurements of the longitudinal Tracking Adolescents ’ Individual Lives Survey (TRAILS), a large regional population-based cohort study of Dutch adolescents, were used. The first measurement took place in 2001–2002 (T1) when partici-pants were age 11, with two follow-up measurements (2003–2004 and 2005–2007; T2 and T3, respectively). A total of 1,797 adolescents participated in all three waves. At T1, they performed a selection of tasks from the Amsterdam Neuropsychological Tasks program (De Sonneville, 1999), which enabled the assessment of the main aspects of neurocognitive functioning. Smoking was assessed with a self-report questionnaire at T1, T2, and T3. In the multivariate analyses we controlled for gender, age, socioeconomic status (SES) and baseline speed. Results: Multivariate logistic regression analyses showed that poor sustained ...

PLOS ONE

Objectives To explore possible working mechanisms of anxiety reduction in women with anxiety diso... more Objectives To explore possible working mechanisms of anxiety reduction in women with anxiety disorders, treated with art therapy (AT). Methods A RCT comparing AT versus waiting list (WL) condition on aspects of self-regulation. Stress regulation (heart rate and heart rate variability) and executive functioning (daily behavioural and cognitive performance aspects of executive functioning (EF)) were evaluated in a prepost design. Participants were women, aged 18-65 years with moderate to severe anxiety symptoms. Results Effectiveness of AT compared to WL was demonstrated in a higher resting HRV post treatment, improvements in aspects of self-reported daily EF (emotion control, working memory, plan/organize and task monitor), but not in cognitive performance of EF, stress responsiveness and down regulation of stress. The decrease in anxiety level was associated with improvements in self-reported daily EF. Conclusions AT improves resting HRV and aspects of EF, the latter was associated with art therapyrelated anxiety reduction.

Regarding dr. Kleen's review: Major recommendations Ad 1) Although Daunorubicin (an anthracycline... more Regarding dr. Kleen's review: Major recommendations Ad 1) Although Daunorubicin (an anthracycline) is mostly known for its cardiotoxicity, it has been demonstrated to be neurotoxic to laboratory rats by increasing CNS levels of nitric oxide (Joshi P, Vig PJ, Veerisetty V, Cameron JA, Sekhon BS, Desaiah D: Increase in brain nitric oxide synthase activity in daunorubicin-treated rats. Pharmacol Toxicol 1996, Feb;78(2):99-103). But this neurotoxic mechanism does not differ from the mechanism associated with e.g. methotrexate (MTX), which also increases CNS levels of nitric oxide and is well-known for its neurotoxicity (Uzar E, Sahin O, Koyuncuoglu HR, Uz E, Bas O, Kilbas S, Yilmaz HR, Yurekli VA, Kucuker H, Songur A: The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: protective effect of caffeic acid phenethyl ester. Toxicology 2006,Feb 1;218(2-3):125-33). MTX was used in both the CT+CRT group and the CT-only group. We cannot think of any other mechanism through which daunorubicin could interact with CRT in a way that none of the other chemotherapeutic agents could. Ad 2) Smaller head size was not measured directly, but meeting with these patients, it was visible with the naked eye. Also, the average smaller head size was implicated by registration problems we encountered during MRI analyses that were also performed in our project. Of course a reference is in place here and has been added to the manuscript (reference n o 21). Ad 3) The 16 patients mentioned in the Methods were excluded during data analyses due to artefacts in the data. These 16 survivors were free from psychiatric disease or CNS disorders. Survivors with CNS disorders were already excluded in an earlier stage. Among those were 2 CRT treated patients with a meningioma discovered in the MRI part of our research. This information was added to the Subjects-section of the Methods. Two CRT-treated patients and 5 CT-treated patients who did not participate, were diagnosed with a psychiatric disease that we know of. But for most of the non-included survivors psychiatric status was unknown, so we do not know if these numbers are representative.

Journal of Autism and Developmental Disorders

Many students with autism spectrum disorders (ASDs) attending higher education drop out premature... more Many students with autism spectrum disorders (ASDs) attending higher education drop out prematurely. The predictive value of self-reported daily executive functioning (EF) and (cognitive) performance-based EF (mental flexibility and working memory) for academic progress was evaluated in 54 young adults with ASD (Mage = 22.5, SD = 2.4, 72% male). Regression analyses showed that autism symptom severity explained 12% of variance in academic progress, which was raised to 36% by adding self-reported daily EF, and to 25% by adding performance-based EF. It is suggested that EF is a candidate marker for academic progress in higher education students with ASD and a candidate target for early intervention.

