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Somatic multicomorbidity and disability in patients with psychiatric disorders in comparison to the general population: a quasi-epidemiological investigation in 54,826 subjects from 40 countries (COMET-G study)
- Konstantinos N. Fountoulakis, Grigorios N. Karakatsoulis, Seri Abraham, Kristina Adorjan, Helal Uddin Ahmed, Renato D. Alarcón, Kiyomi Arai, Sani Salihu Auwal, Michael Berk, Sarah Bjedov, Julio Bobes, Teresa Bobes-Bascaran, Julie Bourgin-Duchesnay, Cristina Ana Bredicean, Laurynas Bukelskis, Akaki Burkadze, Indira Indiana Cabrera Abud, Ruby Castilla-Puentes, Marcelo Cetkovich, Hector Colon-Rivera, Ricardo Corral, Carla Cortez-Vergara, Piirika Crepin, Domenico De Berardis, Sergio Zamora Delgado, David De Lucena, Avinash De Sousa, Ramona Di Stefano, Seetal Dodd, Livia Priyanka Elek, Anna Elissa, Berta Erdelyi-Hamza, Gamze Erzin, Martin J. Etchevers, Peter Falkai, Adriana Farcas, Ilya Fedotov, Viktoriia Filatova, Nikolaos K. Fountoulakis, Iryna Frankova, Francesco Franza, Pedro Frias, Tatiana Galako, Cristian J. Garay, Leticia Garcia-Álvarez, Maria Paz García-Portilla, Xenia Gonda, Tomasz M. Gondek, Daniela Morera González, Hilary Gould, Paolo Grandinetti, Arturo Grau, Violeta Groudeva, Michal Hagin, Takayuki Harada, Tasdik M. Hasan, Nurul Azreen Hashim, Jan Hilbig, Sahadat Hossain, Rossitza Iakimova, Mona Ibrahim, Felicia Iftene, Yulia Ignatenko, Matias Irarrazaval, Zaliha Ismail, Jamila Ismayilova, Asaf Jakobs, Miro Jakovljević, Nenad Jakšić, Afzal Javed, Helin Yilmaz Kafali, Sagar Karia, Olga Kazakova, Doaa Khalifa, Olena Khaustova, Steve Koh, Svetlana Kopishinskaia, Korneliia Kosenko, Sotirios A. Koupidis, Illes Kovacs, Barbara Kulig, Alisha Lalljee, Justine Liewig, Abdul Majid, Evgeniia Malashonkova, Khamelia Malik, Najma Iqbal Malik, Gulay Mammadzada, Bilvesh Mandalia, Donatella Marazziti, Darko Marčinko, Stephanie Martinez, Eimantas Matiekus, Gabriela Mejia, Roha Saeed Memon, Xarah Elenne Meza Martínez, Dalia Mickevičiūtė, Roumen Milev, Muftau Mohammed, Alejandro Molina-López, Petr Morozov, Nuru Suleiman Muhammad, Filip Mustač, Mika S. Naor, Amira Nassieb, Alvydas Navickas, Tarek Okasha, Milena Pandova, Anca-Livia Panfil, Liliya Panteleeva, Ion Papava, Mikaella E. Patsali, Alexey Pavlichenko, Bojana Pejuskovic, Mariana Pinto Da Costa, Mikhail Popkov, Dina Popovic, Nor Jannah Nasution Raduan, Francisca Vargas Ramírez, Elmars Rancans, Salmi Razali, Federico Rebok, Anna Rewekant, Elena Ninoska Reyes Flores, María Teresa Rivera-Encinas, Pilar Saiz, Manuel Sánchez de Carmona, David Saucedo Martínez, Jo Anne Saw, Görkem Saygili, Patricia Schneidereit, Bhumika Shah, Tomohiro Shirasaka, Ketevan Silagadze, Satti Sitanggang, Oleg Skugarevsky, Anna Spikina, Sridevi Sira Mahalingappa, Maria Stoyanova, Anna Szczegielniak, Simona Claudia Tamasan, Giuseppe Tavormina, Maurilio Giuseppe Maria Tavormina, Pavlos N. Theodorakis, Mauricio Tohen, Eva Maria Tsapakis, Dina Tukhvatullina, Irfan Ullah, Ratnaraj Vaidya, Johann M. Vega-Dienstmaier, Jelena Vrublevska, Olivera Vukovic, Olga Vysotska, Natalia Widiasih, Anna Yashikhina, Panagiotis E. Prezerakos, Daria Smirnova
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- Journal:
- CNS Spectrums / Volume 29 / Issue 2 / April 2024
- Published online by Cambridge University Press:
- 25 January 2024, pp. 126-149
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Background
The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.
MethodsThe sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.
ResultsAbout 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15–20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.
ConclusionsThe finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.
Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: a network analysis from the OPTiMiSE trial
- F. Dal Santo, E. Fonseca-Pedrero, M. P. García-Portilla, L. González-Blanco, P. A. Sáiz, S. Galderisi, G. M. Giordano, J. Bobes
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S262-S263
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Introduction
Network analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains.
