71 results on '"Arrojo M"'
Search Results
2. Cognitive and clinical predictors of a long-term course in obsessive compulsive disorder: A machine learning approach in a prospective cohort study
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Segalàs, C., Cernadas, E., Puialto, M., Fernández-Delgado, M., Arrojo, M., Bertolin, S., Real, E., Menchón, J.M., Carracedo, A., Tubío-Fungueiriño, M., Alonso, P., and Fernández-Prieto, M.
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- 2024
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3. The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe
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Selten, J. P., primary, Di Forti, M., additional, Quattrone, D., additional, Jones, P. B., additional, Jongsma, H. E., additional, Gayer-Anderson, C., additional, Szöke, A., additional, Llorca, P. M., additional, Arango, C., additional, Bernardo, M., additional, Sanjuan, J., additional, Santos, J. L., additional, Arrojo, M., additional, Tarricone, I., additional, Berardi, D., additional, Lasalvia, A., additional, Tosato, S., additional, la Cascia, C., additional, Velthorst, E., additional, van der Ven, E. M. A., additional, de Haan, L., additional, Rutten, B. P., additional, van Os, J., additional, Kirkbride, J. B., additional, Morgan, C. M., additional, Murray, R. M., additional, and Termorshuizen, F., additional
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- 2024
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4. Self-reported suicidal ideation among individuals with first episode psychosis and healthy controls:Findings from the international multicentre EU-GEI study
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Heuschen, C. B.B.C.M., Bolhuis, K., Zantvoord, J. B., Bockting, C. L., Denys, D. A.J.P., Lok, A., Arango, C., Arrojo, M., Bernardo, M., Bobes, J., Del-Ben, C. M., Di Forti, M., 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., Murray, R. M., Quattrone, D., Rutten, B. P., Sanjuán, J., Selten, J. P., Szöke, A., Tarricone, I., Tortelli, A., Velthorst, E., de Haan, L., Schirmbeck, F., Heuschen, C. B.B.C.M., Bolhuis, K., Zantvoord, J. B., Bockting, C. L., Denys, D. A.J.P., Lok, A., Arango, C., Arrojo, M., Bernardo, M., Bobes, J., Del-Ben, C. M., Di Forti, M., 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., Murray, R. M., Quattrone, D., Rutten, B. P., Sanjuán, J., Selten, J. P., Szöke, A., Tarricone, I., Tortelli, A., Velthorst, E., de Haan, L., and Schirmbeck, F.
- Abstract
Introduction: Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. Methods: In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. Results: In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. Conclusions: This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. Limitations: Cross-sectional study design, self-reported questionnaires.
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- 2024
5. Antipsychotics, modification of gene expression and prognosis of schizophrenia: a polygenic approach
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Molina, F. Facal, primary, Arrojo, M., additional, Paz, E., additional, Páramo, M., additional, and Costas, J., additional
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- 2023
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6. Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study
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Trotta, G, Rodriguez, V, Quattrone, D, Spinazzola, E, Tripoli, G, Gayer-Anderson, C, Freeman, Tp, Jongsma, He, Sideli, L, Aas, M, Stilo, Sa, La Cascia, C, Ferraro, L, La Barbera, D, Lasalvia, A, Tosato, S, Tarricone, I, D'Andrea, G, Tortelli, A, Schurhoff, F, Szoke, A, Pignon, B, Selten, Jp, Velthorst, E, de Haan, L, Llorca, Pm, Menezes, Pr, Del Ben, Cm, Santos, Jl, Arrojo, M, Bobes, J, Sanjuan, J, Bernardo, M, Arango, C, Kirkbride, Jb, Jones, Pb, Richards, A, Rutten, Bp, Van Os, J, Austin-Zimmerman, I, Zk, Li, Morgan, C, Sham, Pc, Vassos, E, Wong, C, Bentall, R, Fisher, Hl, Murray, Rm, Alameda, L, and Di Forti, M
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trauma ,psychotic disorders ,childhood experience ,mediation ,Cannabis use - Published
- 2023
7. Neuropsychological performance and predictors of pharmacological treatment response in obsessive compulsive disorder
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Tubío-Fungueiriño, M., primary, Alemany-Navarro, M., additional, Alonso, P., additional, Arrojo, M., additional, Real, E., additional, Bertolin, S., additional, Menchón, J.M., additional, Carracedo, A., additional, Fernández-Prieto, M., additional, and Segalàs, C., additional
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- 2022
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8. Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway
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van Os, J., van Os, J., Pries, L.K., ten Have, M., de Graaf, R., van Dorsselaer, S., Delespaul, P., Bak, M., Kenis, G., Lin, B.D., Luykx, J.J., Richards, A.L., Akdede, B., Binbay, T., Altinyazar, V., Yalincetin, B., Gumus-Akay, G., Cihan, B., Soygur, H., Ulas, H., Cankurtaran, E.S., Kaymak, S.U., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Bernardo, M., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., Garcia-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jimenez-Lopez, E., Arrojo, M., Carracedo, A., Lopez, G., Gonzalez-Penas, J., Parellada, M., Maric, N.P., Atbasoglu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., O'Donovan, M., Rutten, B.P.F., Guloksuz, S., van Os, J., van Os, J., Pries, L.K., ten Have, M., de Graaf, R., van Dorsselaer, S., Delespaul, P., Bak, M., Kenis, G., Lin, B.D., Luykx, J.J., Richards, A.L., Akdede, B., Binbay, T., Altinyazar, V., Yalincetin, B., Gumus-Akay, G., Cihan, B., Soygur, H., Ulas, H., Cankurtaran, E.S., Kaymak, S.U., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Bernardo, M., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., Garcia-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jimenez-Lopez, E., Arrojo, M., Carracedo, A., Lopez, G., Gonzalez-Penas, J., Parellada, M., Maric, N.P., Atbasoglu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., O'Donovan, M., Rutten, B.P.F., and Guloksuz, S.
- Abstract
Background There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. Methods We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. Results The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). Conclusions The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.
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- 2022
9. Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study
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Hersenen-Medisch 1, Brain, Pignon, B, Peyre, H, Ayrolles, A, Kirkbride, J B, Jamain, S, Ferchiou, A, Richard, J R, Baudin, G, Tosato, S, Jongsma, H, de Haan, L, Tarricone, I, Bernardo, M, Velthorst, E, Braca, M, Arango, C, Arrojo, M, Bobes, J, Del-Ben, C M, Di Forti, M, Gayer-Anderson, C, Jones, P B, La Cascia, C, Lasalvia, A, Menezes, P R, Quattrone, D, Sanjuán, J, Selten, J P, Tortelli, A, Llorca, P M, van Os, J, Rutten, B P F, Murray, R M, Morgan, C, Leboyer, M, Szöke, A, Schürhoff, F, Hersenen-Medisch 1, Brain, Pignon, B, Peyre, H, Ayrolles, A, Kirkbride, J B, Jamain, S, Ferchiou, A, Richard, J R, Baudin, G, Tosato, S, Jongsma, H, de Haan, L, Tarricone, I, Bernardo, M, Velthorst, E, Braca, M, Arango, C, Arrojo, M, Bobes, J, Del-Ben, C M, Di Forti, M, Gayer-Anderson, C, Jones, P B, La Cascia, C, Lasalvia, A, Menezes, P R, Quattrone, D, Sanjuán, J, Selten, J P, Tortelli, A, Llorca, P M, van Os, J, Rutten, B P F, Murray, R M, Morgan, C, Leboyer, M, Szöke, A, and Schürhoff, F
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- 2022
10. Clinical practice guideline on pharmacological and psychological management of adult patients with depression and a comorbid substance use disorder
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Torrens, M, Tirado-Munoz, J, Fonseca, F, Farre, M, Gonzalez-Pinto, A, Arrojo, M, Bernardo, M, Arranz, B, Garriga, M, Saiz, PA, Florez, G, Goikolea, JM, Zorrilla, I, Cunill, R, Castells, X, Becona, E, Lopez, A, and San, L
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cannabis ,Depression ,substance use disorder ,alcohol ,selective serotonin reuptake inhibitors ,antidepressants ,cocaine ,nicotine - Abstract
Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence.
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- 2022
11. Clinical practice guideline on pharmacological and psychological management of adult patients with schizophrenia spectrum disorders and a comorbid substance use
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Arranz B, Garriga M, Bernardo M, González-Pinto A, Arrojo M, Torrens M, Tirado-Muñoz J, Fonseca F, Sáiz PA, Flórez G, Goikolea JM, Zorrilla I, Cunill R, Castells X, Becoña E, Angeles López Ponce, and San L
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Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).
