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1. Differential predictors of expressed emotion toward individuals with schizophrenia between families and halfway houses

Author

Panagiotis Ferentinos, Stamatina Douki, Eleni Kourkouni, Dimitra Dragoumi, Nikolaos Smyrnis, and Athanassios Douzenis

Subjects
criticism, differential predictors, emotional overinvolvement, expressed emotion, families, halfway houses, Psychiatry, RC435-571
Abstract

BackgroundThis study investigated patient- and caregiver-related predictors of expressed emotion (EE) toward individuals with schizophrenia in families and halfway houses and yet understudied differential effects across settings.MethodsWe included 40 individuals with schizophrenia living with their families (“outpatients”) and 40 “inpatients” in halfway houses and recorded the EE of 56 parents or 22 psychiatric nurses, respectively, through Five Minutes Speech Sample. Each outpatient was rated by one to two parents; each inpatient was rated by two to five nurses. As EE ratings had a multilevel structure, EE predictors were investigated in backward stepwise generalized linear mixed models using the “buildmer” R package. We first fitted models including either caregiver- or patient-related predictors in each setting and finally included both types of predictors. Setting-specific patient-related effects were investigated in interaction analyses. Adjustment for multiple tests identified the most robust associations.ResultsIn multivariate models including either caregiver- or patient-related predictors, nurses’ higher age, shorter work experience and lower inpatients’ negative symptoms robustly predicted higher emotional overinvolvement (EOI). In the final models including both types of predictors, nurses robustly displayed lower EOI (i.e., reduced concern and disengagement) toward inpatients with higher negative symptoms. Several other features were nominally associated with criticism and EOI in each setting. However, no feature robustly predicted criticism in inpatients and criticism/EOI in outpatients after adjustment for multiple tests. In interaction analyses, higher negative symptoms differentially predicted lower EOI in nurses only.ConclusionOur findings suggest setting-specific pathogenetic pathways of EOI and might help customize psychoeducational interventions to staff in halfway houses.

Published
2024
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2. Clinical implementation of preemptive pharmacogenomics in psychiatryResearch in context

Author

Maria Skokou, Kariofyllis Karamperis, Margarita-Ioanna Koufaki, Evangelia-Eirini Tsermpini, Maria-Theodora Pandi, Stavroula Siamoglou, Panagiotis Ferentinos, Marina Bartsakoulia, Theodora Katsila, Christina Mitropoulou, George P. Patrinos, Konstantinos Assimakopoulos, Eleni Georgila, Philippos Gourzis, Aikaterini Karaivazoglou, Olympia Prodromaki, George Rigas, Georgia Voukelatou, Vassiliki Zacharopoulou, Evangelia Barba, Konstantina Chalikiopoulou, Dimitra Dedousi, Georgia Emmanouil, Panagiotis Giannopoulos, Ouliana Ivantsik, Marina Kalogeropoulou, Manoussos E. Kambouris, Filippos Kanellakis, Alexandra Kolliopoulou, Panagiotis Kollios, Zoi Kordou, Ioannis Liopetas, Efrossyni Mendrinou, Konstantinos Mitropoulos, Georgia-Chryssa Samiou, Theano Stamopoulou, Andreas Stathoulias, Apostolos Stratopoulos, Athina Tsikrika, Athanassios Douzenis, Charilaos Gerassimou, Maria-Angeliki Voziki, and Athanassios Vozikis

Subjects
Preemptive pharmacogenomics, Clinical implementation, Schizophrenia, Major depressive disorder, Bipolar disorder, Cost-effectiveness, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. Methods: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. Findings: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively). Interpretation: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. Funding: European Union Horizon 2020.

Published
2024
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3. A Magnetic Resonance Spectroscopy Study on Polarity Subphenotypes in Bipolar Disorder

Author

Georgios D. Argyropoulos, Foteini Christidi, Efstratios Karavasilis, Peter Bede, Georgios Velonakis, Anastasia Antoniou, Ioannis Seimenis, Nikolaos Kelekis, Nikolaos Smyrnis, Olympia Papakonstantinou, Efstathios Efstathopoulos, and Panagiotis Ferentinos

Subjects
hippocampus, cingulate cortex, emotion regulation network, proton magnetic resonance spectroscopy, bipolar disorder, onset polarity, Medicine (General), R5-920
Abstract

Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and therapeutically important onset polarity (OP) and predominant polarity (PP). We conducted a proton MRS study in BD polarity subphenotypes, focusing on emotion regulation brain regions. Forty-one euthymic BD patients stratified according to OP and PP and sixteen healthy controls (HC) were compared. 1H-MRS spectra of the anterior and posterior cingulate cortex (ACC, PCC), left and right hippocampus (LHIPPO, RHIPPO) were acquired at 3.0T to determine metabolite concentrations. We found significant main effects of OP in ACC mI, mI/tNAA, mI/tCr, mI/tCho, PCC tCho, and RHIPPO tNAA/tCho and tCho/tCr. Although PP had no significant main effects, several medium and large effect sizes emerged. Compared to HC, manic subphenotypes (i.e., manic-OP, manic-PP) showed greater differences in RHIPPO and PCC, whereas depressive suphenotypes (i.e., depressive-OP, depressive-PP) in ACC. Effect sizes were consistent between OP and PP as high intraclass correlation coefficients (ICC) were confirmed. Our findings support the utility of MRS in the study of the neurobiological underpinnings of OP and PP, highlighting that the regional specificity of metabolite changes within the emotion regulation network consistently marks both polarity subphenotypes.

Published
2024
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4. Family in Crisis: Do Halfway Houses Perform Better Than Families with Expressed Emotion toward Patients with Schizophrenia? A Direct Adjusted Comparison

Author

Panagiotis Ferentinos, Stamatina Douki, Vasiliki Yotsidi, Eleni Kourkouni, Dimitra Dragoumi, Nikolaos Smyrnis, and Athanasios Douzenis

Subjects
criticism, emotional overinvolvement, expressed emotion, families, halfway houses, schizophrenia, Medicine
Abstract

Expressed emotion (EE) toward patients with schizophrenia is typically reported to be lower in psychiatric halfway houses than in families. This is the first study directly comparing EE between these settings and investigating the pathways mediating EE differences. We included 40 inpatients in halfway houses and 40 outpatients living with their families and recorded 22 psychiatric nurses’ and 56 parents’ EE, respectively, through Five Minutes Speech Samples. Each inpatient was rated by 2–5 nurses and each outpatient by 1–2 parents. As EE ratings had a multilevel structure, generalized linear mixed models were fitted, adjusting for patient-related confounders and caregiver demographics. Mediatory effects were investigated in multilevel structural equation models. Outpatients were younger, less chronic, and better educated, with higher negative symptoms and perceived criticism than inpatients. Nurses were younger and better educated than parents. Before adjustment, EE rates were equally high across settings. After adjusting for patient-related confounders, emotional overinvolvement was significantly higher in parents. However, after also adjusting for caregiver demographics, only criticism was significantly higher in nurses. Patients’ age, negative symptoms, and perceived criticism and caregivers’ age and sex significantly mediated EE group differences. Our findings highlight pathways underlying EE differences between halfway houses and families and underscore the importance of staff and family psychoeducation.

Published
2024
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5. Exploring the impact of exercise and essential amino acid plus cholecalciferol supplementation on physical fitness and body composition in multiple sclerosis: A case study

Author

Theocharis Ispoglou, Panagiotis Ferentinos, Konstantinos Prokopidis, Cameron Blake, Luke Aldrich, Antonis Elia, Matthew Lees, and Karen Hind

Subjects
leucine, physical activity, protein, rehabilitation, sarcopenia, Medicine, Medicine (General), R5-920
Abstract

Key Clinical Message In MS patients, especially those frail or malnourished, combining home‐based exercise twice weekly with essential amino acids and vitamin D may improve body composition, strength, and physical performance, enabling long‐term functional improvements. Abstract Multiple sclerosis (MS) is associated with reduced bone and muscle strength and function. We aimed to investigate the effectiveness of a 24‐week intervention in a 57‐year‐old frail female with MS. The participant completed a 2×/week exercise intervention and ingested 2×/day a supplement containing 7.5 g essential amino acids and 500 IU cholecalciferol. Body composition, 6‐m gait speed (GS), handgrip strength (HGS), 30‐sec arm‐curl test (30ACT), 6‐min walking test (6MWT), 30‐sec chair‐stand test (30CST), and plasma concentrations of 25‐hydroxyvitamin D3 [25(OH)D3], insulin‐like growth factor 1 (IGF‐1), and amino acids were assessed at baseline, and at Weeks 12 and 24. Plasma 25(OH)D3 increased from 23.2 to 41.3 ng/mL and IGF‐1 from 131.6 to 140.7 ng/mL from baseline to post‐intervention. BMI, total lean tissue mass (LTM), fat mass, bone mineral content, and the sum of 17 amino acids increased by 3.8, 1.0, 3.5, 0.2, and 19%, respectively, at Week 24. There were clinically significant increases in regional LTM (6.9% arms and 6.3% legs) and large increases in GS (67.3%), dominant HGS (31.5%), non‐dominant HGS (11.8%), dominant 30ACT (100%), non‐dominant 30ACT (116.7%), 6MWT (125.6%), and 30CST (44.4%). The current intervention was effective in improving components of physical fitness and body composition in a female with MS.

Published
2023
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6. The Prevalence and Characteristics of Intrafamilial Child and Adolescent Homicides in Greece over 11 Years (2010–2020)

Author

Maria Tsellou, Flora Bacopoulou, Panagiotis Ferentinos, Eric Baccino, Laurent Martrille, and Stavroula Papadodima

Subjects
child, adolescent, homicide, filicide, infanticide, domestic violence, Pediatrics, RJ1-570
Abstract

Intrafamilial child/adolescent homicide is the murder of a child/adolescent by one or more family members. This study delves into the medical and sociological consequences of child homicide, shedding light on the broader impact beyond individual families, which extends into the local community. Two Internet search engines and the search engines of major national news websites were surveyed to identify the number of intrafamilial child/adolescent homicide cases that occurred in Greece from January 2010 to December 2020. Over the study period, 34 victims of intrafamilial child/adolescent homicides were identified. The above deaths reflect an intrafamilial child/adolescent homicide rate of 0.15 homicides per year per 100,000 inhabitants. Most of the perpetrators (51.4%) were male, and the victims were equally divided into males and females. The ages of the perpetrators ranged from 13 to 61 years, and the ages of the victims ranged between 0 and 17 years. Most perpetrators (54.5%) had a previous psychiatric history and in many cases, they committed (33.3%) or attempted (15.2%) suicide after the homicide. The most common method of homicide was strangulation (usually combined with suffocation) (25%), followed by abandonment (15.6%). The most commonly reported motives were spousal revenge (26.5%) and psychotic disorders (26.5%). Raising awareness for intrafamilial child and adolescent homicide is of the utmost importance for the prevention of this dreadful phenomenon.

