170 results on '"Modinos G"'
Search Results
2. Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis
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Knight, S.R., primary, Abbasova, L., additional, Zeighami, Y., additional, Hansen, J.Y., additional, Martins, D., additional, Zelaya, F., additional, Dipasquale, O., additional, Liu, T., additional, Shin, D., additional, Bossong, M.G., additional, Azis, M., additional, Antoniades, M., additional, Howes, O., additional, Bonoldi, I., additional, Egerton, A., additional, Allen, P., additional, O’Daly, O., additional, McGuire, P., additional, and Modinos, G., additional
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- 2024
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3. Neural correlates of emotional processing in psychosis risk and onset – A systematic review and meta-analysis of fMRI studies
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Lukow, P.B., Kiemes, A., Kempton, M.J., Turkheimer, F.E., McGuire, P., and Modinos, G.
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- 2021
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4. Acute diazepam challenge normalises hippocampal cerebral blood flow in individuals at clinical high-risk for psychosis
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Livingston, N.R., primary, Kiemes, A., additional, Devenyi, G., additional, Knight, S., additional, Lukow, P., additional, Jelen, L., additional, Reilly, T., additional, Dima, A., additional, Nettis, M.A., additional, Casetta, C., additional, Agyekum, T., additional, Zelaya, F., additional, Spencer, T., additional, Fusar-Poli, P., additional, Williams, S., additional, McGuire, P., additional, Egerton, A., additional, Chakravarty, M.M., additional, and Modinos, G., additional
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- 2024
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- View/download PDF
5. Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings
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Velthorst E., Mollon J., Murray R. M., de Haan L., Germeys I. M., Glahn D. C., Arango C., van der Ven E., Di Forti M., Bernardo M., Guloksuz S., Delespaul P., Mezquida G., Amoretti S., Bobes J., Saiz P. A., Garcia-Portilla M. P., Santos J. L., Jimenez-Lopez E., Sanjuan J., Aguilar E. J., Arrojo M., Carracedo A., Lopez G., Gonzalez-Penas J., Parellada M., Atbasoglu C., Saka M. C., Ucok A., Alptekin K., Akdede B., Binbay T., Altinyazar V., Ulas H., Yalincetin B., Gumus-Akay G., Beyaz B. C., Soygur H., Cankurtaran E. S., Kaymak S. U., Maric N. P., Mihaljevic M. M., Petrovic S. A., Mirjanic T., Del-Ben C. M., Ferraro L., Gayer-Anderson C., Jones P. B., Jongsma H. E., Kirkbride J. B., La Cascia C., Lasalvia A., Tosato S., Llorca P. -M., Menezes P. R., Morgan C., Quattrone D., Menchetti M., Selten J. -P., Szoke A., Tarricone I., Tortelli A., McGuire P., Valmaggia L., Kempton M. J., van der Gaag M., Riecher-Rossler A., Bressan R. A., Barrantes-Vidal N., Nelson B., McGorry P., Pantelis C., Krebs M. -O., Ruhrmann S., Sachs G., Rutten B. P. F., van Os J., Alizadeh B. Z., van Amelsvoort T., Bartels-Velthuis A. A., Bruggeman R., van Beveren N. J., Luykx J. J., Cahn W., Simons C. J. P., Kahn R. S., Schirmbeck F., van Winkel R., Calem M., Tognin S., Modinos G., Pisani S., Kraan T. C., van Dam D. S., Burger N., Amminger G. P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Cristobal-Narvaez P., Racioppi A., Kwapil T. R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Rander L., Krakauer K., Glenthoj L. B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Reichenberg A., Velthorst E., Mollon J., Murray R.M., de Haan L., Germeys I.M., Glahn D.C., Arango C., van der Ven E., Di Forti M., Bernardo M., Guloksuz S., Delespaul P., Mezquida G., Amoretti S., Bobes J., Saiz P.A., Garcia-Portilla M.P., Santos J.L., Jimenez-Lopez E., Sanjuan J., Aguilar E.J., Arrojo M., Carracedo A., Lopez G., Gonzalez-Penas J., Parellada M., Atbasoglu C., Saka M.C., Ucok A., Alptekin K., Akdede B., Binbay T., Altinyazar V., Ulas H., Yalincetin B., Gumus-Akay G., Beyaz B.C., Soygur H., Cankurtaran E.S., Kaymak S.U., Maric N.P., Mihaljevic M.M., Petrovic S.A., Mirjanic T., Del-Ben C.M., Ferraro L., Gayer-Anderson C., Jones P.B., Jongsma H.E., Kirkbride J.B., La Cascia C., Lasalvia A., Tosato S., Llorca P.-M., Menezes P.R., Morgan C., Quattrone D., Menchetti M., Selten J.-P., Szoke A., Tarricone I., Tortelli A., McGuire P., Valmaggia L., Kempton M.J., van der Gaag M., Riecher-Rossler A., Bressan R.A., Barrantes-Vidal N., Nelson B., McGorry P., Pantelis C., Krebs M.-O., Ruhrmann S., Sachs G., Rutten B.P.F., van Os J., Alizadeh B.Z., van Amelsvoort T., Bartels-Velthuis A.A., Bruggeman R., van Beveren N.J., Luykx J.J., Cahn W., Simons C.J.P., Kahn R.S., Schirmbeck F., van Winkel R., Calem M., Tognin S., Modinos G., Pisani S., Kraan T.C., van Dam D.S., Burger N., Amminger G.P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Cristobal-Narvaez P., Racioppi A., Kwapil T.R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Rander L., Krakauer K., Glenthoj L.B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Reichenberg A., RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Neurosciences, Psychiatry, Clinical Developmental Psychology, World Health Organization (WHO) Collaborating Center, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Adult Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
- Subjects
0301 basic medicine ,validity ,medicine.medical_treatment ,CHILDHOOD ,Neuropsychological Tests ,FAMÍLIA ,episode ,Cognition ,0302 clinical medicine ,DEFICITS ,Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat ,Medicine ,Cognitive impairment ,Psychiatry ,Symptom severity ,Cannabis use ,IMPAIRMENT ,ABILITY ,Psychiatry and Mental health ,Schizophrenia ,RELIABILITY ,Neuropsychological Test ,Life Sciences & Biomedicine ,Human ,Clinical psychology ,Adult ,Biochemistry & Molecular Biology ,impairment ,schizophrenia-patients ,ability ,GENETIC RISK ,Psychotic Disorder ,SCHIZOPHRENIA-PATIENTS ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,SDG 3 - Good Health and Well-being ,Settore M-PSI/08 - Psicologia Clinica ,Humans ,In patient ,Cognitive skill ,VALIDITY ,Antipsychotic ,Molecular Biology ,Settore MED/25 - Psichiatria ,Aged ,Cross-Sectional Studie ,DECLINE ,Science & Technology ,reliability ,business.industry ,Working memory ,Siblings ,Neurosciences ,Diagnostic markers ,medicine.disease ,Cross-Sectional Studies ,030104 developmental biology ,deficits ,Psychotic Disorders ,PSYCHOSIS, COGNITION, MULTICENTRIC STUDY ,Neurosciences & Neurology ,business ,EPISODE ,030217 neurology & neurosurgery - Abstract
The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EUGEI); The Spanish sample was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024) (...), Velthorst, E., Mollon, J., Murray, R.M., de Haan, L., Germeys, I.M., Glahn, D.C., Arango, C., van der Ven, E., Di Forti, M., Bernardo, M., Guloksuz, S., Delespaul, P., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., García-Portilla, M.P., Santos, J.L., Jiménez-López, E., Sanjuan, J., Aguilar, E.J., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Atbaşoğlu, C., Saka, M.C., Üçok, A., Alptekin, K., Akdede, B., Binbay, T., Altınyazar, V., Ulaş, H., Yalınçetin, B., Gümüş-Akay, G., Beyaz, B.C., Soygür, H., Cankurtaran, E.Ş., Kaymak, S.U., Maric, N.P., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Del-Ben, C.M., Ferraro, L., Gayer-Anderson, C., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., La Cascia, C., Lasalvia, A., Tosato, S., Llorca, P.-M., Menezes, P.R., Morgan, C., Quattrone, D., Menchetti, M., Selten, J.-P., Szöke, A., Tarricone, I., Tortelli, A., McGuire, P., Valmaggia, L., Kempton, M.J., van der Gaag, M., Riecher-Rössler, A., Bressan, R.A., Barrantes-Vidal, N., Nelson, B., McGorry, P., Pantelis, C., Krebs, M.-O., Ruhrmann, S., Sachs, G., Rutten, B.P.F., van Os, J., Alizadeh, B.Z., van Amelsvoort, T., Bartels-Velthuis, A.A., Bruggeman, R., van Beveren, N.J., Luykx, J.J., Cahn, W., Simons, C.J.P., Kahn, R.S., Schirmbeck, F., van Winkel, R., Calem, M., Tognin, S., Modinos, G., Pisani, S., Kraan, T.C., van Dam, D.S., Burger, N., Amminger, G.P., Politis, A., Goodall, J., Borgwardt, S., Studerus, E., Gadelha, A., Brietzke, E., Asevedo, G., Asevedo, E., Zugman, A., Domínguez-Martínez, T., Monsonet, M., Cristóbal-Narváez, P., Racioppi, A., Kwapil, T.R., Kazes, M., Daban, C., Bourgin, J., Gay, O., Mam-Lam-Fook, C., Nordholm, D., Rander, L., Krakauer, K., Glenthøj, L.B., Glenthøj, B., Gebhard, D., Arnhold, J., Klosterkötter, J., Lasser, I., Winklbaur, B., Reichenberg, A., EU-GEI High Risk Study
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- 2021
6. Acute effects of diazepam on hippocampal resting cerebral blood flow in individuals at clinical high-risk for psychosis
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Livingston, N.R., primary, Kiemes, A., additional, Knight, S., additional, Lukow, P.B., additional, Jelen, L., additional, Reilly, T., additional, Dima, A., additional, Nettis, M.A., additional, Casetta, C., additional, Devenyi, G.A., additional, Agyekum, T., additional, Zelaya, F., additional, Spencer, T., additional, Fusar-Poli, P., additional, Williams, S.C.R., additional, McGuire, P., additional, Egerton, A., additional, Chakravarty, M.M., additional, and Modinos, G., additional
