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1. Self-reported suicidal ideation among individuals with first episode psychosis and healthy controls: Findings from the international multicentre EU-GEI study

Author

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.

Published
2024
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3. Self-reported suicidal ideation among individuals with first episode psychosis and healthy controls:Findings from the international multicentre EU-GEI study

Author

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.

Published
2024

5. Higher emotion regulation flexibility predicts more stable negative emotions and faster affective recovery in early psychosis: An experience sampling study

Author

Li, X, Vaessen, T., Lafit, G., van Aubel, E., Hiekkaranta, A.P., Houben, M., Beijer-Klippel, A., de Haan, L., Schirmbeck, F., Reininghaus, U., Myin-Germeys, I., Li, X, Vaessen, T., Lafit, G., van Aubel, E., Hiekkaranta, A.P., Houben, M., Beijer-Klippel, A., de Haan, L., Schirmbeck, F., Reininghaus, U., and Myin-Germeys, I.

Abstract

Background While evidence shows that people with early psychosis are flexible in using different emotion regulation (ER) strategies to manage the varying contextual demands, no studies have examined the effectiveness of such regulatory flexibility in this population. We addressed this issue by investigating whether and how ER flexibility relate to different dynamic aspects (variability, instability, inertia, and recovery) of negative affect (NA) in a combined early psychosis sample, consisting of both individuals at high clinical risk for psychosis and those diagnosed with first-episode psychosis.Methods Participants were 148 individuals from the INTERACT project, a multi-center randomized controlled trial on the efficacy of acceptance and commitment therapy in early psychosis. We utilized data from the baseline assessment, during which all participants completed six days of experience sampling assessment of momentary NA, as well as end-of-day assessments of ER strategy use.Results Multilevel models of within-person associations showed that greater ER flexibility was associated with more stable NA, and quicker recovery of NA from stressors during the day. Linear regression analyses of between-person associations showed that people who had more variable and unstable NA reported greater ER flexibility generally. No evidence was found for associations with NA inertia.Conclusions The current study identified unique within-person and between-person links between ER flexibility and dynamics of NA in early psychosis. These findings further provide evidence for ER flexibility in early psychosis, emphasizing the adaptive nature of regulatory flexibility in relation to reduced instability in NA and faster recovery from NA in everyday life.

Published
2024

6. Emotion regulation in daily life in early psychosis: The role of contextual appraisals

Author

Li, X., Lafit, G., van Aubel, E., Vaessen, T., Hiekkaranta, A.P., Houben, M., Beijer-Klippel, A., de Haan, L., Schirmbeck, F., Reininghaus, U., Myin-Germeys, I., Li, X., Lafit, G., van Aubel, E., Vaessen, T., Hiekkaranta, A.P., Houben, M., Beijer-Klippel, A., de Haan, L., Schirmbeck, F., Reininghaus, U., and Myin-Germeys, I.

Abstract

Background Little is known about whether and how contextual appraisals relate to emotion regulation (ER) strategy use across the ultra-high risk and first episode stages of psychosis. The present study extends previous research by investigating the extent to which different appraisal dimensions of the most negative and positive events of the day are associated with ER strategy use in individuals with ultra-high risk (UHR) and first-episode psychosis (FEP). Method Sixty-eight UHR individuals and fifty-five FEP individuals filled out an experience sampling evening questionnaire for six consecutive days, in which their appraisal of intensity, importance and perceived control concerning the most negative or positive event of the day, and the ER strategies they deploy in response to these events were measured. Results Multilevel mixed effect models showed that intensity appraisal was most closely associated with ER strategy use, as opposed to importance and controllability appraisals. Higher intense negative events were associated with more rumination and social sharing, while less intense negative events were associated with more reappraisal. Higher intense positive events were associated with a greater number of deployed strategies and more efforts in using savoring, expression and social sharing. The UHR and FEP individuals did not significantly differ regarding effects of above-mentioned appraisal dimensions on ER. Conclusions These results provide evidence supporting ER flexibility in early psychosis, and event intensity emerged as the dimension most strongly associated with ER. Future research should better account for other situational factors (such as social context) that might affect ER use in psychosis.

Published
2023

7. Associations between polygenic risk score loading, psychosis liability, and clozapine use among individuals with schizophrenia

Author

Lin, B.D., Pinzón-Espinosa, J., Blouzard, E., Van Der Horst, M.Z., Okhuijsen-pfeifer, C., Van Eijk, K.R., Guloksuz, S., Peyrot, W.J., Luykx, J.J., Hasan, A., Wagner, E., Pantelis, C., Everall, I.P., Ayhan, Y., Babaoğlu, M.O., Bak, M., Alink, W., Beld, E, Bouhuis, A., Edlinger, M., Erdoğan, I.M., Gutwinski, S., Hallikainen, T., Jeger-land, E., Lähteenvuo, M., De Koning, M.B., Morgenroth, C., Müderrisoğlu, A., Oviedo-salcedo, T., Schreiter, S., Repo-tiihonen, E., Tuppurainen, H., Veereschild, M., Veerman, S.R.T., Cohen, D., de Vos, M., Bogers, J.P.A.M., Anıl Yağcıoğlu, A.E., Tiihonen, J., Ripke, S., Bousman, C.A., Van Beek, H, van der Horst, M., Van Eijk, K., Ertuğrul, A., Yoca, G., Görlitz, T., Grootens, K., Leucht, S., Narang, A., Schneider-thoma, J., Kahn, R.S., Bekema, E., Kleymann, P., Alizadeh, B.Z., van Amelsvoort, T., Cahn, W., de Haan, L., Schirmbeck, F., Simons, C.J.P., van Os, J., Rutten, B., van Winkel, R., Lin, B.D., Pinzón-Espinosa, J., Blouzard, E., Van Der Horst, M.Z., Okhuijsen-pfeifer, C., Van Eijk, K.R., Guloksuz, S., Peyrot, W.J., Luykx, J.J., Hasan, A., Wagner, E., Pantelis, C., Everall, I.P., Ayhan, Y., Babaoğlu, M.O., Bak, M., Alink, W., Beld, E, Bouhuis, A., Edlinger, M., Erdoğan, I.M., Gutwinski, S., Hallikainen, T., Jeger-land, E., Lähteenvuo, M., De Koning, M.B., Morgenroth, C., Müderrisoğlu, A., Oviedo-salcedo, T., Schreiter, S., Repo-tiihonen, E., Tuppurainen, H., Veereschild, M., Veerman, S.R.T., Cohen, D., de Vos, M., Bogers, J.P.A.M., Anıl Yağcıoğlu, A.E., Tiihonen, J., Ripke, S., Bousman, C.A., Van Beek, H, van der Horst, M., Van Eijk, K., Ertuğrul, A., Yoca, G., Görlitz, T., Grootens, K., Leucht, S., Narang, A., Schneider-thoma, J., Kahn, R.S., Bekema, E., Kleymann, P., Alizadeh, B.Z., van Amelsvoort, T., Cahn, W., de Haan, L., Schirmbeck, F., Simons, C.J.P., van Os, J., Rutten, B., and van Winkel, R.

Abstract

Importance: Predictors 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. Objective: To 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 Participants: This 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. Exposures: Polygenic risk scores for SCZ. Main Outcomes and Measures: Multinomial 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. Results: Polygenic 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 RR

Published
2023

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

Author

Velthorst E., Mollon J., Murray R. M., de Haan L., Germeys I. M., Glahn D. C., Arango C., van der Ven E., Di Forti M., Bernardo M., Guloksuz S., Delespaul P., Mezquida G., Amoretti S., Bobes J., Saiz P. A., Garcia-Portilla M. P., Santos J. L., Jimenez-Lopez E., Sanjuan J., Aguilar E. J., Arrojo M., Carracedo A., Lopez G., Gonzalez-Penas J., Parellada M., Atbasoglu C., Saka M. C., Ucok A., Alptekin K., Akdede B., Binbay T., Altinyazar V., Ulas H., Yalincetin B., Gumus-Akay G., Beyaz B. C., Soygur H., Cankurtaran E. S., Kaymak S. U., Maric N. P., Mihaljevic M. M., Petrovic S. A., Mirjanic T., Del-Ben C. M., Ferraro L., Gayer-Anderson C., Jones P. B., Jongsma H. E., Kirkbride J. B., La Cascia C., Lasalvia A., Tosato S., Llorca P. -M., Menezes P. R., Morgan C., Quattrone D., Menchetti M., Selten J. -P., Szoke A., Tarricone I., Tortelli A., McGuire P., Valmaggia L., Kempton M. J., van der Gaag M., Riecher-Rossler A., Bressan R. A., Barrantes-Vidal N., Nelson B., McGorry P., Pantelis C., Krebs M. -O., Ruhrmann S., Sachs G., Rutten B. P. F., van Os J., Alizadeh B. Z., van Amelsvoort T., Bartels-Velthuis A. A., Bruggeman R., van Beveren N. J., Luykx J. J., Cahn W., Simons C. J. P., Kahn R. S., Schirmbeck F., van Winkel R., Calem M., Tognin S., Modinos G., Pisani S., Kraan T. C., van Dam D. S., Burger N., Amminger G. P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Cristobal-Narvaez P., Racioppi A., Kwapil T. R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Rander L., Krakauer K., Glenthoj L. B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Reichenberg A., Velthorst E., Mollon J., Murray R.M., de Haan L., Germeys I.M., Glahn D.C., Arango C., van der Ven E., Di Forti M., Bernardo M., Guloksuz S., Delespaul P., Mezquida G., Amoretti S., Bobes J., Saiz P.A., Garcia-Portilla M.P., Santos J.L., Jimenez-Lopez E., Sanjuan J., Aguilar E.J., Arrojo M., Carracedo A., Lopez G., Gonzalez-Penas J., Parellada M., Atbasoglu C., Saka M.C., Ucok A., Alptekin K., Akdede B., Binbay T., Altinyazar V., Ulas H., Yalincetin B., Gumus-Akay G., Beyaz B.C., Soygur H., Cankurtaran E.S., Kaymak S.U., Maric N.P., Mihaljevic M.M., Petrovic S.A., Mirjanic T., Del-Ben C.M., Ferraro L., Gayer-Anderson C., Jones P.B., Jongsma H.E., Kirkbride J.B., La Cascia C., Lasalvia A., Tosato S., Llorca P.-M., Menezes P.R., Morgan C., Quattrone D., Menchetti M., Selten J.-P., Szoke A., Tarricone I., Tortelli A., McGuire P., Valmaggia L., Kempton M.J., van der Gaag M., Riecher-Rossler A., Bressan R.A., Barrantes-Vidal N., Nelson B., McGorry P., Pantelis C., Krebs M.-O., Ruhrmann S., Sachs G., Rutten B.P.F., van Os J., Alizadeh B.Z., van Amelsvoort T., Bartels-Velthuis A.A., Bruggeman R., van Beveren N.J., Luykx J.J., Cahn W., Simons C.J.P., Kahn R.S., Schirmbeck F., van Winkel R., Calem M., Tognin S., Modinos G., Pisani S., Kraan T.C., van Dam D.S., Burger N., Amminger G.P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Cristobal-Narvaez P., Racioppi A., Kwapil T.R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Rander L., Krakauer K., Glenthoj L.B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Reichenberg A., RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Neurosciences, Psychiatry, Clinical Developmental Psychology, World Health Organization (WHO) Collaborating Center, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Adult Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
0301 basic medicine, validity, medicine.medical_treatment, CHILDHOOD, Neuropsychological Tests, FAMÍLIA, episode, Cognition, 0302 clinical medicine, DEFICITS, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, Medicine, Cognitive impairment, Psychiatry, Symptom severity, Cannabis use, IMPAIRMENT, ABILITY, Psychiatry and Mental health, Schizophrenia, RELIABILITY, Neuropsychological Test, Life Sciences & Biomedicine, Human, Clinical psychology, Adult, Biochemistry & Molecular Biology, impairment, schizophrenia-patients, ability, GENETIC RISK, Psychotic Disorder, SCHIZOPHRENIA-PATIENTS, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Settore M-PSI/08 - Psicologia Clinica, Humans, In patient, Cognitive skill, VALIDITY, Antipsychotic, Molecular Biology, Settore MED/25 - Psichiatria, Aged, Cross-Sectional Studie, DECLINE, Science & Technology, reliability, business.industry, Working memory, Siblings, Neurosciences, Diagnostic markers, medicine.disease, Cross-Sectional Studies, 030104 developmental biology, deficits, Psychotic Disorders, PSYCHOSIS, COGNITION, MULTICENTRIC STUDY, Neurosciences & Neurology, business, EPISODE, 030217 neurology & neurosurgery
Abstract