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- 2022
12. Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use
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Cunill R, Castells X, González-Pinto A, Arrojo M, Bernardo M, Sáiz PA, Florez G, Torrens M, Tirado-Muñoz J, Fonseca F, Arranz B, Garriga M, Goikolea JM, Zorrilla I, Becoña E, Angeles López Ponce, and San L
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mental disorders ,behavioral disciplines and activities - Abstract
Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.
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- 2022
13. Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study
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Pignon, B., primary, Peyre, H., additional, Ayrolles, A., additional, Kirkbride, J. B., additional, Jamain, S., additional, Ferchiou, A., additional, Richard, J. R., additional, Baudin, G., additional, Tosato, S., additional, Jongsma, H., additional, de Haan, L., additional, Tarricone, I., additional, Bernardo, M., additional, Velthorst, E., additional, Braca, M., additional, Arango, C., additional, Arrojo, M., additional, Bobes, J., additional, Del-Ben, C. M., additional, Di Forti, M., additional, Gayer-Anderson, C., additional, Jones, P. B., additional, La Cascia, C., additional, Lasalvia, A., additional, Menezes, P. R., additional, Quattrone, D., additional, Sanjuán, J., additional, Selten, J. P., additional, Tortelli, A., additional, Llorca, P. M., additional, van Os, J., additional, Rutten, B. P. F., additional, Murray, R. M., additional, Morgan, C., additional, Leboyer, M., additional, Szöke, A., additional, and Schürhoff, F., additional
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- 2022
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14. Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study
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B. Pignon, H. Peyre, A. Ayrolles, J. B. Kirkbride, S. Jamain, A. Ferchiou, J. R. Richard, G. Baudin, S. Tosato, H. Jongsma, L. de Haan, I. Tarricone, M. Bernardo, E. Velthorst, M. Braca, C. Arango, M. Arrojo, J. Bobes, C. M. Del-Ben, M. Di Forti, C. Gayer-Anderson, P. B. Jones, C. La Cascia, A. Lasalvia, P. R. Menezes, D. Quattrone, J. Sanjuán, J. P. Selten, A. Tortelli, P. M. Llorca, J. van Os, B. P. F. Rutten, R. M. Murray, C. Morgan, M. Leboyer, A. Szöke, F. Schürhoff, Pignon B., Peyre H., Ayrolles A., Kirkbride J.B., Jamain S., Ferchiou A., Richard J.R., Baudin G., Tosato S., Jongsma H., de Haan L., Tarricone I., Bernardo M., Velthorst E., Braca M., Arango C., Arrojo M., Bobes J., Del-Ben C.M., Di Forti M., Gayer-Anderson C., Jones P.B., La Cascia C., Lasalvia A., Menezes P.R., Quattrone D., Sanjuan J., Selten J.P., Tortelli A., Llorca P.M., van Os J., Rutten B.P.F., Murray R.M., Morgan C., Leboyer M., Szoke A., Schurhoff F., Pignon, B [0000-0003-0526-3136], Ayrolles, A [0000-0002-3202-0781], Kirkbride, JB [0000-0003-3401-0824], Tosato, S [0000-0002-9665-7538], Lasalvia, A [0000-0001-9963-6081], Morgan, C [0000-0002-1386-2369], Apollo - University of Cambridge Repository, Pignon, B, Peyre, H, Ayrolles, A, Kirkbride, J B, Jamain, S, Ferchiou, A, Richard, J R, Baudin, G, Tosato, S, Jongsma, H, de Haan, L, Tarricone, I, Bernardo, M, Velthorst, E, Braca, M, Arango, C, Arrojo, M, Bobes, J, Del-Ben, C M, Di Forti, M, Gayer-Anderson, C, Jones, P B, La Cascia, C, Lasalvia, A, Menezes, P R, Quattrone, D, Sanjuán, J, Selten, J P, Tortelli, A, Llorca, P M, van Os, J, Rutten, B P F, Murray, R M, Morgan, C, Leboyer, M, Szöke, A, Schürhoff, F, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: VPK Flexteam IC (9), MUMC+: MA Psychiatrie (3), and RS: MHeNs - R3 - Neuroscience
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Schizophrenia/genetics ,Environmental effects on human beings ,Risk factors in diseases ,Epidemiology ,Psicosi ,psychosi ,Pathological psychology ,Genes × environment interaction ,Risk Factors ,Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat ,psychosocial stressors ,Humans ,psychosis ,Psychotic Disorders/genetics ,Settore MED/25 - Psichiatria ,Influència del medi ambient en l'home ,Genètica de la conducta ,Factors de risc en les malalties ,Genes × environment interactions ,Public Health, Environmental and Occupational Health ,Psychoses ,polygenic risk score for schizophrenia ,Psicopatologia ,Psychiatry and Mental health ,Psychotic Disorders ,Behavior genetics ,Schizophrenia ,Esquizofrènia ,Gene-Environment Interaction - Abstract
the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI) and FP7-HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS) (...), Pignon B, Peyre H, Ayrolles A, Kirkbride JB, Jamain S, Ferchiou A, Richard JR, Baudin G, Tosato S, Jongsma H, de Haan L, Tarricone I, Bernardo M, Velthorst E, Braca M, Arango C, Arrojo M, Bobes J, Del-Ben CM, Di Forti M, Gayer-Anderson C, Jones PB, La Cascia C, Lasalvia A, Menezes PR, Quattrone D, Sanjuán J, Selten JP, Tortelli A, Llorca PM, van Os J, Rutten BPF, Murray RM, Morgan C, Leboyer M, Szöke A, Schürhoff F
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- 2022
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15. Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study
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Victoria Rodriguez, Luis Alameda, Diego Quattrone, Giada Tripoli, Charlotte Gayer-Anderson, Edoardo Spinazzola, Giulia Trotta, Hannah E. Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Elena Bonora, Stéphane Jamain, Jean-Paul Selten, Eva Velthorst, Lieuwe de Haan, Pierre-Michel Llorca, Manuel Arrojo, Julio Bobes, Miguel Bernardo, Celso Arango, James Kirkbride, Peter B. Jones, Bart P. Rutten, Alexander Richards, Pak C. Sham, Michael O'Donovan, Jim Van Os, Craig Morgan, Marta Di Forti, Robin M. Murray, Evangelos Vassos, Adult Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Rodriguez, V, Alameda, L, Quattrone, D, Tripoli, G, Gayer-Anderson, C, Spinazzola, E, Trotta, G, Jongsma, HE, Stilo, S, La Cascia, C, Ferraro, L, La Barbera, D, Lasalvia, A, Tosato, S, Tarricone, I, Bonora, E, Jamain, S, Selten, JP, Velthorst, E, de Haan, L, Llorca, PM, Arrojo, M, Bobes, J, Bernardo, M, Arango, C, Kirkbride, J, Jones, PB, Rutten, BP, Richards, A, Sham, PC, O'Donovan, M, Van Os, J, Morgan, C, Di Forti, M, Murray, RM, Vassos, E, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, RS: MHeNs - R3 - Neuroscience, and MUMC+: MA Psychiatrie (3)
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bipolar disorder ,Affective psychosis ,diagnosis ,GENETIC-RELATIONSHIPS ,schizophrenia-spectrum disorder ,Psychiatry and Mental health ,Affective psychosis, bipolar disorder, diagnosis, genetics, polygenic score, psychosis, psychotic depression, schizophrenia-spectrum disorder ,LIABILITY ,psychotic depression ,genetics ,polygenic score ,psychosis ,GENOME-WIDE ASSOCIATION ,Applied Psychology - Abstract
This work was supported by funding from the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (Project EU-GEI). (...) CA was supported by the Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), Fundación Familia Alonso and Fundación Alicia Koplowitz. MB was supported by the Ministry of Economy and Competitivity (PI08/0208; PI11/00325; PI14/00612), Instituto de Salud Carlos III – ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM, by the CERCA Programme/Generalitat de Catalunya and Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement (2017SGR1355). Departament de Salut de la Generalitat de Catalunya, en la convocatoria corresponent a l’any 2017 de concessió de subvencions del PERIS 2016-2020, modalitat Projectes de recerca orientats a l’atenció primària, amb el codi d’expedient SLT006/17/00345; and grateful for the support of the Institut de Neurociències, Universitat de Barcelona., Rodriguez V., Alameda L., Quattrone D., Tripoli G., Gayer-Anderson C., Spinazzola E., Trotta G., Jongsma H.E., Stilo S., La Cascia C., Ferraro L., La Barbera D., Lasalvia A., Tosato S., Tarricone I., Bonora E., Jamain S., Selten J.-P., Velthorst E., De Haan L., Llorca P.-M., Arrojo M., Bobes J., Bernardo M., Arango C., Kirkbride J., Jones P.B., Rutten B.P., Richards A., Sham P.C., O'Donovan M., Van Os J., Morgan C., Di Forti M., Murray R.M., Vassos E.
