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1. Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation

Author

Janson, E., Koolschijn, P. C. M. P., Schipper, L., Boerma, T. D., Wijnen, F. N. K., de Boode, W. P., van den Akker, C. H. P., Licht-van der Stap, R. G., Nuytemans, D. H. G. M., Onland, W., Obermann-Borst, S. A., Dudink, J., de Theije, C. G. M., Benders, M. J. N. L., and van der Aa, N. E.

Published
2024
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2. Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation

Author

Janson, E, Koolschijn, P C M P, Schipper, L, Boerma, T D, Wijnen, F N K, de Boode, W P, van den Akker, C H P, Licht-van der Stap, R G, Nuytemans, D H G M, Onland, W, Obermann-Borst, S A, Dudink, J, de Theije, C G M, Benders, M J N L, van der Aa, N E, Janson, E, Koolschijn, P C M P, Schipper, L, Boerma, T D, Wijnen, F N K, de Boode, W P, van den Akker, C H P, Licht-van der Stap, R G, Nuytemans, D H G M, Onland, W, Obermann-Borst, S A, Dudink, J, de Theije, C G M, Benders, M J N L, and van der Aa, N E

Abstract

BACKGROUND: Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm.METHODS: This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R

Published
2024

3. Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation

Author

Genetica Genoom 3, E&R onderzoek, KGW-algemeen, MS Neonatologie, Brain, Child Health, Developmental Disorders, DDOD, Cancer, Circulatory Health, Janson, E., Koolschijn, P. C.M.P., Schipper, L., Boerma, T. D., Wijnen, F. N.K., de Boode, W. P., van den Akker, C. H.P., Licht-van der Stap, R. G., Nuytemans, D. H.G.M., Onland, W., Obermann-Borst, S. A., Dudink, J., de Theije, C. G.M., Benders, M. J.N.L., van der Aa, N. E., Genetica Genoom 3, E&R onderzoek, KGW-algemeen, MS Neonatologie, Brain, Child Health, Developmental Disorders, DDOD, Cancer, Circulatory Health, Janson, E., Koolschijn, P. C.M.P., Schipper, L., Boerma, T. D., Wijnen, F. N.K., de Boode, W. P., van den Akker, C. H.P., Licht-van der Stap, R. G., Nuytemans, D. H.G.M., Onland, W., Obermann-Borst, S. A., Dudink, J., de Theije, C. G.M., Benders, M. J.N.L., and van der Aa, N. E.

Published
2024

4. Trauma-focused treatment for traumatic stress symptoms in unaccompanied refugee minors: a multiple baseline case series

Author

Van Es, C.M., Velu, M.E., Sleijpen, M.J.T., van der Aa, N., Boelen, P.A., Mooren, G.T.M., Van Es, C.M., Velu, M.E., Sleijpen, M.J.T., van der Aa, N., Boelen, P.A., and Mooren, G.T.M.

Abstract

Introduction: Unaccompanied refugee minors (URMs) are at increased risk of developing mental health problems, such as symptoms of posttraumatic stress disorder (PTSD) and depression. In addition, URMs face several barriers to mental health care. Few studies have evaluated trauma-focused interventions for URMs that target these issues. The current study evaluated a multimodal trauma-focused treatment approach for URMs. It aimed to provide an initial indication of the effectiveness of this treatment approach and to provide a qualitative evaluation assessing treatment satisfaction of the participating URMs. Methods: A mixed-methods study was conducted among ten URMs, combining quantitative data with qualitative data through triangulation. Quantitative data were collected using a non-concurrent multiple baseline design in which repeated, weekly assessments were carried out during a randomized baseline period, during treatment, and during a 4-week follow-up period. Questionnaires assessing PTSD (Children’s Revised Impact of Event Scale) and symptoms of depression (The Patient Health Questionnaire-9, modified for adolescents) were used. In addition, treatment satisfaction was measured post-treatment using a semi-structured interview. Results: During the qualitative evaluation, all but one URM noted they found the trauma-focused treatment approach useful and felt the treatment had positively impacted their wellbeing. However, the results of the quantitative evaluation did not show clinically reliable symptom reductions at posttest or follow-up. Implications for clinical practice and research are discussed. Discussion: The current study presents our search in developing a treatment approach for URMs. It adds to the current knowledge about methodological considerations in evaluating treatments for URMs, the potential effects of trauma-focused treatments on URMs, and the implementation of treatments for URMs. Clinical trial registration: The study was

Published
2023

6. Introduction of ultra-high-field MR brain imaging in infants: vital parameters, temperature and comfort

Author

MS Neonatologie, Arts-assistenten Kinderen, Brain, Child Health, Developmental Disorders, Circulatory Health, Regenerative Medicine and Stem Cells, MS Radiologie, Highfield Research Group, Cancer, Beeldverwerking ISI, Computational Imaging, Infection & Immunity, van Ooijen, I. M., Annink, K. V., Benders, M. J.N.L., Dudink, J., Alderliesten, T., Groenendaal, F., Tataranno, M. L., Lequin, M. H., Hoogduin, J. M., Visser, F., Raaijmakers, A. J.E., Klomp, D. W.J., Wiegers, E. C., Wijnen, J. P., van der Aa, N. E., MS Neonatologie, Arts-assistenten Kinderen, Brain, Child Health, Developmental Disorders, Circulatory Health, Regenerative Medicine and Stem Cells, MS Radiologie, Highfield Research Group, Cancer, Beeldverwerking ISI, Computational Imaging, Infection & Immunity, van Ooijen, I. M., Annink, K. V., Benders, M. J.N.L., Dudink, J., Alderliesten, T., Groenendaal, F., Tataranno, M. L., Lequin, M. H., Hoogduin, J. M., Visser, F., Raaijmakers, A. J.E., Klomp, D. W.J., Wiegers, E. C., Wijnen, J. P., and van der Aa, N. E.