Published
2023
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7. Identifying the Common Genetic Basis of Antidepressant Response

Author

Oliver Pain, Karen Hodgson, Vassily Trubetskoy, Stephan Ripke, Victoria S. Marshe, Mark J. Adams, Enda M. Byrne, Adrian I. Campos, Tania Carrillo-Roa, Annamaria Cattaneo, Thomas D. Als, Daniel Souery, Mojca Z. Dernovsek, Chiara Fabbri, Caroline Hayward, Neven Henigsberg, Joanna Hauser, James L. Kennedy, Eric J. Lenze, Glyn Lewis, Daniel J. Müller, Nicholas G. Martin, Benoit H. Mulsant, Ole Mors, Nader Perroud, David J. Porteous, Miguel E. Rentería, Charles F. Reynolds, III, Marcella Rietschel, Rudolf Uher, Eleanor M. Wigmore, Wolfgang Maier, Naomi R. Wray, Katherine J. Aitchison, Volker Arolt, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Qingqin S. Li, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Gustavo Turecki, Richard Weinshilboum, Andrew M. McIntosh, Cathryn M. Lewis, Siegfried Kasper, Joseph Zohar, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Manuel Mattheisen, Maciej Trzaskowski, Abdel Abdellaoui, Esben Agerbo, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R.I. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Klaus Berger, Dorret I. Boomsma, Sven Cichon, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Enrico Domenici, Tõnu Esko, Hans J. Grabe, Steven P. Hamilton, Andrew C. Heath, Kenneth S. Kendler, Stefan Kloiber, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael C. O’Donovan, Sara A. Paciga, Nancy L. Pedersen, Brenda W.J.H. Penninx, Roy H. Perlis, James B. Potash, Martin Preisig, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Kari Stefansson, Henning Tiemeier, Henry Völzke, Myrna M. Weissman, Thomas Werge, Douglas F. Levinson, Gerome Breen, Anders D. Børglum, and Patrick F. Sullivan

Subjects
Antidepressant response, Depression, Genetics, GWAS, MDD, Polygenic score, Psychiatry, RC435-571
Abstract

Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. Methods: Genome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

Published
2022
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8. A Narrative Review of Non-Pharmacological Strategies for Managing Sarcopenia in Older Adults with Cardiovascular and Metabolic Diseases

Author

Theocharis Ispoglou, Oliver Wilson, Deaglan McCullough, Luke Aldrich, Panagiotis Ferentinos, Gemma Lyall, Antonios Stavropoulos-Kalinoglou, Lauren Duckworth, Meghan A. Brown, Louise Sutton, Alexandra J. Potts, Victoria Archbold, Jackie Hargreaves, and Jim McKenna

Subjects
aerobic training, behaviour change, cardiovascular disease, metabolic diseases, nutrition, obesity, Biology (General), QH301-705.5
Abstract

This narrative review examines the mechanisms underlying the development of cardiovascular disease (CVD) and metabolic diseases (MDs), along with their association with sarcopenia. Furthermore, non-pharmacological interventions to address sarcopenia in patients with these conditions are suggested. The significance of combined training in managing metabolic disease and secondary sarcopenia in type II diabetes mellitus is emphasized. Additionally, the potential benefits of resistance and aerobic training are explored. This review emphasises the role of nutrition in addressing sarcopenia in patients with CVD or MDs, focusing on strategies such as optimising protein intake, promoting plant-based protein sources, incorporating antioxidant-rich foods and omega-3 fatty acids and ensuring sufficient vitamin D levels. Moreover, the potential benefits of targeting gut microbiota through probiotics and prebiotic fibres in sarcopenic individuals are considered. Multidisciplinary approaches that integrate behavioural science are explored to enhance the uptake and sustainability of behaviour-based sarcopenia interventions. Future research should prioritise high-quality randomized controlled trials to refine exercise and nutritional interventions and investigate the incorporation of behavioural science into routine practices. Ultimately, a comprehensive and multifaceted approach is essential to improve health outcomes, well-being and quality of life in older adults with sarcopenia and coexisting cardiovascular and metabolic diseases.

Published
2023
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9. Effects of low molecular weight heparin and fondaparinux on mortality, hemorrhagic and thrombotic complications in COVID-19 patients

Author

Paraskevi C. Fragkou, Lina Palaiodimou, Maria Ioanna Stefanou, Aristeidis H. Katsanos, Vaia Lambadiari, Dimitrios Paraskevis, Elisabeth Andreadou, Dimitra Dimopoulou, Christina Zompola, Panagiotis Ferentinos, Theodoros I. Vassilakopoulos, Anastasia Kotanidou, Petros P. Sfikakis, Sotirios Tsiodras, and Georgios Tsivgoulis

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation dose in COVID-19. Objective: We aim to systematically assess the currently available data regarding the effects of different dosing regimens of low molecular weight heparin and/or fondaparinux (LMWH/F) on mortality risk as well as the risk of arterial/venous thrombotic events and hemorrhagic complications in confirmed COVID-19 cases. Design: We conducted a living systematic review and meta-analysis on the effects of different LMWH/F doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients. Data Sources and Methods: MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database, and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH/F among confirmed COVID-19 cases. Results: Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between LMWH/F and mortality during the following comparisons: (1) no LMWH/F versus any LMWH/F; (2) prophylactic versus higher than prophylactic LMWH/F; (3) prophylactic versus therapeutic LMWH/F; (4) intermediate versus therapeutic LMWH/F; and (5) lower than therapeutic versus therapeutic LMWH/F. Mortality was higher in patients receiving prophylactic versus intermediate LMWH/F (OR = 2.01; 95% CI: 1.19–3.39). However, this effect was mostly driven by observational data. No associations were detected between the intensity of LMWH/F and the risk of thrombotic and hemorrhagic events, except the lower risk for hemorrhage in patients on prophylactic compared to higher LMWH/F doses. Conclusion: The risk for all-cause mortality was higher in patients receiving prophylactic LMWH/F compared to those on an intermediate dose of LMWH/F, based on observational data. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies. Registration: The study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (Registration number: CRD42021229771).

Published
2022
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10. Hippocampal Metabolic Alterations in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Spectroscopy Study

Author

Foteini Christidi, Georgios D. Argyropoulos, Efstratios Karavasilis, Georgios Velonakis, Vasiliki Zouvelou, Panagiotis Kourtesis, Varvara Pantoleon, Ee Ling Tan, Ariadne Daponte, Stavroula Aristeidou, Sofia Xirou, Panagiotis Ferentinos, Ioannis Evdokimidis, Michail Rentzos, Ioannis Seimenis, and Peter Bede

Subjects
amyotrophic lateral sclerosis, hippocampus, memory, magnetic resonance spectroscopy, metabolites, grey matter, Science
Abstract

Background: Magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) has been overwhelmingly applied to motor regions to date and our understanding of frontotemporal metabolic signatures is relatively limited. The association between metabolic alterations and cognitive performance in also poorly characterised. Material and Methods: In a multimodal, prospective pilot study, the structural, metabolic, and diffusivity profile of the hippocampus was systematically evaluated in patients with ALS. Patients underwent careful clinical and neurocognitive assessments. All patients were non-demented and exhibited normal memory performance. 1H-MRS spectra of the right and left hippocampi were acquired at 3.0T to determine the concentration of a panel of metabolites. The imaging protocol also included high-resolution T1-weighted structural imaging for subsequent hippocampal grey matter (GM) analyses and diffusion tensor imaging (DTI) for the tractographic evaluation of the integrity of the hippocampal perforant pathway zone (PPZ). Results: ALS patients exhibited higher hippocampal tNAA, tNAA/tCr and tCho bilaterally, despite the absence of volumetric and PPZ diffusivity differences between the two groups. Furthermore, superior memory performance was associated with higher hippocampal tNAA/tCr bilaterally. Both longer symptom duration and greater functional disability correlated with higher tCho levels. Conclusion: Hippocampal 1H-MRS may not only contribute to a better academic understanding of extra-motor disease burden in ALS, but given its sensitive correlations with validated clinical metrics, it may serve as practical biomarker for future clinical and clinical trial applications. Neuroimaging protocols in ALS should incorporate MRS in addition to standard structural, functional, and diffusion sequences.

Published
2023
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11. Interleukin-1 Beta in Peripheral Blood Mononuclear Cell Lysates as a Longitudinal Biomarker of Response to Antidepressants: A Pilot Study

Author

Panagiotis Ferentinos, Eirini Maratou, Anastasia Antoniou, Alessandro Serretti, Nikolaos Smyrnis, and Paraskevi Moutsatsou

Subjects
antidepressants, Interleukin-1 beta, lysates, major depressive disorder, monocytes, response, Psychiatry, RC435-571
Abstract

Interleukin-1 beta (IL1β) is primarily produced by monocytes in the periphery and the brain. Yet, IL1β protein levels have to date been investigated in major depressive disorder (MDD) and antidepressant response using either plasma or serum assays although with contradictory results, while mononuclear cell assays are lacking despite their extensive use in other contexts. In this pilot study, we comparatively assessed IL1β in mononuclear lysates and plasma in depressed MDD patients over treatment and healthy controls (HC). We recruited 31 consecutive adult MDD inpatients and 25 HC matched on age, sex, and BMI. Twenty-six patients completed an 8-week follow-up under treatment. IL1β was measured in both lysates and plasma in patients at baseline (T0) and at study end (T1) as well as in HC. We calculated ΔIL1β(%) for both lysates and plasma as IL1β percent changes from T0 to T1. Seventeen patients (65.4% of completers) were responders at T1 and had lower baseline BMI than non-responders (p = 0.029). Baseline IL1β from either plasma or lysates could not efficiently discriminate between depressed patients and HC, or between responders and non-responders. However, the two response groups displayed contrasting IL1β trajectories in lysates but not in plasma assays (response group by time interactions, p = 0.005 and 0.96, respectively). ΔIL1β(%) in lysates predicted response (p = 0.025, AUC = 0.81; accuracy = 84.6%) outperforming ΔIL1β(%) in plasma (p = 0.77, AUC=0.52) and was robust to adjusting for BMI. In conclusion, ΔIL1β(%) in mononuclear lysates may be a longitudinal biomarker of antidepressant response, potentially helpful in avoiding untimely switching of antidepressants, thereby warranting further investigation.

