Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk

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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk

Alnaes, Dag (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Kaufmann, Tobias (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

van der Meer, Dennis (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

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Cordova-Palomera, Aldo (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Rokicki, Jaroslav (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Moberget, Torgeir (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Bettella, Francesco (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Agartz, Ingrid (författare): Karolinska Institutet

Barch, Deanna M. (författare): Washington Univ, Dept Psychol & Brain Sci, St Louis, MO 63110 USA.

Bertolino, Alessandro (författare): Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Psychiat Neurosci Grp, Bari, Italy.

Brandt, Christine L. (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Cervenka, Simon (författare): Karolinska Institutet

Djurovic, Srdjan (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.;Oslo Univ Hosp, Dept Med Genet, Oslo, Norway.

Doan, Nhat Trung (författare)

Eisenacher, Sarah (författare): Heidelberg Univ, Cent Inst Mental Hlth, Mannheim, Germany.

Fatouros-Bergman, Helena (författare): Karolinska Institutet

Flyckt, Lena (författare): Karolinska Institutet

Di Giorgio, Annabella (författare): Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Psychiat Neurosci Grp, Bari, Italy.;Fdn Ist Ricovero & Cura Carattere Sci Casa Sollie, San Giovanni Rotondo, Italy.

Haatveit, Beathe (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Jonsson, Erik G. (författare): Karolinska Institutet

Kirsch, Peter (författare): Heidelberg Univ, Cent Inst Mental Hlth, Mannheim, Germany.;Heidelberg Univ, Med Fac Mannheim, Mannheim, Germany.

Lund, Martina J. (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Meyer-Lindenberg, Andreas (författare): Heidelberg Univ, Cent Inst Mental Hlth, Mannheim, Germany.;Heidelberg Univ, Med Fac Mannheim, Mannheim, Germany.

Pergola, Giulio (författare): Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Psychiat Neurosci Grp, Bari, Italy.

Schwarz, Emanuel (författare): Heidelberg Univ, Cent Inst Mental Hlth, Mannheim, Germany.

Smeland, Olav B. (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Quarto, Tiziana (författare): Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Psychiat Neurosci Grp, Bari, Italy.

Zink, Mathias (författare): Heidelberg Univ, Cent Inst Mental Hlth, Mannheim, Germany.

Andreassen, Ole A. (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.

Westlye, Lars T. (författare): Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway.;Univ Oslo, Dept Psychol, Oslo, Norway.

Farde, Lars (författare): Karolinska Institutet

Collste, Karin (författare): Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden.

Victorsson, Pauliina (författare): Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm, Sweden.

Engberg, Goran (författare): Karolinska Institutet

Erhardt, Sophie (författare): Karolinska Institutet

Malmqvist, Anna (författare): Karolinska Institutet

Hedberg, Mikael (författare): Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.

Orhan, Funda (författare): Karolinska Institutet

Sellgren, Carl M. (författare): Karolinska Institutet

Schwieler, Lilly (författare): Karolinska Institutet

Piehl, Fredrik (författare): Karolinska Institutet

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Karolinska Institutet Oslo Univ Hosp, Div Mental Hlth & Addict, Norwegian Ctr Mental Disorders Res, KG Jebsen Ctr Psychosis Res, POB 4956 Nydalen, N-0424 Oslo, Norway;Univ Oslo, Inst Clin Med, POB 4956 Nydalen, N-0424 Oslo, Norway. (creator_code:org_t)

AMER MEDICAL ASSOC, 2019
2019
Engelska.
Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748

Relaterad länk:: https://jamanetwork....; visa fler...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; visa färre...

Tidskriftsartikel (refereegranskat)

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ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.

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Av författaren/redakt...: Alnaes, Dag; Kaufmann, Tobias; van der Meer, De ...; Cordova-Palomera ...; Rokicki, Jarosla ...; Moberget, Torgei ...; visa fler...; Bettella, France ...; Agartz, Ingrid; Barch, Deanna M.; Bertolino, Aless ...; Brandt, Christin ...; Cervenka, Simon; Djurovic, Srdjan; Doan, Nhat Trung; Eisenacher, Sara ...; Fatouros-Bergman ...; Flyckt, Lena; Di Giorgio, Anna ...; Haatveit, Beathe; Jonsson, Erik G.; Kirsch, Peter; Lund, Martina J.; Meyer-Lindenberg ...; Pergola, Giulio; Schwarz, Emanuel; Smeland, Olav B.; Quarto, Tiziana; Zink, Mathias; Andreassen, Ole ...; Westlye, Lars T.; Farde, Lars; Collste, Karin; Victorsson, Paul ...; Engberg, Goran; Erhardt, Sophie; Malmqvist, Anna; Hedberg, Mikael; Orhan, Funda; Sellgren, Carl M ...; Schwieler, Lilly; Piehl, Fredrik; visa färre...

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Artiklar i publikationen: JAMA psychiatry

Av lärosätet: Uppsala universitet; Karolinska Institutet

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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk

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