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Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [F(4,1319) = 20.4, P

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

Background: The prevalence of Internet Gaming Disorder (IGD) in the Italian population of gamers is unknown. Several risk factors, including time spent playing (TSP), are proposed as an epiphenomenon of emotional dysregulation. Methods: The study estimated the prevalence of IGD in at-risk Italian online gamers, and the interplay between alexithymia and other risk factors. 5,979 responders were surveyed. IGDS-SF9 estimated pathological gaming. TAS-20 measured Difficult in Identifying (DIF) and Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Results: 43% of participants had pathological IGD scores. Male gender (OR=1.2, 95% C.I.=1, 1.5, p=0.019), TSP (OR=7.6, 95% C.I.=5.5, 10.6, p0.001), DIF (OR=1.5, 95% C.I.=1.1, 2.1, p=0.003), boredom/loneliness feelings (OR=1.8, 95% C.I.=1.5, 2, p0.001), recent negative events (OR=1.1, 95% C.I.=1, 1.3, p=0.026), and a behavioral addiction (OR=2.1, 95% C.I.=1.2, 3.9, p=0.009) independently increased its risk. Conclusions: Almost one on two players joining online communities presented IGD. Some risk factors were crucial, including TSP, independently from emotional dysregulation., Mediterranean Journal of Clinical Psychology, Vol 8, No 3 (2020)

Introduction: Internet gaming disorder (IGD) is a new diagnosis in DSM 5 worth of research. New potentially addictive features are emerging in pay- and free-to-play videogames, involving different at-risk populations of gamers. However, few studies have examined whether and how different game-genres can contribute to the risk of IGD. Objectives: This study aimed to investigate how game-genres can predict IGD, accounting for alexithymia scores, time-related play- ing habits, and other predictors. Methods: Participants were gamers joining online communities, surveyed about which games they played more than 20 hours in their lifetime, time-variables, other stressors and alexithymia scores. A six-steps linear regression with IGD scores and a post hoc logistic regression (outcome: IGD>=21) were performed. Results: 5,979 subjects (88.7% males, 14-18 years), playing at different games (Figure-1). The game-genre explained the 1% of variation only. WoW and similar MMORPGs confirmed their potentiality in promoting IGD, regardless of alexithymia features (B=0.50, p=0.005). However, time-variables completely absorbed the WoW effect (B=0.01, p=0.951). LoL resulted addictive, even if considering time-variables and alexithymia (B=0.88, p0.001). None of the different game- genres was able to push the subject over the threshold of IGD, because other characteristics interacted as additive risk-factors. Conclusions: Alexithymia traits and time-related playing habits mostly moderated the effect of different games in increasing IGD risk. A videogame could engage people with specific characteristics that may, in turn, differentially predispose to IGD.

Introduction: Online gaming is potentially harmful to a group, but not for the entire population, of online gamers. The prevalence varies by geographical areas, however, there are few Italian studies about risk factors for Internet Gaming Disorder (IGD) and its presence among non-occasional gamers. Objectives: This study aimed to describe the presence of IGD in internet gamers who participate in online communities, and how well-established risk-factors can predict it. Methods: Participants were surveyed about their playing habits and other relevant characteristics. IGDS-SF9 diagnosed IGD. TAS-20 measured alexithymia scores, i.e. Difficult in Identifying (DIF) and Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Selected order of variables (via linear regression) and interactions were set in a logistic regression (outcome: IGD≥21). Results: The sample included 5,979 responders (88.7% males; 44% 14-18 years-hold). Alexithymia explained the 11.3% of the variance. IGD was present in the 43% of the subjects, the risk (70% prediction-rate) was increased by male gender (OR=1.2, 95% C.I. =1, 1.5, p=0.019), higher DIF z-scores (OR=1.5, 95% C.I.=1.1, 2.1, p=0.003), boredom/loneliness feelings (OR=1.8, 95% C.I.=1.5, 2, p