Published
2023

8. Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Author

Wang T., Hoekzema K., Vecchio D., Wu H., Sulovari A., Coe B. P., Gillentine M. A., Wilfert A. B., Perez-Jurado L. A., Kvarnung M., Sleyp Y., Earl R. K., Rosenfeld J. A., Geisheker M. R., Han L., Du B., Barnett C., Thompson E., Shaw M., Carroll R., Friend K., Catford R., Palmer E. E., Zou X., Ou J., Li H., Guo H., Gerdts J., Avola E., Calabrese G., Elia M., Greco D., Lindstrand A., Nordgren A., Anderlid B. -M., Vandeweyer G., Van Dijck A., Van der Aa N., McKenna B., Hancarova M., Bendova S., Havlovicova M., Malerba G., Bernardina B. D., Muglia P., van Haeringen A., Hoffer M. J. V., Franke B., Cappuccio G., Delatycki M., Lockhart P. J., Manning M. A., Liu P., Scheffer I. E., Brunetti Pierri N., Rommelse N., Amaral D. G., Santen G. W. E., Trabetti E., Sedlacek Z., Michaelson J. J., Pierce K., Courchesne E., Kooy R. F., Acampado J., Ace A. J., Amatya A., Astrovskaya I., Bashar A., Brooks E., Butler M. E., Cartner L. A., Chin W., Chung W. K., Daniels A. M., Feliciano P., Fleisch C., Ganesan S., Jensen W., Lash A. E., Marini R., Myers V. J., O'Connor E., Rigby C., Robertson B. E., Shah N., Shah S., Singer E., Snyder L. A. G., Stephens A. N., Tjernagel J., Vernoia B. M., Volfovsky N., White L. C., Hsieh A., Shen Y., Zhou X., Turner T. N., Bahl E., Thomas T. R., Brueggeman L., Koomar T., Michael R. J., O'Roak B. J., Barnard R. A., Gibbs R. A., Muzny D., Sabo A., Ahmed K. L. B., Eichler E. E., Siegel M., Abbeduto L., Hilscher B. A., Li D., Smith K., Thompson S., Albright C., Butter E. M., Eldred S., Hanna N., Jones M., Coury D. L., Scherr J., Pifher T., Roby E., Dennis B., Higgins L., Brown M., Alessandri M., Gutierrez A., Hale M. N., Herbert L. M., Schneider H. L., David G., Annett R. D., Sarver D. E., Arriaga I., Camba A., Gulsrud A. C., Haley M., McCracken J. T., Sandhu S., Tafolla M., Yang W. S., Carpenter L. A., Bradley C. C., Gwynette F., Manning P., Shaffer R., Thomas C., Bernier R. A., Fox E. A., Gerdts J. A., Pepper M., Ho T., Cho D., Piven J., Lechniak H., Soorya L. V., Gordon R., Wainer A., Yeh L., Ochoa-Lubinoff C., Russo N., Berry-Kravis E., Booker S., Erickson C. A., Prock L. M., Pawlowski K. G., Matthews E. T., Brewster S. J., Hojlo M. A., Abada E., Lamarche E., Murali S. C., Harvey W. T., Kaplan H. E., Pierce K. L., DeMarco L., Horner S., Pandey J., Plate S., Sahin M., Riley K. D., Carmody E., Constantini J., Esler A., Fatemi A., Hutter H., Landa R. J., McKenzie A. P., Neely J., Singh V., Van Metre B., Wodka E. L., Fombonne E. J., Huang-Storms L. Y., Pacheco L. D., Mastel S. A., Coppola L. A., Francis S., Jarrett A., Jacob S., Lillie N., Gunderson J., Istephanous D., Simon L., Wasserberg O., Rachubinski A. L., Rosenberg C. R., Kanne S. M., Shocklee A. D., Takahashi N., Bridwell S. L., Klimczac R. L., Mahurin M. A., Cotrell H. E., Grant C. A., Hunter S. G., Martin C. L., Taylor C. M., Walsh L. K., Dent K. A., Mason A., Sziklay A., Smith C. J., Nordenskjold M., Romano C., Peeters H., Gecz J., Xia K., SPARK Consortium, Wang, T., Hoekzema, K., Vecchio, D., Wu, H., Sulovari, A., Coe, B. P., Gillentine, M. A., Wilfert, A. B., Perez-Jurado, L. A., Kvarnung, M., Sleyp, Y., Earl, R. K., Rosenfeld, J. A., Geisheker, M. R., Han, L., Du, B., Barnett, C., Thompson, E., Shaw, M., Carroll, R., Friend, K., Catford, R., Palmer, E. E., Zou, X., Ou, J., Li, H., Guo, H., Gerdts, J., Avola, E., Calabrese, G., Elia, M., Greco, D., Lindstrand, A., Nordgren, A., Anderlid, B. -M., Vandeweyer, G., Van Dijck, A., Van der Aa, N., Mckenna, B., Hancarova, M., Bendova, S., Havlovicova, M., Malerba, G., Bernardina, B. D., Muglia, P., van Haeringen, A., Hoffer, M. J. V., Franke, B., Cappuccio, G., Delatycki, M., Lockhart, P. J., Manning, M. A., Liu, P., Scheffer, I. E., Brunetti Pierri, N., Rommelse, N., Amaral, D. G., Santen, G. W. E., Trabetti, E., Sedlacek, Z., Michaelson, J. J., Pierce, K., Courchesne, E., Kooy, R. F., Acampado, J., Ace, A. J., Amatya, A., Astrovskaya, I., Bashar, A., Brooks, E., Butler, M. E., Cartner, L. A., Chin, W., Chung, W. K., Daniels, A. M., Feliciano, P., Fleisch, C., Ganesan, S., Jensen, W., Lash, A. E., Marini, R., Myers, V. J., O'Connor, E., Rigby, C., Robertson, B. E., Shah, N., Shah, S., Singer, E., Snyder, L. A. G., Stephens, A. N., Tjernagel, J., Vernoia, B. M., Volfovsky, N., White, L. C., Hsieh, A., Shen, Y., Zhou, X., Turner, T. N., Bahl, E., Thomas, T. R., Brueggeman, L., Koomar, T., Michael, R. J., O'Roak, B. J., Barnard, R. A., Gibbs, R. A., Muzny, D., Sabo, A., Ahmed, K. L. B., Eichler, E. E., Siegel, M., Abbeduto, L., Hilscher, B. A., Li, D., Smith, K., Thompson, S., Albright, C., Butter, E. M., Eldred, S., Hanna, N., Jones, M., Coury, D. L., Scherr, J., Pifher, T., Roby, E., Dennis, B., Higgins, L., Brown, M., Alessandri, M., Gutierrez, A., Hale, M. N., Herbert, L. M., Schneider, H. L., David, G., Annett, R. D., Sarver, D. E., Arriaga, I., Camba, A., Gulsrud, A. C., Haley, M., Mccracken, J. T., Sandhu, S., Tafolla, M., Yang, W. S., Carpenter, L. A., Bradley, C. C., Gwynette, F., Manning, P., Shaffer, R., Thomas, C., Bernier, R. A., Fox, E. A., Gerdts, J. A., Pepper, M., Ho, T., Cho, D., Piven, J., Lechniak, H., Soorya, L. V., Gordon, R., Wainer, A., Yeh, L., Ochoa-Lubinoff, C., Russo, N., Berry-Kravis, E., Booker, S., Erickson, C. A., Prock, L. M., Pawlowski, K. G., Matthews, E. T., Brewster, S. J., Hojlo, M. A., Abada, E., Lamarche, E., Murali, S. C., Harvey, W. T., Kaplan, H. E., Pierce, K. L., Demarco, L., Horner, S., Pandey, J., Plate, S., Sahin, M., Riley, K. D., Carmody, E., Constantini, J., Esler, A., Fatemi, A., Hutter, H., Landa, R. J., Mckenzie, A. P., Neely, J., Singh, V., Van Metre, B., Wodka, E. L., Fombonne, E. J., Huang-Storms, L. Y., Pacheco, L. D., Mastel, S. A., Coppola, L. A., Francis, S., Jarrett, A., Jacob, S., Lillie, N., Gunderson, J., Istephanous, D., Simon, L., Wasserberg, O., Rachubinski, A. L., Rosenberg, C. R., Kanne, S. M., Shocklee, A. D., Takahashi, N., Bridwell, S. L., Klimczac, R. L., Mahurin, M. A., Cotrell, H. E., Grant, C. A., Hunter, S. G., Martin, C. L., Taylor, C. M., Walsh, L. K., Dent, K. A., Mason, A., Sziklay, A., Smith, C. J., Nordenskjold, M., Romano, C., Peeters, H., Gecz, J., and Xia, K.

