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6. Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions

Author

Müderrisoğlu, Ahmet, Privat, Alba Toll, Bouhuis, Alde, Hasan, Alkomiet, Jongkind, Amy, Gonzalez-Pinto, Ana, Santacana, Anna Mane, D'Agostino, Armando, Ertugrul, Aygün, Yağcioğlu, Ayşe Elif Anil, Crespo-Facorro, Benedicto, Sanchez-Barbero, Bianca, Spuch, Carlos, Morgenroth, Carla Lou, de Pinedo, Carmen Fernandez, Casetta, Cecilia, Bousman, Chad, Pantelis, Christos, Ovejas-Catalán, Claudia, Garcia-Rizo, Clemente, Okhuijsen-Pfeifer, Cynthia, Cohen, Dan, Ristic, Dragana Ignjatovic, Beld, Edwin, Repo-Tiihonen, Eila, Wagner, Elias, Jeger-Land, Ellen, Vilella, Elisabet, Bekema, Erwin, Sepúlveda, Stevan, Seghi, Federico, Wiedenmann, Federico, Martini, Francesca, Serio, Francesca, Vairano, Francesca, Mercuriali, Giacomo, Boido, Giovanni, Yoca, Gökhan, van Beek, Hanneke, Gijsman, Harm, Tuppurainen, Heli, Everall, Ian, Novakovic, Ivona, Zorrilla, Inaki, Erdoğan, Ibrahim Mert, Sapienza, Jacopo, Bogers, Jan, Tiihonen, Jari, Vázquez-Bourgon, Javier, van Os, Jim, Schneider-Thoma, Johannes, Luykx, Jurjen, Grootens, Koen, Mar-Barrutia, Lorea, Martorell, Lourdes, Bak, Maarten, Spangaro, Marco, de Vos, Marije, de Koning, Mariken, Garriga, Marina, Lähteenvuo, Markku, Bosia, Marta, van der Horst, Marte, Babaoğlu, Melih Önder, Veereschild, Mike, Manchia, Mirko, Edlinger, Monika, Fuentes-Pérez, Paloma, Paribello, Pasquale, Lopez-Pena, Purificacion, Kahn, René, Cavallaro, Roberto, Veerman, Selene, Gutwinski, Stefan, Schreiter, Stefanie, Ripke, Stephan, Baltanás, Tania Rivera, Oviedo-Salcedo, Tatiana, Hallikainen, Tero, Görlitz, Thomas, Alink, Wouter, Ayhan, Yavuz, van der Horst, Marte Z., Meijer, Yoeki, de Boer, Nini, Guloksuz, Sinan, Siskind, Dan, and Luykx, Jurjen J.

Published
2023
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7. Be(com)ing Social: Daily-Life Social Interactions and Parental Bonding

Author

Achterhof, Robin, Schneider, Maude, Kirtley, Olivia J., Wampers, Martien, Decoster, Jeroen, Derom, Catherine, De Hert, Marc, Guloksuz, Sinan, Jacobs, Nele, Menne-Lothmann, Claudia, Rutten, Bart P. F., Thiery, Evert, van Os, Jim, van Winkel, Ruud, Wichers, Marieke, and Myin-Germeys, Inez

Abstract

Parents are known to provide a lasting basis for their children's social development. Understanding parent-driven socialization is particularly relevant in adolescence, as an increasing social independence is developed. However, the relationship between key parenting styles of care and control and the microlevel expression of daily-life social interactions has been insufficiently studied. Adolescent and young adult twins and their nontwin siblings (N = 635; mean age = 16.6; age range = 14.2-21.9; 58.6% female; 79.5% in or having completed higher secondary/tertiary education; 2.8% speaking language other than Dutch at home) completed the Parental Bonding Instrument (PBI) on parental care and control. Participants also completed a 6-day experience sampling period (10 daily beeps, mean compliance = 68.0%) to assess daily-life social interactions. Higher overall parental bonding quality (of both parents) related to more positive social experiences in daily life (e.g., belonging in company), but not to more social behaviors (e.g., being with others). Factor analysis indicated a three-factor structure of the PBI, with care, denial of psychological autonomy, and encouragement of behavioral freedom. Paternal care was uniquely predictive of better social experiences. These findings demonstrate how parenting styles may be uniquely associated with how adolescents experience their social world, with a potentially important role for fathers in particular. This complements the long-held idea of socialization through parenting by bringing it into the context of daily life and implies how both conceptualizations of social functioning and interventions aimed at alleviating social dysfunction might benefit from a stronger consideration of day-to-day social experiences.