ObjectivesThe current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.
MethodsBaseline data from the OPTiMiSE trial were analysed. The sample included 446 participants (age 40.0±10.9 years, 70% males). The network was estimated with a Gaussian graphical model (GGM), using scores on individual items of the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.
ResultsNodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network (Fig. 1). The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganisation, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.
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ConclusionsThe current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.
Disclosure of InterestNone Declared
Association between adverse childhood experiences and the number of suicide attempts in lifetime
- J. Andreo-Jover, E. Fernandez-Jimenez, J. Curto-Ramos, N. Angarita-Osorio, N. Roberto, A. De la Torre-Luque, A. Cebria, M. Diaz-Marsa, M. Ruiz-Veguillla, J. B. Bobes Garcia, M. Fe Bravo Ortiz, V. Perez Solá
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S561-S562
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Introduction
Adverse childhood experiences (ACEs), defined as abuse, neglect, or a dysfunctional household in childhood, have been associated with suicidality (Fjeldsted et al., 2020). Every type of ACE has a direct impact on suicide ideation, self-harm and/or suicide attempt (Angelakis et al., 2019).
ObjectivesWe aim to quantify the association between types of ACEs (including emotional, physical, sexual abuse, and emotional and physical neglect) and the number of suicide attempts in lifetime.
MethodsWe included 748 patients who attempted suicide at least once. They were asked to complete the Columbia-Suicide Severity Rating Scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Logistic regression models were run to assess the association between each ACE type and the number of suicide attempts.
ResultsPoisson univariate regression analyses show a linear trend in the relationship between having a higher number of suicide attempts and having suffered every ACE type in childhood (p<0.05). Our results show a lower percentage of previous suicide attempts among participants without ACEs, and an increasing tendency among patients with various types of ACEs. The rate of ACEs types is significantly higher in the group with previous suicide attempts than in the first-attempt group (p=0.000).
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ConclusionsThis study contributes to clarify the role of childhood trauma in the number of suicide attempts in lifetime. This has important implications for reducing suicide rates, and preventing future re-attempts. Further studies analysing every construct of childhood trauma may contribute to the detection of suicidal behaviour.
FundingsThis work was supported by the Instituto de Salud Carlos III (grant number: PI19/00941 SURVIVE) and co-funded by the European Union (grant numbers: COV20/00988, PI17/00768), the European Union’s Horizon 2020 research and innovation programme Societal Challenges (grant number: 101016127), and the Fundación Española de Psiquiatría y Salud Mental
AcknowledgementsSURVIVE project (PI19/00941)
KeywordsSuicide attempt, Adverse Childhood Experiences
ReferencesAngelakis, I., Gillespie, E. L., & Panagioti, M. (2019). Childhood maltreatment and adult suicidality: A comprehensive systematic review with meta-analysis. Psychological Medicine, 49(7), 1057-1078. https://doi.org/10.1017/S0033291718003823
Fjeldsted, R., Teasdale, T. W., & Bach, B. (2020). Childhood trauma, stressful life events, and suicidality in Danish psychiatric outpatients. Nordic Journal of Psychiatry, 74(4), 280-286. https://doi.org/10.1080/08039488.2019.1702096
Disclosure of InterestNone Declared
Gut permeability and low-grade inflammation in bipolar disorder
- M. Couce, G. Paniagua, L. González-Blanco, A. García-Fernández, C. Martínez-Cao, P. Sáiz, J. Bobes, M. P. García-Portilla
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S385-S386
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Introduction
Systemic inflammation has been increasingly related to bipolar disorder -BD- (Tanaka et al. Neurosci Res 2017;115 59-63). Intestinal bacterial translocation has been postulated as one of the causes of this inflammation (Nguyen et al. J Psychiatr Res 2018;99 50-61). A possible pathway is through the lipopolysaccharide, which is presented to CD14 through lipopolysaccharide binding protein (LBP) leading to a release of systemic inflammatory markers like C-reactive protein (CPR) (Funda et al. Infect Immun 2001;69 3772-81).
Objectives1) Describe gut permeability in patients with BD through the determination of intestinal inflammatory markers (LBP, sCD14) in plasma; 2) Analyze variables associated with intestinal inflammation.
MethodsCross-sectional study of 38 patients with BD [mean age=45.50 (SD=10.93; range 23-68); males=15 (39.5%)], recruited from mental health outpatient clinics in Oviedo (Spain).
Assessment: Pro-inflammation biomarkers [CRP (mg/dL), Erythrocyte Sedimentation Rate (ESR) (mm/h), Neutrophil/Lymphocyte, Monocyte/Lymphocyte, Platelet/Lymphocyte and Systemic Immune Inflammation Indexes]. Indirect markers of intestinal bacterial translocation [LBP, soluble CD14 (sCD14)]. Dichotomous variables were created for LBP, considering LBP ≥15 μg/dL as increased gut permeability; and for CPR, considering CRP≥0.3 as systemic inflammation. Metabolic syndrome [ATPIII criteria: glucose, HDL, triglycerides (mg/dl), arterial pressure (mmHg), abdominal circumference (cm)], body mass index (BMI) (kg/m2), smoking, cannabis or alcohol use.