Subjects
0301 basic medicine, Male, CCCTC-Binding Factor, Transcription Factor, Basic Helix-Loop-Helix Transcription Factor, DNA Mutational Analysis, General Physics and Astronomy, RNA-Binding Protein, Heterogeneous-Nuclear Ribonucleoprotein U, VARIANTS, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Neurodevelopmental Disorder, Basic Helix-Loop-Helix Transcription Factors, SPARK Consortium, 2.1 Biological and endogenous factors, Copy-number variation, Aetiology, lcsh:Science, GABRG2, Genetics, Mutation, Multidisciplinary, biology, Neurodevelopmental disorders, RNA-Binding Proteins, High-Throughput Nucleotide Sequencing, Autism spectrum disorders, Multidisciplinary Sciences, DNA-Binding Proteins, Science & Technology - Other Topics, Female, Case-Control Studie, Engineering sciences. Technology, Human, Science, DNA-Binding Protein, Genetic Association Studie, COPY-NUMBER VARIATION, General Biochemistry, Genetics and Molecular Biology, DNA sequencing, Article, KCNQ3 Potassium Channel, DNA Mutational Analysi, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, AUTISM, Gene, Genetic Association Studies, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, DISABILITY, Prevention, Case-control study, General Chemistry, Repressor Protein, medicine.disease, FRAMEWORK, Repressor Proteins, DE-NOVO MUTATION, 030104 developmental biology, CTCF, Neurodevelopmental Disorders, Case-Control Studies, biology.protein, Next-generation sequencing, Autism, lcsh:Q, Cohort Studie, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF, For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

Published
2020

9. The moderating role of individual resilience in refugee and Dutch adolescents after trauma

Author

Sleijpen, M.J.T., van der Aa, N., Mooren, G.T.M., Laban, C.J., Kleber, R.J., Leerstoel Boelen, Leerstoel Kleber, Trauma and Grief, Leerstoel Boelen, Leerstoel Kleber, and Trauma and Grief

Subjects
Male, Adolescent, Social Psychology, media_common.quotation_subject, Refugee, Psychological Trauma, Adolescents, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, Adverse Childhood Experiences, Humans, Personality, 030212 general & internal medicine, Big Five personality traits, Child, Netherlands, media_common, Exposure to Violence, Refugees, Resilience, Life satisfaction, PTSD, Strengths and Difficulties Questionnaire, Resilience, Psychological, Moderation, Mental health, 030227 psychiatry, Clinical Psychology, Cross-Sectional Studies, Female, Psychological resilience, Psychology, Clinical psychology
Abstract

Exposure to potentially traumatic events (PTEs) has been identified as a risk factor for various psychological problems in adolescents generally and in young refugees. The aim of this study was to examine whether individual resilience (assessed as a personality characteristic) can protect adolescents in diverse contexts from negative effects of trauma exposure.A path model was used to assess whether individual resilience buffered the negative effects of exposure to PTEs in a cross-sectional study of adolescent refugees (aged 12-17 years; n = 117) and their Dutch peers (n = 148). Measurements included the Children's Revised Impact of Event Scale, Strengths and Difficulties Questionnaire, Satisfaction with Life Scale and the Resilience Scale.The moderating effects of individual resilience on the relationship between PTEs and mental health problems and life satisfaction were mixed: In the nonrefugee group, but not in the refugee group most moderation effects reached significance.Findings suggest that not all groups benefit similarly from individual-level resilience. Consequently, adolescents, who differ with regard to the risks to which they are exposed, may need different forms of support. This study points to the interplay of factors that contributes to demonstration of individual resilience. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Published
2019
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10. Symptom severity in PTSD and comorbid psychopathology: A latent profile analysis among traumatized veterans

Author

Jongedijk, R.A., van der Aa, N., Haagen, J.F.G., Boelen, P.A., Kleber, R.J., Leerstoel Boelen, Leerstoel Kleber, and Trauma and Grief

Subjects
Adult, Male, Agreeableness, Coping (psychology), media_common.quotation_subject, Population, Dysfunctional family, Comorbidity, Psychological Distress, Stress Disorders, Post-Traumatic, Adaptation, Psychological, medicine, Humans, Personality, education, Netherlands, Veterans, media_common, Subtypes, Neuroticism, education.field_of_study, Predictors, Posttraumatic stress disorder, Latent profile analysis, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Mental Health, Treatment Outcome, Female, Self Report, Psychology, Clinical psychology, Psychopathology
Abstract

Individuals diagnosed with posttraumatic stress disorder (PTSD) show remarkably different symptom presentations. Identification of diagnostic profiles of PTSD may contribute to knowledge about treatment modifications to enhance treatment effectiveness. The present study aimed to identify symptom severity classes among 236 Dutch veterans based on a broad range of psychopathology outcomes, including PTSD, using Latent Profile Analysis (LPA). Moreover, multinomial logistic regression was used to test whether class membership could be predicted by the number and characteristics of traumatic event types, coping and personality dimensions. LPA identified three classes of individuals, defined as average, severe, and highly severe symptom severity classes, respectively. No qualitative differences in the symptom dimensions emerged between classes. Veterans with higher amounts of traumatic experiences and specifically with regard to lack of basic human needs, as well as those using more avoidant and problem-focused coping strategies and with more dysfunctional personality characteristics regarding neuroticism and agreeableness were significantly more often in the severe and/or highly severe symptom classes. In conclusion, general symptom severity was found to be an important diagnostic characteristic in this population. Integrated treatments targeting the broad spectrum of mental health problems may be of importance in treating patients that show low therapeutic recovery.

Published
2019
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13. Uneven distribution of Purkinje cell injury in the cerebellar vermis of term neonates with hypoxic-ischemic encephalopathy

Author

Mjnl Benders, Floris Groenendaal, van der Aa N, Reint K. Jellema, Martin Lammens, Thomas Alderliesten, Jeroen Dudink, van Leeuwen I, Freek E. Hoebeek, Peter G. J. Nikkels, Nijboer C, and Kim V. Annink

Subjects
Pathology, medicine.medical_specialty, business.industry, Purkinje cell, Encephalopathy, Autopsy, Haematoxylin, medicine.disease, Hypoxic Ischemic Encephalopathy, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Cerebellar vermis, Medicine, Distribution (pharmacology), Animal studies, business
Abstract

IntroductionIn term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxic-ischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated. The aim of this study was to determine the distribution of PC injury in the cerebellar vermis of term born neonates with HIE.MethodsTerm born neonates with HIE that underwent post-mortem autopsy of the cerebellar vermis were included. Haematoxylin & Eosin (H&E) stained sections of the vermis were used to determine total PC count and morphology (normal, abnormal or non-classified) at the bases and crown of the folia and of the lobules in both the anterior and posterior lobes. Differences in PC count and PC morphology between the anterior and posterior lobe and between the bases and crown were calculated using the paired samples T-test or Wilcoxon-signed rank test.ResultsThe total number of PCs were significantly higher at the crown compared to the bases (pConclusionThe abnormal PC count and morphology in term neonates with HIE resembles supratentorial ulegyria.

