CNVs conferring risk of autism or schizophrenia affect cognition in controls (original) (raw)

Change history

A middle initial was added in the author list.

References

  1. Stefansson, H. et al. Large recurrent microdeletions associated with schizophrenia. Nature 455, 232–236 (2008)
    Article ADS CAS PubMed PubMed Central Google Scholar
  2. Kirov, G. et al. The penetrance of copy number variations for schizophrenia and developmental delay. Biol. Psychiatry (2013)
  3. Malhotra, D. & Sebat, J. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 148, 1223–1241 (2012)
    Article CAS PubMed PubMed Central Google Scholar
  4. Haukka, J., Suvisaari, J. & Lonnqvist, J. Fertility of patients with schizophrenia, their siblings, and the general population: a cohort study from 1950 to 1959 in Finland. Am. J. Psychiatry 160, 460–463 (2003)
    Article PubMed Google Scholar
  5. Sheehan, D. V. et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59 (Suppl. 20). 22–33 quiz 34–57 (1998)
    PubMed Google Scholar
  6. Meins, W., Jacobsen, G. & Stratmann, C. Social adjustment of psychiatric patients: evaluation of a modified version of the GAF (Global Assessment of Functioning) Scale. [in German with English abstract] Psychiatr. Prax. 22, 206–208 (1995)
    CAS Google Scholar
  7. Sitskoorn, M. M., Aleman, A., Ebisch, S. J., Appels, M. C. & Kahn, R. S. Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophr. Res. 71, 285–295 (2004)
    Article PubMed Google Scholar
  8. Snitz, B. E., Macdonald, A. W., III & Carter, C. S. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophr. Bull. 32, 179–194 (2006)
    Article PubMed PubMed Central Google Scholar
  9. Mesholam-Gately, R. I., Giuliano, A. J., Goff, K. P., Faraone, S. V. & Seidman, L. J. Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology 23, 315–336 (2009)
    Article PubMed Google Scholar
  10. Rund, B. R. A review of longitudinal studies of cognitive functions in schizophrenia patients. Schizophr. Bull. 24, 425–435 (1998)
    Article CAS PubMed Google Scholar
  11. Bjornsdottir, G. et al. The adult reading history questionnaire (ARHQ) in Icelandic: psychometric properties and factor structure. J. Learn. Disabil. (2013)
  12. Lefly, D. L. & Pennington, B. F. Reliability and validity of the adult reading history questionnaire. J. Learn. Disabil. 33, 286–296 (2000)
    Article CAS PubMed Google Scholar
  13. Jacquemont, S. et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 478, 97–102 (2011)
    Article ADS CAS PubMed PubMed Central Google Scholar
  14. Weiss, L. A. et al. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358, 667–675 (2008)
    Article CAS PubMed Google Scholar
  15. McCarthy, S. E. et al. Microduplications of 16p11.2 are associated with schizophrenia. Nature Genet. 41, 1223–1227 (2009)
    Article CAS PubMed Google Scholar
  16. Park, S. & Holzman, P. S. Schizophrenics show spatial working memory deficits. Arch. Gen. Psychiatry 49, 975–982 (1992)
    Article CAS PubMed Google Scholar
  17. Doornbos, M. et al. Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances. Eur. J. Med. Genet. 52, 108–115 (2009)
    Article PubMed Google Scholar
  18. Burnside, R. D. et al. Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay. Hum. Genet. 130, 517–528 (2011)
    Article CAS PubMed PubMed Central Google Scholar
  19. de Kovel, C. G. et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 133, 23–32 (2010)
    Article PubMed Google Scholar
  20. World Health Organization. ICD-10: International Statistical Classification of Diseases and Related Health Problems 10th edn (WHO, 2008)
  21. Radua, J. et al. Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neurosci. Biobehav. Rev. 36, 2325–2333 (2012)
    Article CAS PubMed Google Scholar
  22. Diorio, D., Viau, V. & Meaney, M. J. The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress. J. Neurosci. 13, 3839–3847 (1993)
    Article CAS PubMed PubMed Central Google Scholar
  23. Lederbogen, F. et al. City living and urban upbringing affect neural social stress processing in humans. Nature 474, 498–501 (2011)
    Article CAS PubMed Google Scholar
