CONTEXT: For more than a century, it has been uncertain whether or not the major diagnostic categories of psychosis--schizophrenia and bipolar disorder--are distinct disease entities with specific genetic causes and neuroanatomical substrates. OBJECTIVE: To investigate the relationship between genetic risk and structural variation throughout the entire brain in patients and their unaffected relatives sampled from multiply affected families with schizophrenia or bipolar disorder. DESIGN: Analysis of the association between genetic risk and variation in tissue volume on magnetic resonance images. SETTING: Psychiatric research center. PARTICIPANTS: Subjects comprised 25 patients with schizophrenia, 36 of their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who experienced psychotic symptoms during illness exacerbation, and 50 of their unaffected first-degree relatives. MAIN OUTCOME MEASURES: We used computational morphometric techniques to map significant associations between a continuous measure of genetic liability for each subject and variation in gray or white matter volume. RESULTS: Genetic risk for schizophrenia was specifically associated with distributed gray matter volume deficits in the bilateral fronto-striato-thalamic and left lateral temporal regions, whereas genetic risk for bipolar disorder was specifically associated with gray matter deficits only in the right anterior cingulate gyrus and ventral striatum. A generic association between genetic risk for both disorders and white matter volume reduction in the left frontal and temporoparietal regions was consistent with left frontotemporal disconnectivity as a genetically controlled brain structural abnormality common to both psychotic disorders. CONCLUSIONS: Genetic risks for schizophrenia and bipolar disorder are associated with specific gray matter but generic white matter endophenotypes. Thus, Emil Kraepelin's pivotal distinction was neither wholly right nor wholly wrong: the 2 major psychoses show both distinctive and similar patterns of brain structural abnormality related to variable genetic risk.
CONTEXT: For more than a century, it has been uncertain whether or not the major diagnostic categories of psychosis--schizophrenia and bipolar disorder--are distinct disease entities with specific genetic causes and neuroanatomical substrates. OBJECTIVE: To investigate the relationship between genetic risk and structural variation throughout the entire brain in patients and their unaffected relatives sampled from multiply affected families with schizophrenia or bipolar disorder. DESIGN: Analysis of the association between genetic risk and variation in tissue volume on magnetic resonance images. SETTING: Psychiatric research center. PARTICIPANTS: Subjects comprised 25 patients with schizophrenia, 36 of their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who experienced psychotic symptoms during illness exacerbation, and 50 of their unaffected first-degree relatives. MAIN OUTCOME MEASURES: We used computational morphometric techniques to map significant associations between a continuous measure of genetic liability for each subject and variation in gray or white matter volume. RESULTS: Genetic risk for schizophrenia was specifically associated with distributed gray matter volume deficits in the bilateral fronto-striato-thalamic and left lateral temporal regions, whereas genetic risk for bipolar disorder was specifically associated with gray matter deficits only in the right anterior cingulate gyrus and ventral striatum. A generic association between genetic risk for both disorders and white matter volume reduction in the left frontal and temporoparietal regions was consistent with left frontotemporal disconnectivity as a genetically controlled brain structural abnormality common to both psychotic disorders. CONCLUSIONS: Genetic risks for schizophrenia and bipolar disorder are associated with specific gray matter but generic white matter endophenotypes. Thus, Emil Kraepelin's pivotal distinction was neither wholly right nor wholly wrong: the 2 major psychoses show both distinctive and similar patterns of brain structural abnormality related to variable genetic risk.
Authors: Ulrich Ettinger; Anne Schmechtig; Timothea Toulopoulou; Charmaine Borg; Claire Orrells; Sheena Owens; Kazunori Matsumoto; Neeltje E van Haren; Mei-Hua Hall; Veena Kumari; Philip K McGuire; Robin M Murray; Marco Picchioni Journal: Schizophr Bull Date: 2010-06-10 Impact factor: 9.306
Authors: Vicente Molina; Gemma Galindo; Benjamín Cortés; Alba G Seco de Herrera; Ana Ledo; Javier Sanz; Carlos Montes; Juan A Hernández-Tamames Journal: Eur Arch Psychiatry Clin Neurosci Date: 2010-12-28 Impact factor: 5.270
Authors: Lara C Foland-Ross; Paul M Thompson; Catherine A Sugar; Sarah K Madsen; Jim K Shen; Conor Penfold; Kyle Ahlf; Paul E Rasser; Jeffrey Fischer; Yilan Yang; Jennifer Townsend; Susan Y Bookheimer; Lori L Altshuler Journal: Am J Psychiatry Date: 2011-02-01 Impact factor: 18.112
Authors: Zuowei Wang; David E Kemp; Philip K Chan; Yiru Fang; Stephen J Ganocy; Joseph R Calabrese; Keming Gao Journal: Int J Neuropsychopharmacol Date: 2010-09-29 Impact factor: 5.176
Authors: Amelia Versace; Cecile D Ladouceur; Soledad Romero; Boris Birmaher; David A Axelson; David J Kupfer; Mary L Phillips Journal: J Am Acad Child Adolesc Psychiatry Date: 2010-10-29 Impact factor: 8.829
Authors: David C Glahn; Emma E M Knowles; D Reese McKay; Emma Sprooten; Henriette Raventós; John Blangero; Irving I Gottesman; Laura Almasy Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2014-01-24 Impact factor: 3.568