Published
2020
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14. Severity profiles of posttraumatic stress, depression, anxiety, and somatization symptoms in treatment seeking traumatized refugees

Author

Jongedijk, R.A., Eising, D.D., van der Aa, N., Kleber, R.J., Boelen, P.A., Trauma and Grief, Leerstoel Kleber, and Leerstoel Boelen

Subjects
Clinical Psychology, Psychiatry and Mental health, Refugee, Predictors, Posttraumatic stress disorder, Subtype, Comorbidity, Latent profile analysis
Abstract

Background: Western countries are facing many challenges hosting refugees from several regions in the world. Many of them are severely traumatized and suffer from a variety of mental health symptoms, which complicates the identification and treatment of refugees at risk. This study examined subgroups based on a broad range of psychopathology, and several predictors, including trauma characteristics and gender. Methods: Participants were 1147 treatment-seeking, traumatized refugees. Latent profile analysis was conducted to identify different subgroups based on levels of posttraumatic stress disorder (PTSD), depression, anxiety, and somatic symptoms. Multinomial logistic regression was used to identify predictors of subgroup membership. Results: Three distinct subgroups were identified, reflecting Moderate (10.2%), Severe (43.0%), and Highly Severe (45.9%) symptom severity levels, respectively. Symptom severity of all psychopathology dimensions was distributed equally between the subgroups. Participants in the Severe and Highly Severe Symptoms subgroups reported more types of traumatic events compared to the Moderate subgroup. In particular, traumatic events associated with human right abuses, lack of human needs and separation from others predicted subgroup membership, as did gender. Limitations: The results are confined to treatment-seeking, traumatized refugee populations. Conclusions: Distinguishable symptom severity profiles of PTSD, depression, anxiety and somatic complaints could be identified in this large treatment-seeking refugee population, without qualitative differences in symptom distribution. Instead of focusing on specific mental disorders, classification based on overall symptom severity is of interest in severely traumatized patients. This knowledge will help to identify individuals at risk and to enhance existing treatment programs for specific patient groups.

Published
2020

20. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome

Author

van Bon, B W M, Mefford, H C, Menten, B, Koolen, D A, Sharp, A J, Nillesen, W M, Innis, J W, de Ravel, T J L, Mercer, C L, Fichera, M, Stewart, H, Connell, L E, Õunap, K, Lachlan, K, Castle, B, Van der Aa, N, van Ravenswaaij, C, Nobrega, M A, Serra-Juhé, C, Simonic, I, de Leeuw, N, Pfundt, R, Bongers, E M, Baker, C, Finnemore, P, Huang, S, Maloney, V K, Crolla, J A, van Kalmthout, M, Elia, M, Vandeweyer, G, Fryns, J P, Janssens, S, Foulds, N, Reitano, S, Smith, K, Parkel, S, Loeys, B, Woods, C G, Oostra, A, Speleman, F, Pereira, A C, Kurg, A, Willatt, L, Knight, S J L, Vermeesch, J R, Romano, C, Barber, J C, Mortier, G, Pérez-Jurado, L A, Kooy, F, Brunner, H G, Eichler, E E, Kleefstra, T, and de Vries, B B A

Published
2009
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21. Author Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders (Nature Communications, (2020), 11, 1, (4932), 10.1038/s41467-020-18723-y)

Author

Wang, T., Hoekzema, K., Vecchio, Davide., Wu, H., Sulovari, A., Coe, B. P., Gillentine, M. A., Wilfert, A. B., Perez-Jurado, L. A., Kvarnung, M., Sleyp, Y., Earl, R. K., Rosenfeld, J. A., Geisheker, M. R., Han, L., Du, B., Barnett, C., Thompson, E., Shaw, M., Carroll, R., Friend, K., Catford, R., Palmer, E. E., Zou, X., Ou, J., Li, H., Guo, H., Gerdts, J., Avola, E., Calabrese, Giuseppe, Elia, Maurizio., Greco, Donatella, Lindstrand, A., Nordgren, A., Anderlid, B. -M., Vandeweyer, G., Van Dijck, A., Van der Aa, N., Mckenna, B., Hancarova, M., Bendova, S., Havlovicova, M., Malerba, G., Bernardina, B. D., Muglia, P., van Haeringen, A., Hoffer, M. J. V., Franke, B., Cappuccio, G., Delatycki, M., Lockhart, P. J., Manning, M. A., Liu, P., Scheffer, I. E., Brunetti-Pierri, N., Rommelse, N., Amaral, D. G., Santen, G. W. E., Trabetti, E., Sedlacek, Z., Michaelson, J. J., Pierce, K., Courchesne, E., Kooy, R. F., Acampado, J., Ace, A. J., Amatya, A., Astrovskaya, I., Bashar, A., Brooks, E., Butler, M. E., Cartner, L. A., Chin, W., Chung, W. K., Daniels, A. M., Feliciano, P., Fleisch, C., Ganesan, S., Jensen, W., Lash, A. E., Marini, R., Myers, V. J., O'Connor, E., Rigby, C., Robertson, B. E., Shah, N., Shah, S., Singer, E., Snyder, L. A. G., Stephens, A. N., Tjernagel, J., Vernoia, B. M., Volfovsky, N., White, L. C., Hsieh, A., Shen, Y., Zhou, X., Turner, T. N., Bahl, E., Thomas, T. R., Brueggeman, L., Koomar, T., O'Roak, B. J., Barnard, R. A., Gibbs, R. A., Muzny, D., Sabo, A., Ahmed, K. L. B., Eichler, E. E., Siegel, M., Abbeduto, L., Hilscher, B. A., Li, D., Smith, K., Thompson, S., Albright, C., Butter, E. M., Eldred, S., Hanna, N., Jones, M., Coury, D. L., Scherr, J., Pifher, T., Roby, E., Dennis, B., Higgins, L., Brown, M., Alessandri, M., Gutierrez, A., Hale, M. N., Herbert, L. M., Schneider, H. L., David, G., Annett, R. D., Sarver, D. E., Arriaga, I., Camba, A., Gulsrud, A. C., Haley, M., Mccracken, J. T., Sandhu, S., Tafolla, M., Yang, W. S., Carpenter, L. A., Bradley, C. C., Gwynette, F., Manning, P., Shaffer, R., Thomas, C., Bernier, R. A., Fox, E. A., Gerdts, J. A., Pepper, M., Ho, T., Cho, D., Piven, J., Lechniak, H., Soorya, L. V., Gordon, R., Wainer, A., Yeh, L., Ochoa-Lubinoff, C., Russo, N., Berry-Kravis, E., Booker, S., Erickson, C. A., Prock, L. M., Pawlowski, K. G., Matthews, E. T., Brewster, S. J., Hojlo, M. A., Abada, E., Lamarche, E., Murali, S. C., Harvey, W. T., Kaplan, H. E., Pierce, K. L., Demarco, L., Horner, S., Pandey, J., Plate, S., Sahin, M., Riley, K. D., Carmody, E., Constantini, J., Esler, A., Fatemi, A., Hutter, H., Landa, R. J., Mckenzie, A. P., Neely, J., Singh, V., Van Metre, B., Wodka, E. L., Fombonne, E. J., Huang-Storms, L. Y., Pacheco, L. D., Mastel, S. A., Coppola, L. A., Francis, S., Jarrett, A., Jacob, S., Lillie, N., Gunderson, J., Istephanous, D., Simon, L., Wasserberg, O., Rachubinski, A. L., Rosenberg, C. R., Kanne, S. M., Shocklee, A. D., Takahashi, N., Bridwell, S. L., Klimczac, R. L., Mahurin, M. A., Cotrell, H. E., Grant, C. A., Hunter, S. G., Martin, C. L., Taylor, C. M., Walsh, L. K., Dent, K. A., Mason, A., Sziklay, A., Smith, C. J., Nordenskjold, M., Romano, Corrado, Peeters, H., Gecz, J., and Xia, K.