  24. Seeley, W. W. et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27, 2349–2356 (2007)
    Article CAS PubMed PubMed Central Google Scholar
  25. Palaniyappan, L. & Liddle, P. F. Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. J. Psychiatry Neurosci. 37, 17–27 (2012)
    Article PubMed PubMed Central Google Scholar
  26. Bora, E. et al. Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophr. Res. 127, 46–57 (2011)
    Article PubMed Google Scholar
  27. Arnone, D., McIntosh, A. M., Tan, G. M. & Ebmeier, K. P. Meta-analysis of magnetic resonance imaging studies of the corpus callosum in schizophrenia. Schizophr. Res. 101, 124–132 (2008)
    Article CAS PubMed Google Scholar
  28. Tan, G. M., Arnone, D., McIntosh, A. M. & Ebmeier, K. P. Meta-analysis of magnetic resonance imaging studies in chromosome 22q11.2 deletion syndrome (velocardiofacial syndrome). Schizophr. Res. 115, 173–181 (2009)
    Article PubMed Google Scholar
  29. Linkersdörfer, J., Lonnemann, J., Lindberg, S., Hasselhorn, M. & Fiebach, C. J. Grey matter alterations co-localize with functional abnormalities in developmental dyslexia: an ALE meta-analysis. PLoS ONE 7, e43122 (2012)
    Article ADS PubMed PubMed Central CAS Google Scholar
  30. Rotzer, S. et al. Optimized voxel-based morphometry in children with developmental dyscalculia. Neuroimage 39, 417–422 (2008)
    Article CAS PubMed Google Scholar
  31. Hall, R. C. Global assessment of functioning. A modified scale. Psychosomatics 36, 267–275 (1995)
    Article CAS PubMed Google Scholar
  32. Wechsler, D. Wechsler Memory Scale 3rd edn (Harcourt Brace and Company, 1997)
    Google Scholar
  33. Benton, A. H. K. Multilingual Aphasia Examination (AJA Associates, 1989)
    Google Scholar
  34. Morris, J. C. et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 39, 1159–1165 (1989)
    Article MathSciNet CAS PubMed Google Scholar
  35. Stroop, J. R. Studies of interference in seral verbal reactions. J. Exp. Psychol. 18, 643–662 (1935)
    Article Google Scholar
  36. Reitan, R. M. Validity of the trail making test as an indicator of organic brain damage. Percept. Mot. Skills 8, 271–276 (1958)
    Article Google Scholar
  37. Berg, E. A. A simple objective test for measuring flexibility in thinking. J. Gen. Psychol. 39, 15–22 (1948)
    Article CAS PubMed Google Scholar
  38. Owen, A. M., Downes, J. J., Sahakian, B. J., Polkey, C. E. & Robbins, T. W. Planning and spatial working memory following frontal lobe lesions in man. Neuropsychologia 28, 1021–1034 (1990)
    Article CAS PubMed Google Scholar
  39. Sahakian, B., Jones, G., Levy, R., Gray, J. & Warburton, D. The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Brit. J. Psychiatry 154, 797–800 (1989)
    Article CAS Google Scholar
  40. Wechsler, D. Wechsler Abbreviated Scale of Intelligence (Harcourt Brace and Company, 1999)
    Google Scholar
  41. Wang, K. et al. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res. 17, 1665–1674 (2007)
    Article CAS PubMed PubMed Central Google Scholar
  42. Hall, R. C. & Parks, J. The modified global assessment of functioning scale: addendum. Psychosomatics 36, 416–417 (1995)
    Article CAS PubMed Google Scholar
  43. Golden, C. J. The Stroop color word test (Stoelting Company, 1978)
    Google Scholar
  44. Heaton, R., Chelune, G., Talley, J., Kay, G. & Curtis, G. Wisconsin Card Sorting Test manual (Psychological Assessment Resources, 1993)
    Google Scholar
  45. Feigenbaum, J. D., Polkey, C. E. & Morris, R. G. Deficits in spatial working memory after unilateral temporal lobectomy in man. Neuropsychologia 34, 163–176 (1996)
    Article CAS PubMed Google Scholar
  46. Ashburner, J. & Friston, K. J. Unified segmentation. Neuroimage 26, 839–851 (2005)
    Article PubMed Google Scholar
  47. Manjón, J. V., Coupe, P., Marti-Bonmati, L., Collins, D. L. & Robles, M. Adaptive non-local means denoising of MR images with spatially varying noise levels. J. Magn. Reson. Imaging 31, 192–203 (2010)
    Article PubMed Google Scholar
  48. Ashburner, J. A fast diffeomorphic image registration algorithm. Neuroimage 38, 95–113 (2007)
    Article PubMed Google Scholar