The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EUGEI); The Spanish sample was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024) (...), Velthorst, E., Mollon, J., Murray, R.M., de Haan, L., Germeys, I.M., Glahn, D.C., Arango, C., van der Ven, E., Di Forti, M., Bernardo, M., Guloksuz, S., Delespaul, P., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., García-Portilla, M.P., Santos, J.L., Jiménez-López, E., Sanjuan, J., Aguilar, E.J., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Atbaşoğlu, C., Saka, M.C., Üçok, A., Alptekin, K., Akdede, B., Binbay, T., Altınyazar, V., Ulaş, H., Yalınçetin, B., Gümüş-Akay, G., Beyaz, B.C., Soygür, H., Cankurtaran, E.Ş., Kaymak, S.U., Maric, N.P., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Del-Ben, C.M., Ferraro, L., Gayer-Anderson, C., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., La Cascia, C., Lasalvia, A., Tosato, S., Llorca, P.-M., Menezes, P.R., Morgan, C., Quattrone, D., Menchetti, M., Selten, J.-P., Szöke, A., Tarricone, I., Tortelli, A., McGuire, P., Valmaggia, L., Kempton, M.J., van der Gaag, M., Riecher-Rössler, A., Bressan, R.A., Barrantes-Vidal, N., Nelson, B., McGorry, P., Pantelis, C., Krebs, M.-O., Ruhrmann, S., Sachs, G., Rutten, B.P.F., van Os, J., Alizadeh, B.Z., van Amelsvoort, T., Bartels-Velthuis, A.A., Bruggeman, R., van Beveren, N.J., Luykx, J.J., Cahn, W., Simons, C.J.P., Kahn, R.S., Schirmbeck, F., van Winkel, R., Calem, M., Tognin, S., Modinos, G., Pisani, S., Kraan, T.C., van Dam, D.S., Burger, N., Amminger, G.P., Politis, A., Goodall, J., Borgwardt, S., Studerus, E., Gadelha, A., Brietzke, E., Asevedo, G., Asevedo, E., Zugman, A., Domínguez-Martínez, T., Monsonet, M., Cristóbal-Narváez, P., Racioppi, A., Kwapil, T.R., Kazes, M., Daban, C., Bourgin, J., Gay, O., Mam-Lam-Fook, C., Nordholm, D., Rander, L., Krakauer, K., Glenthøj, L.B., Glenthøj, B., Gebhard, D., Arnhold, J., Klosterkötter, J., Lasser, I., Winklbaur, B., Reichenberg, A., EU-GEI High Risk Study

Published
2021

9. Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders

Author

Okhuijsen-Pfeifer, C., van der Horst, M. Z., Bousman, C. A., Lin, B., van Eijk, K. R., Ripke, S., Ayhan, Y., Babaoglu, M. O., Bak, M., Alink, W., van Beek, H., Beld, E., Bouhuis, A., Edlinger, M., Erdogan, I. M., Ertuğrul, A., Yoca, G., Everall, I. P., Görlitz, T., van Amelsvoort, T., Bartels-Velthuis, A. A., Bruggeman, R., Cahn, W., Guloksuz, S., de Haan, L., Kahn, R. S., Schirmbeck, F., Simons, C. J. P., van Os, J., Alizadeh, B. Z., Luykx, J. J., Rutten, B. P. F., van Winkel, R., Grootens, K. P., Gutwinski, S., Hallikainen, T., Jeger-Land, E., de Koning, M., Lähteenvuo, M., Legge, S. E., Leucht, S., Morgenroth, C., Müderrisoğlu, A., Narang, A., Pantelis, C., Pardiñas, A. F., Oviedo-Salcedo, T., Schneider-Thoma, J., Schreiter, S., Repo-Tiihonen, E., Tuppurainen, H., Veereschild, M., Veerman, S., de Vos, M., Wagner, E., Cohen, D., Bogers, J. P. A. M., Walters, J. T. R., Yağcıoğlu, A. E. Anil, Tiihonen, J., Hasan, A., Clinical Cognitive Neuropsychiatry Research Program (CCNP), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
POLYGENIC RISK SCORE, GENETIC RISK, N-DESMETHYLCLOZAPINE, Schizophrenia/chemically induced, Cytochrome P-450 CYP1A2/genetics, Cellular and Molecular Neuroscience, Cytochrome P-450 CYP1A2, Humans, ddc:610, CYP2C19, BRAIN, Clozapine, POLYMORPHISMS, Biological Psychiatry, IDENTIFICATION, PHARMACOGENETICS, CYTOCHROME-P450, Clozapine/therapeutic use, Cytochrome P-450 CYP2C19, Psychiatry and Mental health, Cytochrome P-450 CYP2D6, Schizophrenia, Cytochrome P-450 CYP2C19/genetics, Antipsychotic Agents/therapeutic use, Cytochrome P-450 CYP2D6/genetics, PHARMACOLOGICAL-TREATMENT, Antipsychotic Agents, Genome-Wide Association Study
Abstract

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

Published
2022

11. Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis

Author

Schirmbeck, F, van der Burg, NC, Blankers, M, Vermeulen, JM, McGuire, P, Valmaggia, LR, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, Amminger, GP, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Nordentoft, M, Glenthoj, B, Fusar-Poli, P, de Haan, L, Schirmbeck, F, van der Burg, NC, Blankers, M, Vermeulen, JM, McGuire, P, Valmaggia, LR, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, Amminger, GP, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Nordentoft, M, Glenthoj, B, Fusar-Poli, P, and de Haan, L

Abstract

INTRODUCTION: Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). METHOD: Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. RESULTS: 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298-7.642]) or decreasing group (OR = 3.137, [1.165-8.450]). In contrast, past (OR = .443, [.179-1.094]) or current (OR = .414, [.156-1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178-3.828]). CONCLUSION: A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.

Published
2022

12. Differential trajectories of tobacco smoking in people at ultra-high risk for psychosis: Associations with clinical outcomes

Author

Schirmbeck, F, van der Ven, E, Boyette, L-L, McGuire, P, Valmaggia, LR, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Barrantes-Vidal, N, Nelson, B, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, Nordentoft, M, de Haan, L, Vermeulen, JM, Schirmbeck, F, van der Ven, E, Boyette, L-L, McGuire, P, Valmaggia, LR, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Barrantes-Vidal, N, Nelson, B, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, Nordentoft, M, de Haan, L, and Vermeulen, JM

Abstract

OBJECTIVE: People at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown. METHODS: We investigated associations between tobacco smoking and clinical outcomes in a prospective study of UHR individuals (n = 324). Latent class mixed model analyses were used to identify trajectories of smoking severity. Mixed effects models were applied to investigate associations between smoking trajectory class and the course of attenuated psychotic symptoms (APS) and affective symptoms, as assessed using the CAARMS. RESULTS: We identified four different classes of smoking trajectory: (i) Persistently High (n = 110), (ii) Decreasing (n = 29), (iii) Persistently Low (n = 165) and (iv) Increasing (n = 20). At two-year follow-up, there had been a greater increase in APS in the Persistently High class than for both the Persistently Low (ES = 9.77, SE = 4.87, p = 0.046) and Decreasing (ES = 18.18, SE = 7.61, p = 0.018) classes. There were no differences between smoking classes in the incidence of psychosis. There was a greater reduction in the severity of emotional disturbance and general symptoms in the Decreasing class than in the High (ES = -10.40, SE = 3.41, p = 0.003; ES = -22.36, SE = 10.07, p = 0.027), Increasing (ES = -11.35, SE = 4.55, p = 0.014; ES = -25.58, SE = 13.17, p = 0.050) and Low (ES = -11.38, SE = 3.29, p = 0.001; ES = -27.55, SE = 9.78, p = 0.005) classes, respectively. CONCLUSIONS: These findings suggests that in UHR subjects persistent tobacco smoking is associated with an unfavorable course of psychotic symptoms, whereas decrease in the number of cigarettes smoked is associated with improvement in affective symptoms. Future research into smoking cessation interventions in the early stages of psychoses is required to shine light on

Published
2022

13. Long-term treatment of antipsychotics and combined therapy with other psychotropic medications inducing weight gain in patients with non-affective psychotic disorder: Evidence from GROUP, a longitudinal study

Author

Burin, L.M., Hahn, M.K., da Rocha, N.S., van Amelsvoort, T., Bartels-Velthuis, A.A., Bruggeman, R., de Haan, L., Schirmbeck, F., Simons, C.J.P., van Os, J., Cahn, W., Burin, L.M., Hahn, M.K., da Rocha, N.S., van Amelsvoort, T., Bartels-Velthuis, A.A., Bruggeman, R., de Haan, L., Schirmbeck, F., Simons, C.J.P., van Os, J., and Cahn, W.