Published
2022
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10. The clinical characterization of the patient with primary psychosis aimed at personalization of management.

Author

Maj, Mario, van Os, Jim, De Hert, Marc, Gaebel, Wolfgang, Galderisi, Silvana, Green, Michael, Guloksuz, Sinan, Harvey, Philip, Jones, Peter, Malaspina, Dolores, McGorry, Patrick, Miettunen, Jouko, Murray, Robin, Nuechterlein, Keith, Peralta, Victor, Thornicroft, Graham, van Winkel, Ruud, and Ventura, Joseph

Subjects
Primary psychosis, environmental exposures, family history, internalized stigma, negative dimension, neurocognition, obstetric complications, personalization of treatment, physical comorbidities, positive dimension, practical needs, protective factors, psychiatric antecedents, psychiatric comorbidities, psychosocial interventions, recovery, resilience, schizophrenia, social cognition, social functioning
Abstract

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica-tion is prescribed, with second-generation antipsychotics usually preferred to first-generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidence-based family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves recovery-oriented, it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological components, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patients needs in terms of employment, housing, self-care, social relationships and education, and offers a focus on identity, meaning and resilience.

Published
2021

11. An international research agenda for clozapine-resistant schizophrenia

Author

Luykx, Jurjen J, Gonzalez-Diaz, Jairo M, Guu, Ta-Wei, van der Horst, Marte Z, van Dellen, Edwin, Boks, Marco P, Guloksuz, Sinan, DeLisi, Lynn E, Sommer, Iris E, Cummins, Russel, Shiers, David, Lee, Jimmy, Every-Palmer, Susanna, Mhalla, Ahmed, Chadly, Zohra, Chan, Sherry K W, Cotes, Robert O, Takahashi, Shun, Benros, Michael E, Wagner, Elias, Correll, Christoph U, Hasan, Alkomiet, Siskind, Dan, Endres, Dominique, MacCabe, James, and Tiihonen, Jari

Published
2023
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13. Decreased mitochondrial electron transport proteins and increased complement mediators in plasma neural-derived exosomes of early psychosis.

Author

Goetzl, Edward J, Srihari, Vinod H, Guloksuz, Sinan, Ferrara, Maria, Tek, Cenk, and Heninger, George R

Subjects
Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Potentially neurotoxic systems involved in traumatic and degenerative diseases of the brain were assessed in acute psychosis. Astrocyte-derived exosomes (ADEs) and neuron-derived exosomes (NDEs) were immunoprecipitated from plasma of ten untreated first-episode psychotics (FPs) and ten matched normal controls (Cs). Neural mitochondrial electron transport and complement proteins were extracted, quantified by ELISAs and normalized with levels of CD81 exosome marker. Levels of subunits 1 and 6 of NADH-ubiquinone oxidoreductase (complex I) and subunit 10 of cytochrome b-c1 oxidase (complex III), but not of subunit 1 of cytochrome C oxidase (complex IV) or superoxide dismutase 1 (SOD1) were significantly lower in ADEs and NDEs of FPs than Cs. This dysregulated pattern of electron transport proteins is associated with increased generation of reactive oxygen species. ADE glial fibrillary acidic protein levels were significantly higher in FPs than Cs, indicating a higher percentage of inflammatory astrocytes in FPs. ADE levels of C3b opsonin were significantly higher and those of C5b-9 attack complex was marginally higher in FPs than Cs. A significantly lower ADE level of the C3 convertase inhibitor CD55 may explain the higher levels of C3 convertase-generated C3b. ADE levels of the neuroprotective protein leukemia inhibitory factor (LIF) were significantly lower in FPs than Cs, whereas levels of IL-6 were no different. Plasma neural exosome levels of electron transport and complement proteins may be useful in predicting FP and guiding therapy. SOD mimetics, C3 convertase inhibitors and LIF receptor agonists also may have therapeutic benefits in FP.

