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9. Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls

Author

Alizadeh, Behrooz Z., Bartels-Velthuis, Agna A., van Amelsvoort, Therese, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Rutten, Bart P.F., Guloksuz, Sinan, Luykx, Jurjen J., van Os, Jim, Simons, Claudia J.P., van Winkel, Ruud, Lin, Bochao Danae, Vermeulen, Jentien M., Bolhuis, K., Chang, Xiao, Schirmbeck, Frederike, van Eijk, Kristel R, Blankers, Matthijs, and van den Brink, W.

Published
2023
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15. Moving from supported to independent living: what are the barriers and facilitators for individuals with psychosis?

Author

Poppe, Anika, Tiles-Sar, Natalia, Konings, Stefan R. A., Habtewold, Tesfa Dejenie, GROUP Investigators, Alizadeh, Behrooz Z., van Amelsvoort, Therese, Bartels-Velthuis, Agna A., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Schirmbeck, Frederike, Simons, Claudia J. P., van Os, Jim, and van der Meer, Lisette

Subjects
YOUNG women, PSYCHOSES, SOCIAL adjustment, COGNITION disorders, OLDER men, DEMOGRAPHIC transition, DEMOGRAPHIC characteristics
Abstract

Purpose: Living independently, as opposed to in sheltered housing or with caregivers, is an important aim in the recovery of individuals with psychosis, but the transition to independence can be challenging. This study aims to investigate how individuals with psychosis move between living arrangements and to identify the barriers and facilitators of moving towards independence. Methods: The living arrangements of 1119 individuals with non-affective psychosis from the Genetic Risk and Outcome of Psychosis study were assessed at baseline, at three- and six-year follow-ups and further categorized as either supported (sheltered housing or with parents) or independent (single or with partner/family). We estimated the probabilities of transitioning between the living statuses and investigated the influence of demographic characteristics, symptomatology, cognition, social support, and premorbid social adjustment on transition using Markov chain modelling. Results: The majority of individuals living in supported housing remained there during the six-year follow-up period (~ 60%). The likelihood of moving from supported to independent living was twice as high for participants who were younger, five-to-six times higher for women, twice as high for individuals with better overall cognition, and five times higher for those with a course of low positive symptoms. Conclusion: This study highlights that a large group of individuals with psychosis in supported housing is unlikely to move to independent living. Older men with cognitive impairments and who show continuous severe positive symptoms are the least likely to move living independently. Tailored interventions for these at-risk individuals could increase their chances of moving to independent living. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study

Author

Thygesen, Johan H., Presman, Amelia, Harju-Seppänen, Jasmine, Irizar, Haritz, Jones, Rebecca, Kuchenbaecker, Karoline, Lin, Kuang, Alizadeh, Behrooz Z., Austin-Zimmerman, Isabelle, Bartels-Velthuis, Agna, Bhat, Anjali, Bruggeman, Richard, Cahn, Wiepke, Calafato, Stella, Crespo-Facorro, Benedicto, de Haan, Liewe, de Zwarte, Sonja M. C., Di Forti, Marta, Díez-Revuelta, Álvaro, Hall, Jeremy, Hall, Mei-Hua, Iyegbe, Conrad, Jablensky, Assen, Kahn, Rene, Kalaydjieva, Luba, Kravariti, Eugenia, Lawrie, Stephen, Luykx, Jurjen J., Mata, Igancio, McDonald, Colm, McIntosh, Andrew M., McQuillin, Andrew, Muir, Rebecca, Ophoff, Roel, Picchioni, Marco, Prata, Diana P., Ranlund, Siri, Rujescu, Dan, Rutten, Bart P. F., Schulze, Katja, Shaikh, Madiha, Schirmbeck, Frederike, Simons, Claudia J. P., Toulopoulou, Timothea, van Amelsvoort, Therese, van Haren, Neeltje, van Os, Jim, van Winkel, Ruud, Vassos, Evangelos, Walshe, Muriel, Weisbrod, Matthias, Zartaloudi, Eirini, Bell, Vaughan, Powell, John, Lewis, Cathryn M., Murray, Robin M., and Bramon, Elvira