Abstract

Introduction: Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics. Methods: Patients with non-affective psychotic disorder from the GROUP study were divided into three groups: AP medication group (APm) (n = 100), AP in combination with other psychotropics (APc) (n = 73), and medication-free (Meds-free) (n = 100). Weight change was examined at inclusion and after three years using a paired-sample t-test. An Independent-sample t-test was performed to evaluate weight change among patients taking clozapine, olanzapine, and quetiapine and individuals not taking these medications. Linear regression was performed to evaluate the association between covariates and weight. Results: Patients in the APm group [mean = 1.800 kg, t(99)=2.849, 95% CI(0.546, 3.054), p = 0.005] and the APc group [mean = 1.877 kg, t(72)=2.688, 95% CI(0.485, 3.268), p = 0.009] showed significant weight gain. Patients taking clozapine, olanzapine or quetiapine showed significant weight gain compared to those not taking these medications [mean difference=1.707 kg, t(271)= 2.061, 95% CI(0.077, 3.337), p = 0.040)]. Conclusion: Patients receiving APs and APs with other psychotropics gain weight during long-term treatment. It is possible that weight gain is mainly driven by APs.

Published
2022

17. Stress reactivity as a putative mechanism linking childhood trauma with clinical outcomes in individuals at ultra-high-risk for psychosis: Findings from the EU-GEI High Risk Study

Author

Paetzold, I., Myin-Germeys, I., Schick, A., Nelson, B., Velthorst, Eva, Schirmbeck, F., Os, J., Morgan, C., Hartmann, J., van der Gaag, Mark, de Haan, Lieuwe, Valmaggia, Lucia R., McGuire, P., Kempton, Matthew J., Reininghaus, U., McGuire, Philip, Calem, Maria, Tognin, Stefania, Modinos, Gemma, Kraan, Tamar C., Burger, Nadine, van Dam, Daniella S., Barrantes-Vidal, Neus, Domínguez-Martínez, Tecelli, Cristóbal-Narváez, Paula, Kwapil, Thomas R., Monsonet-Bardají, Manel, Hinojosa, Lídia, Riecher-Rössler, Anita, Borgwardt, Stefan, Rapp, Charlotte, Ittig, Sarah, Studerus, Erich, Smieskova, Renata, Bressan, Rodrigo, Gadelha, Ary, Brietzke, Elisa, Asevedo, Graccielle, Asevedo, Elson, Zugman, Andre, Ruhrmann, Stephan, Nordholm, Dorte, Randers, Lasse, Nordentoft, Merete, Pantelis, Christos, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, and Amsterdam Neuroscience - Complex Trait Genetics

Subjects
Experience sampling method, Psychosis, Experience sampling method (ESM), Epidemiology, Ultra high risk, At-risk mental state, Affect (psychology), TRANSITION RATE, Stress sensitization, ECOLOGICAL MOMENTARY INTERVENTIONS, Surveys and Questionnaires, medicine, Humans, experience sampling method (ESM), EMOTIONAL REACTIVITY, Ecological momentary assessment (EMA), Depression (differential diagnoses), METAANALYSIS, Psychiatry, Science & Technology, Mechanism (biology), business.industry, Childhood abuse, BLACK-BOX, Public Health, Environmental and Occupational Health, childhood abuse, transition, EXPERIENCE SAMPLING RESEARCH, At risk mental state, medicine.disease, DEPRESSION, DAILY-LIFE STRESS, Psychiatry and Mental health, Psychotic Disorders, Transition, at-risk mental state, stress sensitization, ecological momentary assessment (EMA), SCHIZOPHRENIA SPECTRUM DISORDERS, Original Article, Self Report, SENSITIVITY, Stress reactivity, business, Life Sciences & Biomedicine, Stress, Psychological, Clinical psychology
Abstract

Aims Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis. Methods Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up. Results The association of stress with positive (β = −0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = −2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506). Conclusions Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.

Published
2021

18. A Network of Psychopathological, Cognitive, and Motor Symptoms in Schizophrenia Spectrum Disorders

Author

Moura, B.M., Moura, B.M., Van Rooijen, G., Schirmbeck, F., Wigman, H., Madeira, L., Van Harten, P., Van Os, J., Bakker, P.R., Marcelis, M., Outcome Psychosis GROUP Investigat, van Amelsvoort, Thérèse, Simons, Claudia, Moura, B.M., Moura, B.M., Van Rooijen, G., Schirmbeck, F., Wigman, H., Madeira, L., Van Harten, P., Van Os, J., Bakker, P.R., Marcelis, M., Outcome Psychosis GROUP Investigat, van Amelsvoort, Thérèse, and Simons, Claudia

Abstract

Schizophrenia spectrum disorders (SSDs) are complex syndromes involving psychopathological, cognitive, and also motor symptoms as core features. A better understanding of how these symptoms mutually impact each other could translate into diagnostic, prognostic, and, eventually, treatment advancements. The present study aimed to: (1) estimate a network model of psychopathological, cognitive, and motor symptoms in SSD; (2) detect communities and explore the connectivity and relative importance of variables within the network; and (3) explore differences in subsample networks according to remission status. A sample of 1007 patients from a multisite cohort study was included in the analysis. We estimated a network of 43 nodes, including all the items from the Positive and Negative Syndrome Scale, a cognitive assessment battery and clinical ratings of extrapyramidal symptoms. Methodologies specific to network analysis were employed to address the study's aims. The estimated network for the total sample was densely interconnected and organized into 7 communities. Nodes related to insight, abstraction capacity, attention, and suspiciousness were the main bridges between network communities. The estimated network for the subgroup of patients in remission showed a sparser density and a different structure compared to the network of nonremitted patients. In conclusion, the present study conveys a detailed characterization of the interrelations between a set of core clinical elements of SSD. These results provide potential novel clues for clinical assessment and intervention.

Published
2021

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

Author

Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, Reichenberg, A, Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, and Reichenberg, A

Abstract

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Published
2021

20. Pre-training inter-rater reliability of clinical instruments in an international psychosis research project

Author

Berendsen, S, Kapitein, P, Schirmbeck, F, van Tricht, MJ, McGuire, P, Morgan, C, Gayer-Anderson, C, Kempton, MJ, Valmaggia, L, Quattrone, D, di Forti, M, van der Gaag, M, Kirkbride, JB, Jongsma, HE, Jones, PB, Parellada, M, Arango, C, Arrojo, M, Bernardo, M, Sanjuan, J, Santos, JL, Szoke, A, Tortelli, A, Llorca, P-M, Tarricone, I, Tripoli, G, Ferraro, L, La Cascia, C, Lasalvia, A, Tosato, S, Menezes, PR, Del-Ben, CM, Nelson, B, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Velthorst, E, de Haan, L, Berendsen, S, Kapitein, P, Schirmbeck, F, van Tricht, MJ, McGuire, P, Morgan, C, Gayer-Anderson, C, Kempton, MJ, Valmaggia, L, Quattrone, D, di Forti, M, van der Gaag, M, Kirkbride, JB, Jongsma, HE, Jones, PB, Parellada, M, Arango, C, Arrojo, M, Bernardo, M, Sanjuan, J, Santos, JL, Szoke, A, Tortelli, A, Llorca, P-M, Tarricone, I, Tripoli, G, Ferraro, L, La Cascia, C, Lasalvia, A, Tosato, S, Menezes, PR, Del-Ben, CM, Nelson, B, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Velthorst, E, and de Haan, L

Published
2021

21. Momentary Manifestations of Negative Symptoms as Predictors of Clinical Outcomes in People at High Risk for Psychosis: Experience Sampling Study

Author

Paetzold, I, Hermans, KSFM, Schick, A, Nelson, B, Velthorst, E, Schirmbeck, F, van Os, J, Morgan, C, Gaag, MVD, de Haan, L, Valmaggia, L, McGuire, P, Kempton, M, Myin-Germeys, I, Reininghaus, U, Paetzold, I, Hermans, KSFM, Schick, A, Nelson, B, Velthorst, E, Schirmbeck, F, van Os, J, Morgan, C, Gaag, MVD, de Haan, L, Valmaggia, L, McGuire, P, Kempton, M, Myin-Germeys, I, and Reininghaus, U

Abstract

BACKGROUND: Negative symptoms occur in individuals at ultrahigh risk (UHR) for psychosis. Although there is evidence that observer ratings of negative symptoms are associated with level of functioning, the predictive value of subjective experience in daily life for individuals at UHR has not been studied yet. OBJECTIVE: This study therefore aims to investigate the predictive value of momentary manifestations of negative symptoms for clinical outcomes in individuals at UHR. METHODS: Experience sampling methodology was used to measure momentary manifestations of negative symptoms (blunted affective experience, lack of social drive, anhedonia, and social anhedonia) in the daily lives of 79 individuals at UHR. Clinical outcomes (level of functioning, illness severity, UHR status, and transition status) were assessed at baseline and at 1- and 2-year follow-ups. RESULTS: Lack of social drive, operationalized as greater experienced pleasantness of being alone, was associated with poorer functioning at the 2-year follow-up (b=-4.62, P=.01). Higher levels of anhedonia were associated with poorer functioning at the 1-year follow-up (b=5.61, P=.02). Higher levels of social anhedonia were associated with poorer functioning (eg, disability subscale: b=6.36, P=.006) and greater illness severity (b=-0.38, P=.045) at the 1-year follow-up. In exploratory analyses, there was evidence that individuals with greater variability of positive affect (used as a measure of blunted affective experience) experienced a shorter time to remission from UHR status at follow-up (hazard ratio=4.93, P=.005). CONCLUSIONS: Targeting negative symptoms in individuals at UHR may help to predict clinical outcomes and may be a promising target for interventions in the early stages of psychosis.