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- 2023
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7. Effect of diazepam on brain glutamatergic metabolites in individuals at clinical high risk for psychosis
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Kiemes, A., primary, Livingston, N.R., additional, Lukow, P., additional, Knight, S., additional, Jelen, L., additional, Reilly, T., additional, Dima, A., additional, Nettis, M., additional, Lythgoe, D., additional, Spencer, T., additional, Fusar-Poli, P., additional, Williams, S.C.R., additional, McGuire, P., additional, Davies, C., additional, Stone, J., additional, and Modinos, G., additional
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- 2023
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8. Unique contribution of neurotransmitter maps for predicting cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis
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Knight, S., primary, Zelaya, F., additional, Dipasquale, O., additional, Liu, T., additional, Shin, D., additional, Bossong, M., additional, Azis, M., additional, Egerton, A., additional, Allen, P., additional, O'Daly, O., additional, McGuire, P., additional, and Modinos, G., additional
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- 2023
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9. Failure to deactivate medial prefrontal cortex in people at high risk for psychosis
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Falkenberg, I., Chaddock, C., Murray, R.M., McDonald, C., Modinos, G., Bramon, E., Walshe, M., Broome, M., McGuire, P., and Allen, P.
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- 2015
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10. Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis
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Merritt, K, McCutcheon, RA, Aleman, A, Ashley, S, Beck, K, Block, W, Bloemen, OJN, Borgan, F, Boules, C, Bustillo, JR, Capizzano, AA, Coughlin, JM, David, A, de la Fuente-Sandoval, C, Demjaha, A, Dempster, K, Do, KQ, Du, F, Falkai, P, Galińska-Skok, B, Gallinat, J, Gasparovic, C, Ginestet, CE, Goto, N, Graff-Guerrero, A, Ho, B-C, Howes, O, Jauhar, S, Jeon, P, Kato, T, Kaufmann, CA, Kegeles, LS, Keshavan, MS, Kim, S-Y, King, B, Kunugi, H, Lauriello, J, León-Ortiz, P, Liemburg, E, Mcilwain, ME, Modinos, G, Mouchlianitis, E, Nakamura, J, Nenadic, I, Öngür, D, Ota, M, Palaniyappan, L, Pantelis, C, Patel, T, Plitman, E, and Investigators, 1H-MRS in Schizophrenia
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schizophrenia ,neuroscience ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Molecular Biology - Abstract
Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15,p p = 0.003; Glx: CVR = 0.11,p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14,p = 0.05; Glx: CVR = 0.25,p p = 0.008; Glx: CVR = 0.19,p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age:z = −0.03,p = 0.003, symptoms:z = 0.007,p = 0.02) and temporal lobe (glutamate with age:z = −0.03,p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age:z = 0.01,p = 0.02, glutamine with symptoms:z = 0.01,p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = −0.15,p = 0.03), higher thalamic glutamine (g = 0.53,p g = 0.28,p z = −0.02,p z = −0.03,p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01,p = 0.01) and temporal lobe (z = 0.05,p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.
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- 2023
11. Verbal memory performance predicts remission and functional outcome in people at clinical high-risk for psychosis
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Hedges, EP, Dickson, H, Tognin, S, Modinos, G, Antoniades, M, van der Gaag, M, de Haan, L, McGorry, P, Pantelis, C, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BP, van Os, J, Valmaggia, LR, McGuire, P, Kempton, MJ, Hedges, EP, Dickson, H, Tognin, S, Modinos, G, Antoniades, M, van der Gaag, M, de Haan, L, McGorry, P, Pantelis, C, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BP, van Os, J, Valmaggia, LR, McGuire, P, and Kempton, MJ
- Abstract
Robust deficits in cognitive functioning are present in people with psychosis and are evident in the early stages of the disorder. Impairments in verbal memory and verbal fluency are reliably seen in individuals at clinical high-risk for psychosis (CHR) compared to healthy populations. As previous studies have shown a relationship between cognition and longer-term outcomes in schizophrenia, the aim of this paper was to explore whether verbal memory and verbal fluency performance predicted outcomes in a large CHR sample recruited as part of the EU-GEI High Risk Study. Participants included 316 CHR individuals, 90.8% of whom were not currently on antipsychotic medication, and 60 healthy controls. Verbal memory and verbal fluency performance were measured at baseline. At two-year follow-up, CHR individuals were assessed by three different outcome measures, those who did and did not (1) transition to psychosis, (2) experience burdening impairment or disabilities, or (3) remit clinically from CHR status. Individuals with CHR displayed significant verbal memory and verbal fluency deficits at baseline compared to healthy controls (Hedges' g effect size = 0.24 to 0.66). There were no significant differences in cognitive performance of those who did and did not transition to psychosis. However, impaired immediate verbal recall predicted both functional disability and non-remission from the CHR state. Results remained significant when analyses were restricted to only include antipsychotic-free CHR participants. These findings may inform the development of early interventions designed to improve cognitive deficits in the early stages of psychosis.
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- 2022
12. Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study
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Kirschner, M, Hodzic-Santor, B, Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Bellgrove, MA, Tiego, J, Dannlowski, U, Koch, K, Huelsmann, C, Kugel, H, Enneking, V, Klug, M, Leehr, EJ, Boehnlein, J, Gruber, M, Mehler, D, DeRosse, P, Moyett, A, Baune, BT, Green, M, Quide, Y, Pantelis, C, Chan, R, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, TJ, Fletcher, P, Roessler, W, Smigielski, L, Kumari, V, Premkumar, P, Park, HRP, Wiebels, K, Lemmers-Jansen, I, Gilleen, J, Allen, P, Kozhuharova, P, Marsman, J-B, Lebedeva, I, Tomyshev, A, Mukhorina, A, Kaiser, S, Fett, A-K, Sommer, I, Schuite-Koops, S, Paquola, C, Lariviere, S, Bernhardt, B, Dagher, A, Grant, P, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, Modinos, G, Kirschner, M, Hodzic-Santor, B, Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Bellgrove, MA, Tiego, J, Dannlowski, U, Koch, K, Huelsmann, C, Kugel, H, Enneking, V, Klug, M, Leehr, EJ, Boehnlein, J, Gruber, M, Mehler, D, DeRosse, P, Moyett, A, Baune, BT, Green, M, Quide, Y, Pantelis, C, Chan, R, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, TJ, Fletcher, P, Roessler, W, Smigielski, L, Kumari, V, Premkumar, P, Park, HRP, Wiebels, K, Lemmers-Jansen, I, Gilleen, J, Allen, P, Kozhuharova, P, Marsman, J-B, Lebedeva, I, Tomyshev, A, Mukhorina, A, Kaiser, S, Fett, A-K, Sommer, I, Schuite-Koops, S, Paquola, C, Lariviere, S, Bernhardt, B, Dagher, A, Grant, P, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, and Modinos, G
- Abstract
Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
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- 2022
13. Local molecular and global connectomic contributions to cross-disorder cortical abnormalities.
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Hansen, JY, Shafiei, G, Vogel, JW, Smart, K, Bearden, CE, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, McDonald, CR, Sisodiya, SM, Schmaal, L, Veltman, DJ, van den Heuvel, OA, Stein, DJ, van Erp, TGM, Ching, CRK, Andreassen, OA, Hajek, T, Opel, N, Modinos, G, Aleman, A, van der Werf, Y, Jahanshad, N, Thomopoulos, SI, Thompson, PM, Carson, RE, Dagher, A, Misic, B, Hansen, JY, Shafiei, G, Vogel, JW, Smart, K, Bearden, CE, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, McDonald, CR, Sisodiya, SM, Schmaal, L, Veltman, DJ, van den Heuvel, OA, Stein, DJ, van Erp, TGM, Ching, CRK, Andreassen, OA, Hajek, T, Opel, N, Modinos, G, Aleman, A, van der Werf, Y, Jahanshad, N, Thomopoulos, SI, Thompson, PM, Carson, RE, Dagher, A, and Misic, B
- Abstract
Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21,000 participants and N = 26,000 controls, collected using a harmonised processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find a relationship between molecular vulnerability and white-matter architecture that drives cortical disorder profiles. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, inferior temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local molecular attributes and global connectivity jointly shape cross-disorder cortical abnormalities.
