Browsing by Author "Zwarte, S. M. C."

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    ItemOpen Access
    The Association between familial risk and brain abnormalities Is disease specific: an ENIGMA-relatives study of schizophrenia and bipolar disorder
    (Elsevier, 2019) Zwarte, S. M. C.; Brouwer, R. M.; Agartz, I.; Alda, M.; Aleman, A.; Alpert, K. I.; Bearden, C. E.; Bertolino, A.; Bois, C.; Bonvino, A.; Bramon, E.; Buimer, E.; Cahn, W.; Cannon, D. M.; Cannon, T. D.; Caseras, X.; Castro-Fornieles, J.; Chen, Q.; Serna, E.; Giorgio, A. D.; Doucet, G.; Eker, M. C.; Erk, S.; Fears, S.; Foley, S.; Frangou, S.; Frankland, A.; Fullerton, J.; Glahn, D.; Goghari, V.; Goldman, A.; Gonul, A.; Gruber, O.; Haan, L.; Hajek, T.; Hawkins, E.; Heinz, A.; Hillegers, M.; Pol, H.; Hultman, C.; Ingvar, M.; Johansson, V.; Jönsson, E.; Kane, K.; Kempton, M.; Koenis, M.; Kopecek, M.; Krabbendam, L.; Krämer, B.; Lawrie, S.; Lenroot, R.; Marcelis, M.; Marsman, J-B; Mattay, V.; McDonald, C.; Meyer-Lindenberg, A.; Michielse, S.; Mitchell, P.; Moreno, D.; Murray, R.; Mwangi, B.; Najt, P.; Neilson, E.; Newport, J.; Os, J.; Overs, B.; Özerdem, A.; Picchioni, M.; Richter, A.; Roberts, G.; Aydoğan, A. S.; Schofield, P.; Şimşek, F.; Soares, J.; Sugranyes, G.; Toulopoulou, Timothea; Tronchin, G.; Walter, H.; Wang, L.; Weinberger, D.; Whalley, H.; Yalın, N.; Andreassen, O.; Ching, C.; Erp, T.; Turner, J.; Jahanshad, N.; Thompson, P.; Kahn, R.; Haren, N.
    Abstract Background Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. Methods We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. Results FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = −0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < −0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. Conclusions Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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    ItemOpen Access
    A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains
    (John Wiley & Sons, Inc., 2018) Ranlund, S.; Calafato, S.; Thygesen, J. H.; Lin, K.; Cahn, W.; Crespo-Facorro, B.; Díez, A.; Forti, M. D.; Iyegbe, C.; Jablensky, A.; Jones, R.; Hall, M.; Kahn, R.; Kalaydjieva, L.; Kravariti, E.; McDonald, C.; McIntosh, A. M.; McQuillin, A.; Picchioni, M.; Prata, D. P.; Rujescu, D.; Schulze, K.; Shaikh, M.; Toulopoulou, Timothea; Haren, N.; Zwarte, S. M. C.; Os, J.; Vassos, E.; Walshe, M.; Lewis, C.; Murray, R. M.; Powell, J.; Bramon, E.
    This large multi‐center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi‐modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first‐degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event‐related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the Ray Auditory Verbal Learning Task (N = 2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p = 0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p = 0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p = 0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.