Published
2021

22. Obsessive-Compulsive Symptoms and Other Symptoms of the At-risk Mental State for Psychosis: A Network Perspective

Author

Ong, HL, Isvoranu, A-M, Schirmbeck, F, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, Amminger, GP, McGorry, P, Pantelis, C, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, de Haan, L, Borsboom, D, Ong, HL, Isvoranu, A-M, Schirmbeck, F, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, Amminger, GP, McGorry, P, Pantelis, C, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, de Haan, L, and Borsboom, D

Abstract

BACKGROUND: The high prevalence of obsessive-compulsive symptoms (OCS) among subjects at Ultra-High Risk (UHR) for psychosis is well documented. However, the network structure spanning the relations between OCS and symptoms of the at risk mental state for psychosis as assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS) has not yet been investigated. This article aimed to use a network approach to investigate the associations between OCS and CAARMS symptoms in a large sample of individuals with different levels of risk for psychosis. METHOD: Three hundred and forty-one UHR and 66 healthy participants were included, who participated in the EU-GEI study. Data analysis consisted of constructing a network of CAARMS symptoms, investigating central items in the network, and identifying the shortest pathways between OCS and positive symptoms. RESULTS: Strong associations between OCS and anxiety, social isolation and blunted affect were identified. Depression was the most central symptom in terms of the number of connections, and anxiety was a key item in bridging OCS to other symptoms. Shortest paths between OCS and positive symptoms revealed that unusual thought content and perceptual abnormalities were connected mainly via anxiety, while disorganized speech was connected via blunted affect and cognitive change. CONCLUSIONS: Findings provide valuable insight into the central role of depression and the potential connective component of anxiety between OCS and other symptoms of the network. Interventions specifically aimed to reduce affective symptoms might be crucial for the development and prospective course of symptom co-occurrence.

Published
2021

23. Impact of smoking Behavior on cognitive functioning in persons at risk for psychosis and healthy controls: A longitudinal study

Author

van der Heijden, HS, Schirmbeck, F, Kempton, MJ, van der Gaag, M, Allot, K, Nelson, B, Ruhrmann, S, de Haan, L, Vermeulen, JM, van der Heijden, HS, Schirmbeck, F, Kempton, MJ, van der Gaag, M, Allot, K, Nelson, B, Ruhrmann, S, de Haan, L, and Vermeulen, JM

Abstract

BACKGROUND: The high prevalence of smoking in individuals who are at ultra-high risk (UHR) for psychosis is well known and moderate cognitive deficits have also been found in UHR. However, the association between smoking and cognition in UHR is unknown and longitudinal studies are lacking. METHOD: A cohort study with 330 UHR individuals and 66 controls was conducted, as part of the European network of national schizophrenia networks studying gene-environment interactions (EU-GEI). At baseline and after 6, 12, and 24 months, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a comprehensive test battery. Linear mixed-effects analyses were used to examine the multicross-sectional and prospective associations between (change in) smoking behavior and cognitive functioning, accounting for confounding variables. RESULTS: At baseline, 53% of UHR and 27% of controls smoked tobacco. Smoking UHR and controls did not significantly differ from nonsmoking counterparts on the tested cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, or reasoning/problem solving) across different assessment times. Neither smoking cessation nor initiation was associated with a significant change in cognitive functioning in UHR. CONCLUSIONS: No associations were found between smoking and cognitive impairment in UHR nor in controls. However, the fact that one in every two UHR individuals report daily use of tobacco is alarming. Our data suggest that UHR have fewer cognitive impairments and higher smoking cessation rates compared to patients with first-episode psychosis found in literature. Implications to promote smoking cessation in the UHR stage need further investigation.

Published
2021

24. Association between tobacco use and symptomatology in individuals at ultra-high risk to develop a psychosis: A longitudinal study

Author

van der Heijden, HS, Schirmbeck, F, McGuire, P, Valmaggia, LR, Kempton, MJ, van der Gaag, M, Nelson, B, Riecher-Roessler, A, Bressan, R, Barrantes-Vidal, N, Ruhrmann, S, Sachs, G, de Haan, L, Vermeulen, JM, van der Heijden, HS, Schirmbeck, F, McGuire, P, Valmaggia, LR, Kempton, MJ, van der Gaag, M, Nelson, B, Riecher-Roessler, A, Bressan, R, Barrantes-Vidal, N, Ruhrmann, S, Sachs, G, de Haan, L, and Vermeulen, JM

Abstract

BACKGROUND: The high prevalence rates and impact of tobacco smoking in individuals with a psychotic disorder have become an increasing interest. Little is known about tobacco smoking in individuals at ultra-high risk of psychosis (UHR). METHODS: We studied 345 UHR individuals of the high-risk study of the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI). Smoking status and the number of cigarettes per day were assessed at multiple moments using the CIDI. Symptom severity at each time point was assessed using CAARMS. Linear mixed-effects analyses were conducted to examine the multi-cross-sectional and prospective associations between (change in) smoking behaviour and symptomatology. FINDINGS: At baseline, 175 individuals (53%) smoked tobacco with an average of 12.4 (SD = 9.0) cigarettes per day. Smokers did not significantly differ in symptom severity from non-smokers on general, positive, negative, emotional, cognitive, behavioural, or motor symptoms across time. However, associations were found between the number of cigarettes and the severity of general psychopathology (estimate 0.349, SE 0.146, p = 0.017). Change in the number of cigarettes had no significant effect on change in general symptom severity (estimate 0.330, SE 0.285, p = 0.248). INTERPRETATION: Smoking prevalence in UHR individuals is high. Cigarette consumption was associated with higher levels of general symptoms. However, we observed no association between change in number of cigarettes and symptom severity. Given the fact that smoking is associated with poorer health and worse outcomes in people with psychosis, the clinical high-risk phase offers a window of opportunity for prevention and cessation interventions.

Published
2021

25. Obsessive–compulsive symptoms in at-risk mental states for psychosis: associations with clinical impairment and cognitive function

Author

Zink, M., Schirmbeck, F., Rausch, F., Eifler, S., Elkin, H., Solojenkina, X., Englisch, S., Wagner, M., Maier, W., Lautenschlager, M., Heinz, A., Gudlowski, Y., Janssen, B., Gaebel, W., Michel, T. M., Schneider, F., Lambert, M., Naber, D., Juckel, G., Krueger-Oezguerdal, S., Wobrock, T., Hasan, A., Riedel, M., Müller, H., Klosterkötter, J., and Bechdolf, A.

Published
2014
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27. Implementatie van een stoppen-met-rokenprogramma in een psychiatrisch ziekenhuis: eerste resultaten

Author

Vermeulen, J. M., Doedens, P., Schirmbeck, F., van den Brink, W., de Haan, L., Urban Vitality, Faculteit Gezondheid, Academic Medical Center, APH - Mental Health, Adult Psychiatry, Graduate School, and Nursing

Subjects
Nicotine, Implementation, Smoking cessation
Abstract

BACKGROUND: In contrast to several other countries, smoking is not an integral part of treatment during admission to a psychiatric hospital in The Netherlands. AIM: Implementation of a smoking cessation program for patients and employees of a psychiatric ward of an academic medical center in The Netherlands. METHOD: Prospective, mixed-method study of implementation of a smoking cessation program for patients and employees of a psychiatric academic hospital in Amsterdam. The program consisted of 7 weekly group meetings by certified smoking cessation coaches. Nicotine replacement therapy was provided for free, if necessary. RESULTS: During 14 months, 65 individuals were seeking help to stop smoking: 39 patients and 26 employees. Of these, 29 patients and 16 employees participated in group meetings with an average of 2.6 times per person. There were 20 individuals who visited the group meetings or received individual coaching at least 3 times (6 patients and 14 employees). Fifty-five percent of these individuals reported to be smoke-free at 3 months after joining the first meeting. Employees were much more likely to quit than patients. From interviews with 20 participants, it was noticed that combining patients and employees in one group was perceived as a barrier due to a gap in processing speed. CONCLUSION: On the psychiatric ward of an academic hospital in The Netherlands, there was a positive experience with providing smoking cessation treatment. A small number of employees and patients participated in a smoking cessation program and quitting smoking was reached by only a few patients. Supporting smoking cessation in a psychiatric hospital asks for intensive screening, diagnosing, treatment and smoke-free policies.