Published
2021
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20. Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Author

Velthorst, Eva, Mollon, Josephine, Murray, Robin M., de Haan, Lieuwe, Germeys, Inez Myin, Glahn, David C., Arango, Celso, van der Ven, Els, Di Forti, Marta, Bernardo, Miguel, Guloksuz, Sinan, Delespaul, Philippe, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Santos, José Luis, Jiménez-López, Estela, Sanjuan, Julio, Aguilar, Eduardo J., Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Atbaşoğlu, Cem, Saka, Meram Can, Üçok, Alp, Alptekin, Köksal, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Ulaş, Halis, Yalınçetin, Berna, Gümüş-Akay, Güvem, Beyaz, Burçin Cihan, Soygür, Haldun, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Maric, Nadja P., Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Del-Ben, Cristina Marta, Ferraro, Laura, Gayer-Anderson, Charlotte, Jones, Peter B., Jongsma, Hannah E., Kirkbride, James B., La Cascia, Caterina, Lasalvia, Antonio, Tosato, Sarah, Llorca, Pierre-Michel, Menezes, Paulo Rossi, Morgan, Craig, Quattrone, Diego, Menchetti, Marco, Selten, Jean-Paul, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, McGuire, Philip, Valmaggia, Lucia, Kempton, Matthew J., van der Gaag, Mark, Riecher-Rössler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Nelson, Barnaby, McGorry, Patrick, Pantelis, Chris, Krebs, Marie-Odile, Ruhrmann, Stephan, Sachs, Gabriele, Rutten, Bart P. F., van Os, Jim, Alizadeh, Behrooz Z., van Amelsvoort, Therese, Bartels-Velthuis, Agna A., Bruggeman, Richard, van Beveren, Nico J., Luykx, Jurjen J., Cahn, Wiepke, Simons, Claudia J. P., Kahn, Rene S., Schirmbeck, Frederike, van Winkel, Ruud, and Reichenberg, Abraham

Published
2021
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28. The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

Author

Akcaoglu, Zeynep, Vaessen, Thomas, Velthorst, Eva, Lafit, Ginette, Achterhof, Robin, Nelson, Barnaby, McGorry, Patrick, Schirmbeck, Frederike, Morgan, Craig, Hartmann, Jessica, van der Gaag, Mark, de Haan, Lieuwe, Valmaggia, Lucia, McGuire, Philip, Kempton, Matthew, Steinhart, Henrietta, Klippel, Annelie, Viechtbauer, Wolfgang, Batink, Tim, and van Winkel, Ruud

Subjects
RISK assessment, STATISTICAL models, SELF-evaluation, SCALE analysis (Psychology), PSYCHOLOGICAL distress, ATTITUDES toward illness, RESEARCH funding, CRONBACH'S alpha, DATA analysis, PARANOIA, MULTIPLE regression analysis, INTRACLASS correlation, STATISTICS, PSYCHOSES, INTELLIGENCE tests, DATA analysis software, PSYCHOLOGICAL tests, SOCIAL isolation
Abstract

Background: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. Methods: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. Results: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. Conclusions: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Childhood abuse v. neglect and risk for major psychiatric disorders.