Published
2021
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12. Similar or Different Neuropsychological Profiles? Only Set Shifting Differentiates Women With Bipolar vs. Borderline Personality Disorder

Author

Ioannis Michopoulos, Kalliopi Tournikioti, Antonios Paraschakis, Anna Karavia, Rossetos Gournellis, Nikolaos Smyrnis, and Panagiotis Ferentinos

Subjects
bipolar, borderline, CANTAB, executive function, memory, set shifting, Psychiatry, RC435-571
Abstract

There is ongoing debate about the similarities and differences between bipolar disorder (BD) and borderline personality disorder (BPD). Very few studies have concurrently assessed their neuropsychological profile and only on a narrow array of neuropsychological tests. We aimed to investigate the differences of these two patient groups on visual memory, executive function, and response inhibition. Twenty-nine BD patients, 27 BPD patients and 22 controls (all female) were directly compared on paired associates learning (PAL), set shifting (ID/ED), problem solving (SOC), and response inhibition (SSRT) using Cambridge Neuropsychological Test Automated Battery (CANTAB). Rank-normalized outcomes were contrasted in one-way ANOVA tests. Discriminant analysis was finally performed to predict BD or BPD patient status. BD patients performed significantly worse than controls on all tasks. BPD patients performed significantly worse than HC on all tests except SST. Significant differences between the two patient groups were recorded only on ID/ED, where BPD patients performed worse (p = 0.044). A forward stepwise discriminant analysis model based on ID/ED and SOC predicted correctly patients' group at 67.9% of cases. In conclusion, BD and BPD female patients appear to be more similar than different as regards their neuropsychological functions. This study is the first to show that BPD patients display more deficits than BD patients when directly compared on the set shifting executive function test, a marker of cognitive flexibility. Discerning BD from BPD patients through neuropsychological performance is promising but would improve by using additional subtler tests and psychometric evaluation.

Published
2021
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13. The Derma of Crisis: Imagining Athens in Crisis as an Urban Collage

Author

Panagiotis Ferentinos

Subjects
Athens, collage, crisis, skin, urban space, General Works, Ethnology. Social and cultural anthropology, GN301-674, Social sciences (General), H1-99
Abstract

A close look at the urban surfaces of Athens during the years of the economic crisis reveals the extensive phenomenon of the people’s interaction with the surface of the cityscape, the skin of Athens. A derma of crises that reflects Greece’s socio-political conditions over this period, and the austerity measures enforced by the official state. This rapidly transformed and ever-changing surface imagery can be recorded and used for reading and further understanding of how the public sphere responds to this period of decline, and reacts to the recession’s strategies of sovereignty. The urgency to document, give prominence to this urban field and examine it as a whole is of pivotal importance, considering the fact that the official authorities (such as the mayor of Athens) have recently taken action to eliminate the urban traces. However, these inscriptions bear witness to the continuous crisis mirrored on the Athenian walls and architectural volumes. Over the last years, there have been numerous scholars and researchers that have engaged with the study of the Athenian cityscape. Nonetheless, they particularly focus on graffiti, street art and slogans, and this engagement sometimes facilitates the emerging artistry or the discussion of socio-political connotations. In contrast to this, this article moves towards the identification of the phenomenon as a dynamic potential of a derma–city skin and does not specifically focus on them as mere details (often intentionally made, e.g. a graffiti). It examines the wholeness, the anonymity, the unintentional activity; how they contribute to the formulation of an urban collage, an assemblage of visual elements that co-exist making Athens a unique case of an over-marked city. The study of various dimensions of this skin and of the virtual preservation means aims to add a further layer of understanding to the urban space as a main field of socio-political connotations during the crisis.

Published
2021
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14. Acute Cardiorespiratory Responses to Different Exercise Modalities in Chronic Heart Failure Patients—A Pilot Study

Author

Eleftherios Karatzanos, Panagiotis Ferentinos, Georgios Mitsiou, Stavros Dimopoulos, Argyrios Ntalianis, and Serafeim Nanas

Subjects
cardiac rehabilitation, heart failure, continuous exercise, high intensity interval training, acute exercise, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO2peak intensities between three “iso-work” protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON70) and (c) a lower intensity continuous protocol (CON50) in patients with chronic heart failure (CHF). Ten male CHF patients (aged 55.1 ± 16.2 years) performed in separate days a single session of a HIIT protocol consisted of 4 sets × 4 min cycling at 80% VO2peak with 3 min of recovery at 50% VO2peak, a CON70 protocol corresponding to 70% VO2peak and a CON50 protocol corresponding to 50% VO2peak. Cardiopulmonary data were collected by an online gas analysis system. The HIIT and CON70 elicited higher cardiorespiratory responses compared to CON50 with no differences between them (p > 0.05). In HIIT and CON70, patients exercised longer at >80% and >90% VO2peak. The completion rate was 100% for the three protocols. Not any adverse events were observed in either protocol. Both HIIT and CON70 elicited a stronger physiological stimulus and required shorter time than CON50. Both HIIT and CON70 also induced comparable hemodynamic responses and ventilatory demand.

Published
2021
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15. The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis

Author

Foteini Christidi, Efstratios Karavasilis, Georgios Velonakis, Panagiotis Ferentinos, Michail Rentzos, Nikolaos Kelekis, Ioannis Evdokimidis, and Peter Bede

Subjects
hippocampus, amyotrophic lateral sclerosis, neuropathology, neuroimaging, cognition, Neurology. Diseases of the nervous system, RC346-429
Abstract

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely.

Published
2018
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16. Melancholic features and typical neurovegetative symptoms of major depressive disorder show specific polygenic patterns

Author

Vincenzo Oliva, Giuseppe Fanelli, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Diana De Ronchi, Chiara Fabbri, and Alessandro Serretti

Subjects
Stress Disorders, Post-Traumatic, Depressive Disorder, Major, Multifactorial Inheritance, Psychiatry and Mental health, Clinical Psychology, All institutes and research themes of the Radboud University Medical Center, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Twins, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

Major depressive disorder (MDD) is a highly prevalent psychiatric condition characterised by a heterogeneous clinical presentation and an estimated twin-based heritability of ~40-50 %. Different clinical MDD subtypes might partly reflect distinctive underlying genetics. This study aims to investigate if polygenic risk scores (PRSs) for different psychiatric disorders, personality traits, and substance use-related traits may be associated with different clinical subtypes of MDD (i.e., MDD with melancholic or psychotic features), higher symptom severity, or different clusters of depressive symptoms (i.e., sadness symptoms, typical neurovegetative symptoms, detachment symptoms, and negative thoughts).The target sample included 1149 patients with MDD, recruited by the European Group for the Study of Resistant Depression. PRSs for 25 psychiatric disorders and traits were computed based on the most recent publicly available summary statistics of the largest genome-wide association studies. PRSs were then used as predictors in regression models, adjusting for age, sex, population stratification, and recruitment sites.Patients with MDD having higher PRS for MDD and loneliness were more likely to exhibit melancholic features of MDD (p = 0.0009 and p = 0.005, respectively). Moreover, patients with higher PRS for alcohol intake and post-traumatic stress disorder were more likely to experience greater typical neurovegetative symptoms (p = 0.0012 and p = 0.0045, respectively).The proportion of phenotypic variance explained by the PRSs was limited.This study suggests that melancholic features and typical neurovegetative symptoms of MDD may show distinctive underlying genetics. Our findings provide a new contribution to the understanding of the genetic heterogeneity of MDD.

Published
2023

17. Urban fragments ‘on hold’: Reflections of COVID-19 in the urban Greek environment

Author

Panagiotis Ferentinos

Subjects
General Economics, Econometrics and Finance
Abstract

This study focused on how the urban environment of a Greek city, Patras, visually bore witness to the impact that COVID-19 has had within its public spaces. It also focused on how the human involvement is reflected on the city surfaces, and even its absence denotes the new conditions caused by the pandemic. Time appeared to be frozen on the city surfaces and its visual remainders point to a previous era, when a pandemic may have sounded more like a sci-fi scenario, or over the ‘breaks’ of successive lockdowns. In order to record and document the fragmented spatial and temporal actualities, I relied on fine art practices such as photography, photogrammetry and 3D models for the production of an archive of the current historic imperative.

Published
2022

19. Metabolizing status of CYP2C19 in response and side effects to medications for depression: Results from a naturalistic study

Author

Marco Calabrò, Chiara Fabbri, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Diana De Ronchi, Alessandro Serretti, and Concetta Crisafulli

Subjects
Pharmacology, Depressive Disorder, Major, Drug-Related Side Effects and Adverse Reactions, Depression, Adverse effects, Antidepressive agents, CYP2C19, Cytochrome P450, Metabolism, Pharmacogenetics, Treatment outcome, Cytochrome P-450 CYP2C19, Psychiatry and Mental health, Cytochrome P-450 CYP2D6, Neurology, Humans, Pharmacology (medical), Neurology (clinical), Biological Psychiatry
Abstract

Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Polymorphisms in cytochrome P450 genes (CYP450) were demonstrated to play a significant role in antidepressant response and side effects, but their effect in real-world clinical practice is poorly known. We determined the metabolic status of CYP2C19 based on the combination of *1, *2, *3 and *17 alleles extracted from genome-wide data in 1239 patients with MDD, pharmacologically treated in a naturalistic setting. Symptom improvement and side effects were assessed using the Montgomery and Åsberg Depression Rating Scale and the Udvalg for Kliniske Undersøgelse scale, respectively. We tested if symptom improvement, response and side effects were associated with CYP2C19 metabolic status adjusting for potential confounders. We considered patients treated with drugs for depression having CYP2C19 genotyping recommended by guidelines (T1 Drugs); secondarily, with all psychotropic drugs having CYP2C19 as relevant metabolic path (T2 Drugs). In the group treated with T1 drugs (n = 540), poor metabolizers (PMs) showed higher response and higher symptom improvement compared to normal metabolizers (p = 0.023 and p = 0.009, respectively), but also higher risk of autonomic and neurological side effects (p = 0.022 and p = 0.022 respectively). In patients treated with T2 drugs (n = 801), similar results were found. No associations between metabolizer status and other types of side effects were found (psychic and other side effects). Our study suggests potential advantages of CYP2C19 pharmacogenetic testing to guide treatment prescription, that may not be limited to the drugs currently recommended by guidelines.