Published
2020

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

Author

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

Abstract

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Published
2020
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29. From Speech Illusions to Onset of Psychotic Disorder: Applying Network Analysis to an Experimental Measure of Aberrant Experiences

Author

Boyette, L-L, Isvoranu, A-M, Schirmbeck, F, Velthorst, E, Simons, CJP, Barrantes-Vidal, N, Bressan, R, Kempton, MJ, Krebs, M-O, McGuire, P, Nelson, B, Nordentoft, M, Riecher-Rössler, A, Ruhrmann, S, Rutten, BP, Sachs, G, Valmaggia, LR, van der Gaag, M, Borsboom, D, de Haan, L, van Os, J, Calem, M, Tognin, S, Modinos, G, Kraan, TC, van Dam, DS, Burger, N, McGorry, P, Amminger, GP, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Studerus, E, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Domínguez-Martínez, T, Cristóbal-Narváez, P, Kwapil, TR, Monsonet, M, Hinojosa, L, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthøj, L, Glenthøj, B, Gebhard, D, Arnhold, J, Klosterkötter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Boyette, L-L, Isvoranu, A-M, Schirmbeck, F, Velthorst, E, Simons, CJP, Barrantes-Vidal, N, Bressan, R, Kempton, MJ, Krebs, M-O, McGuire, P, Nelson, B, Nordentoft, M, Riecher-Rössler, A, Ruhrmann, S, Rutten, BP, Sachs, G, Valmaggia, LR, van der Gaag, M, Borsboom, D, de Haan, L, van Os, J, Calem, M, Tognin, S, Modinos, G, Kraan, TC, van Dam, DS, Burger, N, McGorry, P, Amminger, GP, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Studerus, E, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Domínguez-Martínez, T, Cristóbal-Narváez, P, Kwapil, TR, Monsonet, M, Hinojosa, L, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthøj, L, Glenthøj, B, Gebhard, D, Arnhold, J, Klosterkötter, J, Lasser, I, Winklbaur, B, and Delespaul, PA

Abstract

Aberrant perceptional experiences are a potential early marker of psychosis development. Earlier studies have found experimentally assessed speech illusions to be associated with positive symptoms in patients with psychotic disorders, but findings for attenuated symptoms in individuals without psychotic disorders have been inconsistent. Also, the role of affect is unclear. The aim of this study was to use the network approach to investigate how speech illusions relate to individual symptoms and onset of a psychotic disorder. We estimated a network model based on data from 289 Clinical High-Risk (CHR) subjects, participating in the EU-GEI project. The network structure depicts statistical associations between (affective and all) speech illusions, cross-sectional individual attenuated positive and affective symptoms, and transition to psychotic disorder after conditioning on all other variables in the network. Speech illusions were assessed with the White Noise Task, symptoms with the BPRS and transition during 24-month follow-up with the CAARMS. Affective, not all, speech illusions were found to be directly, albeit weakly, associated with hallucinatory experiences. Hallucinatory experiences, in turn, were associated with delusional ideation. Bizarre behavior was the only symptom in the network steadily predictive of transition. Affective symptoms were highly interrelated, with depression showing the highest overall strength of connections to and predictability by other symptoms. Both speech illusions and transition showed low overall predictability by symptoms. Our findings suggest that experimentally assessed speech illusions are not a mere consequence of psychotic symptoms or disorder, but that their single assessment is likely not useful for assessing transition risk.

Published
2020

30. 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

Habtewold, TD, Islam, MA, Liemburg, E J, Bartels-Velthuis, AA, Beveren, JM, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Amelsvoort, T, Haren, NEM, van Os, J, van Winkel, R, Bruggeman, R, Alizadeh, BZ, Habtewold, TD, Islam, MA, Liemburg, E J, Bartels-Velthuis, AA, Beveren, JM, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Amelsvoort, T, Haren, NEM, van Os, J, van Winkel, R, Bruggeman, R, and Alizadeh, BZ

Published
2020

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

Author

Rees, E, Carrera, N, Morgan, J, Hambridge, K, Escott-Price, V, Pocklington, AJ, Richards, AL, Pardinas, AF, McDonald, C, Donohoe, G, Morris, DW, Kenny, E, Kelleher, E, Gill, M, Corvin, A, Kirov, G, Walters, JTR, Holmans, P, Owen, MJ, O'Donovan, MC, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Beveren, JM, Bruggeman, R, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Haren, NE, van Os, J, van Winkel, R, Luykx, JJ, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Neurosciences, and Psychiatry

Subjects
Psychiatry, RISK, Science & Technology, DISORDERS, Neurosciences, OF-FUNCTION VARIANTS, SUSCEPTIBILITY, FRAMEWORK, ARC, NMDAR, INDIVIDUALS, DE-NOVO MUTATIONS, mental disorders, SETD1A, Genetics, Schizophrenia, Sequencing, Neurosciences & Neurology, GENOME-WIDE ASSOCIATION, Voltage-gated sodium channels, BURDEN, Life Sciences & Biomedicine, Biological Psychiatry
Abstract

BACKGROUND: Sequencing studies have pointed to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes; however, larger samples are required to reveal novel genes and specific biological mechanisms. METHODS: We sequenced 187 genes, selected for prior evidence of association with schizophrenia, in a new dataset of 5207 cases and 4991 controls. Included among these genes were members of ARC and NMDAR postsynaptic protein complexes, as well as voltage-gated sodium and calcium channels. We performed a rare variant meta-analysis with published sequencing data for a total of 11,319 cases, 15,854 controls, and 1136 trios. RESULTS: While no individual gene was significantly associated with schizophrenia after genome-wide correction for multiple testing, we strengthen the evidence that rare exonic variants in the ARC (p = 4.0 × 10-4) and NMDAR (p = 1.7 × 10-5) synaptic complexes are risk factors for schizophrenia. In addition, we found that loss-of-function variants and missense variants at paralog-conserved sites were enriched in voltage-gated sodium channels, particularly the alpha subunits (p = 8.6 × 10-4). CONCLUSIONS: In one of the largest sequencing studies of schizophrenia to date, we provide novel evidence that multiple voltage-gated sodium channels are involved in schizophrenia pathogenesis and confirm the involvement of ARC and NMDAR postsynaptic complexes. ispartof: BIOLOGICAL PSYCHIATRY vol:85 issue:7 pages:554-562 ispartof: location:United States status: published

Published
2019

33. Obsessive-compulsive symptoms in psychotic disorders: longitudinal associations of symptom clusters on between- and within-subject levels

Author

Schirmbeck, F., Konijn, Max, Hoetjes, Vera, Zink, Mathias, de Haan, Lieuwe, Alizadeh, B. Z., Bartels-Velthuis, A. A., Bruggeman, R., van Beveren, N. J., Cahn, W., Kahn, R. S., van Haren, N. E., de Haan, L., Meijer, C. J., Simons, C. J. P., van Os, J., Delespaul, P., Myin-Germeys, I., van Winkel, R., Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), and MUMC+: Hersen en Zenuw Centrum (3)

Subjects
Male, Obsessive-Compulsive Disorder, INVENTORY, Comorbidity, Severity of Illness Index, 0302 clinical medicine, SCHIZOPHRENIA, Medicine, Pharmacology (medical), Longitudinal Studies, Prospective cohort study, Subclinical infection, Psychiatry, Obsessive-compulsive, Depression, MULTILEVEL, General Medicine, Middle Aged, Within-subject, PREVALENCE, Psychiatry and Mental health, Distress, Schizophrenia, BETWEEN-PERSON, Female, Life Sciences & Biomedicine, Clinical psychology, Obsessive–compulsive, Adult, Psychosis, Within person, Clinical Neurology, 03 medical and health sciences, Humans, VALIDITY, Biological Psychiatry, METAANALYSIS, Original Paper, SPECTRUM, Science & Technology, business.industry, Siblings, medicine.disease, Obsessive compulsive symptoms, 030227 psychiatry, PSYCHOMETRIC PROPERTIES, Psychotic Disorders, Longitudinal, EXPERIENCE, Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract

Obsessive–compulsive symptoms (OCS) are frequently reported in patients with schizophrenia and have been associated with subjective distress and higher impairment. Recent studies suggest fluctuation in co-occurring OCS and associations with the course of psychotic symptoms. Current evidence is limited by few studies with long assessments intervals and a sole focus on between-subject comparisons. The aim of this study was to specifically investigate co-variation of symptom domains over time within individuals. Patients with a psychotic disorder (n = 56) and un-affected siblings (n = 49) completed monthly assessments of clinical and subclinical symptoms over 6 months. Mixed-model multilevel analyses examined the variability and relationship between OCS and positive, negative, and depressive symptoms on the between- and within-subject level. Symptom domains were associated across subjects and assessment times, in patients and siblings, with the strongest association between OCS and (subclinical) positive symptoms. Within-subjects, substantial variability and co-variation of all symptom domains was found. Particularly, between-subject differences in positive symptoms and within-subject change in depressive symptoms predicted subsequent OCS in patients 1 months later. This is the first prospective study disaggregating between and within-subject associations between co-occurring OCS and symptom cluster of psychosis. Differences on these two levels suggest different underlying mechanisms. The association between depressive symptoms and subsequent increase/decrease of OCS within patients may have important treatment implications. Electronic supplementary material The online version of this article (10.1007/s00406-018-0884-4) contains supplementary material, which is available to authorized users.

Published
2019

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

Author

Rees, E., Carrera, N, Morgan, J. (John), Hambridge, K., Escott-Price, V, Pocklington, AJ, Richards, AL, Pardinas, A.F., McDonald, C. (Colm), Donohoe, G, Morris, D.W. (Derek W), Kenny, A., Kelleher, E., Gill, M. (Michael), Corvin, A. (Aiden), Kirov, G, Walters, JTR, Holmans, P.A. (Peter), Owen, M.J., O'Donovan, M. (Michael), Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, A.A., van Beveren, NJ, Bruggeman, R. (Richard), Cahn, W. (Wiepke), Willigenburg, T. (Theo) van, Delespaul, P., Meijer, C.J., Myin-Germeys, I. (Inez), Kahn, R.S. (René), Schirmbeck, F., Simons, CJP, van Haren, N.E., Os, J. (Jim) van, Winkel, R. (Ruud) van, Luykx, J.J., Rees, E., Carrera, N, Morgan, J. (John), Hambridge, K., Escott-Price, V, Pocklington, AJ, Richards, AL, Pardinas, A.F., McDonald, C. (Colm), Donohoe, G, Morris, D.W. (Derek W), Kenny, A., Kelleher, E., Gill, M. (Michael), Corvin, A. (Aiden), Kirov, G, Walters, JTR, Holmans, P.A. (Peter), Owen, M.J., O'Donovan, M. (Michael), Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, A.A., van Beveren, NJ, Bruggeman, R. (Richard), Cahn, W. (Wiepke), Willigenburg, T. (Theo) van, Delespaul, P., Meijer, C.J., Myin-Germeys, I. (Inez), Kahn, R.S. (René), Schirmbeck, F., Simons, CJP, van Haren, N.E., Os, J. (Jim) van, Winkel, R. (Ruud) van, and Luykx, J.J.