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- 2022
14. The Relationship Between Grey Matter Volume and Clinical and Functional Outcomes in People at Clinical High Risk for Psychosis.
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Tognin, S, Richter, A, Kempton, MJ, Modinos, G, Antoniades, M, Azis, M, Allen, P, Bossong, MG, Perez, J, Pantelis, C, Nelson, B, Amminger, P, Riecher-Rössler, A, Barrantes-Vidal, N, Krebs, M-O, Glenthøj, B, Ruhrmann, S, Sachs, G, Rutten, BPF, de Haan, L, van der Gaag, M, EU-GEI High Risk Study Group, Valmaggia, LR, McGuire, P, Tognin, S, Richter, A, Kempton, MJ, Modinos, G, Antoniades, M, Azis, M, Allen, P, Bossong, MG, Perez, J, Pantelis, C, Nelson, B, Amminger, P, Riecher-Rössler, A, Barrantes-Vidal, N, Krebs, M-O, Glenthøj, B, Ruhrmann, S, Sachs, G, Rutten, BPF, de Haan, L, van der Gaag, M, EU-GEI High Risk Study Group, Valmaggia, LR, and McGuire, P
- Abstract
OBJECTIVE: To examine the association between baseline alterations in grey matter volume (GMV) and clinical and functional outcomes in people at clinical high risk (CHR) for psychosis. METHODS: 265 CHR individuals and 92 healthy controls were recruited as part of a prospective multi-center study. After a baseline assessment using magnetic resonance imaging (MRI), participants were followed for at least two years to determine clinical and functional outcomes, including transition to psychosis (according to the Comprehensive Assessment of an At Risk Mental State, CAARMS), level of functioning (according to the Global Assessment of Functioning), and symptomatic remission (according to the CAARMS). GMV was measured in selected cortical and subcortical regions of interest (ROI) based on previous studies (ie orbitofrontal gyrus, cingulate gyrus, gyrus rectus, inferior temporal gyrus, parahippocampal gyrus, striatum, and hippocampus). Using voxel-based morphometry, we analysed the relationship between GMV and clinical and functional outcomes. RESULTS: Within the CHR sample, a poor functional outcome (GAF < 65) was associated with relatively lower GMV in the right striatum at baseline (P < .047 after Family Wise Error correction). There were no significant associations between baseline GMV and either subsequent remission or transition to psychosis. CONCLUSIONS: In CHR individuals, lower striatal GMV was associated with a poor level of overall functioning at follow-up. This finding was not related to effects of antipsychotic or antidepressant medication. The failure to replicate previous associations between GMV and later psychosis onset, despite studying a relatively large sample, is consistent with the findings of recent large-scale multi-center studies.
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- 2022
15. Erbb4 deletion from fast-spiking interneurons causes psychosis-relevant neuroimaging phenotypes
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Kiemes, A., primary, Serrano Navacerrada, M. E., additional, Kim, E., additional, Randall, K., additional, Simmons, C., additional, Rojo Gonzalez, L., additional, Petrinovic, M.M., additional, Lythgoe, D.J., additional, Rotaru, D., additional, Di Censo, D., additional, Hirshler, L., additional, Barbier, E. L., additional, Vernon, A. C., additional, Stone, J. M., additional, Davies, C., additional, Cash, D., additional, and Modinos, G., additional
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- 2022
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16. Targeting hippocampal circuit dysfunction in the neurodevelopmental trajectory of psychosis
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Knight, S., McCutcheon, R., Dwir, D., Grace, A.A., O'Daly, O., McGuire, P., and Modinos, G.
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- 2022
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17. Neuroimaging-based markers of parvalbumin interneuron disruption
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Kiemes, A., Navacerrada, M.E. Serrano, Kim, E., Randall, K., Simmons, C., Gonzalez, L. Rojo, Petrinovic, M.M., Lythgoe, D.J., Rotaru, D., Di Censo, D., Hirschler, L., Barbier, E.L., Vernon, A., Stone, J.M., Davies, C., Cash, D., and Modinos, G.
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- 2022
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18. Effects of benzodiazepine prescription on real-world clinical outcomes in individuals at clinical high-risk for psychosis
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Livingston, N.R., De Micheli, A., McCutcheon, R., Butler, E., Hamdan, M., Grace, A.A., McGuire, P., Egerton, A., Fusar-Poli, P., and Modinos, G.
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- 2022
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19. P.0276 Cellular and molecular signatures of in vivo gabaergic neurotransmission in the human brain
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Lukow, P., primary, Martins, D., additional, Veronese, M., additional, McGuire, P., additional, Turkheimer, F.E., additional, and Modinos, G., additional
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- 2021
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20. Are we really mapping psychosis risk? Neuroanatomical signature of affective disorders in subjects at ultra high risk
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Modinos, G., Allen, P., Frascarelli, M., Tognin, S., Valmaggia, L., Xenaki, L., Keedwell, P., Broome, M., Valli, I., Woolley, J., Stone, J. M., Mechelli, A., Phillips, M. L., McGuire, P., and Fusar-Poli, P.