Published
2020

14. Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Fusar-Poli, Laura, Prachason, Thanavadee, Erzin, Gamze, Pries, Lotta-Katrin, Brondino, Natascia, Politi, Pierluigi, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria Paz, Sanjuan, Julio, Escarti, Maria Jose, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, van Os, Jim, Rutten, Bart PF, and Guloksuz, Sinan

Published
2023
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15. 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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18. The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Fusar-Poli, Laura, Pries, Lotta-Katrin, van Os, Jim, Radhakrishnan, Rajiv, Pençe, Ayşegül Yay, Erzin, Gamze, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Aguglia, Eugenio, Arango, Celso, Rutten, Bart PF, and Guloksuz, Sinan

Published
2022
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25. Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study

Author

Fusar-Poli, Laura, Pries, Lotta-Katrin, van Os, Jim, Erzin, Gamze, Delespaul, Philippe, Kenis, Gunter, Luykx, Juryen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A., García-Portilla, Maria Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Aguglia, Eugenio, Arango, Celso, O'Donovan, Michael, Rutten, Bart P.F., and Guloksuz, Sinan

Published
2022
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27. The European psychiatric association (EPA) – early career psychiatrists committee survey on trainees' and early-career psychiatrists' attitudes towards therapeutic drug monitoring (TDM) use and utility during antipsychotic treatment.

Author

Schoretsanitis, Georgios, Correll, Christoph U., Agorastos, Agorastos, Compaired Sanchez, Alejandro, Erzin, Gamze, Grigoras, Ruxandra M., Grizelj Benussi, Mateja, Gondek, Tomasz M., Guloksuz, Sinan, Højlund, Mikkel, Jerotic, Stefan, Kilic, Ozge, Metaj, Enita, Sidhu, Deshwinder Singh, Skandali, Nikolina, Skuhareuski, Aliaksei, Tveito, Marit, Wolthusen, Rick P. F., Chumakov, Egor, and de Filippis, Renato

Subjects
DRUG monitoring, ATTITUDES of medical personnel, NOCEBOS, PSYCHIATRISTS, EXPLORATORY factor analysis, HIGH-income countries
Abstract

This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022–31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis. Comparisons between residents and early-career psychiatrists, respondents working in in- and outpatient settings, and low-/middle- and high–income countries were performed. Altogether, 1,237 respondents completed the survey, with 37.9% having never used TDM for antipsychotics. Seven factors explained 41% of response variance; six of them were associated with frequency of TDM use (p < 0.05). Items with highest loadings for factors included clinical benefits of TDM (factors A and E: 0.7), negative expectations for beliefs of patients towards TDM (factor B: 0.6–0.7), weak TDM scientific evidence (factor C: 0.8), and TDM availability (factor D: −0.8). Respondents from low-/middle-income countries were less likely to frequently/almost always use TDM compared to high-income countries (9.4% vs. 21.5%, p < 0.001). TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability. [ABSTRACT FROM AUTHOR]

Published
2024
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28. 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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31. Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial

Author

de Boer, Nini, Guloksuz, Sinan, van Baal, Caroline, Willebrands, Leonie, Deenik, Jeroen, Vinkers, Christiaan H., Rossum, Inge Winter-van, Zinkstok, Janneke, Wilting, Ingeborg, Zantvoord, Jasper B., Backx, Frank, Swildens, Wilma E., Schouw, Marieke, Bogers, Jan, Hulshof, Folkwin, de Knijff, Rudolf, Duindam, Peter, Veereschild, Mike, Bak, Maarten, Frederix, Geert, de Haan, Lieuwe, van Os, Jim, Cahn, Wiepke, and Luykx, Jurjen J.

Published
2021
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34. Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions

Author

van der Horst, Marte Z., primary, Meijer, Yoeki, additional, de Boer, Nini, additional, Guloksuz, Sinan, additional, Hasan, Alkomiet, additional, Siskind, Dan, additional, Wagner, Elias, additional, Okhuijsen-Pfeifer, Cynthia, additional, Luykx, Jurjen J., additional, Müderrisoğlu, Ahmet, additional, Privat, Alba Toll, additional, Bouhuis, Alde, additional, Jongkind, Amy, additional, Gonzalez-Pinto, Ana, additional, Santacana, Anna Mane, additional, D'Agostino, Armando, additional, Ertugrul, Aygün, additional, Yağcioğlu, Ayşe Elif Anil, additional, Crespo-Facorro, Benedicto, additional, Sanchez-Barbero, Bianca, additional, Spuch, Carlos, additional, Morgenroth, Carla Lou, additional, de Pinedo, Carmen Fernandez, additional, Casetta, Cecilia, additional, Bousman, Chad, additional, Pantelis, Christos, additional, Ovejas-Catalán, Claudia, additional, Garcia-Rizo, Clemente, additional, Cohen, Dan, additional, Ristic, Dragana Ignjatovic, additional, Beld, Edwin, additional, Repo-Tiihonen, Eila, additional, Jeger-Land, Ellen, additional, Vilella, Elisabet, additional, Bekema, Erwin, additional, Sepúlveda, Stevan, additional, Seghi, Federico, additional, Wiedenmann, Federico, additional, Martini, Francesca, additional, Serio, Francesca, additional, Vairano, Francesca, additional, Mercuriali, Giacomo, additional, Boido, Giovanni, additional, Yoca, Gökhan, additional, van Beek, Hanneke, additional, Gijsman, Harm, additional, Tuppurainen, Heli, additional, Everall, Ian, additional, Novakovic, Ivona, additional, Zorrilla, Inaki, additional, Erdoğan, Ibrahim Mert, additional, Sapienza, Jacopo, additional, Bogers, Jan, additional, Tiihonen, Jari, additional, Vázquez-Bourgon, Javier, additional, van Os, Jim, additional, Schneider-Thoma, Johannes, additional, Luykx, Jurjen, additional, Grootens, Koen, additional, Mar-Barrutia, Lorea, additional, Martorell, Lourdes, additional, Bak, Maarten, additional, Spangaro, Marco, additional, de Vos, Marije, additional, de Koning, Mariken, additional, Garriga, Marina, additional, Lähteenvuo, Markku, additional, Bosia, Marta, additional, van der Horst, Marte, additional, Babaoğlu, Melih Önder, additional, Veereschild, Mike, additional, Manchia, Mirko, additional, Edlinger, Monika, additional, Fuentes-Pérez, Paloma, additional, Paribello, Pasquale, additional, Lopez-Pena, Purificacion, additional, Kahn, René, additional, Cavallaro, Roberto, additional, Veerman, Selene, additional, Gutwinski, Stefan, additional, Schreiter, Stefanie, additional, Ripke, Stephan, additional, Baltanás, Tania Rivera, additional, Oviedo-Salcedo, Tatiana, additional, Hallikainen, Tero, additional, Görlitz, Thomas, additional, Alink, Wouter, additional, and Ayhan, Yavuz, additional

Published
2023
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36. The impact of eszopiclone on sleep and cognition in patients with schizophrenia and insomnia: A double-blind, randomized, placebo-controlled trial

Author

Tek, Cenk, Palmese, Laura B, Krystal, Andrew D, Srihari, Vinod H, DeGeorge, Pamela C, Reutenauer, Erin L, and Guloksuz, Sinan

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Schizophrenia, Behavioral and Social Science, Clinical Research, Sleep Research, Serious Mental Illness, Clinical Trials and Supportive Activities, Rehabilitation, Mental Health, Brain Disorders, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Mental health, Azabicyclo Compounds, Cognition, Double-Blind Method, Eszopiclone, Female, Humans, Hypnotics and Sedatives, Male, Medical Records, Middle Aged, Patient Dropouts, Piperazines, Psychotic Disorders, Quality of Life, Schizophrenic Psychology, Single-Blind Method, Sleep, Sleep Initiation and Maintenance Disorders, Treatment Outcome, Insomnia, Working memory, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences
Abstract

BackgroundInsomnia is frequent in schizophrenia and may contribute to cognitive impairment as well as overuse of weight inducing sedative antipsychotics. We investigated the effects of eszopiclone on sleep and cognition for patients with schizophrenia-related insomnia in a double-blind placebo controlled study, followed by a two-week, single-blind placebo phase.MethodsThirty-nine clinically stable outpatients with schizophrenia or schizoaffective disorder and insomnia were randomized to either 3mg eszopiclone (n=20) or placebo (n=19). Primary outcome measure was change in Insomnia Severity Index (ISI) over 8 weeks. Secondary outcome measure was change in MATRICS Consensus Cognitive Battery (MATRICS). Sleep diaries, psychiatric symptoms, and quality of life were also monitored.ResultsISI significantly improved more in eszopiclone (mean=-10.7, 95% CI=-13.2; -8.2) than in placebo (mean=-6.9, 95% CI=-9.5; -4.3) with a between-group difference of -3.8 (95% CI=-7.5; -0.2). MATRICS score change did not differ between groups. On further analysis there was a significant improvement in the working memory test, letter-number span component of MATRICS (mean=9.8±9.2, z=-2.00, p=0.045) only for subjects with schizophrenia on eszopiclone. There were improvements in sleep diary items in both groups with no between-group differences. Psychiatric symptoms remained stable. Discontinuation rates were similar. Sleep remained improved during single-blind placebo phase after eszopiclone was stopped, but the working memory improvement in patients with schizophrenia was not durable.ConclusionsEszopiclone stands as a safe and effective alternative for the treatment of insomnia in patients with schizophrenia. Its effects on cognition require further study.