Statistical analyses: t-Student test, multiple linear regression analyses.
ResultsAverage LBP was 14.60 μg/dL (SD=6.4) and 15 patients (39.5%) had increased gut permeability. Moreover, average CPR was 0.40 mg/dL (SD=0.58) and 16 patients (47.1%) showed systemic inflammation. There were no patients with increased levels of sCD14.
Associations were found between LBP and CPR (r=0.357; p=0.032), cannabis use in the last month (t=-2.293; p=0.029), BMI (r=0.433; p=0.008) and abdominal obesity (t=3.006; p=0.005); but no with age or sex.
Subsequently, a multiple linear regression model for LBP was calculated with variables previously mentioned, and age (based on expert criteria). The overall regression was statistically significant (R2=0.49, F=9.273, p<0.001). It was found that CPR, abdominal obesity, and cannabis use in the last month significantly predicted LBP levels (table 1).
Table 1. Multiple linear regression analyses to LBP B SE β t p CPR 4.842 1.529 0.439 3.167 0.004 Abdominal obesity 4.810 1.849 0.362 2.601 0.014 Cannabis use -5.048 2.273 -0.296 -2.221 0.034 ConclusionsMore than one third of patients with BD had increased gut permeability. Almost 50% had systemic inflammation. Intestinal permeability was directly related to abdominal obesity and systemic inflammation, but inversely related to cannabis use.
Disclosure of InterestNone Declared
The response to unfolded proteins in schizophrenia and bipolar disorder
- C. Cachán, I. M. Valle, Y. Potes, A. González Rubio, N. Menéndez Coto, D. López Fanjul, I. Vega Naredo, B. Caballero, P. Saiz, J. Bobes, P. García Portilla, A. Coto Montes
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S636-S637
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Introduction
Schizophrenia (SCH) and bipolar disorder (BD) are severe mental disordes, which have high incidence (Whiteford et al. Lancet 2013; 381 1575-86) and are the main causes of diasibility in young people (WHO 2022; https://www.who.int/news-room/fact-sheets/detail/mental-disorders).
Psycological stress appears in different mental disorders, and this is directly related to oxidative stress (Moller et al. Chem Biol Interact. 1996; 102 17-36)(Pupic-Bakrac et al. 2020; Psychiatr Danub. 32 412-9). Oxidative stress causes reticulum edoplasmic stress (ER stress) and this produces high levels of misfolded proteins. Defective proteins are degraded by the proteasome, but but when the density of misfolded proteins exceeds the capacity of the proteosome, the Unfolded and Misfolded Protein Response (UPR) is triggered through three main pathways: Inositol-requiring enzyme 1α (IRE1α); transcription factor 6 alpha (ATF6α) and protein kinase RNA-Like ER kinase (PERK), trying to recover normal protein synthesis capacity (Bermejo-Millo et al. 2018; Mol Neurobiol. 55 7973-86) (González-Blanco et al. 2022; J Cachexia Sarcopenia Muscle 13 919-31).
ObjectivesCharacterizing ER stress and UPR in SCH and BD.
MethodsWe studied ER stress and UPR in peripheral blood mononuclear cells (PBMC) from 50 patients with SCH and an equal number of patients with BD compared to their corresponding controls in order to achieve our objectives.
Western Blot assay were performed following classical procedure () and the results was normalized to Ponceau as loanding control (Nie et al. 2017; BiochemByophys Resp 12 10-13) (Sander et al. 2019; Anal Biochem 575 44-53). Proteasome activity was assessed using Proteasome Activity Assay Kit (ab107921, Abcam, Cambridge, UK).
ResultsER stress was evaluated with BiP/GRP78. Our results showed significantly increased expression in SCH (p<0,01) and BD (p<0,05), being more increased in SCH. Proteasome activity was increased in SCH and BD, being only statistically significant in SQZ (p<0,05). UPR study showed IRE1a cascade significantly activated in SCH (p<0,001) and only slight increased in BD showed without statistical differences. ATF6a pathway is measured by cleavage to active protein (50-kDa). Results showed higher expression in SCH than in BD and controls (p<0,001). In addition, PERK pathway showed higher statistical levels of p-eIF2a/eiF2a ratio in SCH than in BD and control respectively (p<0,05 and p<0,01).
ConclusionsOur results showed a greater alteration in SCH than in BD at the level of protein synthesis, which implies a greater toxicity at the cellular level and, therefore, a clear risk for the survival of cells in this pathology.
