N.E.M. van Haren

Publications (105) View all

• Article: Brain volumes in schizophrenia: a meta-analysis in over 18,000 subjects.

  Sander Haijma, Neeltje van Haren, Wiepke Cahn, P Cédric MP Koolschijn, Hilleke Hulshoff Pol, René Kahn
  Schizophrenia Bulletin 08/2012; · 8.80 Impact Factor
• Article: Association study of copy number variants with brain volume in schizophrenia patients and healthy controls.

  Afke Terwisscha van Scheltinga, Steven Bakker, Neeltje van Haren, Jacobine Buizer-Voskamp, Heleen Boos, Jacob Vorstman, Wiepke Cahn, Hilleke Hulshoff Pol, Roel Ophoff, René Kahn
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  ABSTRACT: Schizophrenia patients have more copy number variations (CNVs) than healthy controls, and reduced brain volumes. Although this could suggest a causal relationship, we found no association between global CNV burden and three brain volume measures (on a MRI scan) in a sample of 173 schizophrenia patients and 176 healthy controls.
  Psychiatry Research 04/2012; · 2.52 Impact Factor
• Article: Overlapping and segregating structural brain abnormalities in twins with schizophrenia or bipolar disorder.

  Hilleke E Hulshoff Pol, G Caroline M van Baal, Hugo G Schnack, Rachel G H Brans, Astrid C van der Schot, Rachel M Brouwer, Neeltje E M van Haren, Claude Lepage, D Louis Collins, Alan C Evans, Dorret I Boomsma, Willem Nolen, René S Kahn
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  ABSTRACT: The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain structure, family studies suggest more segregating than overlapping neuroanatomical abnormalities in both disorders. To investigate whether patients with schizophrenia and patients with BD display overlapping abnormalities in brain volumes and cortical thickness and whether these are caused by shared genetic or environmental influences. Magnetic resonance imaging findings of monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and discordant for BD, and healthy twin pairs were compared using structural equation modeling. The Netherlands Twin Register and University Medical Center Utrecht. A total of 310 individuals from 158 (152 complete and 6 incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13 MZ and 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ discordant), and 83 healthy twin pairs (44 MZ and 39 DZ). Estimates of additive genetic and unique environmental associations between schizophrenia and BD with overlapping and nonoverlapping volumes and cortical thickness. Higher genetic liabilities for schizophrenia and BD were associated with smaller white matter volume, thinner right (and left) parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal and left superior motor cortices; higher environmental liabilities were associated with thinner right medial occipital cortex. Genetic liability for schizophrenia was associated with thicker right parietal cortex; for BD, with larger intracranial volume. Brain structures reflect overlapping and segregating genetic liabilities for schizophrenia and BD. The overlapping smaller white matter volume and common areas of thinner cortex suggest that both disorders share genetic (neurodevelopmental) roots.
  Archives of general psychiatry 04/2012; 69(4):349-59. · 12.26 Impact Factor
• Article: Altered white matter connectivity in never-medicated patients with schizophrenia.

  René C W Mandl, Monica Rais, Gertrudis Caroline M van Baal, Neeltje E M van Haren, Wiepke Cahn, René S Kahn, Hilleke E Hulshoff Pol
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  ABSTRACT: Numerous diffusion tensor imaging (DTI) studies have implicated white matter brain tissue abnormalities in schizophrenia. However, the vast majority of these studies included patient populations that use antipsychotic medication. Previous research showed that medication intake can affect brain morphology and the question therefore arises to what extent the reported white matter aberrations can be attributed to the disease rather than to the use of medication. In this study we included 16 medication-naïve patients with schizophrenia and compared them to 23 healthy controls to exclude antipsychotic medication use as a confounding factor. For each subject DTI scans and magnetization transfer imaging (MTI) scans were acquired. A new tract-based analysis was used that combines fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer ratio (MTR) to examine group differences in 12 major white matter fiber bundles. Significant group differences in combined FA, MD, MTR values were found for the right uncinate fasciculus and the left arcuate fasciculus. Additional analysis revealed that the largest part of both tracts showed an increase in MTR in combination with an increase in MD for patients with schizophrenia. We interpret these group-related differences as disease-related axonal or glial aberrations that cannot be attributed to antipsychotic medication use. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
  Human Brain Mapping 03/2012; · 5.88 Impact Factor
• Article: The genetic and environmental determinants of the association between brain abnormalities and schizophrenia: the schizophrenia twins and relatives consortium.

  Neeltje E M van Haren, Fruhling Rijsdijk, Hugo G Schnack, Marco M Picchioni, Timothea Toulopoulou, Matthias Weisbrod, Heinrich Sauer, Theo G van Erp, Tyrone D Cannon, Matti O Huttunen, Dorret I Boomsma, Hilleke E Hulshoff Pol, Robin M Murray, Rene S Kahn
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  ABSTRACT: Structural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium). An international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling. The heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (-.22 [-.30/-.14]) and white matter (-.17 [-.25/-.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively). Some of the genes that transmit the risk for Sz also influence cerebral (white matter) volume.
  Biological psychiatry 02/2012; 71(10):915-21. · 8.93 Impact Factor