Published
2022

21. A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response

Author

Bernhard T. Baune, Eduard Maron, Diana De Ronchi, Siegfried Kasper, Panagiotis Ferentinos, Alessandro Serretti, Daniel Souery, Chiara Fabbri, Katharina Domschke, Alessio Squassina, Paolo Martini, Dan Rujescu, Marco Bortolomasi, Diego Albani, Stuart Montgomery, Joseph Zohar, Giuseppe Fanelli, Alessandra Minelli, Massimo Gennarelli, Gianluigi Forloni, and Julien Mendlewicz

Subjects
Multifactorial Inheritance, Remission, Major depressive disorder, Population stratification, Treatment response, symbols.namesake, All institutes and research themes of the Radboud University Medical Center, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Pharmacology (medical), Bipolar disorder, Biological Psychiatry, Neuroticism, Pharmacology, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Mood Disorders, business.industry, Antidepressants, medicine.disease, Antidepressive Agents, Psychiatry and Mental health, Polygenic risk scores, Bonferroni correction, Neurology, Mood disorders, Schizophrenia, Meta-analysis, symbols, Pharmacogenomics, Neurology (clinical), business, Genome-Wide Association Study, Clinical psychology
Abstract

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p = 0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11–1.98, p = 0.007). Nominal associations were also found between MDD-PRS and non-response (p = 0.013), as well as between SCZ-PRS and non-remission (p = 0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.

Published
2022

22. The association of theory of mind with language and visuospatial abilities in amyotrophic lateral sclerosis: a pilot study

Author

Niki Panopoulou, Foteini Christidi, Panagiotis Kourtesis, Panagiotis Ferentinos, Panagiota Karampetsou, Georgios Tsirtsiridis, Thomas Theodosiou, Sofia Xirou, Vasiliki Zouvelou, Ioannis Evdokimidis, Michail Rentzos, Ioannis Zalonis, National and Kapodistrian University of Athens (NKUA), 3D interaction with virtual environments using body and mind (Hybrid), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-MEDIA ET INTERACTIONS (IRISA-D6), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique)

Subjects
Social Cognition, Amyotrophic Lateral Sclerosis, 05 social sciences, Theory of Mind, Pilot Projects, Neuropsychological Tests, 050105 experimental psychology, Executive Function, [SCCO]Cognitive science, 03 medical and health sciences, Cognition, 0302 clinical medicine, Neurology, [SCCO.PSYC]Cognitive science/Psychology, Humans, Dementia, 0501 psychology and cognitive sciences, Neurology (clinical), Visuospatial, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Language
Abstract

International audience; Objective: Dysfunction of social cognition is well-recognized as one of amyotrophic lateral sclerosis (ALS) cognitive impairments. Previous studies have mostly associated social cognition subcomponents, including Theory of Mind (ToM), with executive dysfunction using highlydemanding tasks. In the present study, we investigate dysfunction of affective ToM in a sample of ALS patients without dementia and evaluate any possible associations both with executive and non-executive dysfunction. Methods: We included 42 ALS patients and 30 healthy controls (HC) and administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS). Affective ToM was examined based on the ECAS judgment of preference task; total score and type of errors ("favourite", "unclassified") were recorded for all participants. Results: A significant proportion of ALS patients (31%) were impaired on ToM task, scoring significantly lower compared to HC. Impairments in ToM task were more frequent (45%) in patients with cognitive impairment compared to those with intact cognition (15%). ALS patients showed significantly more errors on ToM task compared to HC. A significant association was found between ToM score and ECAS language and visuospatial abilities but not fluency, executive or memory function. Conclusion: Dysfunction of affective ToM appears prevalent in ALS patients without dementia, and associates with language and visuospatial abilities. These associations align with motor and extra-motor symptoms due to the degeneration across corresponding networks. Impaired ToM should be considered in clinical settings, since it might contribute to patients' social life, as well as the burden of their caregivers and relatives.

Published
2021

23. Psychometric properties of the Revised Child Anxiety and Depression Scale in Greek Adolescents

Author

Paraskevi Bali, Evdokia Pasalari, Dimitra Grammatikaki, Panagiotis Ferentinos, and Ioanna Giannopoulou

Subjects
Male, Adolescent, Psychometrics, Anxiety, Cronbach's alpha, Surveys and Questionnaires, medicine, Humans, Measurement invariance, Child, Depression (differential diagnoses), Psychiatric Status Rating Scales, Greece, Depression, Reproducibility of Results, General Medicine, Strengths and Difficulties Questionnaire, Differential item functioning, Confirmatory factor analysis, Psychiatry and Mental health, Clinical Psychology, Scale (social sciences), Pediatrics, Perinatology and Child Health, Female, medicine.symptom, Factor Analysis, Statistical, Psychology, Clinical psychology
Abstract

The psychometric properties of the Revised Child Anxiety and Depression Scale (RCADS-47) are established cross-culturally but lacking for the Greek population. The present study examined RCADS internal consistency and validity (structural and concurrent) in Greek adolescents, and tested measurement invariance across sex and age groups. We recruited 619 secondary school students ( n = 321 females), aged 12–18 years ( n = 318, 12–14-year-olds). Besides RCADS, all students completed Strengths and Difficulties Questionnaire (SDQ), a subsample ( n = 300) completed Screen for Child Anxiety-Related Emotional Disorders (SCARED), whereas a non-overlapping subsample ( n = 219) completed Depression Self-Rating Scale (DSRS). Structural validity was examined with Confirmatory Factor Analysis and measurement invariance was assessed with Multiple Indicators Multiple Causes (MIMIC) modeling. Convergent and divergent validity were examined using Spearman correlations between RCADS subscales and DSRS, SCARED, and SDQ validators. The six-factor model fitted the data best, validating the originally proposed RCADS structure. Three items displayed differential item functioning for sex, another three for age group, and one item for both, albeit with trivial effect sizes ( d < 0.2). Cronbach’s alpha was .94. Convergent and divergent validity were also established. In conclusion, the RCADS is a valid and reliable instrument for assessing anxiety and depression symptoms in Greek adolescents.

Published
2021

24. Investigating predictors of well-being in type 2 diabetes mellitus patients: the role of undiagnosed depression

Author

Anastasia Antoniou, Alexios Sotiropoulos, Efstathios Skliros, Athanasios Raptis, Rossetos Gournellis, Emmanouil Rizos, Nikolaos Smyrnis, and Panagiotis Ferentinos

Subjects
General Medicine
Abstract

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with various medical and psychological adverse effects. Well-being in patients with T2DM is often compromised. The aim of the present study was to investigate clinicodemographic predictors of well-being in patients with T2DM with no known psychiatric history and explore the mediatory role of undiagnosed anxiety and depression. We recruited 175 outpatients with T2DM (54.3% males, aged 34-79 (mean 59.9) years) followed-up at the Diabetes Center of the General Hospital of Nikaia-Peiraeus in Athens. Patients included had no severe diabetes-related complications or known psychiatric history. Well-being was measured with the Mental Health Continuum Short-Form (MHC-SF), a novel 14-item tool measuring the emotional (EWB), social (SWB) and psychological (PWB) dimensions of well-being, as well as a total score of well-being (WBT). Hospital Anxiety and Depression Scale (HADS) was used for screening for undiagnosed anxiety (HADS-A) and depression (HADS-D). Patients' demographics, Body Mass Index (BMI), glycemic control (HbA1c), T2DM duration, comorbid hypertension or dyslipidemia and type of antidiabetic medication were investigated as predictors of well-being or its dimensions in stepwise linear regression models, also including or excluding HADS-A and HADS-D. Mediational effects of HADS-A and HADS-D were explored in structural equation models through path analyses. Results showed that 21.1% of participants had comorbid depression (HADS-D≥11) and 5.1% comorbid anxiety disorder (HADS-A≥11). In the models without HADS, higher WBT as well as EWB and PWB were significantly predicted by lower HbA1c (all p=0.001) and lower BMI (p=0.015, 0.019 and 0.030, respectively). After being included in the model, HADS-A and HADS-D significantly predicted WBT and every dimension of well-being, but the effects of HbA1c and BMI were no longer statistically significant. In path analyses, the indirect effects of HbA1c and BMI on well-being via HADS-D were statistically significant, while the direct and indirect effects via HADS-A were not. Therefore, the effects of HbA1c and BMI on EWB, PWB and WBT were completely mediated by HADS-D. Concludingly, this is the first study using MHC-SF to measure well-being in patients with T2DM. High levels of undiagnosed depression were recorded, in agreement with other studies. Depression was predicted by HbA1c and BMI and finally predicted well-being. Undiagnosed depression fully explained the effects of HbA1c and BMI on well-being. The interplay of glycemic control and positive mental health should be further investigated.

Published
2022

25. Characterisation of medication side effects in patients with mostly resistant depression in a real-world setting

Author

Fabio Panariello, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Diana De Ronchi, Alessandro Serretti, and Chiara Fabbri

Subjects
Psychiatry and Mental health, Biological Psychiatry
Abstract

This study aimed to identify factors associated with side effects of psychotropic drugs in a real-world setting enriched with treatment-resistant depression (TRD) patients.A total of 1410 depressed patients were treated in a naturalistic setting. Side effects were measured with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU); the total score and UKU subscales were considered. Clinical-demographic variables were tested for association with side effects in univariate and then multivariate analyses.Total, psychic and neurological side effects were associated with depressive symptom severity, while autonomic side effects were higher in those with somatic comorbidities and other side effects were lower in patients receiving trazodone. In multivariate analyses, depressive symptom severity was associated with psychic and total side effects, while generalised anxiety disorder (GAD) with neurological side effects and somatic comorbidities remained associated with autonomic side effects. Trazodone was associated with lower side effects and with augmentation treatments. Augmentation therapies showed opposite effects depending on response status, i.e. increased or decreased the risk of side effects in responders and non-responders/resistant patients, respectively.Psychic side effects may be difficult to distinguish from depressive symptoms and factors associated with different types of side effects are heterogeneous and likely interacting.