Disclosure of InterestNone Declared
SOD and CAT as potential preliminary biomarkers for the differential diagnosis of schizophrenia and bipolar disorder in the first episode of psychosis
- C. Cachán-Vega, E. Antuña, C. García-González, J. C. Bermejo-Millo, F. Baena-Huerta, L. González-Blanco, B. Caballero, I. Vega-Naredo, J. Bobes, M. P. García-Portilla, A. Coto-Montes, Y. Potes
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S449-S450
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Introduction
Schizophrenia (SCH) and bipolar disorder (BD) are severe mental disorders which lead to psychotic, affective and cognitive symptoms and often cause a progressive functional deterioration of the individual. The current diagnosis of SCH and BD essentially depends on clinical observation that often leads to misdiagnosis and the introduction of non-specific treatments. Therefore, an early detection and intervention are determinant for a better prognosis. Improving outcomes of a First Episode of Psychosis (FEP) depends mainly on the identification of reliable and discriminatory biomarkers between both disorders.
ObjectivesGiven that oxidative stress has been tightly involved in multiple metal disorders, the major goal of this work was to characterize oxidative alterations in order to identify potential biomarkers which allow the differential diagnosis in an early stage.
MethodsThe study was carried out on samples from 49 subjects (14 women and 35 men), divided into four groups: a control group of 10 individuals not previously diagnosed with any serious mental disorder, 17 patients who had presented a FEP, 12 patients diagnosed with SCH and 10 patients diagnosed with BP. Biochemical analysis were conducted in erythrocyte fraction to characterize the cellular oxidative damage by measuring lipid peroxidation (LPO) levels and the antioxidant defense system by the evaluation of catalase (CAT) and superoxide dismutase (SOD) activities.
ResultsIn the present work, we observed a significant increase in LPO levels in both SCH and BD disorders that was not neutralized by the antioxidant defense. It was found that SCH patients, despite exhibiting greater activities of SOD and CAT compared to BD individuals, also showed significantly higher levels of oxidative damage. The differential oxidative profile observed between SCH and BD individuals allowed to perform an individually analysis of patients diagnosed with FEP. Although it was not possible to identify the type of psychotic disorder of all the patients with FEP, the results obtained showed that while several individuals exhibited an oxidative prolife similar to that observed in SCH patients, other individuals presented a prolife very similar to that found in patients with BD.
ConclusionsThe current work reveals that LPO is a potential indicator of worse prognosis after being differentially modified in both SCH and BD. Moreover, SOD and CAT have been identified, by presenting an opposite profile between patients with SCH and BD, as potential preliminary biomarkers for a discriminatory diagnosis in an early stage of the disorder.
Disclosure of InterestNone Declared
An empirical staging model for schizophrenia using machine learning
- M.-C. Clara, F. Sánchez-Lasheras, A. García-Fernández, L. González-Blanco, P. A. Sáiz, J. Bobes, M. P. García-Portilla
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S626-S627
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Introduction
One of the great challenges still to be achieved in schizophrenia is the development of a staging model that reflects the progression of the disorder. The previous models suggested have been developed from a theoretical point of view and do not include objective variables such as biomarkers, physical comorbidities, or self-reported subjective variables (Martinez-Cao et al. Transl Psychiatry 2022; 12(1) 1-11).
ObjectivesDevelop a multidimensional staging model for schizophrenia based on empirical data.
MethodsNaturalistic, cross-sectional study. Sample: 212 stable patients with Schizophrenia (F20). Assessments: ad hoc questionnaire (demographic and clinical information); psychopathology: PANSS, CDS, OSQ, CGI-S; functioning: PSP; cognition: MATRICS; laboratory tests: C-Reactive Protein (CRP), IL-1RA, IL-6, Platelets/Lymphocytes (PLR), Neutrophils/Lymphocytes (NLR), and Monocytes/Lymphocytes (MLR) ratios. Statistical analysis: Variables selection was performed with an ad hoc algorithm developed for this research. The referred algorithm makes use of genetic algorithms (GA) to select those variables that show the best performance for the patients classification according to their global CGI-S. The objective function of the GA maximizes the individuals correct classification of a support vector machines (SVM) model that employs as input variables those given by the GA (Díez-Díaz et al. Mathematics 2021; 9(6) 654). Models performance was assessed with the help of 3-fold cross-validation and these process was repeated 10,000 times for each one of the models assessed.
ResultsMean age(SD): 39.5(13.54); men: 63.5%; secondary education: 59.50%. Most patients in our sample had never been married (74.10%), and more than a third received disability benefits due to schizophrenia (37.70%). The mean length of the disease was 11.98(12.02) years. The best SVM model included the following variables: 1)Clinical: number of hospitalizations, positive, negative, depressive symptoms and general psychopathology; 2)Cognition: speed of processing, visual learning and social cognition; 3)Functioning: PSP total score; 4)Biomarkers: PLR, NLR and MLR. This model was executed again 100,000 times applying again 3-fold cross-validation. In 95% of the algorithm executions more than a 53.52% of the patients were classfied in the right CGI-S category. On average the right classification was of 61.93%. About specificity and sensitivity the average values obtained were of 0.85 and 0.64 respectively.