Published
2014

42. 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

44. On the Proportion of Patients Who Experience a Prodrome Prior to Psychosis Onset - A Systematic Review and Meta-analysis

Author

Benrimoh, David, primary, Dlugunovych, Viktor, additional, Wright, Abigail C, additional, Phalen, Peter, additional, Funaro, Melissa C, additional, Ferrara, Maria, additional, Powers, Albert, additional, Woods, Scott W, additional, Guloksuz, Sinan, additional, Yung, Alison R, additional, Srihari, Vinod, additional, and Shah, Jai, additional

Published
2023
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45. 176. Associations Between Resting-State EEG, Psychiatric Diagnoses and Their Polygenic Liabilities

Author

Zandstra, Melissa, primary, Meijs, Hannah, additional, Bosma, Bas, additional, Lin, Bochao, additional, de Wilde, Bieke, additional, van Hecke, Jan, additional, Niemegeers, Peter, additional, van Putten, Nienke, additional, Bekema, Erwin, additional, Kool, Lindy, additional, van Eijk, Kristel, additional, Otte, Willem M., additional, Stam, Cornelis J., additional, Smit, Dirk JA., additional, Guloksuz, Sinan, additional, van Dellen, Edwin, additional, and Luykx, Jurjen, additional

Published
2023
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46. Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls

Author

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

Published
2023
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48. 30. Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation

Author

van der Meer, Dennis, primary, Cheng, Weiqiu, additional, Rokicki, Jaroslav, additional, Rodriguez-Cabello, Sara F., additional, Shadrin, Alexey, additional, Smeland, Olav, additional, Ehrhart, Friederike, additional, Guloksuz, Sinan, additional, Pries, Lotta-Katrin, additional, Lin, Bochao, additional, Rutten, Bart, additional, van Os, Jim, additional, Steen, Nils Eiel, additional, Djurovic, Srdjan, additional, Westlye, Lars, additional, Andreassen, Ole, additional, and Kaufmann, Tobias, additional

Published
2023
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49. Bidirectional relationships between cannabis use, anxiety and depressive symptoms in the mediation of the association with psychotic experience: further support for an affective pathway to psychosis.

Author

Radhakrishnan, Rajiv, Pries, Lotta-Katrin, Erzin, Gamze, ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Gunther, Nicole, Bak, Maarten, Rutten, Bart P. F., van Os, Jim, and Guloksuz, Sinan

Subjects
CANNABIS (Genus), PSYCHOSES, MULTIPLE regression analysis, MENTAL depression, FACTOR analysis, DESCRIPTIVE statistics, RESEARCH funding, ANXIETY, DATA analysis software, LONGITUDINAL method
Abstract

Background: Empirical evidence suggests that people use cannabis to ameliorate anxiety and depressive symptoms, yet cannabis also acutely worsens psychosis and affective symptoms. However, the temporal relationship between cannabis use, anxiety and depressive symptoms and psychotic experiences (PE) in longitudinal studies is unclear. This may be informed by examination of mutually mediating roles of cannabis, anxiety and depressive symptoms in the emergence of PE. Methods: Data were derived from the second longitudinal Netherlands Mental Health Survey and Incidence Study. Mediation analysis was performed to examine the relationship between cannabis use, anxiety/depressive symptoms and PE, using KHB logit in STATA while adjusting for age, sex and education status. Results: Cannabis use was found to mediate the relationship between preceding anxiety, depressive symptoms and later PE incidence, but the indirect contribution of cannabis use was small (for anxiety: % of total effect attributable to cannabis use = 1.00%; for depression: % of total effect attributable to cannabis use = 1.4%). Interestingly, anxiety and depressive symptoms were found to mediate the relationship between preceding cannabis use and later PE incidence to a greater degree (% of total effect attributable to anxiety = 17%; % of total effect attributable to depression = 37%). Conclusion: This first longitudinal cohort study examining the mediational relationship between cannabis use, anxiety/depressive symptoms and PE, shows that there is a bidirectional relationship between cannabis use, anxiety/depressive symptoms and PE. However, the contribution of anxiety/depressive symptoms as a mediator was greater than that of cannabis. [ABSTRACT FROM AUTHOR]

Published
2023
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