Published
2020

22. Feasibility of narrative exposure therapy in an outpatient day treatment programme for refugees: improvement in symptoms and global functioning

Author

de la Rie, S.M., Smid, G.E., van der Aa, N., van Est, L.A.C., Bisseling, E., Boelen, P.A., Leerstoel Boelen, and Trauma and Grief

Subjects
NET, Psychiatry and Mental health, trauma, • A substantial decline in symptoms and better functioning was observed in those improved, treatment, • A socially supportive living environment enhances the acceptability of trauma-focused treatment in refugees, PTSD, • NET embedded in an outpatient day treatment programme is feasible and facilitates the chance of completion of trauma-focused therapy, even in patients with a history of unsuccessful treatment, refugees
Abstract

Background: Refugees are at high risk for developing post-traumatic stress disorder (PTSD). Narrative exposure therapy (NET) is an evidence-based treatment of PTSD, designed for patients exposed to (multiple) traumatic events and recommended for patients with culturally diverse backgrounds. In clinical practice, adherence to the NET-protocol has been challenged because of psychosocial complexities and comorbid disorders. Objective: : The current study investigated the feasibility of NET embedded in an outpatient day treatment programme for refugees and examined reduction in PTSD symptoms and improvement of global functioning as well as correlates of change. Method: Participants were patients who consecutively entered an outpatient daytreatment programme from 2013-2017. The majority had a history of prior unsuccessful treatment. PTSD was assessed with the Clinically Administered PTSD Scale (CAPS) before and after finishing NET. Global Assessment of Functioning (GAF) was used to examine changes in functioning. Changes in PTSD scores and functioning were analyzed using paired t-tests and reliable change indices. Patients showing significant improvement were compared to those who did not, on patient and treatment characteristics, including sex, age, region of origin, childhood trauma and treatment duration and dosage of NET. Results: : Of 97 patients, 76 (78.4%) completed NET. Completers had a longer residency and were more likely to have a partner. Significant reductions in PTSD symptoms and improvements in global functioning were observed. Twenty-eight percent showed reliable improvement with large effect sizes. Four patients did no longer meet the criteria for PTSD. No strong moderators for changes were found. Patients who did not improve more often had a history of childhood trauma. Conclusions: NET embedded in an outpatient day treatment programme appears to be feasible. In those who improved, a substantial decline in symptoms and improvement of functioning were observed. The findings suggest that a socially supportive living environment enhances acceptability of trauma-focused treatment in refugees.

Published
2020

23. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome

Author

Koolen, D A, Sharp, A J, Hurst, J A, Firth, H V, Knight, S J L, Goldenberg, A, Saugier-Veber, P, Pfundt, R, Vissers, L E L M, Destrée, A, Grisart, B, Rooms, L, Van der Aa, N, Field, M, Hackett, A, Bell, K, Nowaczyk, M J M, Mancini, G M S, Poddighe, P J, Schwartz, C E, Rossi, E, De Gregori, M, Antonacci-Fulton, L L, II, McLellan M D, Garrett, J M, Wiechert, M A, Miner, T L, Crosby, S, Ciccone, R, Willatt, L, Rauch, A, Zenker, M, Aradhya, S, Manning, M A, Strom, T M, Wagenstaller, J, Krepischi-Santos, A C, Vianna-Morgante, A M, Rosenberg, C, Price, S M, Stewart, H, Shaw-Smith, C, Brunner, H G, Wilkie, A O M, Veltman, J A, Zuffardi, O, Eichler, E E, and de Vries, B B A

Published
2008
Full Text
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24. Author Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders (Nature Communications, (2020), 11, 1, (4932), 10.1038/s41467-020-18723-y)

Author

Wang, T, Hoekzema, K, Vecchio, D, Wu, H, Sulovari, A, Coe, BP, Gillentine, MA, Wilfert, AB, Perez-Jurado, LA, Kvarnung, M, Sleyp, Y, Earl, RK, Rosenfeld, JA, Geisheker, MR, Han, L, Du, B, Barnett, C, Thompson, E, Shaw, M, Carroll, R, Friend, K, Catford, R, Palmer, EE, Zou, X, Ou, J, Li, H, Guo, H, Gerdts, J, Avola, E, Calabrese, G, Elia, M, Greco, D, Lindstrand, A, Nordgren, A, Anderlid, BM, Vandeweyer, G, Van Dijck, A, Van der Aa, N, McKenna, B, Hancarova, M, Bendova, S, Havlovicova, M, Malerba, G, Bernardina, BD, Muglia, P, van Haeringen, A, Hoffer, MJV, Franke, B, Cappuccio, G, Delatycki, M, Lockhart, PJ, Manning, MA, Liu, P, Scheffer, IE, Brunetti-Pierri, N, Rommelse, N, Amaral, DG, Santen, GWE, Trabetti, E, Sedláček, Z, Michaelson, JJ, Pierce, K, Courchesne, E, Kooy, RF, Acampado, J, Ace, AJ, Amatya, A, Astrovskaya, I, Bashar, A, Brooks, E, Butler, ME, Cartner, LA, Chin, W, Chung, WK, Daniels, AM, Feliciano, P, Fleisch, C, Ganesan, S, Jensen, W, Lash, AE, Marini, R, Myers, VJ, O’Connor, E, Rigby, C, Robertson, BE, Shah, N, Shah, S, Singer, E, Snyder, LAG, Stephens, AN, Tjernagel, J, Vernoia, BM, Volfovsky, N, White, LC, Hsieh, A, Shen, Y, Zhou, X, Turner, TN, Bahl, E, Thomas, TR, Wang, T, Hoekzema, K, Vecchio, D, Wu, H, Sulovari, A, Coe, BP, Gillentine, MA, Wilfert, AB, Perez-Jurado, LA, Kvarnung, M, Sleyp, Y, Earl, RK, Rosenfeld, JA, Geisheker, MR, Han, L, Du, B, Barnett, C, Thompson, E, Shaw, M, Carroll, R, Friend, K, Catford, R, Palmer, EE, Zou, X, Ou, J, Li, H, Guo, H, Gerdts, J, Avola, E, Calabrese, G, Elia, M, Greco, D, Lindstrand, A, Nordgren, A, Anderlid, BM, Vandeweyer, G, Van Dijck, A, Van der Aa, N, McKenna, B, Hancarova, M, Bendova, S, Havlovicova, M, Malerba, G, Bernardina, BD, Muglia, P, van Haeringen, A, Hoffer, MJV, Franke, B, Cappuccio, G, Delatycki, M, Lockhart, PJ, Manning, MA, Liu, P, Scheffer, IE, Brunetti-Pierri, N, Rommelse, N, Amaral, DG, Santen, GWE, Trabetti, E, Sedláček, Z, Michaelson, JJ, Pierce, K, Courchesne, E, Kooy, RF, Acampado, J, Ace, AJ, Amatya, A, Astrovskaya, I, Bashar, A, Brooks, E, Butler, ME, Cartner, LA, Chin, W, Chung, WK, Daniels, AM, Feliciano, P, Fleisch, C, Ganesan, S, Jensen, W, Lash, AE, Marini, R, Myers, VJ, O’Connor, E, Rigby, C, Robertson, BE, Shah, N, Shah, S, Singer, E, Snyder, LAG, Stephens, AN, Tjernagel, J, Vernoia, BM, Volfovsky, N, White, LC, Hsieh, A, Shen, Y, Zhou, X, Turner, TN, Bahl, E, and Thomas, TR

Abstract

The original version of this Article contained an error on page 5 of the Results section, which incorrectly read ‘They are characterized by craniofacial dysmorphisms (9/10), thin vermillion border and lips (4/7), and feeding difficulties (6/11), and exhibit neonatal hypotonia (10/7)’. The correct version states ‘They are characterized by craniofacial dysmorphisms (9/10), thin vermillion border and lips (4/7), and feeding difficulties (6/11), and exhibit neonatal hypotonia (7/10)’.