ConclusionsOur staging model is a robust method that appropriately distributes patients according to the severity of the disorder. Highlights the importance of clinical, functional and cognitive factors to classify patients. Finally, the inflammatory parameters PLR, NLR and MLR have also emerged as potential biomarkers for staging schizophrenia.
Disclosure of InterestNone Declared
Tobacco use in first-episode psychosis, a multinational EU-GEI study
- T. Sánchez-Gutiérrez, E. Rodríguez-Toscano, L. Roldán, L. Ferraro, M. Parellada, A. Calvo, G. López, M. Rapado-Castro, D. La Barbera, C. La Cascia, G. Tripoli, M. Di Forti, R. M. Murray, D. Quattrone, C. Morgan, J. van Os, P. García-Portilla, S. Al-Halabí, J. Bobes, L. de Haan, M. Bernardo, J. L. Santos, J. Sanjuán, M. Arrojo, A. Ferchiou, A. Szoke, B. P. Rutten, S. Stilo, G. D'Andrea, I. Tarricone, EU-GEI WP2 Group, C. M. Díaz-Caneja, C. Arango
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- Psychological Medicine / Volume 53 / Issue 15 / November 2023
- Published online by Cambridge University Press:
- 26 April 2023, pp. 7265-7276
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Background
Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis.
MethodsThe sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use.
ResultsAfter controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1–3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2–2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (β = −2.3; p ⩽ 0.001; 95% CI [−3.7 to −0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0–1.8]); however, these results were no longer significant after controlling for cannabis use.
ConclusionsTobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.
Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depressed patients with suicidal behavior: A systematic review
- A Velasco, A Lengvenyte, J Rodriguez-Revuelta, L Jimenez-Treviño, P Courtet, MP Garcia-Portilla, J Bobes, PA Sáiz
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- European Psychiatry / Accepted manuscript
- Published online by Cambridge University Press:
- 16 April 2023, pp. 1-25
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Trends in the incidence of hospital-treated suicide attempts during the COVID-19 pandemic in Oviedo, Spain
- J. Fernandez-Fernandez, L. Jiménez-Treviño, E. Seijo-Zazo, F. Sánchez Lasheras, M. P. García-Portilla, P. A. Sáiz, J. Bobes
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- Journal:
- European Psychiatry / Volume 66 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 03 February 2023, e23
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Background
The potential impact of the COVID-19 pandemic on suicidal behavior has generated predictions anticipating an increase in suicidal tendencies. The aim of this research is to study its influence on the incidence of hospital-treated suicide attempts throughout the year 2020 in Oviedo, Spain.
MethodsData were collected on all patients admitted to the emergency department of Central University Hospital of Asturias in Oviedo for attempted suicide during 2020. Incidence rates were calculated for three lockdown periods. Suicide attempt trends in 2020 were compared with a non-COVID-19 year (2009) to avoid seasonal variations bias. Chi-square and Fisher’s exact tests were performed. The influence of COVID-19 incidence in Oviedo was analyzed using Spearman’s correlation coefficient.
ResultsThe cumulative incidence rate of attempted suicide per 100,000 person-years was 136.33 (pre-lockdown), 115.15 (lockdown), and 90.25 (post-lockdown) in adults (over 19 years old), and 43.63 (pre-lockdown), 32.72 (lockdown), and 72.72 (post-lockdown) in adolescents (10–19 years old). No association was found with COVID-19 incidence rates (Spearman’s rho −0.222; p = 0.113). Comparing the years 2020 and 2009, statistically significant differences were observed in adolescents (Fisher’s exact test; p = 0.024), but no differences were observed in adults (chi-square test = 3.0401; p = 0.218).
ConclusionsHospital-treated suicide rates attempted during the COVID-19 outbreak in Oviedo, Spain showed a similar trend compared with a non-COVID-19 year. In contrast, the number of adolescents hospital-treated for attempted suicide increased during lockdown, suggesting more vulnerability to COVID-19 restrictions after the initial lockdown period in this age group.
Endocrine biomarkers related to sleep-wake cycle and sleep disturbances in patients with bipolar disorder: A systematic review
- L. Gonzalez-Blanco, C. Moya Lacasa, S. Jiménez-Fernández, M. Valtueña, C. Martinez-Cao, A. García Fernández, P.A. Saiz, M.P. Garcia-Portilla, J. Bobes, L. Gutierrez Rojas
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- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, p. S360
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Introduction
Sleep and circadian disturbances have been widely studied in patients with bipolar disorder (BD) (Duarte Faria et al., 2015; Gonzalez, 2014). However, there is no clear evidence about the role of peripheral biomarkers of circadian cycle in this population.
ObjectivesThis systematic review aims to identify potential endocrine biomarkers of circadian rhythm in blood and study their relationship with sleep problems in BD.
MethodsAn electronic search of Pubmed and PsycoInfo databases were performed. It includes articles about the topic from 1991 to 2021. The search strategy was: (“Peripheral biomarkers” OR “biological markers” OR biomarker OR cortisol OR melatonin OR orexin OR hypocretin) AND (blood OR serum OR plasma) AND (“sleep-wake” OR “circadian rhythm” OR sleep OR insomnia) AND “bipolar”.