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- 2014
21. Cellular and molecular signatures of in vivo GABAergic neurotransmission in the human brain
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Lukow, PB, primary, Martins, D, additional, Veronese, M, additional, Vernon, AC, additional, McGuire, P, additional, Turkheimer, FE, additional, and Modinos, G, additional
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- 2021
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22. Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis
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Pollak, TA, Kempton, MJ, Iyegbe, C, Vincent, A, Irani, SR, Coutinho, E, Menassa, DA, Jacobson, L, de Haan, L, Ruhrmann, S, Sachs, G, Riecher-Roessler, A, Krebs, M-O, Amminger, P, Glenthoj, B, Barrantes-Vidal, N, van Os, J, Rutten, BPF, Bressan, RA, van der Gaag, M, Yolken, R, Hotopf, M, Valmaggia, L, Stone, J, David, AS, McGuire, P, Calem, M, Tognin, S, Modinos, G, Velthorst, E, Kraan, TC, van Dam, DS, Burger, N, Nelson, B, McGorry, P, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Rosa, A, Racioppi, A, Monsonet, M, Hinojosa-Marques, L, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, L, Nordentoft, M, Gebhard, D, Arnhold, J, Klosterkoetter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Pollak, TA, Kempton, MJ, Iyegbe, C, Vincent, A, Irani, SR, Coutinho, E, Menassa, DA, Jacobson, L, de Haan, L, Ruhrmann, S, Sachs, G, Riecher-Roessler, A, Krebs, M-O, Amminger, P, Glenthoj, B, Barrantes-Vidal, N, van Os, J, Rutten, BPF, Bressan, RA, van der Gaag, M, Yolken, R, Hotopf, M, Valmaggia, L, Stone, J, David, AS, McGuire, P, Calem, M, Tognin, S, Modinos, G, Velthorst, E, Kraan, TC, van Dam, DS, Burger, N, Nelson, B, McGorry, P, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Rosa, A, Racioppi, A, Monsonet, M, Hinojosa-Marques, L, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, L, Nordentoft, M, Gebhard, D, Arnhold, J, Klosterkoetter, J, Lasser, I, Winklbaur, B, and Delespaul, PA
- Abstract
Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current
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- 2021
23. Neurobiological correlates of basic self-disturbances in subjects at clinical high risk for psychosis
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Bonoldi, Ilaria, Madeira, L, Allen, P, Azis, M, Quinn, B, Modinos, G, Bossong, M, Stone, J, Perez, J, Howes, O, Fusar-Poli, P, and McGuire, P
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- 2014
24. P.107 Hippocampal GABA-A α5 receptor subunits are down-regulated in the methylazoxymethanol model of schizophrenia
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Kiemes, A., primary, Gomes, F., additional, Cash, D., additional, Singh, N., additional, Turkheimer, F., additional, Grace, A.A., additional, and Modinos, G., additional
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- 2021
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25. Neuroanatomical Correlates of Psychotic-Like Experiences Assessed in 2,695 Individuals via the ENIGMA Consortium
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Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Fornito, A, Dannlowski, U, DeRosse, P, Baune, B, Green, M, Quide, Y, Pantelis, C, Chan, R, Ettinger, U, Debbane, M, Gaser, C, Besteher, B, Diederen, K, Spencer, T, Rossler, W, Kumari, V, Park, H, Lemmers, I, Allen, P, Marsman, J-B, Gilleen, J, Kirschner, M, Dagher, A, Lebedeva, I, Kaiser, S, Fett, A-K, Sommer, I, van Erp, T, Turner, J, Thompson, PM, Aleman, A, Modinos, G, and ENIGMA Schizotypy Working Group
- Subjects
neuroanatomy ,schizotypy ,psychosis ,ENIGMA Consortium ,Biological Psychiatry ,structural MRI - Abstract
Background: Recent meta-analytical evidence indicates that cortical thickness abnormalities in schizophrenia are influenced by illness severity and antipsychotic medication exposure. Schizotypy research allows investigating the neuroanatomical correlates of psychotic-like experiences without illness- and treatment-related confounders. Here we present the first large-scale meta-analysis of cortical thickness in schizotypy across 23 datasets worldwide. Methods: The study involved structural MRI scans from 2,695 healthy individuals (mean [range] age, 29.1 [17-55.8], 46.3% male) who also completed self-report schizotypy questionnaires. Each site used FreeSurfer to extract cortical thickness for 70 Desikan-Killiany atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness), and performed partial correlation analyses with total schizotypy scores in R to predict left, right and mean cortical thickness by region, adjusting by sex and age. Random-effects meta-analyses of partial correlation effect sizes for each region were performed using R’s metafor package. Results: Schizotypy scores were positively associated with mean cortical thickness of the medial orbitofrontal cortex (r=0.077; pFDR=0.006) and the frontal pole (r=0.073; pFDR=0.006). By hemisphere, schizotypy was associated with cortical thickness of the left medial orbitofrontal cortex (r=0.066; pFDR=0.044), and at trend-level with the right medial orbitofrontal cortex and left frontal pole (both r=0.062; pFDR=0.053). Conclusions: Worldwide cooperative analyses of neuroimaging data shows that subclinical psychotic-like experiences are associated with greater prefrontal cortical thickness. The directionality of the effects is opposite to that of thinner cortex in schizophrenia. Given that accelerated prefrontal thinning has been associated with progression to psychosis in at-risk individuals, our findings may reflect mechanisms of resilience in schizotypy. Supported By GM is supported by a Sir Henry Dale Fellowship, jointly funded by The Wellcome Trust and The Royal Society. Keyword, ENIGMA Consortium
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- 2020
26. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
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Thompson, P.M. (Paul), Jahanshad, N. (Neda), Ching, C.R.K. (Christopher), Salminen, L.E. (Lauren E.), Thomopoulos, S.I. (Sophia I.), Bright, J. (Joanna), Baune, B.T., Bertolín, S. (Sara), Bralten, L.B.C. (Linda), Bruin, W.B. (Willem B.), Bülow, R. (Robin), Chen, J. (Jian), Chye, Y. (Yann), Dannlowski, U. (Udo), de Kovel, C.G.F. (Carolien G F), Donohoe, D.J. (Dennis), Eyler, L.T. (Lisa T.), Faraone, S.V. (Stephen), Favre, P. (Pauline), Filippi, C.A. (Courtney A.), Frodl, T. (Thomas), Garijo, D. (Daniel), Gil, Y. (Yolanda), Grabe, H.J. (Hans Jörgen), Grasby, K.L. (Katrina L.), Hajek, T. (Tomas), Han, L.K.M. (Laura K M), Hatton, W., Hilbert, K. (Kevin), Ho, T.C. (Tiffany C.), Holleran, L. (Laurena), Homuth, G. (Georg), Hosten, N. (Norbert), Houenou, J. (Josselin), Ivanov, I. (Iliyan), Jia, T. (Tianye), Kelly, S. (Sinead), Klein, M. (Marieke), Kwon, J.S. (Jun Soo), Laansma, M.A. (Max A.), Leerssen, J. (Jeanne), Lueken, U. (Ulrike), Nunes, A. (Abraham), Neill, J.O. (Joseph O'), Opel, N. (Nils), Piras, F. (Fabrizio), Piras, F. (Federica), Postema, M.C. (Merel C.), Pozzi, E. (Elena), Shatokhina, N. (Natalia), Soriano-Mas, C. (Carles), Spalletta, G. (Gianfranco), Sun, D. (Daqiang), Teumer, A. (Alexander), Tilot, A.K. (Amanda K.), Tozzi, L. (Leonardo), van der Merwe, C. (Celia), Someren, E.J.W. (Eus) van, van Wingen, G.A. (Guido A.), Völzke, H. (Henry), Walton, E. (Esther), Wang, L. (Lei), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Wright, M.J. (Margaret), Yun, J.-Y. (Je-Yeon), Zhang, G. (Guohao), Zhang-James, Y. (Yanli), Adhikari, B.M. (Bhim M.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Aleman, A. (André), Althoff, R.R. (Robert R.), Altmann, A. (A.), Andreassen, O.A. (Ole), Baron, D.A. (David A.), Bartnik-Olson, B.L. (Brenda L.), Marie Bas-Hoogendam, J. (Janna), Baskin-Sommers, A.R. (Arielle R.), Bearden, C.E. (Carrie), Berner, L.A. (Laura A.), Boedhoe, P.S.W. (Premika S W), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan), Caeyenberghs, K. (Karen), Cecil, C.A.M. (Charlotte), Cohen, R.A. (Ronald A.), Cole, J.H. (James H.), Conrod, P. (Patricia), De Brito, S.A. (Stephane A.), de Zwarte, S.M.C. (Sonja M C), Dennis, E.L. (Emily L.), Desrivieres, S. (Sylvane), Dima, D. (Danai), Ehrlich, S.M. (Stefan), Esopenko, C. (Carrie), Fairchild, G. (Graeme), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Francks, C. (Clyde), Frangou, S. (Sophia), Franke, B. (Barbara), Garavan, H.P. (Hugh P.), Glahn, D.C. (David), Groenewold, N.A. (Nynke A.), Gurholt, T.P. (Tiril P.), Gutman, B.A. (Boris A.), Hahn, T. (Tim), Harding, I.H. (Ian H.), Hernaus, D. (Dennis), Hibar, D.P. (Derrek P.), Hillary, F.G. (Frank G.), Hoogman, M. (Martine), Hulshoff Pol, H.E. (Hilleke E.), Jalbrzikowski, M. (Maria), Karkashadze, G.A. (George A.), Klapwijk, E.T. (Eduard T.), Knickmeyer, R.C. (Rebecca C.), Kochunov, P. (Peter), Koerte, I.K. (Inga K.), Kong, X.-Z. (Xiang-Zhen), Liew, S.