Author

Alkema, Anne, Marchi, Mattia, van der Zaag, Jeroen A. J., van der Sluis, Daniëlle, Warrier, Varun, Alizadeh, Behrooz Z., van Amelsvoort, Therese, Cahn, Wiepke, de Haan, Lieuwe, Schirmbeck, Frederike, Simons, Claudia J. P., van Os, Jim, Veling, Wim, Ophoff, Roel A., Kahn, René S., Hovens, Jacqueline G. F. M., Riese, Harriëtte, Scheepers, Floortje, Penninx, Brenda W. J. H., and Cecil, Charlotte

Subjects
SUICIDE risk factors, MENTAL illness risk factors, SCHIZOPHRENIA risk factors, MENTAL depression risk factors, RISK assessment, BIPOLAR disorder, RESEARCH funding, CHILD abuse, MENTAL illness, DESCRIPTIVE statistics, AGITATION (Psychology), ODDS ratio, HALLUCINATIONS, ATTRIBUTION (Social psychology), CONFIDENCE intervals, REGRESSION analysis, SLEEP disorders, DISEASE risk factors
Abstract

Background: Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders. Methods: Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473). Results: Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17–5.67) and neglect for BD (OR 2.69, 95% CI 2.09–3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55–3.01) and suicide attempts (OR 2.16, 95% CI 1.55–3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02–1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08–2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01–0.24). Conclusions: Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Association of schizophrenia polygenic risk score with data-driven cognitive subtypes: A six-year longitudinal study in patients, siblings and controls

Author

Luykx, Jurjen J., Rutten, Bart P.F., van Winkel, Ruud, van Amelsvoort, Therese, Bartels-Velthuis, Agna A., Cahn, Wiepke, de Haan, Lieuwe, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Os, Jim, Habtewold, Tesfa Dejenie, Liemburg, Edith J., Islam, Md Atiqul, de Zwarte, Sonja M.C., Boezen, H. Marike, Bruggeman, Richard, and Alizadeh, Behrooz Z.

Published
2020
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32. Polygenic risk score for schizophrenia was not associated with glycemic level (HbA1c) in patients with non-affective psychosis: Genetic Risk and Outcome of Psychosis (GROUP) cohort study

Author

Bartels-Velthuis, Agna A.A., van Beveren, Nico J., Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Meijer, Carin J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Amelsvoort, Therese, van Haren, Neeltje E., van Os, Jim, van Winkel, Ruud, Habtewold, Tesfa Dejenie, Islam, Md. Atiqul, Liemburg, Edith J., Bruggeman, Richard, and Alizadeh, Behrooz Z.

Published
2020
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33. Expressive deficits and amotivation as mediators of the associations between cognitive problems and functional outcomes: Results from two independent cohorts

Author

Castelein, Stynke, Knegtering, Henderikus, Veling, Wim, Alizadeh, Behrooz Z., van Amelsvoort, Therese, Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Luykx, Jurjen J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Haren, Neeltje E., van Os, Jim, van Winkel, Ruud, Liemburg, Edith J., Enriquez-Geppert, Stefanie, Wardenaar, Klaas J., and Aleman, André

Published
2020
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35. Childhood trauma and coping in patients with psychotic disorders and obsessive-compulsive symptoms and in un-affected siblings

Author

Alizadeh, Behrooz Z., van Amelsvoort, Therese, Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Luykx, Jurjen J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Os, Jim, van Winkel, Ruud, and Renkema, Tristan C.

Published
2020
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37. Longitudinal evidence for a relation between depressive symptoms and quality of life in schizophrenia using structural equation modeling

Author

van Rooijen, Geeske, van Rooijen, Maaike, Maat, Arija, Vermeulen, Jentien M., Meijer, Carin J., Ruhé, Henricus G., de Haan, Lieuwe, Alizadeh, Behrooz Z., Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, Delespaul, Philippe, Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Amelsvoort, Therese, van Haren, Neeltje E., van Os, Jim, and van Winkel, Ruud

Published
2019
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38. Childhood adversities and psychotic symptoms: The potential mediating or moderating role of neurocognition and social cognition

Author

Alizadeh, Behrooz Z., Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Meijer, Carin J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Haren, Neeltje E.M., van Winkel, Ruud, Mansueto, Giovanni, Schruers, Koen, Cosci, Fiammetta, and van Os, Jim