PLOS ONE

Background Anxiety disorders are one of the most diagnosed mental health disorders. Common treatm... more Background Anxiety disorders are one of the most diagnosed mental health disorders. Common treatment consists of cognitive behavioral therapy and pharmacotherapy. In clinical practice, also art therapy is additionally provided to patients with anxiety (disorders), among others because treatment as usual is not sufficiently effective for a large group of patients. There is no clarity on the effectiveness of art therapy (AT) on the reduction of anxiety symptoms in adults and there is no overview of the intervention characteristics and working mechanisms. Methods A systematic review of (non-)randomised controlled trials on AT for anxiety in adults to evaluate the effects on anxiety symptom severity and to explore intervention characteristics, benefitting populations and working mechanisms. Thirteen databases and two journals were searched for the period 1997-October 2017. The study was registered at PROS-PERO (CRD42017080733) and performed according to the Cochrane recommendations. PRISMA Guidelines were used for reporting. Results Only three publications out of 776 hits from the search fulfilled the inclusion criteria: three RCTs with 162 patients in total. All studies have a high risk of bias. Study populations were: students with PTSD symptoms, students with exam anxiety and prisoners with prelease anxiety. Visual art techniques varied: trauma-related mandala design, collage making, free painting, clay work, still life drawing and house-tree-person drawing. There is some evidence of effectiveness of AT for pre-exam anxiety in undergraduate students. AT is possibly effective in reducing pre-release anxiety in prisoners. The AT characteristics varied and narrative synthesis led to hypothesized working mechanisms of AT: induce relaxation; gain

American journal of medical genetics. Part A, Jan 9, 2018

47,XXY (KS) occurs in 1:650 male births, though less than 25% are ever identified. We assessed st... more 47,XXY (KS) occurs in 1:650 male births, though less than 25% are ever identified. We assessed stability of neurocognitive features across diverse populations and quantified factors mediating outcome. Forty-four boys from the Netherlands (NL) and 54 boys from the United States (US) participated. The Wechsler Intelligence Scales assessed intellectual functioning; the ANT program evaluated cognitive function; and the CBCL assessed behavioral functioning. ANOVA was used for group comparisons. Hierarchical regressions assessed variance explained by each independent variable: parental education, timing of diagnosis, testosterone, age, and nationality. Parental education, timing of diagnosis, and hormonal treatment all played an important role in neurocognitive performance. The observed higher IQ and better attention regulation in the US group as compared to the NL group was observed with decreased levels of behavioral problems in the US group. Cognitive measures that were different betwe...

Journal of Child Psychology and Psychiatry

Background: Empathy deficits are hypothesized to underlie impairments in social interaction exhib... more Background: Empathy deficits are hypothesized to underlie impairments in social interaction exhibited by those who engage in antisocial behaviour. Social attention is an essential precursor to empathy; however, no studies have yet examined social attention in relation to cognitive and affective empathy in those exhibiting antisocial behaviour. Methods: Participants were 8-12 year-old children at high risk of developing criminal behaviour (N=114, 80.7% boys) and typically developing controls (N=43, 72.1% boys). The high-risk children were recruited through an ongoing early identification and intervention project of the city of Amsterdam, focusing on the underage siblings or children of delinquents and those failing primary school. Video clips with neutral and emotional content (fear, happiness and pain) were shown while heart rate (HR), skin conductance level (SCL) and skin conductance responses (SCRs) were recorded to measure affective empathy. Answers to questions about emotions in the clips were coded to measure cognitive empathy. Eye tracking was used to evaluate visual scanning patterns towards social relevant cues (eyes and face) in the clips. Results: The high-risk group did not differ from the control group in social attention and cognitive empathy, but showed reduced HR to pain and fear, and reduced SCL and SCRs to pain. Conclusions: Children at high risk of developing criminal behaviour show impaired affective empathy but unimpaired social attention and cognitive empathy. The implications for early identification and intervention studies with antisocial children are discussed.

Behavior genetics, Jan 3, 2017

Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylk... more Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylketonuria (PKU) have often been associated with metabolic control and its history. For the present study executive functioning (EF) was assessed in 21 PKU patients during childhood (T1, mean age 10.4 years, SD = 2.0) and again in adulthood (T2, mean age 25.8 years, SD = 2.3). At T2 additional assessments of EF in daily life and mental health were performed. Childhood (i.e. 0-12 years) blood phenylalanine was significantly related to cognitive flexibility, executive motor control, EF in daily life and mental health in adulthood (i.e. at T2). Patients with a greater increase in phenylalanine levels after the age of 12 performed more poorly on EF-tasks at T2. Group-based analyses showed that patients with phenylalanine <360 µmol/L in childhood and phenylalanine ≥360 µmol/L from age 13 onwards (n = 11) had better cognitive flexibility and executive motor control than those who had phenylal...