Introduction: Videogames have become more popular across females, although their widespread diffusion among males. How- ever, few studies have examined differences between female and male gamers and gender-specific risk factors for Internet Gaming Disorder (IGD). Objectives: The study aimed to describe males and females’ differ- ences in a sample of gamers, and to identify gender-specific risk- factors for IGD, accounting for alexithymia, playing habits, and other perceived stressors. Methods: Participants were gamers joining online communities, tested by IGDS-SF9 and TAS-20 for alexithymia. To explore isk-factors for IGD (outcome: IGD>=21), we set a binary logistic regression stratified by gender. Results: 5,305 males and 674 females differed in most of the descrip- tive characteristics (Figure-1) and game-genres preferences (Figure- 2). Higher DIF scores increased the risk of IGD in both males (OR=1.8 95% C.I. 1.6, 2) and females (OR=1.3 95% C.I. 1.1, 1.7) while higher EOT in males only (OR=1.2 95% C.I. 1.1, 1.3). Having another hobby apart from gaming was protective for males (OR=0.5, 95% C.I. 0.4, 0.6). Having started playing before their ten-years was a risk factor for females (OR=2.3 95% C.I. 1.2, 4.6). Loneliness and boredom feelings predicted IGD in males (OR=1.7 95% C.I. 1.5, 2) and, even more, in females (OR=2.7 95% C.I. 1.8, 4.2). Playing more than six hours/per day increased IGD-risk up to seven times in males (OR=7.3 95% C.I. 5.1, 10.3) and of almost sixteen times in females (OR=15.9 95% C.I. 5.4, 46.7) (Figure-3). Conclusions: Female gamers presented specific characteristics and a greater vulnerability to the increased time spent playing as a risk- factor for IGD

The work was supported by: Clinician Scientist Medical Research Council fellowship (project reference MR/M008436/1) to MDF; the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust to DQ; DFG Heisenberg professorship (no. 389624707) to UR. National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (Project EU-GEI). The Brazilian study was funded by the São Paulo Research Foundation under grant number 2012/0417-0., Quattrone, D., Ferraro, L., Tripoli, G., La Cascia, C., Quigley, H., Quattrone, A., Jongsma, H.E., Del Peschio, S., Gatto, G., Gayer-Anderson, C., Jones, P.B., Kirkbride, J.B., La Barbera, D., Tarricone, I., Berardi, D., Tosato, S., Lasalvia, A., Szöke, A., Arango, C., Bernardo, M., Bobes, J., Del Ben, C.M., Menezes, P.R., Llorca, P.-M., Santos, J.L., Sanjuán, J., Tortelli, A., Velthorst, E., De Haan, L., Rutten, B.P.F., Lynskey, M.T., Freeman, T.P., Sham, P.C., Cardno, A.G., Vassos, E., Van Os, J., Morgan, C., Reininghaus, U., Lewis, C.M., Murray, R.M., Di Forti, M.

BACKGROUND: Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns.; METHODS: We used case-control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20-F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data.; RESULTS: Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69-2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31-1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22-1.89) and linguistic distance (OR 1.22, 95% CI 0.95-1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively.; CONCLUSION: Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders. © Crown copyright 2021.

Purpose The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. Conclusions This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted.

Psychotic patients with a lifetime history of cannabis use generally show better cognitive functioning than other psychotic patients. Some authors suggest that cannabis-using patients may have been less cognitively impaired and less socially withdrawn in their premorbid life. Using a dataset comprising 948 patients with first-episode psychosis (FEP) and 1313 population controls across 6 countries, we examined the extent to which IQ and both early academic (Academic Factor [AF]) and social adjustment (Social Factor [SF]) are related to the lifetime frequency of cannabis use in both patients and controls. We expected a higher IQ and a better premorbid social adjustment in psychotic patients who had ever used cannabis compared to patients without any history of use. We did not expect such differences in controls. In both patients and controls, IQ was 3 points higher among occasional-users than in never-users (mean difference [Mdiff] = 2.9, 95% CI = [1.2, 4.7]). Both cases and control daily-users had lower AF compared to occasional (Mdiff = -0.3, 95% CI = [-0.5; -0.2]) and never-users (Mdiff = -0.4, 95% CI = [-0.6; -0.2]). Finally, patient occasional (Mdiff = 0.3, 95% CI = [0.1; 0.5]) and daily-users (Mdiff = 0.4, 95% CI = [0.2; 0.6]) had better SF than their never-using counterparts. This difference was not present in controls (Fgroup*frequency(2, 2205) = 4.995, P = .007). Our findings suggest that the better premorbid social functioning of FEP with a history of cannabis use may have contributed to their likelihood to begin using cannabis, exposing them to its reported risk-increasing effects for Psychotic Disorders. © The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.