Results92 records were obtained after excluding duplicates. Only five studies met the inclusion criteria (n = 499; BD = 125; unipolar depression = 148; schizophrenia = 80; controls = 146). The endocrine parameters analyzed were: cortisol (3 studies), melatonin (1 study) and orexin-A (1 study). Overall, no significant associations between these biomarkers and sleep disturbances, assessed with subjective (psychometric evaluation) and/or objective (polysomnography) measures, were detected.
ConclusionsThis systematic review highlights the lack of studies that explores the role of endocrine biomarkers related to circadian function in the pathophysiology of sleep disturbances in BD.
DisclosureNo significant relationships.
Orexins and bipolar disorder: A review
- C. Moya Lacasa, L. Gonzalez-Blanco, C. Martinez-Cao, C.M. Alvarez-Vazquez, E. Martin-Gil, A. García Fernández, P.A. Saiz, J. Bobes, M.P. Garcia-Portilla
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, p. S400
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Introduction
Bipolar disorder (BD) is a chronic deteriorating illness which has a strong impact on functionality. In the past few years, orexins have gained importance as possible biomarkers of circadian rhythms, affected in BD. Up to this date, we have not found any bibliographical review evaluating the association of orexins and BD.
ObjectivesTo review published literature in relation to the associaton of orexins and BD.
MethodsA bibliographical search was conducted in PubMed. Inclusion criteria were a) the study evaluated orexins in plasma or cerebrospinal fluid, and b) patients with BD were included within the subjects of study.
Reference lists of the articles that met inclusion criteria were also examined.
ResultsTen articles were retrieved from the initial search. Only three met inclusion criteria and another one was selected from the reference list examination. One study observed significantly higher levels of orexin A in plasma of BD patients versus depression and controls. Other found higher concentration of orexin A of unipolar and bipolar depression versus controls, but this result was not statistically significant. Another one did not find differences in orexin A concentration between mania, depression and controls. The remaining study detected significantly lower concentration of orexin A in BD versus depression, schizophrenia and controls.
ConclusionsDespite being heterogenous, the results point out there are differences in orexin levels in BD when compared to other diagnostic groups or controls. This sets a starting point to focus research on this subject and continue analyzing the role of orexins as biomarkers in BD.
DisclosureNo significant relationships.
Factors associated with real-world functioning in first stages of schizophrenia disorder
- C. Martínez-Cao, A. García-Fernández, M. Valtueña-García, M.P. García-Portilla, J. Bobes
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S805
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Introduction
Schizophrenia is one of the most disabling diseases affecting the patient’s ability to live independently, to be socially active and to work or study1,2. Therefore, identifying predictors of functioning in the first stages of the disease is important to prevent a negative progression of functional outcome in these patients3.
ObjectivesTo identify the factors associated with real-world functioning in patients with recent onset of the disease.
MethodsSecondary analysis of a cross-sectional, naturalistic study. 84 patients with Schizophrenia (F20), aged 18-71 in their first five years of the disorder under maintenance treatment. Assessments: PANSS, CDS, CGI-S, CAINS; functioning: PSP, cognition: MATRICS. Statistical analysis: student-t test, ANOVA, Pearson correlation and lineal regression.
ResultsMean age (SD): 31.30 (10.08); men: 62.8%. Statistical significant differences (p<0.05) were found in work status, benzodiazepines and antidepressants use. Furthermore, significant correlations (p<0.05) were found with depressive, positive and negative symptoms (avolition, anhedonia, alogia and affective flattening) and cognition. A significant predictive model was obtained that explains the 72.1% of the variance [F(5,74)= 20.952; p< 0.001]. This model included depressive symptoms (B= -0.940; p= 0.001), negative symptoms (B= -1.696; p< 0.001), avolition and anhedonia (B= -0.643; p= 0.001), affective flattening and alogia (B= 1.197; p= 0.003), and visual learning (B= 0.202 p= 0.039).
ConclusionsNegative and depressive symptoms are the main determinants of real-world functioning in patients with recent onset of schizophrenia. Visual learning also contributes to this outcome. On the other hand, the positive relationship between expressive domain and functioning needs furthermore investigation.
DisclosureNo significant relationships.
Insomnia associated with neutrophil/lymphocyte ratio in female patients with schizophrenia
- G. Paniagua, L. González-Blanco, F. Dal Santo, C. Martínez-Cao, C. Moya-Lacasa, M. Valtueña-García, E. Martín Gil, L. García-Alvarez, P.A. Saiz, M.P. García-Portilla, J. Bobes
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S806
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Introduction
Worse sleep quality and increased inflammatory markers in women with schizophrenia (Sch) have been reported (Lee et al. 2019). However, the physiological mechanisms underlying the interplay between sleep and the inflammatory pathways are not yet well understood (Fang et al. 2016).
ObjectivesAnalyze the relationship between Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR) and Platelet/Lymphocyte (PLR) ratios, and insomnia in Sch stratified by sex.