Published
2020

27. Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders (vol 11, 4932, 2020)

Author

Wang, T, Hoekzema, K, Vecchio, D, Wu, H, Sulovari, A, Coe, BP, Gillentine, MA, Wilfert, AB, Perez-Jurado, LA, Kvarnung, M, Sleyp, Y, Earl, RK, Rosenfeld, JA, Geisheker, MR, Han, L, Du, B, Barnett, C, Thompson, E, Shaw, M, Carroll, R, Friend, K, Catford, R, Palmer, EE, Zou, X, Ou, J, Li, H, Guo, H, Gerdts, J, Avola, E, Calabrese, G, Elia, M, Greco, D, Lindstrand, A, Nordgren, A, Anderlid, B-M, Vandeweyer, G, Van Dijck, A, Van der Aa, N, McKenna, B, Hancarova, M, Bendova, S, Havlovicova, M, Malerba, G, Bernardina, BD, Muglia, P, van Haeringen, A, Hoffer, MJV, Franke, B, Cappuccio, G, Delatycki, M, Lockhart, PJ, Manning, MA, Liu, P, Scheffer, IE, Brunetti-Pierri, N, Rommelse, N, Amaral, DG, Santen, GWE, Trabetti, E, Sedlacek, Z, Michaelson, JJ, Pierce, K, Courchesne, E, Kooy, RF, Nordenskjold, M, Romano, C, Peeters, H, Bernier, RA, Gecz, J, Xia, K, Eichler, EE, Wang, T, Hoekzema, K, Vecchio, D, Wu, H, Sulovari, A, Coe, BP, Gillentine, MA, Wilfert, AB, Perez-Jurado, LA, Kvarnung, M, Sleyp, Y, Earl, RK, Rosenfeld, JA, Geisheker, MR, Han, L, Du, B, Barnett, C, Thompson, E, Shaw, M, Carroll, R, Friend, K, Catford, R, Palmer, EE, Zou, X, Ou, J, Li, H, Guo, H, Gerdts, J, Avola, E, Calabrese, G, Elia, M, Greco, D, Lindstrand, A, Nordgren, A, Anderlid, B-M, Vandeweyer, G, Van Dijck, A, Van der Aa, N, McKenna, B, Hancarova, M, Bendova, S, Havlovicova, M, Malerba, G, Bernardina, BD, Muglia, P, van Haeringen, A, Hoffer, MJV, Franke, B, Cappuccio, G, Delatycki, M, Lockhart, PJ, Manning, MA, Liu, P, Scheffer, IE, Brunetti-Pierri, N, Rommelse, N, Amaral, DG, Santen, GWE, Trabetti, E, Sedlacek, Z, Michaelson, JJ, Pierce, K, Courchesne, E, Kooy, RF, Nordenskjold, M, Romano, C, Peeters, H, Bernier, RA, Gecz, J, Xia, K, and Eichler, EE

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

28. Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Author

Wang, T, Hoekzema, K, Vecchio, D, Wu, H, Sulovari, A, Coe, BP, Gillentine, MA, Wilfert, AB, Perez-Jurado, LA, Kvarnung, M, Sleyp, Y, Earl, RK, Rosenfeld, JA, Geisheker, MR, Han, L, Du, B, Barnett, C, Thompson, E, Shaw, M, Carroll, R, Friend, K, Catford, R, Palmer, EE, Zou, X, Ou, J, Li, H, Guo, H, Gerdts, J, Avola, E, Calabrese, G, Elia, M, Greco, D, Lindstrand, A, Nordgren, A, Anderlid, B-M, Vandeweyer, G, Van Dijck, A, Van der Aa, N, McKenna, B, Hancarova, M, Bendova, S, Havlovicova, M, Malerba, G, Dalla Bernardina, B, Muglia, P, van Haeringen, A, Hoffer, MJV, Franke, B, Cappuccio, G, Delatycki, M, Lockhart, PJ, Manning, MA, Liu, P, Scheffer, IE, Brunetti-Pierri, N, Rommelse, N, Amaral, DG, Santen, GWE, Trabetti, E, Sedlacek, Z, Michaelson, JJ, Pierce, K, Courchesne, E, Kooy, RF, Nordenskjold, M, Romano, C, Peeters, H, Bernier, RA, Gecz, J, Xia, K, Eichler, EE, Wang, T, Hoekzema, K, Vecchio, D, Wu, H, Sulovari, A, Coe, BP, Gillentine, MA, Wilfert, AB, Perez-Jurado, LA, Kvarnung, M, Sleyp, Y, Earl, RK, Rosenfeld, JA, Geisheker, MR, Han, L, Du, B, Barnett, C, Thompson, E, Shaw, M, Carroll, R, Friend, K, Catford, R, Palmer, EE, Zou, X, Ou, J, Li, H, Guo, H, Gerdts, J, Avola, E, Calabrese, G, Elia, M, Greco, D, Lindstrand, A, Nordgren, A, Anderlid, B-M, Vandeweyer, G, Van Dijck, A, Van der Aa, N, McKenna, B, Hancarova, M, Bendova, S, Havlovicova, M, Malerba, G, Dalla Bernardina, B, Muglia, P, van Haeringen, A, Hoffer, MJV, Franke, B, Cappuccio, G, Delatycki, M, Lockhart, PJ, Manning, MA, Liu, P, Scheffer, IE, Brunetti-Pierri, N, Rommelse, N, Amaral, DG, Santen, GWE, Trabetti, E, Sedlacek, Z, Michaelson, JJ, Pierce, K, Courchesne, E, Kooy, RF, Nordenskjold, M, Romano, C, Peeters, H, Bernier, RA, Gecz, J, Xia, K, and Eichler, EE

Abstract

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.