-L. (Sook-Lei), Lin, A.P. (Alexander P.), Logue, M.W. (Mark W.), Luders, E. (Eileen), Macciardi, F. (Fabio), Mackey, S. (Scott), Mayer, A.R. (Andrew R.), McDonald, C.R. (Carrie R.), McMahon, A.B. (Agnes B.), Medland, S.E. (Sarah), Modinos, G. (Gemma), Morey, R.A. (Rajendra A.), Mueller, S.C. (Sven C.), Mukherjee, P. (Pratik), Namazova-Baranova, L. (L.), Nir, T.M. (Talia M.), Olsen, A. (Alexander), Paschou, P. (Peristera), Pine, D.S. (Daniel S.), Pizzagalli, F. (Fabrizio), Rentería, M.E. (Miguel), Rohrer, J.D. (Jonathan D.), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schumann, G. (Gunter), Shiroishi, M.S. (Mark S.), Sisodiya, S.M. (Sanjay), Smit, D.J.A. (Dirk J A), Sønderby, I.E. (Ida E.), Stein, D.J. (Dan J.), Stein, J.L., Tahmasian, M. (Masoud), Tate, D.F. (David F.), Turner, J. (Jessica), Heuvel, O.A. (Odile A.), Wee, N.J. (Nic) van der, van der Werf, Y.D. (Ysbrand), Erp, T.G.M. (Theo G.) van, van Haren, N.E.M. (Neeltje E M), van Rooij, D. (Daan), Van Velzen, L.S., Veer, I.M. (Ilya), Veltman, D.J. (Dick), Villalon-Reina, J.E. (Julio E.), Walter, H.J. (Henrik), Whelan, C.D. (Christopher), Wilde, E.A. (Elisabeth A.), Zarei, M. (Mojtaba), Zelman, V. (Vladimir), Thompson, P.M. (Paul), Jahanshad, N. (Neda), Ching, C.R.K. (Christopher), Salminen, L.E. (Lauren E.), Thomopoulos, S.I. (Sophia I.), Bright, J. (Joanna), Baune, B.T., Bertolín, S. (Sara), Bralten, L.B.C. (Linda), Bruin, W.B. (Willem B.), Bülow, R. (Robin), Chen, J. (Jian), Chye, Y. (Yann), Dannlowski, U. (Udo), de Kovel, C.G.F. (Carolien G F), Donohoe, D.J. (Dennis), Eyler, L.T. (Lisa T.), Faraone, S.V. (Stephen), Favre, P. (Pauline), Filippi, C.A. (Courtney A.), Frodl, T. (Thomas), Garijo, D. (Daniel), Gil, Y. (Yolanda), Grabe, H.J. (Hans Jörgen), Grasby, K.L. (Katrina L.), Hajek, T. (Tomas), Han, L.K.M. (Laura K M), Hatton, W., Hilbert, K. (Kevin), Ho, T.C. (Tiffany C.), Holleran, L. (Laurena), Homuth, G. (Georg), Hosten, N. (Norbert), Houenou, J. (Josselin), Ivanov, I. (Iliyan), Jia, T. (Tianye), Kelly, S. (Sinead), Klein, M. (Marieke), Kwon, J.S. (Jun Soo), Laansma, M.A. (Max A.), Leerssen, J. (Jeanne), Lueken, U. (Ulrike), Nunes, A. (Abraham), Neill, J.O. (Joseph O'), Opel, N. (Nils), Piras, F. (Fabrizio), Piras, F. (Federica), Postema, M.C. (Merel C.), Pozzi, E. (Elena), Shatokhina, N. (Natalia), Soriano-Mas, C. (Carles), Spalletta, G. (Gianfranco), Sun, D. (Daqiang), Teumer, A. (Alexander), Tilot, A.K. (Amanda K.), Tozzi, L. (Leonardo), van der Merwe, C. (Celia), Someren, E.J.W. (Eus) van, van Wingen, G.A. (Guido A.), Völzke, H. (Henry), Walton, E. (Esther), Wang, L. (Lei), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Wright, M.J. (Margaret), Yun, J.-Y. (Je-Yeon), Zhang, G. (Guohao), Zhang-James, Y. (Yanli), Adhikari, B.M. (Bhim M.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Aleman, A. (André), Althoff, R.R. (Robert R.), Altmann, A. (A.), Andreassen, O.A. (Ole), Baron, D.A. (David A.), Bartnik-Olson, B.L. (Brenda L.), Marie Bas-Hoogendam, J. (Janna), Baskin-Sommers, A.R. (Arielle R.), Bearden, C.E. (Carrie), Berner, L.A. (Laura A.), Boedhoe, P.S.W. (Premika S W), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan), Caeyenberghs, K. (Karen), Cecil, C.A.M. (Charlotte), Cohen, R.A. (Ronald A.), Cole, J.H. (James H.), Conrod, P. (Patricia), De Brito, S.A. (Stephane A.), de Zwarte, S.M.C. (Sonja M C), Dennis, E.L. (Emily L.), Desrivieres, S. (Sylvane), Dima, D. (Danai), Ehrlich, S.M. (Stefan), Esopenko, C. (Carrie), Fairchild, G. (Graeme), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Francks, C. (Clyde), Frangou, S. (Sophia), Franke, B. (Barbara), Garavan, H.P. (Hugh P.), Glahn, D.C. (David), Groenewold, N.A. (Nynke A.), Gurholt, T.P. (Tiril P.), Gutman, B.A. (Boris A.), Hahn, T. (Tim), Harding, I.H. (Ian H.), Hernaus, D. (Dennis), Hibar, D.P. (Derrek P.), Hillary, F.G. (Frank G.), Hoogman, M. (Martine), Hulshoff Pol, H.E. (Hilleke E.), Jalbrzikowski, M. (Maria), Karkashadze, G.A. (George A.), Klapwijk, E.T. (Eduard T.), Knickmeyer, R.C. (Rebecca C.), Kochunov, P. (Peter), Koerte, I.K. (Inga K.), Kong, X.-Z. (Xiang-Zhen), Liew, S.-L. (Sook-Lei), Lin, A.P. (Alexander P.), Logue, M.W. (Mark W.), Luders, E. (Eileen), Macciardi, F. (Fabio), Mackey, S. (Scott), Mayer, A.R. (Andrew R.), McDonald, C.R. (Carrie R.), McMahon, A.B. (Agnes B.), Medland, S.E. (Sarah), Modinos, G. (Gemma), Morey, R.A. (Rajendra A.), Mueller, S.C. (Sven C.), Mukherjee, P. (Pratik), Namazova-Baranova, L. (L.), Nir, T.M. (Talia M.), Olsen, A. (Alexander), Paschou, P. (Peristera), Pine, D.S. (Daniel S.), Pizzagalli, F. (Fabrizio), Rentería, M.E. (Miguel), Rohrer, J.D. (Jonathan D.), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schumann, G. (Gunter), Shiroishi, M.S. (Mark S.), Sisodiya, S.M. (Sanjay), Smit, D.J.A. (Dirk J A), Sønderby, I.E. (Ida E.), Stein, D.J. (Dan J.), Stein, J.L., Tahmasian, M. (Masoud), Tate, D.F. (David F.), Turner, J. (Jessica), Heuvel, O.A. (Odile A.), Wee, N.J. (Nic) van der, van der Werf, Y.D. (Ysbrand), Erp, T.G.M. (Theo G.) van, van Haren, N.E.M. (Neeltje E M), van Rooij, D. (Daan), Van Velzen, L.S., Veer, I.M. (Ilya), Veltman, D.J. (Dick), Villalon-Reina, J.E. (Julio E.), Walter, H.J. (Henrik), Whelan, C.D. (Christopher), Wilde, E.A. (Elisabeth A.), Zarei, M. (Mojtaba), and Zelman, V. (Vladimir)
- Abstract
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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- 2020
- Full Text
- View/download PDF
27. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
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Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, Zelman, V, Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, and Zelman, V
- Abstract
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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- 2020
28. M156. CORTICAL NEUROANATOMICAL SIGNATURE OF SCHIZOTYPY IN 2,695 INDIVIDUALS ASSESSED IN A WORLDWIDE ENIGMA STUDY
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Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Dannlowski, U, DeRosse, P, Moyett, A, Baune, B, Green, M, Quide, Y, Pantelis, C, Chan, RCK, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, T, Rössler, W, Smigielski, L, Kumari, V, Park, H, Wiebels, K, Lemmers-Jansen, I, Allen, P, Kozhuharova, P, Marsman, J-B, Gilleen, J, Kirschner, M, Dagher, A, Lebedeva, I, Tomyshev, A, Kaiser, S, Fett, A-K, Sommer, I, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, Modinos, G, Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Dannlowski, U, DeRosse, P, Moyett, A, Baune, B, Green, M, Quide, Y, Pantelis, C, Chan, RCK, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, T, Rössler, W, Smigielski, L, Kumari, V, Park, H, Wiebels, K, Lemmers-Jansen, I, Allen, P, Kozhuharova, P, Marsman, J-B, Gilleen, J, Kirschner, M, Dagher, A, Lebedeva, I, Tomyshev, A, Kaiser, S, Fett, A-K, Sommer, I, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, and Modinos, G
- Abstract
Background Cortical neuroanatomical abnormalities have been reported along a continuum between individuals with chronic schizophrenia, first-episode psychosis, clinical high risk for psychosis, and healthy individuals self-reporting subclinical psychotic-like experiences (or schizotypy). Recently, the Schizophrenia Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust cortical thickness abnormalities in schizophrenia, while also indicating that these abnormalities are influenced by illness severity and treatment with antipsychotic medications. In this context, schizotypy research allows the investigation of cortical neuroanatomy associated with the expression of subclinical psychotic-like symptoms without the potential influence of a psychotic illness, its severity, or the use of antipsychotics. This study presents the first large-scale imaging meta-analysis of cortical thickness in schizotypy using standardized methods from 23 datasets worldwide. Methods Cortical thickness and surface area were assessed in MRI scans of 2,695 healthy individuals (mean [range] age of 29.1 [17–55.8], 46.3% male) who had also completed validated self-report schizotypy questionnaires. Each site processed their local T1-weighted MRI scans using FreeSurfer and, following the protocol outlined in the ENIGMA Schizophrenia Working Group study, extracted cortical thickness for 70 Desikan-Killiany (DK) atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness). At each site, partial correlation analyses were performed between regional cortical thickness by ROI and total schizotypy scores in R, predicting the left, right and mean cortical thickness, adjusting for sex, age and site. Random-effects meta-analyses of partial correlation effect sizes for each of the DK atlas regions were performed using R’s metafor package. False discovery rate (pFDR < .05) was used to c
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- 2020
29. Emotion Recognition and Adverse Childhood Experiences in Individuals at Clinical High Risk of Psychosis
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Tognin, S, Catalan, A, Modinos, G, Kempton, MJ, Bilbao, A, Nelson, B, Pantelis, C, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, de Haan, L, van der Gaag, M, McGuire, P, Valmaggia, LR, Tognin, S, Catalan, A, Modinos, G, Kempton, MJ, Bilbao, A, Nelson, B, Pantelis, C, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, de Haan, L, van der Gaag, M, McGuire, P, and Valmaggia, LR