Published
2019
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39. Targeted Sequencing of 10,198 Samples Confirms Abnormalities in Neuronal Activity and Implicates Voltage-Gated Sodium Channels in Schizophrenia Pathogenesis

Author

Alizadeh, Behrooz Z., van Amelsvoort, Therese, Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Meijer, Carin J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Haren, Neeltje E., van Os, Jim, van Winkel, Ruud, Luykx, Jurjen J., Rees, Elliott, Carrera, Noa, Morgan, Joanne, Hambridge, Kirsty, Escott-Price, Valentina, Pocklington, Andrew J., Richards, Alexander L., Pardiñas, Antonio F., McDonald, Colm, Donohoe, Gary, Morris, Derek W., Kenny, Elaine, Kelleher, Eric, Gill, Michael, Corvin, Aiden, Kirov, George, Walters, James T.R., Holmans, Peter, Owen, Michael J., and O’Donovan, Michael C.

Published
2019
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41. Smoking, symptoms, and quality of life in patients with psychosis, siblings, and healthy controls: a prospective, longitudinal cohort study

Author

Alizadeh, Behrooz Z, van Amelsvoort, Therese, Bartels-Velthuis, Agna A, van Beveren, Nico J, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Luykx, Jurjen J, Myin-Germeys, Inez, Kahn, Rene S, Schirmbeck, Frederike, Simons, Claudia J P, van Haren, Neeltje E, van Os, Jim, van Winkel, Ruud, Vermeulen, Jentien, Blankers, Matthijs, van Tricht, Mirjam, and van den Brink, Wim

Published
2019
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42. Patterns of obsessive-compulsive symptoms and social functioning in schizophrenia; a replication study

Author

Swets, Marije, van Dijk, Floor A., Schirmbeck, Frederike, Peen, Jaap, de Haan, Lieuwe, Alizadeh, Behrooz Z., van Amelsvoort, Therese, Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, Delespaul, Philippe, Luykx, Jurjen J., Myin-Germeys, Inez, Kahn, Rene S., Simons, Claudia J.P., van Haren, Neeltje E., van Os, Jim, and van Winkel, Ruud

Published
2019
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43. Acceptance and Commitment Therapy for individuals at risk for psychosis or with a first psychotic episode: A qualitative study on patients' perspectives.

Author

Bouws, Jara, Henrard, Ann, de Koning, Mariken, Schirmbeck, Frederike, van Ghesel Grothe, Sophia, van Aubel, Evelyne, Reininghaus, Ulrich, de Haan, Lieuwe, and Myin‐Germeys, Inez

Subjects
ACCEPTANCE & commitment therapy, PATIENTS' attitudes, PSYCHOSES, QUALITATIVE research, THEMATIC analysis
Abstract

Aim: The aim of this qualitative study is to explore patients' perspectives on Acceptance and Commitment Therapy for early stages of psychosis. Therefore, we interviewed participants of the INTERACT study, that quantitatively investigated Acceptance and Commitment Therapy in Daily Life (ACT‐DL) in combination with treatment as usual, for early stages of psychosis, comparing it to treatment as usual. Methods: Within 6 months after finishing ACT‐DL, we conducted semi‐structured, individual interviews with 19 participants. All interviews were audio‐recorded and transcribed. Thematic analysis was used for coding and analysis. Results: Two overarching themes were formed: 'the meaning of ACT' and 'what to improve'. Considering the first, participants generally understood and connected with the meaning of ACT, noticing more awareness and acceptance of their thoughts and feelings, and living more in line with their personal values. The second theme included comments on the protocol not being personal or psychosis specific enough and some elements of ACT being too difficult to understand when having active psychotic symptoms. Conclusions: This study suggests that ACT is an acceptable and promising new form of treatment for early stages of psychosis, and it provides relevant information to further develop ACT for this group. [ABSTRACT FROM AUTHOR]

Published
2024
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44. The relationship between substance use and self-reported aspects of social functioning in patients with a psychotic disorder.