Download references

Acknowledgements

The authors are grateful to the participants and we thank the research nurses and staff at the Krókháls recruitment centre and roentgentechnicians at Röntgen Domus. We also thank the staff at deCODE genetics core facilities and all our colleagues for their important contribution to this work. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EU funded FP7-People-2011-IAPP grant PsychDPC (GA 286213).

Author information

Author notes

  1. Hreinn Stefansson and Andreas Meyer-Lindenberg: These authors contributed equally to this work.

Authors and Affiliations

  1. deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland,
    Hreinn Stefansson, Stacy Steinberg, Sunna Arnarsdottir, Gyda Bjornsdottir, G. Bragi Walters, Gudrun A. Jonsdottir, Solveig Kristjansdottir, Heimir Snorrason, Larus J. Gudmundsson, Gudbjorn F. Jonsson, Berglind Stefansdottir & Kari Stefansson
  2. Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany,
    Andreas Meyer-Lindenberg, Katrin Morgen, Heike Tost & Oliver Grimm
  3. Department of Psychiatry, Landspitali, National University Hospital, IS-101 Reykjavík, Iceland,
    Brynja Magnusdottir, Sunna Arnarsdottir, Solveig R. Davidsdottir, Isafold Helgadottir, Magnus Haraldsson & Engilbert Sigurdsson
  4. Institute of Psychiatry, King’s College, 16 De Crespigny Park, London SE5 8AF, UK,
    Orla M. Doyle, Michael Brammer & Shitij Kapur
  5. University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavík, Iceland,
    Magnus Haraldsson, Jonas G. Halldorsson, Evald Saemundsen & Engilbert Sigurdsson
  6. Röntgen Domus, Egilsgötu 3, IS-101 Reykjavík, Iceland,
    Birna Jonsdottir
  7. Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Boserupvej 2, DK-4000 Roskilde, Denmark,
    Johan H. Thygesen
  8. Tailored Therapeutics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 1940, Indianapolis, 46285, Indiana, USA
    Adam J. Schwarz
  9. H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark,
    Michael Didriksen & Tine B. Stensbøl
  10. The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland,
    Stefan Hreidarsson & Evald Saemundsen