Published
2022

26. New‑onset neuropsychiatric sequelae and 'long‑COVID' syndrome (Review)

Author

Vasiliki Efstathiou, Maria-Ioanna Stefanou, Marina Demetriou, Nikolaos Siafakas, Eleni Katsantoni, Michael Makris, Georgios Tsivgoulis, Vassilios Zoumpourlis, Stylianos Kympouropoulos, James Tsoporis, Demetrios Spandidos, Panagiotis Ferentinos, Nikolaos Smyrnis, and Emmanouil Rizos

Subjects
Cancer Research, Immunology and Microbiology (miscellaneous), General Medicine
Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had a widespread impact on individuals' mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post-acute 'long-COVID' phase. In addition to the COVID-19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID-19, there is accumulating evidence that a diagnosis of COVID-19 may also be associated with new-onset neuropsychiatric morbidity among survivors without pre-existing mental health disorders. In particular, studies investigating the incidence of post-acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new-onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID-19 survivors were compared with SARS-CoV-2-negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies. While there is evidence of an association between SARS-CoV-2 infection and the subsequent occurrence of new-onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships.

Published
2022

28. PHARMACOGENETICS OF CYP2C19 IN RESPONSE AND SIDE EFFECTS TO MAJOR DEPRESSIVE DISORDER TREATMENT: A MACHINE LEARNING APPROACH

Author

Marco Calabrò, Chiara Fabbri, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Diana De Ronchi, Alessandro Serretti, and Concetta Crisafulli

Subjects
Pharmacology, Psychiatry and Mental health, Neurology, Pharmacology (medical), Neurology (clinical), Biological Psychiatry
Published
2022

29. Mental health of unaccompanied refugee minors in Greece living 'in limbo'

Author

Ioanna Giannopoulou, Lida Mourloukou, Vasiliki Efstathiou, Athanassios Douzenis, and Panagiotis Ferentinos

Subjects
Male, Minors, Stress Disorders, Post-Traumatic, Refugees, Cross-Sectional Studies, Mental Health, Greece, Humans, General Medicine, Child
Abstract

The closure of the Balkan migration route in 2016, had implications for unaccompanied refugee minors (URMs), given that the vast majority, who perceived Greece as "stopover" for their desired final destination, were forced to remain in the country for an indeterminate period of time. This created for URMs a challenging situation of living "in limbo" uncertain about their future awaiting for a long time the outcome of their asylum application. This cross-sectional study aimed to explore the mental health of URMs, who arrived in Greece in 2016. The sample comprised 90 URMs (76 boys), aged 13-17 years, consisting of 46 Syrians and 44 originating from other countries. Participants completed socio-demographic information and a range of clinical measures, including Children's Revised Impact of Events Scale (CRIES), Depression Self-Rating Scale (DSRS), Children's Post-Traumatic Cognitions Inventory (cPTCI), a measure of trauma exposure and perceived social support. Syrian URMs were significantly more likely than URMs originating from other countries to score within the probable clinical depression range (71.7% versus 47.7% respectively, p=0.020), to display probable posttraumatic stress disorder (PTSD), i.e., score within clinically significant range of posttraumatic stress symptoms and negative post-trauma cognitions (87% versus 65.9%, p=0.018), and meet the comorbidity PTSD/depression criterion (65.2% versus 40.9%, p=0.021). Multiple linear stepwise regression analyses showed that legal status (seeking asylum in Europe through family reunification procedure) significantly predicted higher levels of depressive symptoms (β=0.29, p=0.004), posttraumatic stress symptoms (β=0.21, p=0.034) and negative cognitions (β=0.33, p=0.001). The total number of stressful/traumatic experiences and male gender were found to be significantly related only with posttraumatic symptoms severity score (β=0.29, p=0.003), whereas lower levels of perceived social support were associated with increased levels of depressive symptoms (β=0.24, p=0.018) and negative cognitions and appraisals of the world and the self (β=0.26, p=0.008). These findings highlight the burden of living "in limbo" situation and add weight to the argument for amending restrictive EU asylum policies and accelerating the family reunification procedure under Dublin-III Regulation, as well as the pressing need for improved URMs access to mental health services and psychosocial support.

Published
2022

30. Identifying the Common Genetic Basis of Antidepressant Response

Author

Sara A. Paciga, Richard M. Weinshilboum, Andrew M. McIntosh, Tim B. Bigdeli, Stephanie H. Witt, Sven Cichon, Glyn Lewis, Henning Teismann, Brenda W.J.H. Penninx, Gerome Breen, Roseann E. Peterson, Saira Saeed Mirza, Diego Albani, Lisa Jones, Andreas J. Forstner, Sara Mostafavi, Julien Bryois, Qingqin S. Li, Kenneth S. Kendler, Thomas Damm Als, Fernando S. Goes, Marie Bækvad-Hansen, Nancy L. Pedersen, Gianluigi Forloni, Per Qvist, Carsten Horn, Per Hoffmann, Steven P. Hamilton, Georg Homuth, Michael Gill, Julien Mendlewicz, Katharina Domschke, Volker Arolt, Adrian I. Campos, Christine Søholm Hansen, Scott D. Gordon, Hogni Oskarsson, Peter McGuffin, Oliver Pain, Eric Jorgenson, Victoria S. Marshe, Stacy Steinberg, Bertram Müller-Myhsok, Mark Adams, J. Raymond DePaulo, Rick Jansen, Katherine J. Aitchison, Vassily Trubetskoy, Henry Völzke, Manuel Mattheisen, Bernard Ng, James A. Knowles, Dorret I. Boomsma, Tracy Air, Elisabeth B. Binder, Ian B. Hickie, Christel M. Middeldorp, Tõnu Esko, David M. Hougaard, E.J.C. de Geus, Toni-Kim Clarke, Helena Gaspar, Bernhard T. Baune, Abdel Abdellaoui, Engilbert Sigurdsson, Andres Metspalu, Klaus Berger, Jorge A. Quiroz, Patrick F. Sullivan, Aartjan T.F. Beekman, Thomas Hansen, Panagiotis Ferentinos, Jürgen Wellmann, Miguel E. Rentería, Daniel Umbricht, Marcella Rietschel, Stanley I. Shyn, Chiara Fabbri, Hreinn Stefansson, Jerome C. Foo, Daniel Souery, Zoltán Kutalik, Yu-Li Liu, Paul F. O'Reilly, Michael John Owen, Nese Direk, Douglas F. Levinson, Stuart Montgomery, Hamdi Mbarek, David M. Howard, Guido Bondolfi, Lucía Colodro-Conde, Pippa A. Thomson, Merete Nordentoft, Stefan Kloiber, Yunpeng Wang, Michael Conlon O'Donovan, Grant C.B. Sinnamon, Alexander Viktorin, Hilary K. Finucane, Esben Agerbo, Stefan Herms, Markus M. Nöthen, Till F. M. Andlauer, Divya Mehta, Bradley T. Webb, Joanna M. Biernacka, David J. Porteous, Jordan W. Smoller, Jonathan R. I. Coleman, Dean F. MacKinnon, Farnush Farhadi Hassan Kiadeh, Baptiste Couvy-Duchesne, Evelin Mihailov, Eleanor M. Wigmore, Franziska Degenhardt, Jianxin Shi, Dale R. Nyholt, Enda M. Byrne, Stephan Ripke, Ole Mors, Patrik K. E. Magnusson, Eric J. Lenze, Warren W. Kretzschmar, Masaki Kato, Marcus Ising, Ian Jones, Lynsey S. Hall, Wouter J. Peyrot, Ling Shen, Nader Perroud, Na Cai, Maciej Trzaskowski, Matthias Nauck, Isaac S. Kohane, Enrico Domenici, Fabian Streit, James L. Kennedy, Peter M. Visscher, Valentina Escott-Price, Donald J. MacIntyre, Enrique Castelao, Margarita Rivera, Mojca Z. Dernovsek, John P. Rice, Joseph Zohar, Gail Davies, Andrew C. Heath, Josef Frank, Wesley K. Thompson, Caroline Hayward, Penelope A. Lind, Thorgeir E. Thorgeirsson, Rudolf Uher, Jana Strohmaier, Henriette N. Buttenschøn, Erin C. Dunn, Jonas Bybjerg-Grauholm, Alexander Teumer, Jakob Grove, Eske M. Derks, Nicholas G. Martin, Jodie N. Painter, Myrna M. Weissman, Preben Bo Mortensen, Michel G. Nivard, Catherine Schaefer, Yihan Li, Daniel J. Smith, Shih-Jen Tsai, Niamh Mullins, Jian Yang, Marianne Giørtz Pedersen, Dan Rujescu, Thomas G. Schulze, Lili Milani, Yuri Milaneschi, Giorgio Pistis, James B. Potash, Neven Henigsberg, Nicholas John Craddock, Karen Hodgson, Silviu-Alin Bacanu, Shantel Weinsheimer, Charles F. Reynolds, Johannes H. Smit, Gonneke Willemsen, Futao Zhang, Henning Tiemeier, Grant W. Montgomery, Martin Preisig, Udo Dannlowski, Thalia C. Eley, Thomas Werge, Katherine E. Tansey, Jane H. Christensen, Julia Kraft, Ian J. Deary, Cathryn M. Lewis, Sarah E. Medland, André G. Uitterlinden, Daniel J. Müller, Carsten Bøcker Pedersen, Gustavo Turecki, Hans J. Grabe, Matthew Traylor, Brien P. Riley, Roy H. Perlis, Patrick J. McGrath, Conor V. Dolan, Hualin S. Xi, Jonathan Marchini, Robert A. Schoevers, Albert M. van Hemert, Anders D. Børglum, Susanne Lucae, Jouke-Jan Hottenga, Kari Stefansson, Benoit H. Mulsant, Francis M. Mondimore, Naomi R. Wray, Yang Wu, Wolfgang Maier, Danielle Posthuma, Annamaria Cattaneo, Gregory E. Crawford, Siegfried Kasper, Alessandro Serretti, Tania Carrillo-Roa, Robert Maier, Pamela A. F. Madden, Eva C. Schulte, Jens Treutlein, Joanna Hauser, Sandra Van der Auwera, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Methodology, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Adult Psychiatry, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Epidemiology, Child and Adolescent Psychiatry / Psychology, and Internal Medicine

Subjects
Oncology, MDD, medicine.medical_specialty, Single-nucleotide polymorphism, Genome-wide association study, Biology, Antidepressant response, Depression, GWAS, Genetics, Polygenic score, SDG 3 - Good Health and Well-being, Internal medicine, Genetic variation, medicine, ddc:610, Genetic association, General Medicine, Heritability, medicine.disease, Schizophrenia, Sample size determination, Settore BIO/14 - Farmacologia, Major depressive disorder
Abstract

Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction.Methods: Genome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA.Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response.Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