Author

van der Heijden, H. S., Kikkert, Martijn, de Haan, Lieuwe, Segeren, Menno, Molman, Simone, Schirmbeck, Frederike, and Vermeulen, Jentien

Subjects
PSYCHOSES, SOCIAL skills, SUBSTANCE abuse, SOCIAL participation, PATHOLOGICAL psychology
Abstract

Background. In patients with a psychotic disorder, rates of substance use (tobacco, cannabis, and alcohol) are higher compared to the general population. However, little is known about associations between substance use and self-reported aspects of social functioning in patients with a psychotic disorder. Methods. In this cross-sectional study of 281 community-dwelling patients with a psychotic disorder, linear regression models were used to assess associations between substance use (tobacco, cannabis, or alcohol) and self-reported aspects of social functioning (perceived social support, stigmatization, social participation, or loneliness) adjusting for confounders (age, gender, and severity of psychopathology). Results. Compared to nonsmokers, both intermediate and heavy smokers reported lower scores on loneliness (E = -0.580, SE = 0.258, p = 0.025 and E = -0.547, SE = 0,272, p = 0.046, respectively). Daily cannabis users reported less social participation deficits than non-cannabis users (E = -0.348, SE = 0.145, p = 0.017). Problematic alcohol use was associated with more perceived social support compared to non-alcohol use (E = 3.152, SE = 1.102, p = 0.005). Polysubstance users reported less loneliness compared to no users (E = -0.569, SE = 0.287, p = 0.049). Conclusions. Substance use in patients with psychosis is associated with more favorable scores on various self-reported aspects of social functioning. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Associations Between Polygenic Risk Score Loading, Psychosis Liability, and Clozapine Use Among Individuals With Schizophrenia

Author

Lin, Bochao D., Pinzón-Espinosa, Justo, Blouzard, Elodie, Van Der Horst, Marte Z., Okhuijsen-pfeifer, Cynthia, Van Eijk, Kristel R., Guloksuz, Sinan, Peyrot, Wouter J., Luykx, Jurjen J., Hasan, Alkomiet, Wagner, Elias, Pantelis, Christos, Everall, Ian P., Ayhan, Y., Babaoğlu, M. O., Bak, Maarten, Alink, Wouter, Beld, E, Bouhuis, A, Edlinger, M, Erdoğan, I .m., Gutwinski, Stefan, Hallikainen, Tero, Jeger-land, E, Lähteenvuo, Markku, De Koning, Mariken B., Morgenroth, Carla, Müderrisoğlu, A., Oviedo-salcedo, Tatiana, Schreiter, Stefanie, Repo-tiihonen, Eila, Tuppurainen, Heli, Veereschild, Mike, Veerman, Selene R.t., Cohen, Dan, De Vos, M, Bogers, Jan P.a.m., Anıl Yağcıoğlu, A.e., Tiihonen, Jari, Ripke, Stephan, Bousman, Chad A., Van Beek, H, Van Der Horst, Marte, Van Eijk, Kristel, Ertuğrul, A., Yoca, G., Görlitz, T., Grootens, K., Leucht, Stefan, Narang, A., Schneider-thoma, J., Kahn, René S., Bekema, Erwin, Kleymann, Phillip, Alizadeh, Behrooz Z., Van Amelsvoort, Therese, Cahn, Wiepke, De Haan, Lieuwe, Schirmbeck, Frederike, Simons, Claudia J.p., Van Os, Jim, Rutten, Bart, Van Winkel, Ruud, RS: MHeNs - R3 - Neuroscience, RS: MHeNs - R2 - Mental Health, Psychiatry 1, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Geestelijke Gezondheidszorg, Tranzo, Scientific center for care and wellbeing, Psychiatry, APH - Mental Health, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Adult, Psychiatry and Mental health, Schizophrenia/drug therapy, SDG 3 - Good Health and Well-being, Risk Factors, Humans, Female, Antipsychotic Agents/adverse effects, Psychotic Disorders/drug therapy, Multifactorial Inheritance/genetics, Clozapine/adverse effects
Abstract

ImportancePredictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices.ObjectiveTo examine associations between PRS-SCZ loading and groups with different liabilities to SSD (individuals with SSD taking clozapine, individuals with SSD taking other antipsychotics, their parents and siblings, and unrelated healthy controls) and between PRS-SCZ and the likelihood of receiving a prescription of clozapine relative to other antipsychotics.Design, Setting, and ParticipantsThis genetic association study was a multicenter, observational cohort study with 6 years of follow-up. Included were individuals diagnosed with SSD who were taking clozapine or other antipsychotics, their parents and siblings, and unrelated healthy controls. Data were collected from 2004 until 2021 and analyzed between October 2021 and September 2022.ExposuresPolygenic risk scores for SCZ.Main Outcomes and MeasuresMultinomial logistic regression was used to examine possible differences between groups by computing risk ratios (RRs), ie, ratios of the probability of pertaining to a particular group divided by the probability of healthy control status. We also computed PRS-informed odd ratios (ORs) for clozapine use relative to other antipsychotics.ResultsPolygenic risk scores for SCZ were generated for 2344 participants (mean [SD] age, 36.95 years [14.38]; 994 female individuals [42.4%]) who remained after quality control screening (557 individuals with SSD taking clozapine, 350 individuals with SSD taking other antipsychotics during the 6-year follow-up, 542 parents and 574 siblings of individuals with SSD, and 321 unrelated healthy controls). All RRs were significantly different from 1; RRs were highest for individuals with SSD taking clozapine (RR, 3.24; 95% CI, 2.76-3.81; P = 2.47 × 10−46), followed by individuals with SSD taking other antipsychotics (RR, 2.30; 95% CI, 1.95-2.72; P = 3.77 × 10−22), parents (RR, 1.44; 95% CI, 1.25-1.68; P = 1.76 × 10−6), and siblings (RR, 1.40; 95% CI, 1.21-1.63; P = 8.22 × 10−6). Polygenic risk scores for SCZ were positively associated with clozapine vs other antipsychotic use (OR, 1.41; 95% CI, 1.22-1.63; P = 2.98 × 10−6), suggesting a higher likelihood of clozapine prescriptions among individuals with higher PRS-SCZ.Conclusions and RelevanceIn this study, PRS-SCZ loading differed between groups of individuals with SSD, their relatives, and unrelated healthy controls, with patients taking clozapine at the far end of PRS-SCZ loading. Additionally, PRS-SCZ was associated with a higher likelihood of clozapine prescribing. Our findings may inform early intervention and prognostic studies of the value of using PRS-SCZ to personalize antipsychotic treatment.

Published
2023

46. The role of cognitive functioning in the relationship between childhood trauma and a mixed phenotype of affective-anxious-psychotic symptoms in psychotic disorders

Author

Mansueto, Giovanni, van Nierop, Martine, Schruers, Koen, Alizadeh, Berhooz Z., Bartels-Velthuis, Agna A., van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Delespaul, Philippe, Meijer, Carin J., Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Haren, Neeltje E.M., van Os, Jim, and van Winkel, Ruud

Published
2018
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48. An experience sampling study on the ecological validity of the SWN-20: Indication that subjective well-being is associated with momentary affective states above and beyond psychosis susceptibility

Author

Pos, Karin, de Wit, Iris E., van Dijk, Floor A., Bartels-Velthuis, Agna A., Bruggeman, Richard, Meijer, Carin J., de Haan, Lieuwe, Alizadeh, Berhooz Z., Van Beveren, Nico J., Cahn, Wiepke, Delespaul, Phillipe, Myin-Germeys, Inez, Kahn, Rene S., Schirmbeck, Frederike, Simons, Claudia J.P., van Haren, Neeltje E., van Os, Jim, and van Winkel, Ruud

Published
2017
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