- Abstract
OBJECTIVE: To investigate the association between facial affect recognition (FAR) and type of adverse childhood experiences (ACEs) in a sample of clinical high risk (CHR) individuals and a matched sample of healthy controls (HCs). METHODS: In total, 309 CHR individuals and 51 HC were recruited as part of an European Union-funded multicenter study (EU-GEI) and included in this work. During a 2-year follow-up period, 65 CHR participants made a transition to psychosis (CHR-T) and 279 did not (CHR-NT). FAR ability was measured using a computerized version of the Degraded Facial Affect Recognition (DFAR) task. ACEs were measured using the Childhood Experience of Care and Abuse Questionnaire, the Childhood Trauma Questionnaire, and the Bullying Questionnaire. Generalized regression models were used to investigate the relationship between ACE and FAR. Logistic regressions were used to investigate the relationship between FAR and psychotic transition. RESULTS: In CHR individuals, having experienced emotional abuse was associated with decreased total and neutral DFAR scores. CHR individuals who had experienced bullying performed better in the total DFAR and in the frightened condition. In HC and CHR, having experienced the death of a parent during childhood was associated with lower DFAR total score and lower neutral DFAR score, respectively. Analyses revealed a modest increase of transition risk with increasing mistakes from happy to angry faces. CONCLUSIONS: Adverse experiences in childhood seem to have a significant impact on emotional processing in adult life. This information could be helpful in a therapeutic setting where both difficulties in social interactions and adverse experiences are often addressed.
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- 2020
30. Towards Precision Medicine in Psychosis: Benefits and Challenges of Multimodal Multicenter Studies-PSYSCAN: Translating Neuroimaging Findings From Research into Clinical Practice
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Tognin, S, van Hell, HH, Merritt, K, Winter-van Rossum, I, Bossong, MG, Kempton, MJ, Modinos, G, Fusar-Poli, P, Mechelli, A, Dazzan, P, Maat, A, de Haan, L, Crespo-Facorro, B, Glenthoj, B, Lawrie, SM, McDonald, C, Gruber, O, van Amelsvoort, T, Arango, C, Kircher, T, Nelson, B, Galderisi, S, Bressan, R, Kwon, JS, Weiser, M, Mizrahi, R, Sachs, G, Maatz, A, Kahn, R, McGuire, P, Tognin, S, van Hell, HH, Merritt, K, Winter-van Rossum, I, Bossong, MG, Kempton, MJ, Modinos, G, Fusar-Poli, P, Mechelli, A, Dazzan, P, Maat, A, de Haan, L, Crespo-Facorro, B, Glenthoj, B, Lawrie, SM, McDonald, C, Gruber, O, van Amelsvoort, T, Arango, C, Kircher, T, Nelson, B, Galderisi, S, Bressan, R, Kwon, JS, Weiser, M, Mizrahi, R, Sachs, G, Maatz, A, Kahn, R, and McGuire, P
- Abstract
In the last 2 decades, several neuroimaging studies investigated brain abnormalities associated with the early stages of psychosis in the hope that these could aid the prediction of onset and clinical outcome. Despite advancements in the field, neuroimaging has yet to deliver. This is in part explained by the use of univariate analytical techniques, small samples and lack of statistical power, lack of external validation of potential biomarkers, and lack of integration of nonimaging measures (eg, genetic, clinical, cognitive data). PSYSCAN is an international, longitudinal, multicenter study on the early stages of psychosis which uses machine learning techniques to analyze imaging, clinical, cognitive, and biological data with the aim of facilitating the prediction of psychosis onset and outcome. In this article, we provide an overview of the PSYSCAN protocol and we discuss benefits and methodological challenges of large multicenter studies that employ neuroimaging measures.
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- 2020
31. Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis
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Modinos, G, Kempton, MJ, Tognin, S, Calem, M, Porffy, L, Antoniades, M, Mason, A, Azis, M, Allen, P, Nelson, B, McGorry, P, Pantelis, C, Riecher-Rossler, A, Borgwardt, S, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, B, van Os, J, de Haan, L, Velthorst, E, van der Gaag, M, Valmaggia, LR, McGuire, P, Kraan, TC, van Dam, DS, Burger, N, Amminger, GP, Politis, A, Goodall, J, Rapp, C, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Dominguez-Martinez, T, Monsonet, M, Hinojosa, L, Racioppi, A, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, LB, Gebhard, D, Arnhold, J, Klosterkotter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Modinos, G, Kempton, MJ, Tognin, S, Calem, M, Porffy, L, Antoniades, M, Mason, A, Azis, M, Allen, P, Nelson, B, McGorry, P, Pantelis, C, Riecher-Rossler, A, Borgwardt, S, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, B, van Os, J, de Haan, L, Velthorst, E, van der Gaag, M, Valmaggia, LR, McGuire, P, Kraan, TC, van Dam, DS, Burger, N, Amminger, GP, Politis, A, Goodall, J, Rapp, C, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Dominguez-Martinez, T, Monsonet, M, Hinojosa, L, Racioppi, A, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, LB, Gebhard, D, Arnhold, J, Klosterkotter, J, Lasser, I, Winklbaur, B, and Delespaul, PA
- Abstract
IMPORTANCE: The development of adverse clinical outcomes in patients with psychosis has been associated with behavioral and neuroanatomical deficits related to emotion processing. However, the association between alterations in brain regions subserving emotion processing and clinical outcomes remains unclear. OBJECTIVE: To examine the association between alterations in emotion processing and regional gray matter volumes in individuals at clinical high risk (CHR) for psychosis, and the association with subsequent clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: This naturalistic case-control study with clinical follow-up at 12 months was conducted from July 1, 2010, to August 31, 2016, and collected data from 9 psychosis early detection centers (Amsterdam, Basel, Cologne, Copenhagen, London, Melbourne, Paris, The Hague, and Vienna). Participants (213 individuals at CHR and 52 healthy controls) were enrolled in the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) project. Data were analyzed from October 1, 2018, to April 24, 2019. MAIN MEASURES AND OUTCOMES: Emotion recognition was assessed with the Degraded Facial Affect Recognition Task. Three-Tesla magnetic resonance imaging scans were acquired from all participants, and gray matter volume was measured in regions of interest (medial prefrontal cortex, amygdala, hippocampus, and insula). Clinical outcomes at 12 months were evaluated for transition to psychosis using the Comprehensive Assessment of At-Risk Mental States criteria, and the level of overall functioning was measured through the Global Assessment of Functioning [GAF] scale. RESULTS: A total of 213 individuals at CHR (105 women [49.3%]; mean [SD] age, 22.9 [4.7] years) and 52 healthy controls (25 women [48.1%]; mean [SD] age, 23.3 [4.0] years) were included in the study at baseline. At the follow-up within 2 years of baseline, 44 individuals at CHR (20.7%) had developed psychosis and 169 (79.3%) had n
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- 2020
32. From Speech Illusions to Onset of Psychotic Disorder: Applying Network Analysis to an Experimental Measure of Aberrant Experiences
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Boyette, L-L, Isvoranu, A-M, Schirmbeck, F, Velthorst, E, Simons, CJP, Barrantes-Vidal, N, Bressan, R, Kempton, MJ, Krebs, M-O, McGuire, P, Nelson, B, Nordentoft, M, Riecher-Rössler, A, Ruhrmann, S, Rutten, BP, Sachs, G, Valmaggia, LR, van der Gaag, M, Borsboom, D, de Haan, L, van Os, J, Calem, M, Tognin, S, Modinos, G, Kraan, TC, van Dam, DS, Burger, N, McGorry, P, Amminger, GP, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Studerus, E, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Domínguez-Martínez, T, Cristóbal-Narváez, P, Kwapil, TR, Monsonet, M, Hinojosa, L, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthøj, L, Glenthøj, B, Gebhard, D, Arnhold, J, Klosterkötter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Boyette, L-L, Isvoranu, A-M, Schirmbeck, F, Velthorst, E, Simons, CJP, Barrantes-Vidal, N, Bressan, R, Kempton, MJ, Krebs, M-O, McGuire, P, Nelson, B, Nordentoft, M, Riecher-Rössler, A, Ruhrmann, S, Rutten, BP, Sachs, G, Valmaggia, LR, van der Gaag, M, Borsboom, D, de Haan, L, van Os, J, Calem, M, Tognin, S, Modinos, G, Kraan, TC, van Dam, DS, Burger, N, McGorry, P, Amminger, GP, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Studerus, E, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Domínguez-Martínez, T, Cristóbal-Narváez, P, Kwapil, TR, Monsonet, M, Hinojosa, L, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthøj, L, Glenthøj, B, Gebhard, D, Arnhold, J, Klosterkötter, J, Lasser, I, Winklbaur, B, and Delespaul, PA