Neuropsychology, Jan 20, 2017

Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive funct... more Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive functions compared to healthy controls. Cognitive problems in phenylketonuria have often been associated with phenylalanine levels. The present study examined the cognitive profile and mental health in adult phenylketonuria, in relation to phenylalanine levels and tetrahydrobiopterin treatment. Fifty-seven early treated adult patients with phenylketonuria and 57 healthy matched controls (18-40 years) performed IQ subtests and executive function tests from the Amsterdam Neuropsychological Tasks. They also completed the Adult Self-Report on mental health problems. Analyses of variance were performed to examine group differences. Patients with phenylketonuria had normal IQs although lower than controls. They performed poorer on working memory, inhibitory control, and sustained attention tasks. Patients reported Depressive and Avoidant Personality problems more frequently. Specifically, patients ...

Child Neuropsychology, 2016

Children with 22q11.2 deletion syndrome (22q11DS; velo-cardiofacial-syndrome) are at risk for the... more Children with 22q11.2 deletion syndrome (22q11DS; velo-cardiofacial-syndrome) are at risk for the developmental disorders, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In this study, the relation between executive functioning (EF) and the severity of ADHD and ASD symptoms is examined, since EF is known to be important in relation to emotional and behavioral problems. The participants consist of 58 children (38 females) with a mean age of 13.5 years (SD 2.6). Standardized assessment was used to evaluate the severity of ASD and ADHD symptomatology. The major aspects of EF, i.e., cognitive flexibility, inhibition, sustained attention, distractibility, working memory and reaction speed, were evaluated. The profile of EF in 22q11DS was found to be characterized by weaker performance compared to the norms on all subdomains of EF. Poor cognitive flexibility and inhibition, as well as high distractibility, were found to be related to more severe ASD symptoms, while poor quality of sustained attention and high distractibility were found to be related to more severe ADHD symptoms. It is concluded that children with 22q11DS experience impairments in EF, and that the degree of impairment on specific EF subdomains is related to the severity of ASD and/or ADHD symptomatology. These results may help in defining the mediating role of neurocognitive dysfunctions in the development of social and behavioral problems in 22q11DS.

Clinical genetics, Jan 26, 2016

This paper examines how COMT(158) genotypes and plasma proline levels are associated with variabl... more This paper examines how COMT(158) genotypes and plasma proline levels are associated with variable penetrance of social behavioural and social-cognitive problems in 22q11.2 deletion syndrome (22q11DS). Severity of autistic spectrum symptoms of 45 participants with 22q11DS was assessed using the Autism Diagnostic Interview Revised. Face and facial emotion recognition was evaluated using standardized computer-based test-paradigms. Associations with COMT(158) genotypes and proline levels were examined. High proline levels and poor face recognition in individuals with the COMT(MET) allele, and poor facial emotion recognition, explained almost 50% of the variance in severity of autism symptomatology in individuals with 22q11DS. High proline levels and a decreased capacity to break down dopamine as a result of the COMT(MET) variant are both relevant in the expression of the social phenotype in patients. This epistatic interaction effect between the COMT(158) genotype and proline on the ex...

Journal of inherited metabolic disease, Jan 25, 2016

Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still ... more Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills. Ninety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4, N = 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined. PKU-patients showed poorer social-cognitive functioning and reportedly had poorer social...

European Journal of Paediatric Neurology, 2015

BACKGROUND AND AIMS Besides motor function the cerebellum subserves frontal lobe functions. Thus,... more BACKGROUND AND AIMS Besides motor function the cerebellum subserves frontal lobe functions. Thus, we investigated executive functions in pediatric posterior fossa tumor survivors. METHODS We tested information processing, aspects of attention, planning and intelligence in 42 pediatric posterior fossa tumor survivors (mean age 14.63 yrs, SD 5.03). Seventeen low-grade tumor patients (LGCT) were treated with surgery only and 25 high-grade tumors patients (HGCT) received postsurgical adjuvant treatment. We evaluated simple reaction time, executive functioning, i.e. visuospatial memory, inhibition, and mental flexibility using the Amsterdam Neuropsychological Tasks program, whereas forward thinking was assessed with the Tower of London-test. Intelligence was determined using the Wechsler Intelligence Scale. Ataxia was assessed with the International Cooperative Ataxia Rating Scale. RESULTS About one third of each patient group showed forward thinking scores below one standard deviation of the norm. Impaired forward thinking correlated significantly with degree of ataxia (r = -0.39, p = 0.03) but not with fluid intelligence. Both patient groups exhibited executive function deficits in accuracy and reaction speed in more difficult tasks involving information speed and attention flexibility. Still, HGCT patients were significantly slower and committed more errors. Working memory was inferior in HGCT patients. CONCLUSION Pediatric cerebellar tumor survivors with different disease and treatment related brain damage exhibit similar patterns of impairment in executive functioning, concerning forward thinking, inhibition and mental flexibility. The deficits are larger in high-grade tumor patients. The pattern of function loss seen in both groups is most probably due to comparable lesions to cerebro-cerebellar circuits that are known to modulate critical executive functions.