The EU-GEI Project was funded by the European Community’s Seventh Framework Programme under grant agreement No.HEALTH-F2-2010-241909 (Project EU-GEI). The work was further funded by: Clinician Scientist Medical Research Council fellowship (project reference MR/M008436/1) to MDF; Veni grant from the Netherlands Organisation for Scientific Research (grant no. 451-13-022) to UR; Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101272/Z/13/Z) to JBK; National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. The Brazilian study was funded by the Säo Paulo Research Foundation under grant number 2012/04170., Quattrone, D., Di Forti, M., Gayer-Anderson, C., Ferraro, L., Jongsma, H.E., Tripoli, G., La Cascia, C., La Barbera, D., Tarricone, I., Berardi, D., Szöke, A., Arango, C., Lasalvia, A., Tortelli, A., Llorca, P.-M., De Haan, L., Velthorst, E., Bobes, J., Bernardo, M., Sanjuán, J., Santos, J.L., Arrojo, M., Del-Ben, C.M., Menezes, P.R., Selten, J.-P., Jones, P.B., Kirkbride, J.B., Richards, A.L., O'Donovan, M.C., Sham, P.C., Vassos, E., Rutten, B.P.F., Van Os, J., Morgan, C., Lewis, C.M., Murray, R.M., Reininghaus, U.

Introduction There are strong enough evidences of the fact that risk of psychosis is augmented by cannabis use. In a recent analysis, the strongest predictor of case-control status was daily-skunk use, i.e. the ORs for skunk users increase with the frequency of use5. We know also that FEP who smoked cannabis in their lifetime are less neuropsychologically impaired i.e. they have better premorbid and current IQ6. In this study we wanted to test what augments the probability to be everyday users, taking into account premorbid social and academic adjustment and cognition as predictors, along with age at first cannabis-use and % of THC in cannabis used. Methods The sample was made of 834 First Episode Psychosis (FEP) cannabis-using and non-using patients from different European countries and 1.061 healthy controls, as part of the EUGEI-STUDY. A logistic regression was computed, using frequency of cannabis use among those who reported to have used cannabis in their lifetime, as an outcome variable in order to estimate the risk to be an everyday-user (heavy user) or a less-than-everyday user (recreational user), taking into account a list of predictors: sociodemographics, age at first cannabis-use, % of THC, premorbid social factor (PSF), premorbid academic factor (PAF), extracted from the Premorbid Adjustment Scale (PAS) and the four scales of WAIS-brief version. Results The risk to be an everyday-smoker was higher for cases, in interaction with age at first use, i.e. while the risk of controls diminishes when age at first use increases, this is not true for cases, whose risk stay higher even when age at first use increases (OR=1.2, p=0.001, CI 95% 1.09, 1.45). THC absolute concentration >10% augmented almost 2 folds the risk to be an everyday-smoker (OR=1.8, p=0.001, CI 95% 1.29, 2.60). A lower premorbid academic adjustment (OR=0.8, p=0.040, CI 95% 0.68, 0.99) and higher premorbid social adjustment before 16 years (OR=1.6, p=0.019, CI 95% 1.08, 2.60) increased the risk to be a heavy cannabis user, along with having a lower education level and being unemployed (all p

Aims.In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach.Method.The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded.Results.During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation.Conclusions.The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that recommend avoiding the concurrent use of two or more antipsychotic drugs, and the confirmation of a link between citalopram and QTc prolongation supports the need for routine QTc monitoring. The relatively low proportion of patients with QTc prolongation not only suggests compliance with current safety warnings issued by regulatory authorities, but also casts some doubts on the clinical relevance of QTc prolongation related to some psychotropic drugs.

Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.