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- 2022
16. Cannabis use and cognitive biases in people with first-episode psychosis and their siblings.
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Roldan L, Sánchez-Gutiérrez T, Fernández-Arias I, Rodríguez-Toscano E, López G, Merchán-Naranjo J, Calvo A, Rapado-Castro M, Parellada M, Moreno C, Ferraro L, La Barbera D, La Cascia C, Tripoli G, Di Forti M, Murray RM, Quattrone D, Morgan C, Gayer-Anderson C, Jones PB, Jongsma HE, Kirkbride JB, van Os J, García-Portilla P, Al-Halabí S, Bobes J, de Haan L, Bernardo M, Santos JL, Sanjuán J, Arrojo M, Szoke A, Rutten BP, Stilo SA, Tarricone I, Lasalvia A, Tosato S, Llorca PM, Menezes PR, Selten JP, Tortelli A, Velthorst E, Del-Ben CM, Arango C, and Díaz-Caneja CM
- Abstract
Background: Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls., Methods: We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables., Results: FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123-2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368-0.997 and OR = 0.646, CI 0.457-0.913 respectively) and JTC bias (OR = 0.625, CI 0.422-0.925 and OR = 0.602, CI 0.460-0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297-2.578, FRP deficits (OR = 1.393, CI 1.031-1.882, and JTC (OR = 1.661, CI 1.271-2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups., Conclusions: Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.
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- 2024
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17. Prediction of pharmacological response in OCD using machine learning techniques and clinical and neuropsychological variables.
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Tubío Fungueiriño M, Cernadas E, Fernández-Delgado M, Arrojo M, Bertolin S, Real E, Menchon JM, Carracedo A, Alonso P, Fernández-Prieto M, and Segalàs C
- Abstract
Introduction: Obsessive Compulsive Disorder is associated with affected executive functioning, including memory, cognitive flexibility, and organizational strategies. As it was reported in previous studies, patients with preserved executive functions respond better to pharmacological treatment, whilst others need to keep trying different pharmacological strategies., Material and Methods: In this work we used machine learning techniques to predict pharmacological response (OCD patients' symptomatology reduction) based on executive functioning and clinical variables. Among those variables we used anxiety, depression and obsessive-compulsive symptoms scores by applying State-Trait Anxiety Inventory, Hamilton Depression Rating Scale and Yale-Brown Obsessive Compulsive Scale respectively, whilst Rey-Osterrieth Complex Figure Test was used to assess organisation skills and non-verbal memory; Digits' subtests from Wechsler Adult Intelligence Scale-IV were used to assess short-term memory and working memory; and Raven's Progressive Matrices were applied to assess problem solving and abstract reasoning., Results: As a result of our analyses, we created a reliable algorithm that predicts Y-BOCS score after 12 weeks based on patients' clinical characteristics (sex at birth, age, pharmacological strategy, depressive and obsessive-compulsive symptoms, years passed since diagnostic and Raven progressive matrices score) and Digits' scores. A high correlation (0.846) was achieved in predicted and true values., Conclusions: The present study proves the viability to predict if a patient would respond or not to a certain pharmacological strategy with high reliability based on sociodemographics, clinical variables and cognitive functions as short-term memory and working memory. These results are promising to develop future prediction models to help clinical decision making., (Copyright © 2024. Published by Elsevier España S.L.U.)
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- 2024
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18. Variation of subclinical psychosis as a function of population density across different European settings: Findings from the multi-national EU-GEI study.
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D'Andrea G, Quattrone D, Tripoli G, Spinazzola E, Gayer-Anderson C, Jongsma HE, Sideli L, Stilo SA, La Cascia C, Ferraro L, La Barbera D, Tortelli A, Velthorst E, de Haan L, Llorca PM, Santos JL, Arrojo M, Bobes J, Sanjuán J, Bernardo M, Arango C, Kirkbride JB, Jones PB, Rutten BP, Schürhoff F, Szöke A, van Os J, Vassos E, Selten JP, Morgan C, Di Forti M, Tarricone I, and Murray RM
- Abstract
Background: Urbanicity is a well-established risk factor for psychosis. Our recent multi-national study found an association between urbanicity and clinical psychosis in Northern Europe but not in Southern Europe. In this study, we hypothesized that the effect of current urbanicity on variation of schizotypy would be greater in North-western Europe countries than in Southern Europe ones., Methods: We recruited 1080 individuals representative of the populations aged 18-64 of 14 different sites within 5 countries, classified as either North-western Europe (England, France, and The Netherlands) with Southern Europe (Spain and Italy). Our main outcome was schizotypy, assessed through the Structured Interview for Schizotypy-Revised. Our main exposure was current urbanicity, operationalized as local population density. A priori confounders were age, sex, ethnic minority status, childhood maltreatment, and social capital. Schizotypy variation was assessed using multi-level regression analysis. To test the differential effect of urbanicity between North-western and Southern European, we added an interaction term between population density and region of recruitment., Results: Population density was associated with schizotypy (β = 0.248,95%CI = 0.122-0.375;p < 0.001). The addition of the interaction term improved the model fit (likelihood test ratio:χ
2 = 6.85; p = 0.009). The effect of urbanicity on schizotypy was substantially stronger in North-western Europe (β = 0.620,95%CI = 0.362-0.877;p < 0.001) compared with Southern Europe (β = 0.190,95%CI = 0.083-0.297;p = 0.001)., Conclusions: The association between urbanicity and both subclinical schizotypy and clinical psychosis, rather than being universal, is context-specific. Considering that urbanization is a rapid and global process, further research is needed to disentangle the specific factors underlying this relationship., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)- Published
- 2024
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19. The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis.
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Alameda L, Rodriguez V, Di Forti M, Spinazzola E, Trotta G, Arango C, Arrojo M, Bernardo M, Bobes J, de Haan L, Del-Ben CM, Gayer-Anderson C, Sideli L, Jones PB, Kirkbride JB, La Cascia C, Tripoli G, Ferraro L, La Barbera D, Lasalvia A, Tosato S, Llorca PM, Menezes PR, van Os J, Rutten BP, Santos JL, Sanjuán J, Selten JP, Szöke A, Tarricone I, Tortelli A, Velthorst E, Jongsma HE, Vassos E, Quattrone D, Murray RM, and Aas M
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- Humans, Female, Male, Adult, Case-Control Studies, Young Adult, Gene-Environment Interaction, Adolescent, Risk Factors, Middle Aged, Genetic Risk Score, Multifactorial Inheritance, Psychotic Disorders genetics, Psychotic Disorders psychology, Adverse Childhood Experiences psychology, Bipolar Disorder genetics, Bipolar Disorder psychology, Depressive Disorder, Major genetics, Schizophrenia genetics, Genetic Predisposition to Disease
- Abstract
Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = -0.34, 95% CI = [-0.660, -0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity., (© 2024. The Author(s).)
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- 2024
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20. Methylomic signature of current cannabis use in two first-episode psychosis cohorts.
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Dempster EL, Wong CCY, Burrage J, Hannon E, Quattrone D, Trotta G, Rodriguez V, Alameda L, Spinazzola E, Tripoli G, Austin-Zimmerman I, Li Z, Gayer-Anderson C, Freeman TP, Johnson EC, Jongsma HE, Stilo S, La Cascia C, Ferraro L, La Barbera D, Lasalvia A, Tosato S, Tarricone I, D'Andrea G, Galatolo M, Tortelli A, Pompili M, Selten JP, de Haan L, Menezes PR, Del Ben CM, Santos JL, Arrojo M, Bobes J, Sanjuán J, Bernardo M, Arango C, Jones PB, Breen G, Mondelli V, Dazzan P, Iyegbe C, Vassos E, Morgan C, Mukherjee D, van Os J, Rutten B, O'Donovan MC, Sham P, Mill J, Murray R, and Di Forti M
- Abstract
The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure., (© 2024. The Author(s).)
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- 2024
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21. Spanish validation of the Empirically Developed Clinical Staging Model (EmDe-5) for patients with bipolar disorder.