MethodsFinal sample included 176 Sch patients (ICD-10 criteria) [mean age: 38.9±13.39; males: 111(63.1%)]. Assessment: PANSS, Calgary Depression Scale (CDSS), and Oviedo Sleep Questionnaire (OSQ) to identify a comorbid diagnosis of insomnia based on ICD-10. Fasting counting blood cell were performed to calculate ratios. Statistics: U Mann-Whitney, logistic regression.
ResultsInsomnia as comorbid diagnosis was present in 22 Sch (12.5%) with no differences between sex [14 males (12.6%), 8 females (12.3%)], neither in their age. Female patients with insomnia showed increased NLR [2.44±0.69 vs. 1.88±0.80, U=122.00 (p=0.034)]. However, no differences in PLR and MLR were found, neither in any ratio in males. Regression models using insomnia as dependent variable and covariates (age, PANSS-positive, PANSS-negative, CDSS) were estimated. Females: presence of insomnia was associated with NLR [OR=3.564 (p=0.032)], PANSS-positive [OR=1.263 (p=0.013)] and CDSS [OR=1.198 (p=0.092)]. Males: only PANSS-positive [OR=1.123 (p=0.027)] and CDSS scores [OR=1.220 (p=0.005)] were associated with insomnia.
ConclusionsNLR represent an inflammatory marker of insomnia in Sch but only in female patients. Improving sleep quality in these patients could help to decrease their inflammatory response.
DisclosureNo significant relationships.
The mediating role of impulsivity in the relationship between suicidal behaviour and early traumatic experiences in depressed subjects
- F. Dal Santo, J.J. Carballo, Á. Velasco, L. Jiménez-Treviño, J. Rodríguez-Revuelta, C. Martínez-Cao, I. Irene Caro-Cañizares, L. De La Fuente-Tomás, I. Menéndez-Miranda, L. González-Blanco, M.P. García-Portilla, J. Bobes, P.A. Saiz
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S583
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Introduction
Depressed patients with early traumatic experiences may represent a clinically distinct subtype with worse clinical outcome. Since early traumatic experiences alter the development of systems that regulate the stress response, certain personality features may influence coping strategies, putting individuals with depression and a history of early traumatic experiences at greater risk of suicidal behaviour.
ObjectivesTo determine whether impulsivity mediates the relationship between early traumatic experiences and suicidal behaviour in patients with major depressive disorder (MDD).
MethodsThe sample included 190 patients [mean age (SD)=53.71 (10.37); females: 66.3%], with current MDD. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the List of Threatening Experiences (LTE), and the Barratt Impulsiveness Scale-11 (BIS-11) were used to assess childhood and adulthood adverse life events and impulsivity. We developed mediation models by bootstrap sampling methods.
Results81 (42.6%) patients had previous suicide attempts (SA). CTQ-SF-Total and BIS-11-Total scores were higher in MDD patients with previous SA. Correlation analyses revealed significant correlations between the CTQ-SF-Total and BIS-11-Total, CTQ-SF-Total and HDRS-Total, and BIS-11-Total and HDRS-Total scores. Regression models found that CTQ-SF-Total, BIS-11-Total, and HDRS-Total scores were associated with SA. Mediation analyses further revealed the association between CTQ-SF-Total and SA was mediated by the indirect effect of the BIS-11-Total score (b=0.007, 95% CI=0.001, 0.015), after controlling for sex, HDRS-Total, and LTE-Total.
ConclusionsImpulsivity could mediate the influence of childhood trauma on suicidal behaviour. This will help understand the role of risk factors in suicidal behaviour and aid in the development of prevention interventions focused on modifiable mediators when risk factors are non-modifiable.
Association of traumatic events in childhood, impulsivity and decision-making with previous suicide attempt and/or current suicidal ideation in adult patients with major depressive disorder
- A. Roman, J. Rodríguez-Revuelta, F. Dal Santo, L. García-Alvarez, L. De La Fuente-Tomás, C. Martínez-Cao, L. Jiménez-Treviño, L. González-Blanco, M.P. García-Portilla, J. Bobes, P.A. Saiz
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, pp. S177-S178
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Introduction
Suicidal behavior has a great impact on world public health. The literature describes the possible existence of an association between neurobiological, clinical and cognitive factors in suicidal behavior.
ObjectivesTo determine the possible relationship between clinical variables (history of abuse/maltreatment in childhood), psychopathology (impulsivity traits) and cognitive (decision-making) with a history of suicide attempt and/or current suicidal idea in patients with major depressive disorder.
MethodsCross-sectional study in a sample of adult patients with major depressive disorder in which two types of comparisons are made. In the first case, two groups were compared based on the presence or absence of history of suicide attempt. In the second case, two groups were compared based on the presence or absence of suicidal ideation in the same sample of patients. Finally, sociodemographic, clinical and cognitive variables were evaluated in that population sample.