Published
2022

31. The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease

Author

Panagiotis Ferentinos, Costas Tsakirides, Michelle Swainson, Adam Davison, Marrissa Martyn-St James, and Theocharis Ispoglou

Subjects
Physiology, Public Health, Environmental and Occupational Health, Stroke Volume, General Medicine, Metabolic Diseases, Physiology (medical), embryonic structures, cardiovascular system, Humans, Orthopedics and Sports Medicine, Endothelium, Vascular, Exercise, Endothelial Progenitor Cells, circulatory and respiratory physiology
Abstract

Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs. Objectives: to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Results: six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction. Conclusion: the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term. Graphical abstract

Published
2022

32. Cortisol to Dehydroepiandrosterone Sulphate Ratio and Executive Function in Bipolar Disorder

Author

Ioannis Michopoulos, Panagiotis Ferentinos, Constantin R. Soldatos, Dimitris Dikeos, Maria Alevizaki, Kalliopi Tournikioti, Athanasios Douzenis, and Aimilia Mantzou

Subjects
endocrine system, medicine.medical_specialty, Bipolar Disorder, Hydrocortisone, medicine.drug_class, Neuropsychological Tests, Audiology, Spatial memory, Executive Function, Humans, Medicine, Effects of sleep deprivation on cognitive performance, Bipolar disorder, Biological Psychiatry, Dehydroepiandrosterone Sulfate, business.industry, Cambridge Neuropsychological Test Automated Battery, Mood stabilizer, Executive functions, medicine.disease, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Verbal memory, business, Neurocognitive, hormones, hormone substitutes, and hormone antagonists
Abstract

Introduction: Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. Methods: Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). Results: Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). Conclusions: This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.

Published
2021

33. Social withdrawal as a trans-diagnostic predictor of short-term remission: A meta-analysis of five clinical cohorts

Author

Alessandro Serretti, Diego Albani, Giuseppe Fanelli, Daniel Souery, Chiara Fabbri, Vincenzo Oliva, Martien J H Kas, Stuart Montgomery, Joseph Zohar, Siegfried Kasper, Diana De Ronchi, Dan Rujescu, Panagiotis Ferentinos, Julien Mendlewicz, Gianluigi Forloni, Kas lab, Oliva V., Fanelli G., Kasper S., Zohar J., Souery D., Montgomery S., Albani D., Forloni G., Ferentinos P., Rujescu D., Mendlewicz J., Kas M.J., de Ronchi D., Fabbri C., and Serretti A.

Subjects
medicine.medical_specialty, Bipolar Disorder, Social withdrawal, Psychopharmacology, Remission, Major depressive disorder, Disease, Logistic regression, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Humans, Pharmacology (medical), Disengagement theory, Transdiagnostic, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Mental Disorders, medicine.disease, Psychiatry and Mental health, Social Isolation, Schizophrenia, Meta-analysis, business, Psychopathology
Abstract

Social withdrawal is an early manifestation of several neuropsychiatric disorders, and it is characterised by a gradual disengagement from social interactions, potentially leading to complete isolation. This study investigated the association between social withdrawal at baseline and short-term symptom remission in five independent cohorts, including patients with major depressive disorder (MDD), bipolar spectrum disorders, and schizophrenia. Measures of social withdrawal were derived in each study, and clinical remission was estimated based on the psychopathological severity assessed after short-term psychopharmacological treatment (12weeks). Logistic regression was performed in each sample, adjusting for age and baseline psychopathological severity residualised for social withdrawal. Results were then meta-analysed across samples within a random-effect framework. A total of 4461 patients were included in the analyses (3195 patients with MDD, 655 with bipolar spectrum disorders and 611 with schizophrenia). The meta-analysis showed that higher baseline levels of social withdrawal were associated with a decreased likelihood of short-term remission (ORadj=0.67, 95% CI, 0.58-0.79, P=5.28×10−7), with the strongest effect in patients with schizophrenia. Overall, our study highlighted the need to address social withdrawal in the early phases of the disease to promote symptom remission in patients with major psychiatric disorders. Understanding the neurobiology underlying social withdrawal may aid the development of medications that can specifically reverse social impairment, thereby fostering clinical remission. Int Clin Psychopharmacol 37: 38-45 Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Published
2022

35. Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia : an international multicenter study

Author

Nikolaos Smyrnis, Felicia Iftene, Olivera Vuković, Henry K. Karlsson, Jan Hilbig, Dan J. Stein, Marc De Hert, C. Bredicean, Ion Papava, Sanja Vodopic, Jean-Michel Azorin, Athanasios Douzenis, Maija Walta, Hasan Karadağ, Petra Furstova, Filip Spaniel, Klaudia Domowicz, Anuja Bendre, María Paz García-Portilla, Gamze Erzin, Erik Thys, Valentina Corigliano, Paweł Wójciak, Anastasia Konsta, Amresh Shrivastava, Anca-Livia Panfil, Dora Vajda, Elmars Rancans, Martien Wampers, Lidija Injac Stevovic, Leticia García-Álvarez, Anita Juhasz, Oluremi Oladele, Xenofon Atmatzidis, Alvydas Navickas, Ioannis Michopoulos, Pavel Knytl, Ida S. Haussleiter, Trayana Hristova, Rajiv Tandon, Dusica Lecic-Tosevski, Maria Luísa Figueira, Fleur M. Howells, Laurynas Bukelskis, Daria Smirnova, Leonidas Mantonakis, Olga Izmailova, Joana Crawford, Justine Bouniard, Panagiotis Ferentinos, Vincent Russell, Oluyomi Esan, Julie Montant, Tobias Wiklund, Tiina From, Luchezar Hranov, Roumen Milev, Georg Juckel, Nikolaos K. Fountoulakis, Michael Berk, Janusz K. Rybakowski, Ioannis Nimatoudis, Elena Dragioti, Cyril Höschl, Julio Bobes, Zsófia Nemes, Anna Comparelli, Bojana Pejuskovic, Olivia M Dean, Konstantinos N. Fountoulakis, Avinash De Sousa, Loukas Athanasiadis, Daniil Aptalidis, Ludgero Linhares, Henk Temmingh, Raimo K. R. Salokangas, Antonis T. Theofilidis, John L. Waddington, Xenia Gonda, Christopher Osunbote, Siegfried Kasper, and Maurizio Pompili

Subjects
Male, Pediatrics, medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Age of Onset, Depression (differential diagnoses), Positive and Negative Syndrome Scale, business.industry, Confounding, medicine.disease, Mental health, 030227 psychiatry, 3. Good health, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Schizophrenia, Anxiety, Female, Neurology (clinical), Analysis of variance, Human medicine, medicine.symptom, business, 030217 neurology & neurosurgery, Diagnosis of schizophrenia
Abstract

BackgroundThe aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.MethodsTwenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.ResultsThere was a 3-year later age at onset for females (P P P P = .001). No significant effects were found concerning duration of illness.DiscussionOur results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Published
2022

36. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author

Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. 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J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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T.F.M., Bacanu S.-A., Baekvad-Hansen M., Beekman A.T.F., Bryois J., Buttenschon H.N., Bybjerg-Grauholm J., Cai N., Christensen J.H., Clarke T.-K., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Escott-Price V., Hassan Kiadeh F.F., Finucane H.K., Frank J., Gaspar H.A., Gill M., Goes F.S., Gordon S.D., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Boomsma D.I., Dannlowski U., de Geus E.J.C., Depaulo J.R., Domenici E., Domschke K., Esko T., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Hougaard D.M., Howard D.M., Jansen R., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., Middeldorp C.M., Mihailov E., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Lewis G., Li Q.S., Madden P.A.F., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Nordentoft M., Paciga S.A., Pedersen N.L., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Sigurdsson E., Sinnamon G.C.B., Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Perlis R.H., Porteous D.J., Schaefer C., Stefansson K., Tiemeier H., Uher R., Werge T., Lewis C.M., Breen G., Borglum A.D., Sullivan P.F., O'Connell K.S., Coombes B., Qiao Z., Als T.D., Borte S., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.

Subjects
LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Published
2022

37. Executive Dysfunction, Social Cognition Impairment, and Gray Matter Pathology in Myotonic Dystrophy Type 2: A Pilot Study

Author

Thomas Theodosiou, Foteini Christidi, Sofia Xirou, Efstratios Karavasilis, Peter Bede, Constantinos Papadopoulos, Georgios D. Argyropoulos, Panagiotis Kourtesis, Varvara Pantolewn, Panagiotis Ferentinos, Evangelia Kararizou, Georgios Velonakis, Ioannis Zalonis, Georgios Papadimas, National and Kapodistrian University of Athens (NKUA), Trinity College Dublin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 3D interaction with virtual environments using body and mind (Hybrid), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-RÉALITÉ VIRTUELLE, HUMAINS VIRTUELS, INTERACTIONS ET ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)

Subjects
Cognitive Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, executive impairment, [SHS.PSY]Humanities and Social Sciences/Psychology, Bayes Theorem, Pilot Projects, General Medicine, social cognition, Neuropsychological Tests, Magnetic Resonance Imaging, Psychiatry and Mental health, Cognition, Neuropsychology and Physiological Psychology, [SCCO.PSYC]Cognitive science/Psychology, Humans, Myotonic Dystrophy, voxel-based morphometry, Cognitive Dysfunction, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Atrophy, Gray Matter, myotonic dystrophy type 2, cognitive impairment
Abstract

In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized.To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2.Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: PFDR0.05 and Bayes factor (BF 10 )10.The DM2 group exhibited cognitive impairment (ECAS Total score; PFDR = 0.001; BF 10 = 108.887), which was dominated by executive impairment ( PFDR = 0.003; BF 10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami.DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.