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de la Fuente-Tomás L, Arranz B, Sierra P, Sánchez-Autet M, García-Blanco A, Gutiérrez-Rojas L, Balanzá-Martínez V, Vidal-Rubio S, Vieta E, Jiménez E, Hernández C, Arrojo M, Gómez-Trigo J, Zapico-Merayo Y, Pelayo-Terán JM, Pérez-Solà V, Mur E, Cardoner N, González-Pinto A, Zorrilla I, Ruiz-Veguilla M, Catalán-Barragán R, Safont G, Martínez-Cao C, Sáiz P, Bobes J, and García-Portilla MP
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- Humans, Female, Male, Spain epidemiology, Adult, Middle Aged, Severity of Illness Index, Disease Progression, Suicide, Attempted statistics & numerical data, Reproducibility of Results, Comorbidity, Bipolar Disorder epidemiology, Bipolar Disorder pathology
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Introduction: Bipolar disorder (BD) has been reconceptualised as a progressive disorder that develops from mild to severe presentations. An empirical staging model - the Empirically Developed Clinical Staging Model for BD (EmDe-5) - was developed in a previous study. This study aims to further validate that model using a larger and more representative Spanish sample., Material and Methods: 183 BD outpatients were recruited at 11 sites in Spain. Assessment included clinical characteristics of the BD (number of hospitalisations, number of suicide attempts, comorbid personality disorders), physical health (BMI, metabolic syndrome, number of physical illnesses), cognition (SCIP), functioning (permanently disabled due to BD, FAST), and quality of life (SF-36). The CGI-S, VAS-S, and psychopharmacological treatment pattern were used as external validators., Results: Ten patients (51.5%) were classified as stage 1, 33 (18%) as stage 2, 93 (508%) as stage 3, 37 (202%) as stage 4, and 10 (55%) as stage 5. All profilers, other than number of suicide attempts (p=0.311) and comorbid personality disorder (p=0.061), exhibited worse scores from stage 1 to 5. As expected, VAS-S and CGI-S scores were worse in the later stages. Regarding treatment, early stages (1-2) were associated with the use of one to three drugs while late stages (4-5) were associated with four or more drugs (p=0.002)., Conclusions: We confirm the EmDe-5 staging model's construct validity. The ease of obtaining the profilers, together with the operational criteria provided to quantify them, will facilitate the use of the EmDe-5 staging model in daily clinical practice., (Copyright © 2021. Published by Elsevier España S.L.U.)
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- 2024
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22. Meta-analysis of the effects of adjuvant drugs in co-occurring bipolar and substance use disorder.
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Radua J, Fortea L, Goikolea JM, Zorrilla I, Bernardo M, Arrojo M, Cunill R, Castells X, Becoña E, López-Durán A, Torrens M, Tirado-Muñoz J, Fonseca F, Arranz B, Garriga M, Sáiz PA, Flórez G, San L, and González-Pinto A
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- Humans, Diagnosis, Dual (Psychiatry), Randomized Controlled Trials as Topic, Comorbidity, Substance-Related Disorders epidemiology, Bipolar Disorder drug therapy
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Background: Individuals with bipolar disorder (BD) often have co-occurring substance use disorders (SUDs), which substantially impoverish the course of illness. Despite the importance of this dual diagnosis, the evidence of the efficacy and safety of adjuvant treatments is mostly unknown., Objective: To perform a meta-analysis to evaluate the efficacy and safety of adjuvant drugs in patients with co-occurring BD and SUD., Methods: We searched PubMed, Scopus, and Web of Knowledge until 30th April 2022 for randomized clinical trials (RCT) evaluating the efficacy and safety of adjuvant drugs compared to placebo in patients with a dual diagnosis of BD and SUD. We meta-analyzed the effect of adjuvant drugs on general outcomes (illness severity, mania, depression, anxiety, abstinence, substance craving, substance use, gamma-GT, adherence, and adverse events) and used the results to objectively assess the quality of the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. For completeness, we also report the specific effects of specific adjuvant drugs in patients with specific substance disorders., Results: We included 15 RCT studies (9 alcohol, 3 cocaine, 2 nicotine, and 1 cannabis) comprising 628 patients allocated to treatment and 622 to placebo. There was low-quality evidence that adjuvant drugs may reduce illness severity (g=-0.25, 95% CI: -0.44, -0.06), and very-low quality evidence that they may decrease substance use (g=-0.23, 95% CI: -0.44, -0.02) and increase substance abstinence (g=0.21, 95% CI: 0.04, 0.38)., Discussion: There is low-quality evidence that adjuvant drugs may help reduce illness severity, probably via facilitating abstinence and lower substance use. However, the evidence is weak; thus, these results should be considered cautiously until better evidence exists., (Copyright © 2023 SEP y SEPB. Published by Elsevier España S.L.U. All rights reserved.)
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- 2024
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23. Association between psychiatric admissions in patients with schizophrenia and IL-6 plasma levels polygenic score.
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Facal F, Arrojo M, Páramo M, and Costas J
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- Humans, Female, Male, Adult, Middle Aged, Schizophrenia blood, Interleukin-6 blood, Multifactorial Inheritance
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Schizophrenia diagnosis and admission history were associated with a polygenic score (PGS) for schizophrenia based on a subset of variants that act by modifying the expression of genes whose expression is also modified by antipsychotics. This gene set was enriched in cytokine production. Interleukin-6 (IL-6) is the only cytokine whose plasma levels were associated both with schizophrenia diagnosis and with acute decompensations in the largest meta-analysis. Therefore, we hypothesized that an IL-6 PGS, but not other cytokines PGSs, would be associated with schizophrenia chronicity/psychiatric admissions. Using the IL-6 PGS model from The PGS Catalog, IL-6 PGS was calculated in 427 patients with schizophrenia and data regarding admission history. Association between IL-6 PGS and chronicity, measured as number and duration of psychiatric admissions, or ever readmission was analyzed by multivariate ordinal and logistic regression, respectively. Specificity of results was assessed by analysis of PGSs from the other cytokines at The PGS Catalog with meta-analytic evidence of association with schizophrenia diagnosis or acute decompensations, IL-1RA, IL-4, IL-8, and IL-12. IL-6 PGS was associated with schizophrenia chronicity, explaining 1.51% of variability (OR = 1.29, 95% CI 1.07-1.55, P = 0.007). There was no association with ever readmission. Other cytokines PGSs were not associated with chronicity. Association with IL-6 PGS was independent of association with schizophrenia PGS. Our results provide evidence that genetically regulated higher levels of IL-6 are involved in schizophrenia chronicity, highlighting the relevance of immunity processes for a subgroup of patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2024
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24. Brief psychological intervention for suicide prevention based on problem-solving applied in different formats to people over 50 years old: protocol for a randomized controlled trial.
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Vázquez FL, Torres ÁJ, Blanco V, Bouza Q, Otero P, Andrade E, Simón MÁ, Bueno AM, Arrojo M, Páramo M, and Fernández A
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- Humans, Middle Aged, Male, Female, Suicidal Ideation, Psychosocial Intervention methods, Psychotherapy, Brief methods, Aged, Mobile Applications, Problem Solving, Suicide Prevention
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Background: Suicide is a major public health problem, especially among individuals over 50 years old. Despite the suitability of this life stage for prevention, research on the efficacy of psychological interventions is scarce and methodologically limited, affecting their clinical utility and efficacy. Brief, flexible interventions that can be applied both in-person and remotely are needed. This study aims to evaluate the efficacy of a brief problem-solving-based suicide prevention program applied through various modalities to individuals over 50 years old., Methods: A randomized controlled trial will be conducted. A sample of 212 adults aged 50 or older with suicidal ideation will be randomly assigned to a problem-solving-based psychological intervention administered face-to-face (PSPI-P; n = 53), by telephone multiconference (PSPI-M; n = 53), via a smartphone app (PSPI-A; n = 53), or to a usual care control group (UCCG; n = 53). The intervention will be delivered in 7 sessions or modules of 90 min each. Blind trained evaluators will conduct assessments at pre-intervention, post-intervention, and follow-ups at 3, 6, and 12 months. The primary outcome will be suicidal ideation evaluated using the Suicidal Ideation Scale (SSI) and the Columbia Suicide Severity Rating Scale (C-SSRS). Secondary outcomes will include hopelessness, anxiety and depression symptoms, reasons for living, impulsivity, problem-solving skills, social support, anger syndrome, gratitude, personality, dropouts, treatment adherence, and satisfaction with the intervention., Discussion: This study will provide evidence of the efficacy of a brief problem-solving-based intervention for suicide prevention in individuals over 50 years old, administered face-to-face, by telephone multiconference, and via a smartphone app. If results are favorable, it will indicate that an effective, accessible, clinically and socially useful suicide prevention intervention has been developed for affected individuals, families, and communities., Trial Registration: ClinicalTrials.gov NCT06338904. Registered April 1, 2024., (© 2024. The Author(s).)