- Abstract
Aberrant perceptional experiences are a potential early marker of psychosis development. Earlier studies have found experimentally assessed speech illusions to be associated with positive symptoms in patients with psychotic disorders, but findings for attenuated symptoms in individuals without psychotic disorders have been inconsistent. Also, the role of affect is unclear. The aim of this study was to use the network approach to investigate how speech illusions relate to individual symptoms and onset of a psychotic disorder. We estimated a network model based on data from 289 Clinical High-Risk (CHR) subjects, participating in the EU-GEI project. The network structure depicts statistical associations between (affective and all) speech illusions, cross-sectional individual attenuated positive and affective symptoms, and transition to psychotic disorder after conditioning on all other variables in the network. Speech illusions were assessed with the White Noise Task, symptoms with the BPRS and transition during 24-month follow-up with the CAARMS. Affective, not all, speech illusions were found to be directly, albeit weakly, associated with hallucinatory experiences. Hallucinatory experiences, in turn, were associated with delusional ideation. Bizarre behavior was the only symptom in the network steadily predictive of transition. Affective symptoms were highly interrelated, with depression showing the highest overall strength of connections to and predictability by other symptoms. Both speech illusions and transition showed low overall predictability by symptoms. Our findings suggest that experimentally assessed speech illusions are not a mere consequence of psychotic symptoms or disorder, but that their single assessment is likely not useful for assessing transition risk.
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- 2020
33. T162. THICKER PREFRONTAL CORTEX IS ASSOCIATED WITH SUBCLINICAL NEGATIVE SYMPTOMS IN SCHIZOTYPY - AN ENIGMA CONSORTIUM META-ANALYSIS
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Kirschner, M, Hodzic-Santor, B, Kircher, T, Nenadic, I, Fornito, A, Green, M, Quide, Y, Pantelis, C, Dannlowski, U, DeRosse, P, Chan, R, Debbané, M, Rössler, W, Lebedeva, I, Park, H, Marsman, J-B, Gilleen, J, Fett, A-K, van Erp, T, Turner, J, Thompson, P, Aleman, A, Modinos, G, Kaiser, S, Kirschner, M, Hodzic-Santor, B, Kircher, T, Nenadic, I, Fornito, A, Green, M, Quide, Y, Pantelis, C, Dannlowski, U, DeRosse, P, Chan, R, Debbané, M, Rössler, W, Lebedeva, I, Park, H, Marsman, J-B, Gilleen, J, Fett, A-K, van Erp, T, Turner, J, Thompson, P, Aleman, A, Modinos, G, and Kaiser, S
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- 2020
34. A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer's disease
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Tarraga, L., Boada, M., Modinos, G., Espinosa, A., Diego, S., Morera, A., Guitart, M., Balcells, J., Lopez, O.L., and Becker, J.T.
- Subjects
Interactive computer systems -- Usage ,Interactive computer systems -- Research ,Interactive media -- Usage ,Interactive media -- Research ,Brain stimulation -- Research ,Cognition in old age -- Physiological aspects ,Alzheimer's disease -- Care and treatment ,Interactive technology ,Health ,Psychology and mental health - Published
- 2006
35. Schizotypy and brain structure: a voxel-based morphometry study
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Modinos, G., Mechelli, A., Ormel, J., Groenewold, N. A., Aleman, A., and McGuire, P. K.
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- 2010
36. Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome
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Modinos, G., Allen, P. M., Zugman, A., Dima, D., Azis, M., Samson, C., Bonoldi, I., Quinn, B., Gifford, G. W. G., Smart, S. E., Antoniades, M., Bossong, M. G., Broome, M. R., Perez, J., Howes, O. D., Stone, J. M., Grace, A. A., and McGuire, P.
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nervous system ,RC0321 ,BF - Abstract
Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis.
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- 2019
37. P.1.25 Effects of antipsychotic treatment on GABA-A receptor function
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Peris, A., primary, Kiemes, A., additional, Cash, D., additional, Vernon, A., additional, and Modinos, G., additional
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- 2019
- Full Text
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38. Neuroimaging studies of GABA in schizophrenia:A systematic review with meta-analysis
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Egerton, A, Modinos, G, Ferrera, D, and McGuire, P
- Abstract
Data from animal models and from postmortem studies suggest that schizophrenia is associated with brain GABAergic dysfunction. The extent to which this is reflected in data from in vivo studies of GABA function in schizophrenia is unclear. The Medline database was searched to identify articles published until 21 October 2016. The search terms included GABA, proton magnetic resonance spectroscopy (1H-MRS), positron emission tomography (PET), single photon emission computed tomography (SPECT), schizophrenia and psychosis. Sixteen GABA 1H-MRS studies (538 controls, 526 patients) and seven PET/SPECT studies of GABAA/benzodiazepine receptor (GABAA/BZR) availability (118 controls, 113 patients) were identified. Meta-analyses of 1H-MRS GABA in the medial prefrontal cortex (mPFC), parietal/occipital cortex (POC) and striatum did not show significant group differences (mFC: G=-0.3, 409 patients, 495 controls, 95% confidence interval (CI):-0.6 to 0.1; POC: G=-0.3, 139 patients, 111 controls, 95% CI:-0.9 to 0.3; striatum: G=-0.004, 123 patients, 95 controls, 95% CI:-0.7 to 0.7). Heterogeneity across studies was high (I2 >50%), and this was not explained by subsequent moderator or meta-regression analyses. There were insufficient PET/SPECT receptor availability studies for meta-analyses, but a systematic review did not suggest replicable group differences in regional GABA A/BZR availability. The current literature does not reveal consistent alterations in in vivo GABA neuroimaging measures in schizophrenia, as might be hypothesized from animal models and postmortem data. The analysis highlights the need for further GABA neuroimaging studies with improved methodology and addressing potential sources of heterogeneity.
- Published
- 2017
39. Corticolimbic hyper-response to emotion and glutamatergic function in people with high schizotypy: a multimodal fMRI-MRS study
- Author
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Modinos, G, McLaughlin, A, Egerton, A, McMullen, K, Kumari, V, Barker, G J, Keysers, C, Williams, S C R, Brein en Cognitie (Psychologie, FMG), FMG, and Netherlands Institute for Neuroscience (NIN)
- Subjects
nervous system ,Journal Article - Abstract
Animal models and human neuroimaging studies suggest that altered levels of glutamatergic metabolites within a corticolimbic circuit have a major role in the pathophysiology of schizophrenia. Rodent models propose that prefrontal glutamate dysfunction could lead to amygdala hyper-response to environmental stress and underlie hippocampal overdrive in schizophrenia. Here we determine whether changes in brain glutamate are present in individuals with high schizotypy (HS), which refers to the presence of schizophrenia-like characteristics in healthy individuals, and whether glutamate levels are related to altered corticolimbic response to emotion. Twenty-one healthy HS subjects and 22 healthy subjects with low schizotypy (LS) were selected based on their Oxford and Liverpool Inventory of Feelings and Experiences rating. Glutamate levels were measured in the anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, followed by a functional magnetic resonance imaging (fMRI) scan to measure corticolimbic response during emotional processing. fMRI results and fMRI × glutamate interactions were considered significant after voxel-wise Po0.05 family-wise error correction. While viewing emotional pictures, HS individuals showed greater activation than did subjects with LS in the caudate, and marginally in the ACC, hippocampus, medial prefrontal cortex (MPFC) and putamen. Although no between-group differences were found in glutamate concentrations, within the HS group ACC glutamate was negatively correlated with striatal activation (left: z = 4.30, P = 0.004 and right: z = 4.12 P = 0.008 caudate; left putamen: z = 3.89, P = 0.018) and marginally with MPFC (z = 3.55, P = 0.052) and amygdala (left: z = 2.88, P = 0.062; right: z = 2.79, P = 0.079), correlations that were not present in LS subjects. These findings provide, to our knowledge, the first evidence that brain glutamate levels are associated with hyper-responsivity in brain regions thought to be critical in the pathophysiology of psychosis.