Abstract

Background Sequencing studies have pointed to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes; however, larger samples are required to reveal novel genes and specific biological mechanisms. Methods We sequenced 187 genes, selected for prior evidence of association with schizophrenia, in a new dataset of 5207 cases and 4991 controls. Included among these genes were members of ARC and NMDAR postsynaptic protein complexes, as well as voltage

Published
2019
Full Text
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35. Obsessive-compulsive symptoms in psychotic disorders: longitudinal associations of symptom clusters on between- and within-subject levels

Author

Genetica, Onderzoek, Brain, Onderzoeksgroep 11, Onderzoeksgroep 1, Hersenen-Medisch 1, Schirmbeck, F., Konijn, Max, Hoetjes, Vera, Zink, Mathias, de Haan, Lieuwe, Alizadeh, B. Z., Bartels-Velthuis, A. A., Bruggeman, R., van Beveren, N. J., Cahn, W., Kahn, R. S., van Haren, N. E., de Haan, L., Meijer, C. J., Simons, C. J. P., van Os, J., Delespaul, P., Myin-Germeys, I., van Winkel, R., Genetica, Onderzoek, Brain, Onderzoeksgroep 11, Onderzoeksgroep 1, Hersenen-Medisch 1, Schirmbeck, F., Konijn, Max, Hoetjes, Vera, Zink, Mathias, de Haan, Lieuwe, Alizadeh, B. Z., Bartels-Velthuis, A. A., Bruggeman, R., van Beveren, N. J., Cahn, W., Kahn, R. S., van Haren, N. E., de Haan, L., Meijer, C. J., Simons, C. J. P., van Os, J., Delespaul, P., Myin-Germeys, I., and van Winkel, R.

Published
2019

36. 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, G, van Nierop, M, Schruers, K, Alizadeh, BZ, Bartels-Velthuis, AA, Beveren, JM, Bruggeman, R, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Haren, Neeltje, van Os, J, van Winkel, R, Mansueto, G, van Nierop, M, Schruers, K, Alizadeh, BZ, Bartels-Velthuis, AA, Beveren, JM, Bruggeman, R, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Haren, Neeltje, van Os, J, and van Winkel, R

Published
2018

37. Aanbevelingen voor diagnostiek en behandeling van dwangsymptomen bij schizofrenie

Author

Muller, D., Schirmbeck, F., de Haan, L., Adult Psychiatry, and Amsterdam Neuroscience

Subjects
mental disorders
Abstract

Obsessive-compulsive symptoms (OCS) are common in patients with schizophrenia. Although these symptoms are associated with an unfavourable course of the illness, in many cases they are not recognised or treated. The situation for patients with schizophrenia and obsessive-compulsive disorder (OCD) could improve considerably now that more advanced diagnostic techniques and better treatment options have been available. To provide an overview of current knowledge regarding diagnosis and treatment options. We searched the literature for relevant articles. With careful diagnosis OCS could be better noticed. Based on the time of onset of the OCS and the relationship between these symptoms and the use of antipsychotics, we propose a treatment strategy. Cognitive behavioural therapy, as well as various pharmacotherapeutic strategies, are promising treatment options that could deployed more frequently to treat persistent OCD in schizophrenia. Although the research findings are homogeneous, the methodological quality of the studies is still low

Published
2016

38. Identification of common variants associated with human hippocampal and intracranial volumes

Author

Stein, Jason L, Medland, Sarah E, Bernard, Manon, Nauck, Matthias, Nöthen, Markus M., Olvera, Rene L, Pandolfo, Massimo, Pike, G Bruce, Puls, Ralf, Reinvang, Ivar, Rentería, Miguel E, Rietschel, Marcella, Roffman, Joshua L, Brown, Andrew A, Royle, Natalie A, Rujescu, Dan, Savitz, Jonathan, Schnack, Hugo G, Schnell, Knut, Seiferth, Nina, Smith, Colin, Steen, Vidar M, Valdés Hernández, Maria C, Van den Heuvel, Martijn, Cannon, Dara M, van der Wee, Nic J, Van Haren, Neeltje E M, Veltman, Joris A, Völzke, Henry, Walker, Robert, Westlye, Lars T, Whelan, Christopher D, Agartz, Ingrid, Boomsma, Dorret I, Cavalleri, Gianpiero L, Chakravarty, M Mallar, Dale, Anders M, Djurovic, Srdjan, Drevets, Wayne C, Hagoort, Peter, Hall, Jeremy, Heinz, Andreas, Jack, Clifford R, Foroud, Tatiana M, Le Hellard, Stephanie, Macciardi, Fabio, Christoforou, Andrea, Montgomery, Grant W, Poline, Jean Baptiste, Porteous, David J, Sisodiya, Sanjay M, Starr, John M, Sussmann, Jessika, Toga, Arthur W, Veltman, Dick J, Walter, Henrik, Weiner, Michael W, Domin, Martin, Initiative, Alzheimer's Disease Neuroimaging, Consortium, EPIGEN, Consortium, IMAGEN, Group, Saguenay Youth Study, Bis, Joshua C, Ikram, M Arfan, Smith, Albert V, Gudnason, Vilmundur, Tzourio, Christophe, Vernooij, Meike W, Grimm, Oliver, Launer, Lenore J, DeCarli, Charles, Seshadri, Sudha, Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology, Andreassen, Ole A, Apostolova, Liana G, Bastin, Mark E, Blangero, John, Brunner, Han G, Buckner, Randy L, Hollinshead, Marisa, Cichon, Sven, Coppola, Giovanni, de Zubicaray, Greig I, Deary, Ian J, Donohoe, Gary, de Geus, Eco J C, Espeseth, Thomas, Fernández, Guillén, Glahn, David C, Grabe, Hans J, Holmes, Avram J, Hardy, John, Hulshoff Pol, Hilleke E, Jenkinson, Mark, Kahn, René S, McDonald, Colm, McIntosh, Andrew M, McMahon, Francis J, McMahon, Katie L, Meyer-Lindenberg, Andreas, Morris, Derek W, Homuth, Georg, Müller-Myhsok, Bertram, Nichols, Thomas E, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W, Potkin, Steven G, Sämann, Philipp G, Saykin, Andrew J, Schumann, Gunter, Vasquez, Alejandro Arias, Hottenga, Jouke-Jan, Smoller, Jordan W, Wardlaw, Joanna M, Weale, Michael E, Martin, Nicholas G, Franke, Barbara, Wright, Margaret J, Thompson, Paul M, Consortium, Enhancing Neuro Imaging Genetics through Meta-Analysis, Weiner, Michael, Aisen, Paul, Langan, Camilla, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Green, Robert C, Morris, John, Liu, Enchi, Lopez, Lorna M, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Hansell, Narelle K, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Hwang, Kristy S, Thompson, Paul, Schuff, Norbert, Alexander, Gene, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Kim, Sungeun, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Laje, Gonzalo, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lee, Phil H, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Liu, Xinmin, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Loth, Eva, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Hibar, Derrek P, Lourdusamy, Anbarasu, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, Mattingsdal, Morten, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Coleman, R Edward, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Mohnke, Sebastian, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Mulnard, Ruth A, Thai, Gaby, Maniega, Susana Muñoz, Mc-Adams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Nho, Kwangsik, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Lu, Po H, Bartzokis, George, Silverman, Daniel H S, Graff-Radford, Neill R, Nugent, Allison C, Parfitt, Francine, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, O'Brien, Carol, Bergman, Howard, Hosei, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Ging-Yuek Robin, Feldman, Howard, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Papmeyer, Martina, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Pütz, Benno, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Ramasamy, Adaikalavan, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine, Jacobson, Sandra, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Senstad, Rudy E, Rasmussen, Jerod, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Bwayo, Salome K, Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Rijpkema, Mark, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Risacher, Shannon L, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Roddey, J Cooper, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Anderson, Karen, Santulli, Robert B, Schwartz, Eben S, Sink, Kaycee M, Rose, Emma J, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Ryten, Mina, Miller, Bruce L, Mintzer, Jacobo, Longmire, Crystal Flynn, Spicer, Kenneth, Finger, Elizabeth, Rachinsky, Irina, Drost, Dick, Cavalleri, Gianpiero, Alhusaini, Saud, Delanty, Norman, Whelan, Christopher, Sisodiya, Sanjay, Kasperaviciute, Dalia, Matarin, Mar, Depondt, Chantal, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Sprooten, Emma, Radtke, Rodney, Ottmann, Ruth, Sergievsky, G. H., Schumann, G., Conrod, P., Reed, L., Barker, G., Williams, S., Loth, E., Struve, M., Strengman, Eric, Lourdusamy, A., Cattrell, A., Nymberg, C., Topper, L., Smith, L., Havatzias, S., Stueber, K., Mallik, C., Stacey, D., Wong, C Peng, Teumer, Alexander, Werts, H., Andrew, C., Desrivieres, S., Heinz, A., Gallinat, J., Häke, I., Ivanov, N., Klär, A., Reuter, J., Winkler, Anderson M, Trabzuni, Daniah, Palafox, C., Hohmann, C., Schilling, C., Lüdemann, K., Romanowski, A., Ströhle, A., Wolff, E., Rapp, M., Ittermann, B., Brühl, R., Turner, Jessica, Ihlenfeld, A., Walaszek, B., Schubert, F., Garavan, H., Connolly, C., Jones, J., Lalor, E., McCabe, E., Ní Shiothcháin, A., Whelan, R., van Eijk, Kristel, Spanagel, R., Leonardi-Essmann, F., Sommer, W., Flor, H., Vollstaedt-Klein, S., Nees, F., Banaschewski, T., Poustka, L., Steiner, S., Mann, K., van Erp, Theo G M, Buehler, M., Rietschel, M., Stolzenburg, E., Schmal, C., Schirmbeck, F., Paus, T., Gowland, P., Heym, N., Lawrence, C., Newman, C., van Tol, Marie-Jose, Pausova, Z., Smolka, M., Huebner, T., Ripke, S., Mennigen, E., Muller, K., Ziesch, V., Büchel, C., Bromberg, U., Fadai, T., Wittfeld, Katharina, Lueken, L., Yacubian, J., Finsterbusch, J., Martinot, J. L., Artiges, E., Bordas, N., de Bournonville, S., Bricaud, Z., Gollier Briand, F., Lemaitre, H., Wolf, Christiane, Massicotte, J., Miranda, R., Paillère Martinot, M. L., Penttilä, J., Poline, J. B., Barbot, A., Schwartz, Y., Lalanne, C., Frouin, V., Thyreau, B., Woudstra, Saskia, Dalley, J., Mar, A., Robbins, T., Subramaniam, N., Theobald, D., Richmond, N., de Rover, M., Molander, A., Jordan, E., Robinson, E., Aleman, Andre, Hipolata, L., Moreno, M., Arroyo, M., Stephens, D., Ripley, T., Crombag, H., Pena, Y., Lathrop, M., Zelenika, D., Heath, S., Lanzerath, D., Heinrichs, B., Spranger, T., Fuchs, B., Speiser, C., Resch, F., Haffner, J., Parzer, P., Brunner, R., Klaassen, A., Toro, Roberto, Almasy, Laura, Klaassen, I., Constant, P., Mignon, X., Thomsen, T., Zysset, S., Vestboe, A., Ireland, J., Rogers, J., Binder, Elisabeth B, Chakravarty, Mallar, Smith, Albert Vernon, van der Lijn, Fedde, Crivello, Fabrice, Fornage, Myriam, Shulman, Joshua M, Brohawn, David G, Schmidt, Helena, Srikanth, Velandai, Schuur, Maaike, Yu, Lei, Choi, Seung-Hoan, Sigurdsson, Sigurdur, Verhaaren, Benjamin F J, DeStefano, Anita L, Lambert, Jean-Charles, Cantor, Rita M, Struchalin, Maksim, Stankovich, Jim, Ibrahim-Verbaas, Carla A, Fleischman, Debra, Zijdenbos, Alex, den Heijer, Tom, Mazoyer, Bernard, Coker, Laura H, Enzinger, Christian, Danoy, Patrick, Carless, Melanie A, Amin, Najaf, Arfanakis, Konstantinos, van Buchem, Mark A, de Bruijn, Renée F A G, Beiser, Alexa, Dufouil, Carole, Huang, Juebin, Cavalieri, Margherita, Thomson, Russell, Niessen, Wiro J, Corvin, Aiden, Chibnik, Lori B, Gislason, Gauti K, Hofman, Albert, Pikula, Aleksandra, Amouyel, Philippe, Freeman, Kevin B, Phan, Thanh G, Oostra, Ben A, Nalls, Michael A, Uitterlinden, Andre G, Czisch, Michael, Au, Rhoda, Elbaz, Alexis, Beare, Richard J, van Swieten, John C, Lopez, Oscar, Harris, Tamara B, Chouraki, Vincent, Breteler, Monique M B, De Jager, Philip L, Becker, James T, Curran, Joanne E, Knopman, David, Fazekas, Franz, Wolf, Philip A, van der Lugt, Aad, Longstreth, W. T., Brown, Mathew A, Bennett, David A, van Duijn, Cornelia M, Davies, Gail, Mosley, Thomas H, Schmidt, Reinhold, de Almeida, Marcio A A, Appel, Katja, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fagerness, Jesen, Fox, Peter T, Freimer, Nelson B, Gill, Michael, Göring, Harald H H, Bartecek, Richard, Hagler, Donald J, Hoehn, David, Holsboer, Florian, Hoogman, Martine, Hosten, Norbert, Jahanshad, Neda, Johnson, Matthew P, Kent, Jack W, Kochunov, Peter, Bergmann, Ørjan, Lancaster, Jack L, Lawrie, Stephen M, Liewald, David C, Mandl, René, Mattheisen, Manuel, Meisenzahl, Eva, Melle, Ingrid, Moses, Eric K, Mühleisen, Thomas W, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Queensland Institute of Medical Research, Radboud University Medical Center [Nijmegen], Yale University School of Medicine, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Universität Greifswald - University of Greifswald, Universität Heidelberg [Heidelberg], University Medical Center [Utrecht], University of Oslo (UiO), University of Toronto, National University of Ireland [Galway] (NUI Galway), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], University of Bergen (UiB), Harvard University [Cambridge], VU University Amsterdam, University of Edinburgh, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], National Institutes of Health [Bethesda] (NIH), Department of Forensic and Neurodevelopmental Sciences, King‘s College London, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Georgia State University, University System of Georgia (USG), Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Leiden University Medical Center (LUMC), Dundee Technopole, CXR Biosciences Ltd, University of Groningen [Groningen], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Department of Genetics, Southwest Foundation for Biomedical Research, Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, The University of Texas Health Science Center at Houston (UTHealth), Center for Neurobehavioral Genetics, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Computer Science, Durham University, Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of California, Institute of Neurology [London], University College of London [London] (UCL), University of California [San Francisco] (UCSF), Department of Medicine, University of Washington [Seattle], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Émile Durkheim (CED), Sciences Po Bordeaux - Institut d'études politiques de Bordeaux (IEP Bordeaux)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Salermo, Università degli Studi di Salerno (UNISA), School of Psychology, University of Queensland, University of Queensland [Brisbane], Hartford Hospital, Lancaster University, Centre for Advanced Imaging, McConnell Brain Imaging Centre (MNI), McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Faculteit Medische Wetenschappen/UMCG, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Biological Psychology, Neuroscience Campus Amsterdam - Brain Imaging, EMGO+ - Mental Health, EPIGEN Consortium, IMAGENConsortium, Saguenay Youth Study Group, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium, Psychiatry, NCA - Brain Imaging, EMGO - Mental health, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Virology, Epidemiology, Clinical Chemistry, Erasmus MC other, Radiology & Nuclear Medicine, University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Harvard University, Vrije Universiteit Amsterdam [Amsterdam] (VU), University of California [Irvine] (UC Irvine), Universiteit Leiden, University of California (UC), University of California [San Francisco] (UC San Francisco), Università degli Studi di Salerno = University of Salerno (UNISA), University of Iceland [Reykjavik], McGill University, University of Bergen (UIB), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Bijvoet Center of Biomolecular Research, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, UMR5116, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and McGill University-McGill University