Journal of the International Neuropsychological Society : JINS, 2015

The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are... more The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are now aging into adulthood, and concerns are growing about the development of radiotherapy-induced cognitive deficits in the aging brain. These deficits are hypothesized to increase over time. Their impact on daily functioning of older survivors, and the accompanying need for interventions, should be anticipated. By describing a detailed profile of executive function deficits and their associations with age, specific targets for neuropsychological intervention can be identified. Fifty survivors of childhood lymphoid malignancies and 58 related controls were assessed with the Amsterdam Neuropsychological Tasks program. The survivors were on average 31.1 (4.9) years old, treated with 22.5 (6.8) Gy cranial irradiation, and examined on average 25.5 (3.1) years after diagnosis. The survivors showed significantly decreased response speed, irrespective of the task at hand. Furthermore, we found ...

Autism Research, 2014

Autism spectrum disorders (ASD) are associated with early disturbances in brain maturation proces... more Autism spectrum disorders (ASD) are associated with early disturbances in brain maturation processes and these interferences presumably have their consequences for the progressive emergence of cognitive deficits later in life, as expressed in intelligence profiles. In this study, we addressed the impact of age on cognitive functioning of 6- to 15-year-old children and adolescents with ASD. Intelligence profiles were measured by the Wechsler Intelligence Scale for Children and compared among four consecutive age cohorts (children aged 6.17-8.03 years, 8.04-9.61 years, and 9.68-11.50 years and adolescents aged 11.54-15.85 years) of 237 high-functioning boys with ASD. The results clearly demonstrated that the global intelligence level was lower in children aged 8 years and older, when compared with 6- and 7-year-old children with ASD. This is mostly due to the Freedom From Distractibility factor, suggesting that older children were less able to sustain their attention, they were more distractible, or had more graph motor difficulties. Moreover, an effect of age was also found with respect to the relatively poor performance on the subtest Comprehension when compared with other verbal comprehension subtests, indicating that specifically the impairments in verbal comprehension and social reasoning abilities were more profound in older children when compared with 6- and 7-year-old children with ASD. Findings of this cross-sectional study showed that it is relevant to take age into account when evaluating the impact of cognitive impairments on intelligence in children with ASD, because the impact of these developmental disorders might be different at different ages.

Schizophrenia Research, 2011

This study addresses the unraveling of the relationship between autism spectrum and schizophrenia... more This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well.

Molecular Genetics and Metabolism, 2014

Schizophrenia Research, 2014

Background: Medication nonadherence in patients with schizophrenia presents a serious clinical pr... more Background: Medication nonadherence in patients with schizophrenia presents a serious clinical problem. Research on interventions incorporating motivational interviewing (MI) to improve adherence have shown mixed results. Primary aim is to determine the effectiveness of a MI intervention on adherence and hospitalization rates in patients, with multiepisode schizophrenia or schizoaffective disorder, who have experienced a psychotic relapse following medication nonadherence. Secondary aim is to evaluate whether MI is more effective in specific subgroups. Methods: We performed a randomized controlled study including 114 patients who experienced a psychotic relapse due to medication nonadherence in the past year. Participants received an adapted form of MI or an active control intervention, health education (HE). Both interventions consisted of 5-8 sessions, which patients received in adjunction to the care as usual. Patients were assessed at baseline and at 6 and 12 months follow-up. Results: Our results show that MI did not improve medication adherence in previously nonadherent patients who experienced a psychotic relapse. Neither were there significant differences in hospitalization rates at follow-up between MI and HE (27% vs 40%, P=0.187). However, MI resulted in reduced hospitalization rates for female patients (9% vs 63%, P=0.041), non-cannabis users (20% vs 53%, P=0.041), younger patients (14% vs 50%, P=0.012), and patients with shorter illness duration (14% vs 42%, P=0.040). Discussion: Targeted use of MI may be of benefit for improving medication adherence in certain groups of patients, although this needs further examination. References: [1] Barkhof E, Meijer CJ, de Sonneville LM, Linszen DH, de Haan L. The effect of motivational interviewing on medication adherence and hospitalization rates in nonadherent patients with multi-episode schizophrenia.

Schizophrenia Research, 2010

These results imply that sex hormone changes during fetal period might play some roles in the dev... more These results imply that sex hormone changes during fetal period might play some roles in the development of schizophrenia.