- Published
- 2017
40. Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis
- Author
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Egerton, A, primary, Modinos, G, additional, Ferrera, D, additional, and McGuire, P, additional
- Published
- 2017
- Full Text
- View/download PDF
41. Identifying gene-environment interactions in schizophrenia: Contemporary challenges for integrated, large-scale investigations
- Author
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Van Os, J. Rutten, B.P. Myin-Germeys, I. Delespaul, P. Viechtbauer, W. Van Zelst, C. Bruggeman, R. Reininghaus, U. Morgan, C. Murray, R.M. Di Forti, M. McGuire, P. Valmaggia, L.R. Kempton, M.J. Gayer-Anderson, C. Hubbard, K. Beards, S. Stilo, S.A. Onyejiaka, A. Bourque, F. Modinos, G. Tognin, S. Calem, M. O'Donovan, M.C. Owen, M.J. Holmans, P. Williams, N. Craddock, N. Richards, A. Humphreys, I. Meyer-Lindenberg, A. Leweke, F.M. Tost, H. Akdeniz, C. Rohleder, C. Bumb, J.M. Schwarz, E. Alptekin, K. Üçok, A. Saka, M.C. Atbagoǧlu, E.C. Gülöksüz, S. Gumus-Akay, G. Cihan, B. Karadaǧ, H. Soygür, H. Cankurtaran, E.S. Ulusoy, S. Akdede, B. Binbay, T. Ayer, A. Noyan, H. Karadayi, G. Akturan, E. Ulaş, H. Arango, C. Parellada, M. Bernardo, M. Sanjuán, J. Bobes, J. Arrojo, M. Santos, J.L. Cuadrado, P. Solano, J.J.R. Carracedo, A. Bernardo, E.G. Roldán, L. López, G. Cabrera, B. Cruz, S. Mesa, E.M.D. Pouso, M. Jiménez, E. Sánchez, T. Rapado, M. González, E. Martínez, C. Sánchez, E. Olmeda, M.S. De Haan, L. Velthorst, E. Van Der Gaag, M. Selten, J.-P. Van Dam, D. Van Der Ven, E. Van Der Meer, F. Messchaert, E. Kraan, T. Burger, N. Leboyer, M. Szoke, A. Schürhoff, F. Llorca, P.-M. Jamain, S. Tortelli, A. Frijda, F. Vilain, J. Galliot, A.-M. Baudin, G. Ferchiou, A. Richard, J.-R. Bulzacka, E. Charpeaud, T. Tronche, A.-M. De Hert, M. Van Winkel, R. Decoster, J. Derom, C. Thiery, E. Stefanis, N.C. Sachs, G. Aschauer, H. Lasser, I. Winklbaur, B. Schlögelhofer, M. Riecher-Rössler, A. Borgwardt, S. Walter, A. Harrisberger, F. Smieskova, R. Rapp, C. Ittig, S. Soguel-Dit-Piquard, F. Studerus, E. Klosterkötter, J. Ruhrmann, S. Paruch, J. Julkowski, D. Hilboll, D. Sham, P.C. Cherny, S.S. Chen, E.Y.H. Campbell, D.D. Li, M. Romeo-Casabona, C.M. Cirión, A.E. Mora, A.U. Jones, P. Kirkbride, J. Cannon, M. Rujescu, D. Tarricone, I. Berardi, D. Bonora, E. Seri, M. Marcacci, T. Chiri, L. Chierzi, F. Storbini, V. Braca, M. Minenna, M.G. Donegani, I. Fioritti, A. La Barbera, D. La Cascia, C.E. Mulè, A. Sideli, L. Sartorio, R. Ferraro, L. Tripoli, G. Seminerio, F. Marinaro, A.M. McGorry, P. Nelson, B. Amminger, G.P. Pantelis, C. Menezes, P.R. Del-Ben, C.M. Tenan, S.H.G. Shuhama, R. Ruggeri, M. Tosato, S. Lasalvia, A. Bonetto, C. Ira, E. Nordentoft, M. Krebs, M.-O. Barrantes-Vidal, N. Cristóbal, P. Kwapil, T.R. Brietzke, E. Bressan, R.A. Gadelha, A. Maric, N.P. Andric, S. Mihaljevic, M. Mirjanic, T.
- Abstract
Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. © 2014 The Author.
- Published
- 2014
42. Gray Matter Reductions in Cortical Midline Structures Related to Basic Self Disturbances in People at “ultra High Risk” for Psychosis
- Author
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Bonoldi, I., primary, Allen, P., additional, Tognin, S., additional, Madeira, L., additional, Azis, M., additional, Samson, C., additional, Quinn, B., additional, Modinos, G., additional, Bossong, M., additional, Stone, J., additional, Perez, J., additional, Howes, O., additional, Fusar-Poli, P., additional, and McGuire, P., additional
- Published
- 2015
- Full Text
- View/download PDF
43. P.1.i.013 Altered hippocampal glutamate function in people at ultra high risk for psychosis
- Author
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Bossong, M.G., primary, Allen, P., additional, Samson, C., additional, Rasheed, H., additional, Quinn, B., additional, Bonoldi, I., additional, Modinos, G., additional, Stone, J., additional, Howes, O.D., additional, and McGuire, P., additional
- Published
- 2014
- Full Text
- View/download PDF
44. Neuroimaging Auditory Hallucinations in Schizophrenia: From Neuroanatomy to Neurochemistry and Beyond
- Author
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Allen, P., primary, Modinos, G., additional, Hubl, D., additional, Shields, G., additional, Cachia, A., additional, Jardri, R., additional, Thomas, P., additional, Woodward, T., additional, Shotbolt, P., additional, Plaze, M., additional, and Hoffman, R., additional
- Published
- 2012
- Full Text
- View/download PDF
45. Schizotypy and brain structure: a voxel-based morphometry study
- Author
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Modinos, G., primary, Mechelli, A., additional, Ormel, J., additional, Groenewold, N. A., additional, Aleman, A., additional, and McGuire, P. K., additional
- Published
- 2009
- Full Text
- View/download PDF
46. Theory of Mind in Different Dementia Profiles
- Author
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Modinos, G., primary, Obiols, J. E., additional, Pousa, E., additional, and Vicens, J., additional
- Published
- 2009
- Full Text
- View/download PDF
47. Structural covariance in the hallucinating brain: a voxel-based morphometry study.
- Author
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Modinos G, Vercammen A, Mechelli A, Knegtering H, McGuire PK, and Aleman A
- Published
- 2009
48. Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD): validación española.
- Author
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Boada, M., Tárraga, L., Modinos, G., Diego, S., and Reisberg, B.
- Subjects
ALZHEIMER'S disease ,PRESENILE dementia ,PATHOLOGICAL psychology ,DEMENTIA ,NEUROBEHAVIORAL disorders ,NURSING home patients - Abstract
Copyright of Neurologia (Grupo ARS XXI de Comunicacion, S.A.) is the property of Grupo ARS XXI de Comunicacion, S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2006
49. Neuropsychiatric Inventory-Nursing Home version (NPI-NH): validación española.
- Author
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Boada, M., Tárraga, L., Modinos, G., López, O. L., and Cummings, J. L.
- Subjects
NURSING care facilities ,NEUROPSYCHIATRY ,MEDICAL screening ,LONG-term care facilities ,HEALTH facilities - Abstract
Copyright of Neurologia (Grupo ARS XXI de Comunicacion, S.A.) is the property of Grupo ARS XXI de Comunicacion, S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2005
50. M156. CORTICAL NEUROANATOMICAL SIGNATURE OF SCHIZOTYPY IN 2,695 INDIVIDUALS ASSESSED IN A WORLDWIDE ENIGMA STUDY
- Author
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Antoniades M, Nenadic I, Kircher T, Krug A, Meller T, Grotegerd D, Fornito A, Arnatkeviciute A, Dannlowski U, DeRosse P, Moyett A, Baune B, Green M, and Modinos G
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