Authors

  1. Hreinn Stefansson
    You can also search for this author inPubMed Google Scholar
  2. Andreas Meyer-Lindenberg
    You can also search for this author inPubMed Google Scholar
  3. Stacy Steinberg
    You can also search for this author inPubMed Google Scholar
  4. Brynja Magnusdottir
    You can also search for this author inPubMed Google Scholar
  5. Katrin Morgen
    You can also search for this author inPubMed Google Scholar
  6. Sunna Arnarsdottir
    You can also search for this author inPubMed Google Scholar
  7. Gyda Bjornsdottir
    You can also search for this author inPubMed Google Scholar
  8. G. Bragi Walters
    You can also search for this author inPubMed Google Scholar
  9. Gudrun A. Jonsdottir
    You can also search for this author inPubMed Google Scholar
  10. Orla M. Doyle
    You can also search for this author inPubMed Google Scholar
  11. Heike Tost
    You can also search for this author inPubMed Google Scholar
  12. Oliver Grimm
    You can also search for this author inPubMed Google Scholar
  13. Solveig Kristjansdottir
    You can also search for this author inPubMed Google Scholar
  14. Heimir Snorrason
    You can also search for this author inPubMed Google Scholar
  15. Solveig R. Davidsdottir
    You can also search for this author inPubMed Google Scholar
  16. Larus J. Gudmundsson
    You can also search for this author inPubMed Google Scholar
  17. Gudbjorn F. Jonsson
    You can also search for this author inPubMed Google Scholar
  18. Berglind Stefansdottir
    You can also search for this author inPubMed Google Scholar
  19. Isafold Helgadottir
    You can also search for this author inPubMed Google Scholar
  20. Magnus Haraldsson
    You can also search for this author inPubMed Google Scholar
  21. Birna Jonsdottir
    You can also search for this author inPubMed Google Scholar
  22. Johan H. Thygesen
    You can also search for this author inPubMed Google Scholar
  23. Adam J. Schwarz
    You can also search for this author inPubMed Google Scholar
  24. Michael Didriksen
    You can also search for this author inPubMed Google Scholar
  25. Tine B. Stensbøl
    You can also search for this author inPubMed Google Scholar
  26. Michael Brammer
    You can also search for this author inPubMed Google Scholar
  27. Shitij Kapur
    You can also search for this author inPubMed Google Scholar
  28. Evald Saemundsen
    You can also search for this author inPubMed Google Scholar
  29. Engilbert Sigurdsson
    You can also search for this author inPubMed Google Scholar
  30. Kari Stefansson
    You can also search for this author inPubMed Google Scholar

Contributions

H.St., A.M-L., S.S., B.M., S.A., G.B., G.B.W., M.D., T.B.S., M.B., S. Ka., J.H., S.H., E.Sa., E.Si. and K.S. were involved in study design. B.M., S.A., G.A.J., S. Kr., H.Sn., S.R.D., B.S., I.H., M.H., B.J., J.G.H., S.H., E.Sa. and E.Si. were involved with cohort ascertainment, phenotypic characterization and recruitment. H.St., K.M., G.B., G.B.W., O.M.D., H.T., O.G., G.F.J., J.H.T and L.J.G. were involved with informatics and data management. H.St., A.M-L., S.S., K.M., G.B., G.B.W., O.M.D., H.T., O.G., M.B. and A.J.S. carried out statistical analysis. H.St., A.M-L., S.S., B.M., K.M., S.A., G.B., G.B.W., G.A.J., O.M.D., H.T., O.G., S. Kr., H.Sn., S.R.D., L.J.G., G.F.J., B.S., I.H., M.H., B.J., J.H.T., M.D., T.B.S., M.B., S. Ka., J.G.H., S.H., E.Sa., E.Si. and K.S. wrote the manuscript.

Corresponding authors

Correspondence toAndreas Meyer-Lindenberg or Kari Stefansson.

Ethics declarations

Competing interests

H.St., S.S., S.A., G.B., G.B.W., G.J., S. Kr., H.Sn., S.R.D., L.J.G., G.F.J., B.S. and K.S. are employees of deCODE genetics/Amgen. B.J. is an employee of Röntgen domus. A.J.S. is an employee of Eli Lilly and Company. M.D. and T.B.S. are employees of H. Lundbeck A/S.

Additional information

The authors declare competing financial interests: details are available in the online version of the paper.

Supplementary information

PowerPoint slides

Rights and permissions

About this article

Cite this article

Stefansson, H., Meyer-Lindenberg, A., Steinberg, S. et al. CNVs conferring risk of autism or schizophrenia affect cognition in controls.Nature 505, 361–366 (2014). https://doi.org/10.1038/nature12818

Download citation