Subjects
Netherlands Twin Register (NTR), Pathology, 110 012 Social cognition of verbal communication, [SDV]Life Sciences [q-bio], Hippocampus, Genome-wide association study, DCN PAC - Perception action and control, Hippocampal formation, physiopathology [Brain], Bioinformatics, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, TEMPORAL-LOBE EPILEPSY, 110 014 Public activities, Renal disorder [IGMD 9], 0303 health sciences, medicine.diagnostic_test, Translational research Immune Regulation [ONCOL 3], Brain, Human brain, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], ALZHEIMERS-DISEASE, medicine.anatomical_structure, Brain size, genetics [Chromosomes, Human, Pair 12], genetics [Polymorphism, Single Nucleotide], Biomarker (medicine), NA+/H+ EXCHANGER, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Genetic Markers, medicine.medical_specialty, 110 000 Neurocognition of Language, DCN MP - Plasticity and memory, A neurocomputational model for the Processing of Linguistic Utterances based on the Unification-Space architecture [110 007 PLUS], BRAIN VOLUME, UNIFIED APPROACH, 110 013 Binding and the MUC-model, Neuroimaging, Biology, GENOTYPE IMPUTATION, Polymorphism, Single Nucleotide, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], 03 medical and health sciences, AUTOMATED SEGMENTATION, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, ddc:570, FUNCTIONAL IMPLICATIONS, Genetics, medicine, Humans, GENOME-WIDE ASSOCIATION, 030304 developmental biology, Chromosomes, Human, Pair 12, Magnetic resonance imaging, Genetic Loci, physiopathology [Hippocampus], 110 009 The human brain and Chinese prosody, Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6], HUMAN HEIGHT, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Contains fulltext : 108202.pdf (Publisher’s version ) (Closed access) Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)). 01 mei 2012

Published
2012

39. Longitudinal association between cognitive performance and obsessive-compulsive symptoms in patients with psychosis and unaffected siblings

Author

Schirmbeck, F., Swets, M., Meijer, C. J., Zink, M., de Haan, L., Kahn, Rene S., Cahn, Wiepke, de Haan, Lieuwe, Meijer, Carin J., van Os, Jim, Myin-Germeys, Inez, Bruggeman, Richard, Bartels-Velthuis, Agna A., Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Graduate School, Other departments, Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and Psychiatrie & Neuropsychologie

Subjects
cognition, DISORDER, Adult, Male, Psychosis, medicine.medical_specialty, Obsessive-Compulsive Disorder, SAMPLE, Adolescent, obsessive-compulsive, Comorbidity, NEUROPSYCHOLOGY, 03 medical and health sciences, Executive Function, Young Adult, 0302 clinical medicine, medicine, Humans, Cognitive skill, Effects of sleep deprivation on cognitive performance, psychosis, Longitudinal Studies, Risk factor, Psychiatry, SCALE, METAANALYSIS, RISK, INSTRUMENT, Recall, Siblings, Neuropsychology, Cognition, Middle Aged, medicine.disease, 030227 psychiatry, PREVALENCE, schizophrenia, MODEL, Psychiatry and Mental health, Cross-Sectional Studies, Psychotic Disorders, Schizophrenia, Mental Recall, Female, Psychology, Cognition Disorders, 030217 neurology & neurosurgery, Psychomotor Performance
Abstract

ObjectiveObsessive-compulsive symptoms (OCS) frequently occur in psychotic disorders. Cross-sectional associations between OCS and cognitive impairment have led to different causal explanations. Whereas one assumes that higher cognitive impairment reflects a risk factor for psychotic patients to develop OCS, another suggests that deficits reflect a consequence of OCS. This study investigated the longitudinal interrelation between OCS and cognitive functioning.MethodBaseline and follow-up data from 622 patients and 670 un-affected siblings from the Genetic Risk and Outcome in Psychosis' study were analyzed. Participants were allocated to groups according to the presence or absence of OCS at assessments and compared on several cognitive domains.ResultsCross-sectional comparisons revealed no group differences in cognitive performance. Longitudinal analyses comparing the groups with changes in OCS revealed one significant group effect with more problems in set-shifting abilities in patient who reported OCS development at follow-up. Significant time and interaction effects were mainly due to improvement in immediate verbal recall and digit-symbol coding in patients and siblings who reported remission of OCS.ConclusionAlthough insight into causality needs further exploration, our results do not confirm the hypothesis of pre-existing cognitive risk constellations. Findings suggest that remission of comorbid OCS results in improved immediate verbal recall and processing speed.