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- 2024
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25. Accelerated Cortical Thinning in Schizophrenia Is Associated With Rare and Common Predisposing Variation to Schizophrenia and Neurodevelopmental Disorders.
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González-Peñas J, Alloza C, Brouwer R, Díaz-Caneja CM, Costas J, González-Lois N, Gallego AG, de Hoyos L, Gurriarán X, Andreu-Bernabeu Á, Romero-García R, Fañanás L, Bobes J, González-Pinto A, Crespo-Facorro B, Martorell L, Arrojo M, Vilella E, Gutiérrez-Zotes A, Perez-Rando M, Moltó MD, Buimer E, van Haren N, Cahn W, O'Donovan M, Kahn RS, Arango C, Pol HH, Janssen J, and Schnack H
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- Humans, Adult, Middle Aged, Male, Female, Adolescent, Young Adult, Aged, Cerebral Cortical Thinning genetics, Cerebral Cortical Thinning diagnostic imaging, Cerebral Cortical Thinning pathology, Magnetic Resonance Imaging, Longitudinal Studies, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Genetic Predisposition to Disease genetics, Schizophrenia genetics, Schizophrenia pathology, Schizophrenia diagnostic imaging, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders pathology, Neurodevelopmental Disorders diagnostic imaging
- Abstract
Background: Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the life span. Studies have reported a shared genetic basis between schizophrenia and cortical thickness. However, no genes whose expression is related to abnormal cortical thinning in schizophrenia have been identified., Methods: We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample (n
cases = 169 and ncontrols = 298, ages 16-70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. Finally, we explored the functional and genetic underpinnings of the genes that contribute most to accelerated thinning., Results: We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences., Conclusions: Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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26. The Role of Social Deprivation and Cannabis Use in Explaining Variation in the Incidence of Psychotic Disorders: Findings From the EU-GEI Study.
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Brink V, Andleeb H, Gayer-Anderson C, Arango C, Arrojo M, Berardi D, Bernardo M, Bobes J, Del-Ben CM, Ferraro L, de Haan L, La Barbera D, La Cascia C, Lasalvia A, Llorca PM, Menezes PR, Pignon B, Sanjuán J, Santos JL, Selten JP, Tarricone I, Tortelli A, Tripoli G, Velthorst E, Rutten BPF, van Os J, Quattrone D, Murray RM, Jones PB, Morgan C, Di Forti M, Jongsma HE, and Kirkbride JB
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- Humans, Adult, Male, Female, Incidence, Young Adult, Adolescent, Middle Aged, Europe epidemiology, Psychosocial Deprivation, Marijuana Use epidemiology, Psychotic Disorders epidemiology
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Background and Hypothesis: Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings., Study Design: We used incidence data in people aged 18-64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group., Study Results: Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61-0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55-0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02-2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings., Conclusions: Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)
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- 2024
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27. Variation of subclinical psychosis across 16 sites in Europe and Brazil: findings from the multi-national EU-GEI study.
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D'Andrea G, Quattrone D, Malone K, Tripoli G, Trotta G, Spinazzola E, Gayer-Anderson C, Jongsma HE, Sideli L, Stilo SA, La Cascia C, Ferraro L, Lasalvia A, Tosato S, Tortelli A, Velthorst E, de Haan L, Llorca PM, Rossi Menezes P, Santos JL, Arrojo M, Bobes J, Sanjuán J, Bernardo M, Arango C, Kirkbride JB, Jones PB, Rutten BP, Van Os J, Selten JP, Vassos E, Schürhoff F, Szöke A, Pignon B, O'Donovan M, Richards A, Morgan C, Di Forti M, Tarricone I, and Murray RM
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- Humans, Male, Female, Europe epidemiology, Adult, Brazil epidemiology, Young Adult, Adolescent, Incidence, Middle Aged, Phenotype, Psychotic Disorders epidemiology, Schizotypal Personality Disorder epidemiology
- Abstract
Background: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP., Methods: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately., Results: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia., Conclusions: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.
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- 2024
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28. Tobacco use in first-episode psychosis, a multinational EU-GEI study.
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Sánchez-Gutiérrez T, Rodríguez-Toscano E, Roldán L, Ferraro L, Parellada M, Calvo A, López G, Rapado-Castro M, La Barbera D, La Cascia C, Tripoli G, Di Forti M, Murray RM, Quattrone D, Morgan C, van Os J, García-Portilla P, Al-Halabí S, Bobes J, de Haan L, Bernardo M, Santos JL, Sanjuán J, Arrojo M, Ferchiou A, Szoke A, Rutten BP, Stilo S, D'Andrea G, Tarricone I, Díaz-Caneja CM, and Arango C
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- Humans, Tobacco Use epidemiology, Psychotic Disorders epidemiology, Psychotic Disorders diagnosis, Schizophrenia epidemiology, Cannabis adverse effects, Substance-Related Disorders
- Abstract
Background: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis., Methods: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use., Results: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [ p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day ( p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset ( β = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use., Conclusions: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.
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- 2023
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29. Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.
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Trotta G, Rodriguez V, Quattrone D, Spinazzola E, Tripoli G, Gayer-Anderson C, Freeman TP, Jongsma HE, Sideli L, Aas M, Stilo SA, La Cascia C, Ferraro L, La Barbera D, Lasalvia A, Tosato S, Tarricone I, D'Andrea G, Tortelli A, Schürhoff F, Szöke A, Pignon B, Selten JP, Velthorst E, de Haan L, Llorca PM, Rossi Menezes P, Del Ben CM, Santos JL, Arrojo M, Bobes J, Sanjuán J, Bernardo M, Arango C, Kirkbride JB, Jones PB, Richards A, Rutten BP, Van Os J, Austin-Zimmerman I, Li Z, Morgan C, Sham PC, Vassos E, Wong C, Bentall R, Fisher HL, Murray RM, Alameda L, and Di Forti M
- Abstract
Background: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis., Methods: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use., Results: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord., Conclusions: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.
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- 2023
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30. The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.
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Spinazzola E, Quattrone D, Rodriguez V, Trotta G, Alameda L, Tripoli G, Gayer-Anderson C, Freeman TP, Johnson EC, Jongsma HE, Stilo S, La Cascia C, Ferraro L, La Barbera D, Lasalvia A, Tosato S, Tarricone I, D'Andrea G, Galatolo M, Tortelli A, Tagliabue I, Turco M, Pompili M, Selten JP, de Haan L, Rossi Menezes P, Del Ben CM, Santos JL, Arrojo M, Bobes J, Sanjuán J, Bernardo M, Arango C, Kirkbride JB, Jones PB, O'Donovan M, Rutten BP, Van Os J, Morgan C, Sham PC, Austin-Zimmerman I, Li Z, Vassos E, Murray RM, and Di Forti M
- Subjects
- Humans, Case-Control Studies, Risk Factors, Cannabis adverse effects, Marijuana Smoking adverse effects, Psychotic Disorders epidemiology
- Abstract
Background: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis., Methods: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status., Results: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ
2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status., Conclusions: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.- Published
- 2023
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31. A simulated pedagogical intervention to educate nurse practitioner students about human trafficking.
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Valdes B, Salani D, Falcon A, McKay M, Arrojo M, Quintana A, and DeSantis JP
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- Humans, United States, Health Personnel education, Educational Status, Students, Human Trafficking prevention & control, Nurse Practitioners education
- Abstract
Abstract: Human trafficking (HT) affects an estimated 40.3 million people globally with 24.9 million people affected in forced labor and 4.8 million in forced sexual exploitation. An estimated 18,000 people are trafficked yearly into the United States. Reports suggest that between 63% and 87% of trafficked persons were seen by health care professionals and were unrecognized while in captivity. The authors designed and implemented an innovative pedagogical intervention for nurse practitioner (NP) students using a 10-min simulation-based education encounter with a standardized patient depicting a potential sex or labor HT clinical presentation. Results demonstrated that simulation-based education is a feasible way to provide HT education to NP students. It is imperative that future NPs receive education/training about HT to recognize potential victims and promote access to appropriate resources., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2023 American Association of Nurse Practitioners.)
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- 2023
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32. The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study.