Published
2020

29. The dissociative post-traumatic stress disorder (PTSD) subtype: A treatment outcome cohort study in veterans with PTSD

Author

Haagen, J.F.G., van Rijn, A., Knipscheer, J.W., van der Aa, N., Kleber, R.J., Trauma and Grief, Leerstoel Boelen, and Leerstoel Kleber

Subjects
Adult, Male, 050103 clinical psychology, Coping (psychology), medicine.drug_class, Dissociative Disorders, Dissociative, behavioral disciplines and activities, DSM-5, Stress Disorders, Post-Traumatic, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Stress Disorders, Post-Traumatic/diagnosis, mental disorders, Dissociative Disorders/etiology, medicine, Prevalence, Humans, 0501 psychology and cognitive sciences, Dissociative disorders, Prospective Studies, Prospective cohort study, Veterans, Post-traumatic stress disorder (PTSD), Stress Disorders, 05 social sciences, General Medicine, medicine.disease, 030227 psychiatry, Diagnostic and Statistical Manual of Mental Disorders, Clinical Psychology, Post-Traumatic/diagnosis, Treatment Outcome, Veterans/psychology, Female, Psychology, Cohort study, Clinical psychology, Psychopathology
Abstract

Objectives Dissociation is a prevalent phenomenon among veterans with post-traumatic stress disorder (PTSD) that may interfere with the effectiveness of treatment. This study aimed to replicate findings of a dissociative PTSD subtype, to identify corresponding patterns in coping style, symptom type, and symptom severity, and to investigate its impact on post-traumatic symptom improvement. Methods Latent profile analysis (LPA) was applied to baseline data from 330 predominantly (97%) male treatment-seeking veterans (mean age 39.5 years) with a probable PTSD. Multinomial logistic models were used to identify predictors of dissociative PTSD. Eighty veterans with PTSD that commenced with psychotherapy were invited for a follow-up measure after 6 months. The majority (n = 64, 80% response rate) completed the follow-up measure. Changes in post-traumatic stress between baseline and follow-up were explored as a continuous distal outcome. Results Latent profile analysis revealed four distinct patient profiles: 'low' (12.9%), 'moderate' (33.2%), 'severe' (45.1%), and 'dissociative' (8.8%) PTSD. The dissociative PTSD profile was characterized by more severe pathology levels, though not post-traumatic reactions symptom severity. Veterans with dissociative PTSD benefitted equally from PTSD treatment as veterans with non-dissociative PTSD with similar symptom severity. Conclusions Within a sample of veterans with PTSD, a subsample of severely dissociative veterans was identified, characterized by elevated severity levels on pathology dimensions. The dissociative PTSD subtype did not negatively impact PTSD treatment. Practitioner points The present findings confirmed the existence of a distinct subgroup veterans that fit the description of dissociative PTSD. Patients with dissociative PTSD subtype symptoms uniquely differed from patients with non-dissociative PTSD in the severity of several psychopathology dimensions. Dissociative and non-dissociative PTSD patients with similar post-traumatic severity levels showed similar levels of improvement after PTSD treatment. The observational design and small sample size caution interpretation of the treatment outcome data. The IES-R questionnaire does not assess all PTSD DSM-IV diagnostic criteria (14 of 17), although it is considered a valid measure for an indication of PTSD.

Published
2018

36. NEURODEVELOPMENTAL OUTCOME AFTER PERINATAL ARTERIAL ISCHEMIC STROKE: THE IMPORTANCE OF VASCULAR DISTRIBUTION

Author

MS Neonatologie, Brain, Arts-assistenten Kinderen, Child Health, Regenerative Medicine and Stem Cells, Wagenaar, N., Martinez-Biarge, Miriam, van der Aa, N. E., van Haastert, I. C., Groenendaal, F., Benders, M. J. N. L., Cowan, Frances M., de Vries, L. S., MS Neonatologie, Brain, Arts-assistenten Kinderen, Child Health, Regenerative Medicine and Stem Cells, Wagenaar, N., Martinez-Biarge, Miriam, van der Aa, N. E., van Haastert, I. C., Groenendaal, F., Benders, M. J. N. L., Cowan, Frances M., and de Vries, L. S.

Published
2017

37. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Author

Koolen, D.A., Pfundt, R.P., Linda, K., Beunders, G., Veenstra-Knol, H.E., Conta, J.H., Fortuna, A.M., Gillessen-Kaesbach, G., Dugan, S., Halbach, S., Abdul-Rahman, O.A., Winesett, H.M., Chung, W.K., Dalton, M., Dimova, P.S., Mattina, T., Prescott, K., Zhang, H.Z., Saal, H.M., Hehir-Kwa, J.Y., Willemsen, M.H., Ockeloen, C.W., Jongmans, M.C.J., Van der Aa, N., Failla, P., Barone, C., Avola, E., Brooks, A.S., Kant, S.G., Gerkes, E.H., Firth, H.V., Ounap, K., Bird, L.M., Masser-Frye, D., Friedman, J.R., Sokunbi, M.A., Dixit, A., Splitt, M., Kukolich, M.K., McGaughran, J., Coe, B.P., Florez, J., Nadif Kasri, N., Brunner, H.G., Thompson, E.M., Gecz, J., Romano, C, Eichler, E.E., Vries, B. de, Koolen, D.A., Pfundt, R.P., Linda, K., Beunders, G., Veenstra-Knol, H.E., Conta, J.H., Fortuna, A.M., Gillessen-Kaesbach, G., Dugan, S., Halbach, S., Abdul-Rahman, O.A., Winesett, H.M., Chung, W.K., Dalton, M., Dimova, P.S., Mattina, T., Prescott, K., Zhang, H.Z., Saal, H.M., Hehir-Kwa, J.Y., Willemsen, M.H., Ockeloen, C.W., Jongmans, M.C.J., Van der Aa, N., Failla, P., Barone, C., Avola, E., Brooks, A.S., Kant, S.G., Gerkes, E.H., Firth, H.V., Ounap, K., Bird, L.M., Masser-Frye, D., Friedman, J.R., Sokunbi, M.A., Dixit, A., Splitt, M., Kukolich, M.K., McGaughran, J., Coe, B.P., Florez, J., Nadif Kasri, N., Brunner, H.G., Thompson, E.M., Gecz, J., Romano, C, Eichler, E.E., and Vries, B. de

Abstract

Contains fulltext : 168191.pdf (publisher's version ) (Closed access), The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

Published
2016

38. NEURODEVELOPMENTAL OUTCOME AFTER PERINATAL ARTERIAL ISCHEMIC STROKE IN PRETERM AND FULL-TERM INFANTS: THE IMPORTANCE OF VASCULAR DISTRIBUTION

Author

MS Neonatologie, Brain, Child Health, Regenerative Medicine and Stem Cells, Arts-assistenten Kinderen, Wagenaar, N., Benders, M. J. N. L., Groenendaal, F., van Haastert, I. C., van der Aa, N. E., de Vries, L. S., MS Neonatologie, Brain, Child Health, Regenerative Medicine and Stem Cells, Arts-assistenten Kinderen, Wagenaar, N., Benders, M. J. N. L., Groenendaal, F., van Haastert, I. C., van der Aa, N. E., and de Vries, L. S.