Published
2022

38. Acute Cardiorespiratory Responses to Different Exercise Modalities in Chronic Heart Failure Patients—A Pilot Study

Author

Argyrios Ntalianis, Georgios Mitsiou, Stavros Dimopoulos, Panagiotis Ferentinos, Serafeim Nanas, and Eleftherios Karatzanos

Subjects
medicine.medical_specialty, heart failure, high intensity interval training, Hemodynamics, acute exercise, Article, Interval training, continuous exercise, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, Pharmacology (medical), In patient, General Pharmacology, Toxicology and Pharmaceutics, Adverse effect, business.industry, Cardiorespiratory fitness, medicine.disease, Intensity (physics), cardiac rehabilitation, RC666-701, Heart failure, Cardiology, business, High-intensity interval training, human activities
Abstract

The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO2peak intensities between three “iso-work” protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON70) and (c) a lower intensity continuous protocol (CON50) in patients with chronic heart failure (CHF). Ten male CHF patients (aged 55.1 ± 16.2 years) performed in separate days a single session of a HIIT protocol consisted of 4 sets × 4 min cycling at 80% VO2peak with 3 min of recovery at 50% VO2peak, a CON70 protocol corresponding to 70% VO2peak and a CON50 protocol corresponding to 50% VO2peak. Cardiopulmonary data were collected by an online gas analysis system. The HIIT and CON70 elicited higher cardiorespiratory responses compared to CON50 with no differences between them (p > 0.05). In HIIT and CON70, patients exercised longer at >80% and >90% VO2peak. The completion rate was 100% for the three protocols. Not any adverse events were observed in either protocol. Both HIIT and CON70 elicited a stronger physiological stimulus and required shorter time than CON50. Both HIIT and CON70 also induced comparable hemodynamic responses and ventilatory demand.

Published
2021

39. The impact of different forms of exercise on endothelial progenitor cells in healthy populations

Author

Panagiotis Ferentinos, Costas Tsakirides, Michelle Swainson, Adam Davison, Marrissa Martyn-St James, and Theocharis Ispoglou

Subjects
Physiology, Public Health, Environmental and Occupational Health, General Medicine, High-Intensity Interval Training, Flow Cytometry, Exercise Therapy, Physiology (medical), embryonic structures, cardiovascular system, Humans, Orthopedics and Sports Medicine, Exercise, circulatory and respiratory physiology, Aged, Endothelial Progenitor Cells
Abstract

Circulating endothelial progenitor cells (EPCs) contribute to vascular healing and neovascularisation, while exercise is an effective means to mobilise EPCs into the circulation. Objectives: to systematically examine the acute and chronic effects of different forms of exercise on circulating EPCs in healthy populations. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Results: thirty-one articles met the inclusion criteria including 747 participants aged 19 to 76 years. All included trials used flow cytometry for identification of circulating EPCs. Eight and five different EPC phenotypes were identified in the acute and chronic trials, respectively. In the acute trials, moderate intensity continuous (MICON), maximal, prolonged endurance, resistance and high intensity interval training (HIIT) exercise protocols were utilised. Prolonged endurance and resistance exercise had the most profound effect on circulating EPCs followed by maximal exercise. In the chronic trials, MICON exercise, HIIT, HIIT compared to MICON and MICON compared to exergame (exercise modality based on an interactive video game) were identified. MICON exercise had a positive effect on circulating EPCs in older sedentary individuals which was accompanied by improvements in endothelial function and arterial stiffness. Long-stage HIIT (4 min bouts) appears to be an effective means and superior than MICON exercise in mobilising circulating EPCs. In conclusion, both in acute and chronic trials the degree of exercise-induced EPC mobilisation depends upon the exercise regime applied. In future, more research is warranted to examine the dose–response relationship of different exercise forms on circulating EPCs using standardised methodology and EPC phenotype. Graphical abstract

Published
2021

41. Similar or Different Neuropsychological Profiles? Only Set Shifting Differentiates Women With Bipolar vs. Borderline Personality Disorder

Author

Nikolaos Smyrnis, Antonios Paraschakis, Rossetos Gournellis, Ioannis Michopoulos, Panagiotis Ferentinos, Anna Karavia, and Kalliopi Tournikioti

Subjects
RC435-571, behavioral disciplines and activities, memory, 03 medical and health sciences, 0302 clinical medicine, Visual memory, mental disorders, Medicine, Bipolar disorder, Borderline personality disorder, Response inhibition, Psychiatry, business.industry, Cambridge Neuropsychological Test Automated Battery, borderline, Neuropsychology, Cognitive flexibility, CANTAB, Brief Research Report, medicine.disease, bipolar, 030227 psychiatry, Psychiatry and Mental health, executive function, set shifting, Analysis of variance, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

There is ongoing debate about the similarities and differences between bipolar disorder (BD) and borderline personality disorder (BPD). Very few studies have concurrently assessed their neuropsychological profile and only on a narrow array of neuropsychological tests. We aimed to investigate the differences of these two patient groups on visual memory, executive function, and response inhibition. Twenty-nine BD patients, 27 BPD patients and 22 controls (all female) were directly compared on paired associates learning (PAL), set shifting (ID/ED), problem solving (SOC), and response inhibition (SSRT) using Cambridge Neuropsychological Test Automated Battery (CANTAB). Rank-normalized outcomes were contrasted in one-way ANOVA tests. Discriminant analysis was finally performed to predict BD or BPD patient status. BD patients performed significantly worse than controls on all tasks. BPD patients performed significantly worse than HC on all tests except SST. Significant differences between the two patient groups were recorded only on ID/ED, where BPD patients performed worse (p = 0.044). A forward stepwise discriminant analysis model based on ID/ED and SOC predicted correctly patients' group at 67.9% of cases. In conclusion, BD and BPD female patients appear to be more similar than different as regards their neuropsychological functions. This study is the first to show that BPD patients display more deficits than BD patients when directly compared on the set shifting executive function test, a marker of cognitive flexibility. Discerning BD from BPD patients through neuropsychological performance is promising but would improve by using additional subtler tests and psychometric evaluation.

Published
2021

42. Effects of low molecular weight heparin and fondaparinux on mortality, hemorrhagic and thrombotic complications in COVID-19 patients

Author

Paraskevi C. Fragkou, Lina Palaiodimou, Maria Ioanna Stefanou, Aristeidis H. Katsanos, Vaia Lambadiari, Dimitrios Paraskevis, Elisabeth Andreadou, Dimitra Dimopoulou, Christina Zompola, Panagiotis Ferentinos, Theodoros I. Vassilakopoulos, Anastasia Kotanidou, Petros P. Sfikakis, Sotirios Tsiodras, and Georgios Tsivgoulis

Subjects
Pharmacology, Neurology, Neurology (clinical)
Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation dose in COVID-19. Objective: We aim to systematically assess the currently available data regarding the effects of different dosing regimens of low molecular weight heparin and/or fondaparinux (LMWH/F) on mortality risk as well as the risk of arterial/venous thrombotic events and hemorrhagic complications in confirmed COVID-19 cases. Design: We conducted a living systematic review and meta-analysis on the effects of different LMWH/F doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients. Data Sources and Methods: MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database, and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH/F among confirmed COVID-19 cases. Results: Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between LMWH/F and mortality during the following comparisons: (1) no LMWH/F versus any LMWH/F; (2) prophylactic versus higher than prophylactic LMWH/F; (3) prophylactic versus therapeutic LMWH/F; (4) intermediate versus therapeutic LMWH/F; and (5) lower than therapeutic versus therapeutic LMWH/F. Mortality was higher in patients receiving prophylactic versus intermediate LMWH/F (OR = 2.01; 95% CI: 1.19–3.39). However, this effect was mostly driven by observational data. No associations were detected between the intensity of LMWH/F and the risk of thrombotic and hemorrhagic events, except the lower risk for hemorrhage in patients on prophylactic compared to higher LMWH/F doses. Conclusion: The risk for all-cause mortality was higher in patients receiving prophylactic LMWH/F compared to those on an intermediate dose of LMWH/F, based on observational data. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies. Registration: The study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (Registration number: CRD42021229771).

Published
2021

43. A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response

Author

Joseph Zohar, Siegfried Kasper, Alessandro Serretti, Alessandra Minelli, Alessio Squassina, Marco Bortolomasi, Paolo Martini, Chiara Fabbri, Diana De Ronchi, Diego Albani, Massimo Gennarelli, Dan Rujescu, Giuseppe Fanelli, Katharina Domschke, Daniel Souery, Bernhard T. Baune, Stuart Montgomery, Eduard Maron, Julien Mendlewicz, Panagiotis Ferentinos, and Gianluigi Forloni

Subjects
business.industry, medicine.disease, Population stratification, Neuroticism, symbols.namesake, Bonferroni correction, Mood disorders, Schizophrenia, Meta-analysis, symbols, Medicine, Major depressive disorder, Bipolar disorder, business, Clinical psychology
Abstract

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p=0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11-1.98, p=0.007). Nominal associations were also found between MDD-PRS and non-response (p=0.013), as well as between SCZ-PRS and non-remission (p=0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.

Published
2021

44. The effects of HMG-CoA reductase inhibitors on disease activity in multiple sclerosis: A systematic review and meta-analysis

Author

Vaia Lambadiari, Lina Palaiodimou, Panagiotis Halvatsiotis, Maria Kosmidou, Haralampos Milionis, Georgios Marinos, Georgios Tsivgoulis, Konstantinos Voumvourakis, Panagiotis Ferentinos, John Tzartos, Aikaterini Theodorou, Sotirios Giannopoulos, Aristeidis H. Katsanos, Maria-Ioanna Stefanou, and Elizabeth Andreadou

Subjects
Oncology, medicine.medical_specialty, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Medicine, Humans, Optic neuritis, Randomized Controlled Trials as Topic, Clinically isolated syndrome, biology, business.industry, Multiple sclerosis, General Medicine, Odds ratio, Interferon-beta, Multiple Sclerosis, Chronic Progressive, medicine.disease, Clinical trial, Neurology, Simvastatin, Meta-analysis, HMG-CoA reductase, biology.protein, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, medicine.drug
Abstract

Objective To assess whether statins (3‑hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert disease-modifying effects in multiple sclerosis (MS). Approach A systematic review and meta-analysis was performed including randomized-controlled clinical trials (RCTs) on statin use in MS. A random-effects model was applied to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), when comparing patients treated with statins alone or adjunct to disease modifying treatment (DMT) to non-statin-treated patients. Results We identified 7 RCTs including 789 patients with relapsing-remitting MS (RRMS), all of whom received additional DMT with IFN-β. Single identified RCTs in secondary-progressive MS (SPMS), clinically isolated syndrome (CIS) and optic neuritis (ON) were not meta-analyzed. In RRMS, add-on statin use was not associated with the risk of clinical relapse (OR=1.30, 95%CI: 0.90 1.87) or EDSS-progression from baseline, neither appeared related to the risk of new contrast-enhancing or T2 lesions (OR=1.28, 95%CI: 0.36 4.58), and the risk of whole-brain volume reduction on MRI. Add-on statins to IFN-β were safe and well-tolerated. In SPMS, stand-alone simvastatin led to significantly reduced annualized rate of whole-brain volume reduction. In CIS and ON, statins were associated with reduced risk for new T2 lesions and improved visual recovery, respectively. Conclusions We detected no benefit from statin treatment as add-on to IFN-β in RRMS. However, a potential beneficial effect in SPMS, CIS and ON deserves independent confirmation and further evaluation within adequately powered RCTs.