ResultsWhen the joint influence of sociodemographic, clinical and cognitive characteristics are present, it can be said that being single/divorced/separated, a history of sexual abuse in childhood and an alteration in decision-making, specifically a lower number of choices of deck D in the IGT test, are associated with a higher probability of a personal history of suicide attempt. While a higher score on the Barrat impulsivity scale is associated with a greater probability of presenting current suicidal ideation once the influence of sociodemographic, clinical and cognitive variables has been taken into account.
ConclusionsDifferent sociodemographic, clinical and cognitive factors are associated with the presence of a history of suicide attempt and/or current suicidal ideation.
DisclosureNo significant relationships.
COVID-19 psychological impact in patients with depressive disorder: Differences based on their age
- E. Martín Gil, M. Valtueña-García, L. González-Blanco, F. Dal Santo, C. Moya-Lacasa, C. Álvarez Vázquez, C. Martínez-Cao, L. García-Alvarez, M.P. García-Portilla, P.A. Saiz, J. Bobes
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, pp. S674-S675
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Introduction
COVID-19 pandemic and lockdown have provoked a considerable psychological impact in Spain. Some studies have reported greater psychological impact in the younger population. To date, no previous study has focused on depressive disorder (DD) patients based on their age.
ObjectivesTo describe the psychological impact on DD according to age.
MethodsCross-sectional study of an online survey available from 19 to 26 March 2020. Out of a total of 21207 respondents, 608 (2.9%) reported suffering from DD (mean age ±SD = 41.2 years±14.07 [18-82], 80.6% women). The subsample (608) was divided according to age, “youngsters” <45 (57.4%)/ “elders” ≥45. DASS-21 and IES scales were employed. Statistical analyses: Chi-square, t-Student test.
ResultsBoth groups did not differ (p>0.05) in sex, having COVID-19 symptoms, having family/friends infected, or income changes. While youngsters were single more frequently (68.8% vs 14.3%, χ² = 179.7, p<0.001), elders had somatic illness more frequently (64.8% vs 39.7% χ² =30.401, p<0.001). Youngsters obtained higher scores in depression (4.69 vs 4.1, T=5.413, p<0.001), anxiety (2.86 vs 1.97, T=5.249, p<0.001) and stress (4.48 vs 3.17, T=6.355, p<0.001) DASS-21 subscales, as in intrusive (3.42 vs 3.05, T=1.984, p=0.048) and avoidant (4.64 vs 4.11, T=3.056, p=0.002) IES scores.
ConclusionsDespite the group of elders with depression being more vulnerable to severe COVID-19 disease and presenting more frequently somatic comorbidities, younger depressive patients suffered more from depressive, anxiety, stress and avoidant symptoms and intrusive thoughts, in line with previous reports in the general population.
DisclosureNo significant relationships.
Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study
- Gamze Erzin, Lotta-Katrin Pries, Jim van Os, Laura Fusar-Poli, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Marina M. Mihaljevic, Sanja Andric-Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, Maria Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, Jose Luis Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, Celso Arango, Micheal C. O’Donovan, Bart P. F. Rutten, Sinan Guloksuz
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- Journal:
- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 19 March 2021, e25
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Background
A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.
MethodsThis cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.
ResultsES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.
ConclusionsOur findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
- L.-K. Pries, G. A. Dal Ferro, J. van Os, P. Delespaul, G. Kenis, B. D. Lin, J. J. Luykx, A. L. Richards, B. Akdede, T. Binbay, V. Altınyazar, B. Yalınçetin, G. Gümüş-Akay, B. Cihan, H. Soygür, H. Ulaş, E. Şahin Cankurtaran, S. Ulusoy Kaymak, M. M. Mihaljevic, S. Andric Petrovic, T. Mirjanic, M. Bernardo, G. Mezquida, S. Amoretti, J. Bobes, P. A. Saiz, M. Paz García-Portilla, J. Sanjuan, E. J. Aguilar, J. L. Santos, E. Jiménez-López, M. Arrojo, A. Carracedo, G. López, J. González-Peñas, M. Parellada, N. P. Maric, C. Atbaşoğlu, A. Ucok, K. Alptekin, M. Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, C. Arango, M. O'Donovan, S. Tosato, B. P. F. Rutten, S. Guloksuz
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 17 November 2020, e182
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Aims
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
MethodsThe sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
ResultsBoth genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
ConclusionsThe interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway
- Jim van Os, Lotta-Katrin Pries, Margreet ten Have, Ron de Graaf, Saskia van Dorsselaer, Philippe Delespaul, Maarten Bak, Gunter Kenis, Bochao D. Lin, Jurjen J. Luykx, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Marina M. Mihaljevic, Sanja Andric Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, María Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, José Luis Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram Can Saka, Celso Arango, Michael O'Donovan, Bart P. F. Rutten, Sinan Guloksuz
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- Psychological Medicine / Volume 52 / Issue 10 / July 2022
- Published online by Cambridge University Press:
- 19 October 2020, pp. 1910-1922
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Background
There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.
MethodsWe analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.
ResultsThe impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).
ConclusionsThe results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.