Published
2015

42. G72 and its association with major depression and neuroticism in large population-based groups from Germany

Author

Rietschel, M., Beckmann, L., Strohmaier, J., Georgi, A., Karpushova, A., Schirmbeck, F., Boesshenz, K. V., Schmäl, C., Bürger, C., Jamra, R. A., Schumacher, J., Höfels, S., Kumsta, Robert, Entringer, S., Krug, A., Markov, V., Maier, W., Propping, P., Wüst, S., Kircher, T., Nöthen, M. M., Cichon, S., Schulze, Tabea Sophie, Rietschel, M., Beckmann, L., Strohmaier, J., Georgi, A., Karpushova, A., Schirmbeck, F., Boesshenz, K. V., Schmäl, C., Bürger, C., Jamra, R. A., Schumacher, J., Höfels, S., Kumsta, Robert, Entringer, S., Krug, A., Markov, V., Maier, W., Propping, P., Wüst, S., Kircher, T., Nöthen, M. M., Cichon, S., and Schulze, Tabea Sophie

Published
2008

48. Pre-training inter-rater reliability of clinical instruments in an international psychosis research project

Author

Steven Berendsen, Pim Kapitein, Frederike Schirmbeck, Mirjam J. van Tricht, Philip McGuire, Craig Morgan, Charlotte Gayer-Anderson, Matthew J. Kempton, Lucia Valmaggia, Diego Quattrone, Marta di Forti, Mark van der Gaag, James B. Kirkbride, Hannah E. Jongsma, Peter B. Jones, Maria Parellada, Celso Arango, Manuel Arrojo, Miguel Bernardo, Julio Sanjuán, José Luis Santos, Andrei Szöke, Andrea Tortelli, Pierre-Michel Llorca, Ilaria Tarricone, Giada Tripoli, Laura Ferraro, Caterina La Cascia, Antonio Lasalvia, Sarah Tosato, Paulo Rossi Menezes, Cristina Marta Del-Ben, Barnaby Nelson, Anita Riecher-Rössler, Rodrigo Bressan, Neus Barrantes-Vidal, Marie-Odile Krebs, Merete Nordentoft, Stephan Ruhrmann, Gabriele Sachs, Bart P.F. Rutten, Jim van Os, Eva Velthorst, Lieuwe de Haan, Maria Calem, Stefania Tognin, Gemma Modinos, Sara Pisani, Tamar C. Kraan, Daniella S. van Dam, Nadine Burger, Patrick McGorry, G. Paul Amminger, Athena Politis, Joanne Goodall, Stefan Borgwardt, Erich Studerus, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Domínguez-Martínez, Manel Monsonet, Lidia Hinojosa, Paula Cristóbal-Narváez, Anna Racioppi, Thomas R. Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Birte Glenthøj, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A. Delespaul, Graduate School, Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Berendsen S., Kapitein P., Schirmbeck F., van Tricht M.J., McGuire P., Morgan C., Gayer-Anderson C., Kempton M.J., Valmaggia L., Quattrone D., di Forti M., van der Gaag M., Kirkbride J.B., Jongsma H.E., Jones P.B., Parellada M., Arango C., Arrojo M., Bernardo M., Sanjuan J., Santos J.L., Szoke A., Tortelli A., Llorca P.-M., Tarricone I., Tripoli G., Ferraro L., La Cascia C., Lasalvia A., Tosato S., Menezes P.R., Del-Ben C.M., Nelson B., Riecher-Rossler A., Bressan R., Barrantes-Vidal N., Krebs M.-O., Nordentoft M., Ruhrmann S., Sachs G., Rutten B.P.F., van Os J., Velthorst E., de Haan L., Calem M., Tognin S., Modinos G., Pisani S., Kraan T.C., van Dam D.S., Burger N., McGorry P., Amminger G.P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Hinojosa L., Cristobal-Narvaez P., Racioppi A., Kwapil T.R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Randers L., Krakauer K., Glenthoj L.B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Delespaul P.A., RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R2 - Mental Health, and MUMC+: Hersen en Zenuw Centrum (3)

Subjects
Research design, Psychosis, INFORMATION, IMPACT, Applied psychology, MEDLINE, Assessor selection, Pre-training inter-rater reliability, Psychosis instruments, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Observer Variation, REPRODUTIBILIDADE DE RESULTADOS, business.industry, Pre-training inter-rater reliability, Reproducibility of Results, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Inter-rater reliability, Assessor selection, TRIALS, Psychotic Disorders, Research Design, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MEASUREMENT ERROR, business, Observer variation, 030217 neurology & neurosurgery, Psychosis instruments
Abstract

International audience

Published
2019

49. Engagement and Acceptability of Acceptance and Commitment Therapy in Daily Life in Early Psychosis: Secondary Findings From a Multicenter Randomized Controlled Trial.

Author

van Aubel E, Vaessen T, Uyttebroek L, Steinhart H, Beijer-Klippel A, Batink T, van Winkel R, de Haan L, van der Gaag M, van Amelsvoort T, Marcelis M, Schirmbeck F, Reininghaus U, and Myin-Germeys I

Subjects
Humans, Female, Male, Adult, Middle Aged, Adolescent, Young Adult, Aged, Ecological Momentary Assessment, Acceptance and Commitment Therapy, Psychotic Disorders therapy, Psychotic Disorders psychology, Patient Acceptance of Health Care psychology
Abstract

Background: Acceptance and commitment therapy (ACT) is promising in the treatment of early psychosis. Augmenting face-to-face ACT with mobile health ecological momentary interventions may increase its treatment effects and empower clients to take treatment into their own hands., Objective: This study aimed to investigate and predict treatment engagement with and acceptability of acceptance and commitment therapy in daily life (ACT-DL), a novel ecological momentary intervention for people with an ultrahigh risk state and a first episode of psychosis., Methods: In the multicenter randomized controlled trial, 148 individuals with ultrahigh risk or first-episode psychosis aged 15-65 years were randomized to treatment as usual only (control) or to ACT-DL combined with treatment as usual (experimental), consisting of 8 face-to-face sessions augmented with an ACT-based smartphone app, delivering ACT skills and techniques in daily life. For individuals in the intervention arm, we collected data on treatment engagement with and acceptability of ACT-DL during and after the intervention. Predictors of treatment engagement and acceptability included baseline demographic, clinical, and functional outcomes., Results: Participants who received ACT-DL in addition to treatment as usual (n=71) completed a mean of 6 (SD 3) sessions, with 59% (n=42) of participants completing all sessions. App engagement data (n=58) shows that, on a weekly basis, participants used the app 13 times and were compliant with 6 of 24 (25%) notifications. Distribution plots of debriefing scores (n=46) show that 85%-96% of participants reported usefulness on all acceptability items to at least some extent (scores ≥2; 1=no usefulness) and that 91% (n=42) of participants reported perceived burden by number and length of notifications (scores ≥2; 1=no burden). Multiple linear regression models were fitted to predict treatment engagement and acceptability. Ethnic minority backgrounds predicted lower notification response compliance (B=-4.37; P=.01), yet higher app usefulness (B=1.25; P=.049). Negative (B=-0.26; P=.01) and affective (B=0.14; P=.04) symptom severity predicted lower and higher ACT training usefulness, respectively. Being female (B=-1.03; P=.005) predicted lower usefulness of the ACT metaphor images on the app., Conclusions: Our results corroborate good treatment engagement with and acceptability of ACT-DL in early psychosis. We provide recommendations for future intervention optimization., Trial Registration: OMON NL46439.068.13; https://onderzoekmetmensen.nl/en/trial/24803., (©Evelyne van Aubel, Thomas Vaessen, Lotte Uyttebroek, Henrietta Steinhart, Annelie Beijer-Klippel, Tim Batink, Ruud van Winkel, Lieuwe de Haan, Mark van der Gaag, Thérèse van Amelsvoort, Machteld Marcelis, Frederike Schirmbeck, Ulrich Reininghaus, Inez Myin-Germeys. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.11.2024.)

Published
2024
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50. Perspective matters in recovery: the views of persons with severe mental illness, family and mental health professionals on collaboration during recovery, a qualitative study.

Author

Burger TJ, van Eck RM, Lachmeijer M, de Wilde-Schutten KRG, Lansen M, van Alphen C, van Haasteren N, Groen K, Schirmbeck F, Vellinga A, Kikkert MJ, Dekker J, de Haan L, and de Koning MB

Subjects
Humans, Female, Male, Adult, Middle Aged, Psychotic Disorders psychology, Cooperative Behavior, Health Personnel psychology, Focus Groups, Attitude of Health Personnel, Mental Health Services, Qualitative Research, Mental Disorders psychology, Family psychology
Abstract

Background: Recovery from severe mental illness, including psychosis has been described as a personal and unique process, but it rarely is a journey undertaken without profound influences of significant others (family, mental health professionals). Diverging perspectives between persons with severe mental illness, family and professionals are frequent during the recovery process, notably in psychotic disorders. We aimed to explore processes of collaboration during recovery, to inform recovery supporting practices., Methods: Current qualitative study had a participatory design and was set within long-term mental healthcare for severe mental illness. We conducted semi-structured interviews and focus groups with persons with severe mental illness (most had a history of psychosis), family and professionals on their mutual contact during recovery. Using reflexive thematic analysis, we developed themes representing processes of collaboration during recovery., Results: We described roles persons with severe mental illness, family and professionals attribute to each other in mutually influential terms of unconditional and meaningful contact (which takes time to establish) and problem-oriented aspects. Secondly, experienced differences over problem definition, "needing help" and consequently over the role parties attribute to one another, may result in negative interactions, in the area of having expectations; (not) informing; (not) having agency to change; experiencing (dis)agreement or struggle., Conclusions: unconditional, meaningful contact and knowing each other's perspective are important to fruitful interaction in a triad when perspectives on mental health problems diverge. Relationally centered and process oriented care with continuity of family and professionals involved are needed to advance recovery in severe mental illness, especially psychosis., Competing Interests: Declarations Ethics approval and consent to participate The study protocol has been reviewed by the institutional review board of the Vrije Universiteit Medical Centre (reference 2018/196). The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All respondents gave written informed consent to participate. When patients had a court-appointed legal representative, which especially occurred in respondents living in long-term inpatient services, we additionally obtained their informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Published
2024
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