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Sideli L, Aas M, Quattrone D, La Barbera D, La Cascia C, Ferraro L, Alameda L, Velthorst E, Trotta G, Tripoli G, Schimmenti A, Fontana A, Gayer-Anderson C, Stilo S, Seminerio F, Sartorio C, Marrazzo G, Lasalvia A, Tosato S, Tarricone I, Berardi D, D'Andrea G, Arango C, Arrojo M, Bernardo M, Bobes J, Sanjuán J, Santos JL, Menezes PR, Del-Ben CM, Jongsma HE, Jones PB, Kirkbride JB, Llorca PM, Tortelli A, Pignon B, de Haan L, Selten JP, Van Os J, Rutten BP, Bentall R, Di Forti M, Murray RM, Morgan C, and Fisher HL
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- Adult, Humans, Child, Case-Control Studies, Cognition, Psychotic Disorders genetics, Schizophrenia epidemiology, Schizophrenia genetics, Child Abuse
- Abstract
This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood., (© 2023. The Author(s).)
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- 2023
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33. Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study.
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D'Andrea G, Lal J, Tosato S, Gayer-Anderson C, Jongsma HE, Stilo SA, van der Ven E, Quattrone D, Velthorst E, Berardi D, Rossi Menezes P, Arango C, Parellada M, Lasalvia A, La Cascia C, Ferraro L, La Barbera D, Sideli L, Bobes J, Bernardo M, Sanjuán J, Santos JL, Arrojo M, Del-Ben CM, Tripoli G, Llorca PM, de Haan L, Selten JP, Tortelli A, Szöke A, Muratori R, Rutten BP, van Os J, Jones PB, Kirkbride JB, Murray RM, di Forti M, Tarricone I, and Morgan C
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- Child, Humans, Ethnicity, Incidence, Psychotic Disorders epidemiology, Transients and Migrants, Child Abuse
- Abstract
Background: Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status., Methods: We included FEP patients aged 18-64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status., Results: We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ
2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations., Conclusions: The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations.- Published
- 2023
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34. Differences in Patterns of Stimulant Use and Their Impact on First-Episode Psychosis Incidence: An Analysis of the EUGEI Study.
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Rodríguez-Toscano E, Alloza C, Fraguas D, Durán-Cutilla M, Roldán L, Sánchez-Gutiérrez T, López-Montoya G, Parellada M, Moreno C, Gayer-Anderson C, Jongsma HE, Di Forti M, Quattrone D, Velthorst E, de Haan L, Selten JP, Szöke A, Llorca PM, Tortelli A, Bobes J, Bernardo M, Sanjuán J, Luis Santos J, Arrojo M, Tarricone I, Berardi D, Ruggeri M, Lasalvia A, Ferraro L, La Cascia C, La Barbera D, Menezes PR, Del-Ben CM, Rutten BP, van Os J, Jones PB, Murray RM, Kirkbride JB, Morgan C, Díaz-Caneja CM, and Arango C
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- Humans, Europe, Ethnicity, Incidence, Psychotic Disorders epidemiology, Psychotic Disorders psychology, Cannabis adverse effects, Central Nervous System Stimulants
- Abstract
Background: Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP., Methods: We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP., Findings: Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries., Interpretation: Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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35. Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study.
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Rodriguez V, Alameda L, Quattrone D, Tripoli G, Gayer-Anderson C, Spinazzola E, Trotta G, Jongsma HE, Stilo S, La Cascia C, Ferraro L, La Barbera D, Lasalvia A, Tosato S, Tarricone I, Bonora E, Jamain S, Selten JP, Velthorst E, de Haan L, Llorca PM, Arrojo M, Bobes J, Bernardo M, Arango C, Kirkbride J, Jones PB, Rutten BP, Richards A, Sham PC, O'Donovan M, Van Os J, Morgan C, Di Forti M, Murray RM, and Vassos E
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- Humans, Case-Control Studies, Genetic Predisposition to Disease, Risk Factors, Multifactorial Inheritance, Schizophrenia diagnosis, Schizophrenia genetics, Psychotic Disorders diagnosis, Psychotic Disorders genetics, Psychotic Disorders psychology
- Abstract
Background: Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD)., Methods: Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons., Results: In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54-0.92] and PRS-D (OR = 1.31, 95% CI 1.06-1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23-3.74)., Conclusions: Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
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- 2023
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36. Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis-findings from the EU-GEI study.
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Alameda L, Liu Z, Sham PC, Aas M, Trotta G, Rodriguez V, Di Forti M, Stilo SA, Kandaswamy R, Arango C, Arrojo M, Bernardo M, Bobes J, de Haan L, Del-Ben CM, Gayer-Anderson C, Sideli L, Jones PB, Jongsma HE, Kirkbride JB, La Cascia C, Lasalvia A, Tosato S, Llorca PM, Menezes PR, van Os J, Quattrone D, Rutten BP, Santos JL, Sanjuán J, Selten JP, Szöke A, Tarricone I, Tortelli A, Velthorst E, Morgan C, Dempster E, Hannon E, Burrage J, Dwir D, Arumuham A, Mill J, Murray RM, and Wong CCY
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- Humans, Child, DNA Methylation genetics, Epigenome, Adverse Childhood Experiences, Psychotic Disorders genetics, Psychological Tests, Self Report
- Abstract
Abtract: Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = <0.001; abuse: OR = 2.16; p < 0.001; neglect: OR = 2.27; p = <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p < 8.1 × 10
-8 ). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p < 5 × 10-5 ) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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37. Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.
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Fusar-Poli L, Prachason T, Erzin G, Pries LK, Brondino N, Politi P, Delespaul P, Kenis G, Luykx JJ, Lin BD, Richards AL, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran EŞ, Kaymak SU, Mihaljevic MM, Andric-Petrovic S, Mirjanic T, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Escarti MJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Üçok A, Alptekin K, Saka MC, Arango C, O'Donovan M, van Os J, Rutten BP, and Guloksuz S
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- Adult, Humans, Cross-Sectional Studies, Schizophrenia epidemiology, Siblings psychology, Case-Control Studies, Cognition Disorders epidemiology, Male, Female, Cognition, Exposome, Schizophrenic Psychology
- Abstract
Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls., Methods: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group., Results: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings., Conclusions: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum., Competing Interests: Declaration of Competing Interest Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Julio Bobes has received research grants and served as a consultant, advisor, or speaker within the last 5 years for AB-Biotics, Acadia Pharmaceuticals, Alkermes, Allergan, Ambrosetti-Angelini, Biogen, Casen Recordati, D&A Pharma, Exeltis, Gilead, Indivior, GW Pharmaceuticals, Janssen-Cilag, Jazz Pharmaceuticals, Lundbeck, Mundipharma, Newron, Otsuka, Pfizer, Roche, Sage Therapeutics, Servier, Schwabe Farma Ibérica, Shire, and Takeda and has received research funding from the Spanish Ministry of Economy and Competiveness –Centro de Investigación Biomedica en Red area de Salud Mental (CIBERSAM) and Instituto de Salud Carlos III– and the Spanish Ministry of Health. Maria Paz García-Portilla has been a consultant to and/or has received honoraria/grants from Angelini, Otsuka-Lundbeck Alliance, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and Sage Therapeutics. Pilar A. Sáiz has been a consultant to and/or has received honoraria/research grants from Adamed, Alter Medica, Angelini Pharma, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas, and Servier. Miguel Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda., (Copyright © 2023. Published by Elsevier B.V.)
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- 2023
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38. Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.
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Aas M, Alameda L, Di Forti M, Quattrone D, Dazzan P, Trotta A, Ferraro L, Rodriguez V, Vassos E, Sham P, Tripoli G, Cascia C, Barbera D, Tarricone I, Muratori R, Berardi D, Lasalvia A, Tosato S, Szöke A, Llorca PM, Arango C, Tortelli A, de Haan L, Velthorst E, Bobes J, Bernardo M, Sanjuán J, Santos JL, Arrojo M, Del-Ben CM, Menezes PR, Selten JP, Jones PB, Jongsma HE, Kirkbride JB, Rutten BPF, van Os J, Gayer-Anderson C, Murray RM, and Morgan C
- Subjects
- Humans, Genomics, Multifactorial Inheritance, Odds Ratio, Adverse Childhood Experiences, Psychotic Disorders etiology, Psychotic Disorders genetics
- Abstract
Background: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone., Methods: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)
exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders., Results: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88)., Conclusions: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.- Published
- 2023
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39. Epidemiological characteristics and hospitalization trajectories prior to suicide in Galicia between 2013 and 2016.