Published
2016

39. Evaluation of Clinical Manifestations in Patients with Severe Lymphedema with and without CCBE1 Mutations

Author

Alders, M, Mendola, A, Ades, L, Al Gazali, L, Bellini, C, Dallapiccola, B, Edery, P, Frank, U, Hornshuh, F, Huisman, Sander, Jagadeesh, S, Kayserili, H, Keng, WT, Lev, D, Prada, CE, Sampson, JR, Schmidtke, J, Shashi, V, Bever, Yolande, Van der Aa, N, Verhagen, Judith, Verheij, JBGM, Vikkula, M, Hennekam, RCM, Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, Other Research, Human Genetics, Graduate School, Amsterdam Neuroscience, Amsterdam Public Health, Paediatrics, Surgery, and Clinical Genetics

Subjects
Original Article
Abstract

The lymphedema-lymphangiectasia-intellectual disability (Hennekam) syndrome (HS) is characterised by a widespread congenital lymph vessel dysplasia manifesting as congenital lymphedema of the limbs and intestinal lymphangiectasia, accompanied by unusual facial morphology, variable intellectual disabilities and infrequently malformations. The syndrome is heterogeneous as mutations in the gene CCBE1 have been found responsible for the syndrome in only a subset of patients. We investigated whether it would be possible to predict the presence of a CCBE1 mutation based on phenotype by collecting clinical data of patients diagnosed with HS, with or without a CCBE1 mutation. We report here the results of 13 CCBE1 positive patients, 16 CCBE1 negative patients, who were clinically found to have classical HS, and 8 patients in whom the diagnosis was considered possible, but not certain, and in whom no CCBE1 mutation was identified. We found no statistically significant phenotypic differences between the 2 groups with the clinical HS phenotype, although the degree of lymphatic dysplasia tended to be more pronounced in the mutation positive group. We also screened 158 patients with less widespread and less pronounced forms of lymphatic dysplasia for CCBE1 mutations, and no mutation was detected in this group. Our results suggest that (1) CCBE1 mutations are present only in patients with a likely clinical diagnosis of HS, and not in patients with less marked forms of lymphatic dysplasia, and (2) that there are no major phenotypic differences between HS patients with or without CCBE1 mutations.

Published
2012

40. Genetic and Environmental Influences on Individual Differences in Sedentary Behavior During Adolescence

Author

van der Aa, N., Bartels, M., te Velde, S.J., Boomsma, D.I., de Geus, E.J.C., Brug, J., Epidemiology and Data Science, EMGO - Mental health, Biological Psychology, and EMGO+ - Mental Health

Subjects
Netherlands Twin Register (NTR)
Abstract

Objective: To investigate the degree to which genetic and environmental influences affect individual differences in sedentary behavior throughout adolescence. Design: Cross-sectional twin-family design. Setting: Data on self-reported sedentary behavior from Dutch twins and their nontwin siblings. Participants: The total sample consisted of 5074 adolescent twins (aged 13-19 years) and 937 siblings (aged 12-20 years) from 2777 families. Main Outcome Measures: Screen-viewing sedentary behavior was assessed with survey items about weekly frequency of television viewing, playing electronic games, and computer/Internet use. Based on these items, an overall score for screen-viewing sedentary behavior was computed. Results: The genetic architecture of screen-viewing sedentary behavior differed by age. Variation in sedentary behavior among 12-year-olds was accounted for by genetic (boys: 35%; girls: 19%), shared environmental (boys: 29%; girls: 48%), and nonshared environmental (boys: 36%; girls: 34%) factors. Variation in sedentary behavior among 20-year-olds was accounted for by genetic (boys: 48%; girls: 34%) and nonshared environmental (boys: 52%; girls: 66%) factors. Conclusion: The shift from shared environmental factors in the etiology of sedentary behavior among younger adolescents to genetic and nonshared environmental factors among older adolescents requires age-specific tailoring of intervention programs.

Published
2012
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41. Trends in adolescent alcohol use: Effects of age, sex and cohort on prevalence and heritability

Author

Geels, L.M., Bartels, M., van Beijsterveldt, C.E.M., Willemsen, G., van der Aa, N., Boomsma, D.I., Vink, J.M., Biological Psychology, and EMGO+ - Mental Health

Subjects
Netherlands Twin Register (NTR), SDG 3 - Good Health and Well-being
Abstract

Aims To determine the effect of age, sex and cohort on the prevalence and genetic architecture of adolescent alcohol use (AAU). Design Survey study in participants registered with the Netherlands Twin Register. Setting Twins from the general population. Participants Two cohorts (data collected in 1993 and 2005-08) of twins aged 13-15, 16-17 and 18-21 years. In 1993 and 2005-08 a total of 3269 and 8207 twins, respectively, took part. Measurements Survey data on initiation and frequency of alcohol use and quantity of alcohol consumed. Findings The prevalence of alcohol initiation increased between 1993 and 2005-08 for both males and females. The largest difference was for girls observed at ages 13-15, where the prevalence increased from 59.5% to 72.4%. We also found increases in prevalence across cohorts for quantity of alcohol consumed and non-significant increases for frequency of alcohol use. From age 16 onwards, boys drank more frequently and larger quantities than girls. Genetic model fitting revealed that the genetic architecture of AAU did not differ between birth cohorts, nor were there differences between boys and girls. Genetic factors explained between 21% and 55% of individual differences in alcohol measures throughout adolescence. Shared environment explained between 17% and 64% of variance in alcohol use, across different age groups and alcohol measures. Conclusions In the Netherlands, the prevalence of alcohol initiation, frequency and quantity has increased in adolescents over a 15-year period, but there are no changes in the genetic architecture of adolescent alcohol use. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Published
2012
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42. Environmental factors in subjective wellbeing: Evidence from discordant and concordant monozygotic twins

Author

Bartels, M., Stap, F., van der Aa, N., van Beijsterveldt, C.E.M., Boomsma, D.I., Biological Psychology, and EMGO+ - Mental Health

Subjects
Netherlands Twin Register (NTR), musculoskeletal, neural, and ocular physiology, behavior and behavior mechanisms, lipids (amino acids, peptides, and proteins), behavioral disciplines and activities, psychological phenomena and processes
Published
2011
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43. Level of Posttraumatic Stress Disorder Symptoms, Social Support and Quality of the Therapeutic Alliance as Predictors of Therapy Course: A Mediational Model

Author

Commandeur, R.A., Sleijpen, M. (Thesis Advisor), van der Aa, N., Commandeur, R.A., Sleijpen, M. (Thesis Advisor), and van der Aa, N.

Abstract

Background: Potential traumatic events can have severe consequences. No consensus has been achieved as to how several factors interact in influencing the therapy course of traumatised people. Aims: Firstly, investigated was if level of Posttraumatic Stress Disorder [PTSD] symptoms and social support before therapy, predicted therapy course. Secondly, investigated was if this relationship of level of PTSD symptoms and social support with therapy course was mediated by the quality of the therapeutic alliance. Methods: Several questionnaires were obtained from 130 clients who are being treated at Foundation Centrum ’45. To measure level of PTSD symptoms, the Dutch Zelfinventarisatielijst Posttraumatische Stressstoornis and the Harvard Trauma Questionnaire were used. The Resources Questionnaire was completed to obtain information about the level of social support someone experiences during stressful situations. The Outcome Rating Scale and the Session Rating Scale were routinely obtained to measure therapy course and quality of the therapeutic alliance respectively. Results: Level of PTSD symptoms and quality of the therapeutic alliance were found to influence therapy course. Social support did not prove to influence therapy course. Neither the level of PTSD symptoms nor the level of social support seemed to influence the quality of the therapeutic alliance. In this way, no mediating role for the quality of the therapeutic alliance was found. Conclusions: A first move has been made into the creation of clarity around the factors that influence the therapy course of people with PTSD symptoms. Indicated is that attention for the therapeutic alliance should be more integrated into therapy. More research is needed to find out why levels of PTSD symptoms influences therapy course, and what the exact role of social support is in the treatment process.

Published
2015

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