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Blanco V, Tajes Alonso M, Peleteiro Pensado LF, Naveira Barbeito G, Núñez Arias D, Torres ÁJ, Arrojo M, Páramo M, Otero P, and Vázquez FL
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- Male, Humans, Middle Aged, Hospitalization, Research Design, Suicide psychology, Mental Disorders epidemiology
- Abstract
Introduction: Addressing suicide requires an understanding of regional patterns of epidemiology, with health variables being central. However, the clinical profile of people who commit suicide has received little attention. The objectives of this study were to analyze the sociodemographic, clinical, and forensic characteristics of persons who committed suicide in Galicia between 2013 and 2016, analyze suicide mortality rates, and identify trajectories of hospitalizations and associated variables., Material and Methods: A population study was carried out on the 1354 people who died by suicide in Galicia., Results: The most common profile was a retired man, 57.9 years old (SD=18.5), from an urban and inner area. 43.6% had been previously hospitalized, 41.6% had been diagnosed with physical disorders, and 26.8% with mental disorders. 48.2% had been prescribed psychiatric medications and 29.6% had received outpatient psychiatric care. The highest prevalence of death by suicide (27.5%) was in 2014, with the predominant method being hanging (59.1%). The average raw rate was 12.3/100,000. Three trajectories of hospitalizations emerged: 94.83% had experienced few hospitalizations; 2.95% an increasing pattern; and 2.22% a decreasing pattern. These trajectories were associated with number of psychiatric appointments, prescription of psychiatric medications, and diagnoses of physical and mental disorders., Conclusions: These findings are crucial for detection and prevention., (Copyright © 2021 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)
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- 2023
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40. Authors' response: Highly pathogenic influenza A(H5N1) viruses in farmed mink outbreak contain a disrupted second sialic acid binding site in neuraminidase, similar to human influenza A viruses.
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Agüero M, Monne I, Sánchez A, Zecchin B, Fusaro A, Ruano MJ, Del Valle Arrojo M, Fernández-Antonio R, Souto AM, Tordable P, Cañás J, Bonfante F, Giussani E, Terregino C, and Orejas JJ
- Subjects
- Animals, Binding Sites, Disease Outbreaks veterinary, Hemagglutinin Glycoproteins, Influenza Virus, Mink virology, N-Acetylneuraminic Acid, Neuraminidase genetics, Influenza A virus, Influenza A Virus, H5N1 Subtype genetics, Orthomyxoviridae Infections epidemiology, Orthomyxoviridae Infections veterinary
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- 2023
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41. Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022.
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Agüero M, Monne I, Sánchez A, Zecchin B, Fusaro A, Ruano MJ, Del Valle Arrojo M, Fernández-Antonio R, Souto AM, Tordable P, Cañás J, Bonfante F, Giussani E, Terregino C, and Orejas JJ
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- Humans, Animals, Mink, Spain epidemiology, Farms, Phylogeny, Influenza in Birds epidemiology, Influenza A Virus, H5N1 Subtype genetics, Influenza A virus, Influenza, Human epidemiology
- Abstract
In October 2022, an outbreak in Europe of highly pathogenic avian influenza (HPAI) A(H5N1) in intensively farmed minks occurred in northwest Spain. A single mink farm hosting more than 50,000 minks was involved. The identified viruses belong to clade 2.3.4.4b, which is responsible of the ongoing epizootic in Europe. An uncommon mutation (T271A) in the PB2 gene with potential public health implications was found. Our investigations indicate onward mink transmission of the virus may have occurred in the affected farm.
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- 2023
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42. The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.
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Fusar-Poli L, Pries LK, van Os J, Radhakrishnan R, Pençe AY, Erzin G, Delespaul P, Kenis G, Luykx JJ, Lin BD, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran EŞ, Kaymak SU, Mihaljevic MM, Andric-Petrovic S, Mirjanic T, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Aguilar EJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Üçok A, Alptekin K, Saka MC, Aguglia E, Arango C, Rutten BP, and Guloksuz S
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- Cannabinoid Receptor Agonists, Cross-Sectional Studies, Emotions, Humans, Siblings psychology, Cannabis, Facial Recognition, Psychotic Disorders psychology, Schizophrenia complications
- Abstract
Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples., Competing Interests: Conflicts of Interest Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Maria Paz Garcia-Portilla has been a consultant to and/or has received honoraria/grants from Angelini, Alianza Otsuka-Lundbeck, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and SAGE Therapeutics., (Copyright © 2022. Published by Elsevier B.V.)
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- 2022
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43. Migration history and risk of psychosis: results from the multinational EU-GEI study.
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Tarricone I, D'Andrea G, Jongsma HE, Tosato S, Gayer-Anderson C, Stilo SA, Suprani F, Iyegbe C, van der Ven E, Quattrone D, di Forti M, Velthorst E, Rossi Menezes P, Arango C, Parellada M, Lasalvia A, La Cascia C, Ferraro L, Bobes J, Bernardo M, Sanjuán I, Santos JL, Arrojo M, Del-Ben CM, Tripoli G, Llorca PM, de Haan L, Selten JP, Tortelli A, Szöke A, Muratori R, Rutten BP, van Os J, Jones PB, Kirkbride JB, Berardi D, Murray RM, and Morgan C
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- Humans, Case-Control Studies, Ethnicity, Psychotic Disorders epidemiology, Schizophrenia epidemiology, Schizophrenia etiology, Transients and Migrants
- Abstract
Background: Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration., Methods: We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case-control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models., Results: In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06-2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02-3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03-1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672-2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose-response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06-96.47, p = 0.007)., Conclusions: The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.
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- 2022
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44. Facial Emotion Recognition in Psychosis and Associations With Polygenic Risk for Schizophrenia: Findings From the Multi-Center EU-GEI Case-Control Study.
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Tripoli G, Quattrone D, Ferraro L, Gayer-Anderson C, La Cascia C, La Barbera D, Sartorio C, Seminerio F, Rodriguez V, Tarricone I, Berardi D, Jamain S, Arango C, Tortelli A, Llorca PM, de Haan L, Velthorst E, Bobes J, Bernardo M, Sanjuán J, Luis Santos J, Arrojo M, Marta Del-Ben C, Rossi Menezes P, van der Ven E, Jones PB, Jongsma HE, Kirkbride JB, Tosato S, Lasalvia A, Richards A, O'Donovan M, Rutten BPF, van Os J, Morgan C, Sham PC, Di Forti M, Murray RM, and Murray GK
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- Case-Control Studies, Emotions, Facial Expression, Humans, Psychiatric Status Rating Scales, Depressive Disorder, Major complications, Depressive Disorder, Major genetics, Facial Recognition, Psychotic Disorders complications, Schizophrenia complications, Schizophrenia genetics
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Background and Hypothesis: Facial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is associated with facial emotion recognition., Study Design: 828 First Episode Psychosis (FEP) patients and 1308 population-based controls completed assessments of the Degraded Facial Affect Recognition Task (DFAR) and a subsample of 524 FEP and 899 controls provided blood or saliva samples from which we extracted DNA, performed genotyping and computed polygenic risk scores for schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MD)., Study Results: A worse ability to globally recognize facial emotion expressions was found in patients compared with controls [B= -1.5 (0.6), 95% CI -2.7 to -0.3], with evidence for stronger effects on negative emotions (fear [B = -3.3 (1.1), 95% CI -5.3 to -1.2] and anger [B = -2.3 (1.1), 95% CI -4.6 to -0.1]) than on happiness [B = 0.3 (0.7), 95% CI -1 to 1.7]. Pooling all participants, and controlling for confounds including case/control status, facial anger recognition was associated significantly with Schizophrenia Polygenic Risk Score (SZ PRS) [B = -3.5 (1.7), 95% CI -6.9 to -0.2]., Conclusions: Psychosis is associated with impaired recognition of fear and anger, and higher SZ PRS is associated with worse facial anger recognition. Our findings provide evidence that facial emotion recognition of anger might play a role as an intermediate phenotype for psychosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)
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- 2022
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45. Norovirus GII.3[P12] Outbreak Associated with the Drinking Water Supply in a Rural Area in Galicia, Spain, 2021.
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Jacqueline C, Del Valle Arrojo M, Bellver Moreira P, Rodríguez Feijóo MA, Cabrerizo M, and Fernandez-Garcia MD
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- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Child, Preschool, Disease Outbreaks, Female, Genotype, Humans, Infant, Infant, Newborn, Male, Middle Aged, Spain epidemiology, Water Supply, Young Adult, Caliciviridae Infections epidemiology, Norovirus genetics
- Abstract
On 30 September 2021, the city council of Muxia, Spain (population of 4,564 inhabitants), reported an unusual increase of patients with acute gastroenteritis (AGE). Because geographically widespread villages belonging to the same water supply were affected, a waterborne outbreak was suspected. Overall, 115 probable cases were ascertained during epidemiological investigations carried out by the local health authority (attack rate, 5.7%); the age range was 0 to 92 years, and 54% were female. The main symptoms were vomiting (78.1%) and diarrhea (67.5%). Primary cases peaked on 29 September and subsided on 1 October, compatible with a point-source outbreak followed by possible secondary cases until 7 October. We conducted an unmatched case-control study using phone surveys. The case-control study included 62 cases and 46 controls. Univariate analysis showed that cases had a higher exposure to tap water through direct consumption (odds ratio [OR] = 86; 95% confidence interval [CI], 18 to 409) or vegetable washing (OR = 27; 95% CI, 7 to 98). Norovirus GII was detected in two terminal points of the water supply system, and 14 cases were laboratory confirmed after detection of GII in stool samples. A unique genotype (GII.3[P12]) was identified in stool samples. On 1 October, a tap water ban was put in place and the water was purged and chlorinated. The rapid increase in the number of cases and its decline after implementing control measures suggested a waterborne point-source outbreak among the residents of Muxia sharing the same water distribution system. IMPORTANCE Noroviruses are likely to be underrecognized in most suspected waterborne outbreaks. Therefore, effective norovirus detection and the early recognition of water as a possible source of infection are important to reduce morbidity as appropriate steps are taken to control the source. In our study, we combined epidemiological, environmental, and microbiological investigations to demonstrate that it was a waterborne outbreak caused by norovirus. Metagenomic sequencing in one norovirus-positive stool sample confirmed norovirus etiology and the absence of other potential pathogens. Detection of fecal indicator bacteria and the fact that the drinking water was not chlorinated suggest a breakdown in chlorination as the cause of the outbreak. This outbreak investigation also demonstrated the importance of timely communication to the public about the risk linked to tap water consumption.
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- 2022
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46. Association between psychiatric hospitalizations of patients with schizophrenia and polygenic risk scores based on genes with altered expression by antipsychotics.
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Facal F, Arrojo M, Paz E, Páramo M, and Costas J
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- Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Hospitalization, Humans, Multifactorial Inheritance, Risk Factors, Antipsychotic Agents therapeutic use, Schizophrenia drug therapy, Schizophrenia genetics
- Abstract
Objective: To test whether a schizophrenia polygenic risk score (PRS) based on the subset of polymorphisms that affect brain expression of genes with altered expression by antipsychotics (exprAP PRS) is associated with psychiatric readmission of patients with schizophrenia., Methods: The study involved 427 patients with schizophrenia. Genes with altered expression by antipsychotics were extracted from the Comparative Toxigenomics Database. ExprAP PRS was estimated using the clumping and thresholding (p < 0.05) method. Two additional PRS were tested based on subsets of exprAP polymorphisms whose schizophrenia risk allele has the same (unrestored PRS) or opposite (restored PRS) direction of effect on gene expression than antipsychotics. A general SCZ PRS was tested for comparison. Logistic and ordinal regression were used to test for association of each PRS with ever readmission and admission history, an outcome based on length and number of admissions, respectively. Webgestalt was used for Gene Ontology enrichment analysis., Results: ExprAP PRS was associated with ever readmission (OR = 1.48, 95%CI:1.10-1.97) and admission history (OR = 1.30, 95%CI 1.07-1.57). SCZ PRS (OR = 1.22, 95%CI: 1.01-1.48) and unrestored PRS (OR = 1.26, 95%CI 1.04-1.53) were only associated with admission history. Genes at exprAP PRS were enriched in regulation of cytokine production., Conclusion: Our findings suggest that PRS based on genes with altered expression by antipsychotics may be better predictors of readmission than SCZ PRS, warranting further investigation in larger cohorts of patients. The action of antipsychotics may be related to brain gene expression, mainly in genes involved in immunity., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2022
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47. Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway.
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van Os J, Pries LK, Ten Have M, de Graaf R, van Dorsselaer S, Delespaul P, Bak M, Kenis G, Lin BD, Luykx JJ, Richards AL, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran EŞ, Kaymak SU, Mihaljevic MM, Petrovic SA, Mirjanic T, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Aguilar EJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Ucok A, Alptekin K, Saka MC, Arango C, O'Donovan M, Rutten BPF, and Guloksuz S
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- Humans, Hallucinations etiology, Hallucinations genetics, Multifactorial Inheritance, Risk, Delusions diagnosis, Psychotic Disorders etiology, Psychotic Disorders genetics, Schizophrenia etiology, Schizophrenia genetics
- Abstract
Background: There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation., Methods: We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 ( n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI ( n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls., Results: The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465)., Conclusions: The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.
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- 2022
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48. A replication study of JTC bias, genetic liability for psychosis and delusional ideation.
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Henquet C, van Os J, Pries LK, Rauschenberg C, Delespaul P, Kenis G, Luykx JJ, Lin BD, Richards AL, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran ES, Kaymak SU, Mihaljevic MM, Petrovic SS, Mirjanic T, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Aguilar EJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Ucok A, Alptekin K, Saka MC, Arango C, O'Donovan M, Rutten BPF, and Gülöksüz S
- Subjects
- Bias, Decision Making, Delusions psychology, Hallucinations, Humans, Psychotic Disorders psychology, Schizophrenia genetics
- Abstract
Background: This study attempted to replicate whether a bias in probabilistic reasoning, or 'jumping to conclusions'(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation., Methods: Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses., Results: JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46-5.17 for siblings and aRR: 5.07 CI 95% 4.13-6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67-8.51, and in patients: 2.15 CI 95% 0.94-4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences., Conclusions: These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
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- 2022
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49. Childhood Maltreatment, Educational Attainment, and IQ: Findings From a Multicentric Case-control Study of First-episode Psychosis (EU-GEI).
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Sideli L, Schimmenti A, La Barbera D, La Cascia C, Ferraro L, Aas M, Alameda L, Velthorst E, Fisher HL, Caretti V, Trotta G, Tripoli G, Quattrone D, Gayer-Anderson C, Seminerio F, Sartorio C, Marrazzo G, Lasalvia A, Tosato S, Tarricone I, Berardi D, D'Andrea G, Arango C, Arrojo M, Bernardo M, Bobes J, Sanjuán J, Santos JL, Menezes PR, Del-Ben CM, Jongsma HE, Jones PB, Kirkbride JB, Llorca PM, Tortelli A, Pignon B, de Haan L, Selten JP, Van Os J, Rutten BP, Di Forti M, Morgan C, and Murray RM
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- Affective Disorders, Psychotic, Case-Control Studies, Child, Humans, Intelligence Tests, Child Abuse psychology, Psychotic Disorders epidemiology, Psychotic Disorders etiology, Psychotic Disorders psychology
- Abstract
Background and Hypothesis: Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses., Study Design: 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were assessed for child maltreatment, education attainment, and IQ., Study Results: In both the FEP and control group, childhood maltreatment was associated with lower educational attainment. The association between childhood maltreatment and lower IQ was robust to adjustment for confounders only among controls. Whereas childhood neglect was consistently associated with lower attainment and IQ in both groups, childhood abuse was associated with IQ only in controls. Among both patients with affective and nonaffective psychoses, negative associations between childhood maltreatment and educational attainment were observed, but the crude association with IQ was only evident in affective psychoses., Conclusions: Our findings underscore the role of childhood maltreatment in shaping academic outcomes and cognition of people with FEP as well as controls., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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50. The incidence of psychotic disorders among migrants and minority ethnic groups in Europe: findings from the multinational EU-GEI study.
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Termorshuizen F, van der Ven E, Tarricone I, Jongsma HE, Gayer-Anderson C, Lasalvia A, Tosato S, Quattrone D, La Cascia C, Szöke A, Berardi D, Llorca PM, de Haan L, Velthorst E, Bernardo M, Sanjuán J, Arrojo M, Murray RM, Rutten BP, Jones PB, van Os J, Kirkbride JB, Morgan C, and Selten JP
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- Ethnicity, Europe epidemiology, Humans, Incidence, Minority Groups psychology, Psychotic Disorders epidemiology, Transients and Migrants psychology
- Abstract
Background: In Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: 'minorities'). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population)., Methods: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20-F33) from 13 sites., Results: The standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32-1.53) in Valencia to 2.47 (95% CI 1.66-3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66-3.93)., Conclusions: Incidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.
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- 2022
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