Published
2021

45. Well‐being in Patients with Affective Disorders Compared to Nonclinical Participants: A Multi‐Model Evaluation of the Mental Health Continuum‐Short Form

Author

Evgenia Porichi, Athanassios Douzenis, Charalambos Papageorgiou, Panagiotis Ferentinos, Vasiliki Yotsidi, and Anastassios Stalikas

Subjects
Adult, Male, 050103 clinical psychology, Adolescent, Psychometrics, Personal Satisfaction, Structural equation modeling, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Internal consistency, Humans, 0501 psychology and cognitive sciences, In patient, Reliability (statistics), Aged, Aged, 80 and over, Psychiatric Status Rating Scales, Mood Disorders, 05 social sciences, Discriminant validity, Reproducibility of Results, Middle Aged, Mental health, Confirmatory factor analysis, 030227 psychiatry, Clinical Psychology, Well-being, Female, Psychology, Clinical psychology
Abstract

OBJECTIVES The Mental Health Continuum-Short Form (MHC-SF), measuring emotional, social, and psychological well-being, has scarcely been validated in clinical populations. We evaluated MHC-SF in 203 patients with affective disorders and 163 nonclinical participants. METHOD Traditional confirmatory factor analysis (CFA), bifactor CFA, three-factor exploratory structural equation modeling (ESEM), and bifactor ESEM models were compared. Convergent/discriminant validity was tested against classic well-being validators and current mood state. RESULTS All three subscales were significantly lower in patients. Test-retest reliability in patients was moderate. Bifactor ESEM fitted data best and displayed full scalar gender and partial scalar invariance across groups. Factor strength indices suggested that MHC-SF is primarily unidimensional, especially in patients. However, subscales differed considerably on size, internal consistency, distinctness, discriminant validity, and temporal stability. CONCLUSIONS MHC-SF was valid and reliable for monitoring well-being in both clinical and nonclinical samples, but further research is needed before safely concluding on its dimensionality.

Published
2019

46. W29. METABOLIZING STATUS OF CYP2C19 IN ANTIDEPRESSANT RESPONSE AND SIDE EFFECTS: RESULTS FROM A NATURALISTIC STUDY

Author

Stuart Montgomery, Chiara Fabbri, Panagiotis Ferentinos, Dan Rujescu, Alessandro Serretti, Siegfried Kasper, Marco Calabrò, Joseph Zohar, Concetta Crisafulli, Diego Albani, Diana De Ronchi, Gianluigi Forloni, Julien Mendlewicz, and Daniel Souery

Subjects
Pharmacology, medicine.medical_specialty, business.industry, CYP2C19, Psychiatry and Mental health, Naturalistic observation, Neurology, medicine, Antidepressant, Pharmacology (medical), Neurology (clinical), Psychiatry, business, Biological Psychiatry
Published
2021

47. Childhood trauma and suicidality in bipolar disorder: The mediatory role of impulsivity

Author

Sofia Dramilaraki, Vassiliki Efstathiou, Panagiotis Ferentinos, Evgenia Porichi, Anastasia Antoniou, Rossetos Gournellis, Ioannis Michopoulos, and Athanassios Douzenis

Subjects
Male, Mediation (statistics), Bipolar Disorder, General Medicine, medicine.disease, Impulsivity, Suicide, Physical abuse, Surveys and Questionnaires, Impulsive Behavior, medicine, Humans, Female, Self Report, Bipolar disorder, medicine.symptom, Psychology, Clinical psychology
Abstract

Childhood trauma (CT) is correlated with suicidality among patients with bipolar disorder (BD). However, it has not been adequately investigated if a third factor, for instance impulsivity, mediates the effect of CT on suicidality in BD. This study aimed to explore potential mediatory effects of impulsivity in the pathway from CT to suicidality in BD. CT was assessed with the Early Trauma Inventory Self Report-Short Form (ETI-SR-SF), impulsivity with the Barratt Impulsivity Scale-11 (BIS-11) while lifetime suicidality was investigated with the Suicidal Behaviors Questionnaire-Revised (SBQ-R). The effect of childhood trauma on suicidality and impulsivity as well as the effect of impulsivity on suicidality were examined with multiple linear regressions, including gender, age and diagnosis (BD-I, BD-II) as covariates. Structural equation models were built and path analyses were performed (with AMOS 25 software and using bootstrapping in 1000 samples) for the examination of the mediatory role of BIS-11 and its subtypes in the effect of childhood trauma and its subtypes on suicidality. We included 78 BD euthymic patients (60.3% female, 67.9% BD-I). ETI-SR-SF significantly predicted SBQ-R (p=0.004) and BIS-11 (p

Published
2021

48. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

James McKay, Frank Bellivier, Mark A. Frye, Bertram Müller-Myhsok, Fermín Mayoral, I. Nicol Ferrier, Marion Leboyer, Fabian Streit, Dan J. Stein, James L. Kennedy, Christine Søholm Hansen, Scott D. Gordon, Beata Świątkowska, Valentina Escott-Price, Michael Bauer, Lina Martinsson, Donald J. MacIntyre, Oleksandr Frei, Daniel J. Smith, Sara A. Paciga, Takeo Saito, Jennifer L. Moran, Verneri Antilla, C Pantelis, Tomas Olsson, Swapnil Awasthi, Lena Backlund, Eirini Maratou, Martin Schalling, John B. Vincent, Niamh Mullins, Sarah E. Bergen, Niamh L. O'Brien, Marco P. Boks, Carsten Bøcker Pedersen, Mikael Landén, Franziska Degenhardt, Hang Zhou, Margarita Rivera, Andrew M. McIntosh, Manuel Mattheisen, Shawn Levy, Roy H. Perlis, John P. Rice, Sigurdur H. Magnusson, Amanda Dobbyn, Michael Conlon O'Donovan, Julien Bryois, Wolfgang Maier, John-Anker Zwart, J. Raymond DePaulo, Martin Alda, Laura G. Sloofman, Friederike Sophie David, James A. Knowles, Aiden Corvin, Thomas G. Schulze, Markus M. Nöthen, Nolan Kamitaki, Nina Dalkner, Brandon J. Coombes, Gustavo Turecki, Allan H. Young, Caroline M. Nievergelt, Patricia T. Michie, Ingrid Agartz, Towfique Raj, Diego Albani, Maria Grigoroiu-Serbanescu, Bernhard T. Baune, Kyooseob Ha, Vincent Millischer, Engilbert Sigurdsson, Eva C. Beins, Nicholas G. Martin, Gulja Babadjanova, Josef Frank, Eva Z. Reininghaus, Patrick F. Sullivan, Ian R. Gizer, Guy A. Rouleau, Carmel M. Loughland, Christine Lochner, Thorsten M. Kranz, Amy Perry, Arne E. Vaaler, Mariam M. Al Eissa, Simon Xi, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Ketil J. Oedegaard, Helmut Vedder, Carol A. Mathews, Panagiotis Ferentinos, Tim B. Bigdeli, Derek W. Morris, Per Hoffmann, Mark Hyman Rapaport, Peter P. Zandi, Michael John Owen, Douglas M. Ruderfer, Anders D. Børglum, Catharina Lavebratt, Thorgeir E. Thorgeirsson, Paul A. Tooney, Michiaki Kubo, Steven A. Kushner, Jan Hillert, Loes M. Olde Loohuis, Anastasia Antoniou, Murielle Brum, Chikashi Terao, Nathaniel W. McGregor, Fabio Rivas, James B. Potash, Kevin S. O’Connell, Susanne Lucae, Brian M. Schilder, Katrin Gade, Stephan Ripke, Kristina Adorjan, Kari Stefansson, Tiffany A. Greenwood, Panos Roussos, Sarah Kittel-Schneider, Steven A. McCarroll, Sergi Papiol, Heon Jeong Lee, Assen Jablensky, Liliya Abramova, Dennis Hellgren, Jonas Bybjerg-Grauholm, Martin Lundberg, Hong-Hee Won, William Byerley, Lars Alfredsson, Joel Gelernter, Andrew McQuillin, Claire Slaney, Marta Ribasés, Stephanie H. Witt, Yoichiro Kamatani, Kyung Sue Hong, Marie Bækvad-Hansen, María Soler Artigas, Julie M. Cunningham, Fanny Senner, Stacy Steinberg, Paul D. Shilling, Nakao Iwata, Eystein Stordal, Armin Birner, Sarah E. Medland, Miquel Casas, Ben Michael Brumpton, Erlend Bøen, Bryan J. Mowry, Jolanta Lissowska, Francis J. McMahon, Howard J. Edenberg, Grant W. Montgomery, John I. Nurnberger, Stéphane Jamain, Claudio Toma, Ney Alliey-Rodriguez, Ole Mors, Micha Gawlik, David Curtis, Catrin Lewis, Evangelia-Eirini Tsermpini, Georgia Panagiotaropoulou, Marcella Rietschel, Jessica Yang, Ian Jones, Eduard Vieta, Ole A. Andreassen, Richard M. Myers, Dimitris Dikeos, Melissa J. Green, Janet L. Sobell, Maria Koromina, Piotr M. Czerski, Lilijana Oruc, Sven Cichon, Udo Dannlowski, Bruno Etain, Monika Budde, Alessia Fiorentino, Naomi R. Wray, Qingqin S. Li, Murray J. Cairns, Jonathan R. I. Coleman, Jose Guzman-Parra, Andreas J. Forstner, Hannah Young, Alfredo B. Cuellar-Barboza, Julian Roth, Torbjørn Elvsåshagen, Zhen Qiao, Thomas Werge, Athanassios Douzenis, Cristiana Cruceanu, Rolf Adolfsson, Peter Holmans, Vaughan J. Carr, Thomas W. Weickert, Masashi Ikeda, Joanna M. Biernacka, Lea Sirignano, Adam X. Maihofer, Ralph W. Kupka, John Strauss, Anders M. Dale, Elliot S. Gershon, Jakob Grove, Arianna Di Florio, Helena Medeiros, Ingrid Melle, Preben Bo Mortensen, Kristi Krebs, Saskia P. Hagenaars, Liz Forty, Stanley V. Catts, David M. Hougaard, Marianne Giørtz Pedersen, Andreas Reif, Toni-Kim Clarke, Anne T. Spijker, Danielle Posthuma, Manolis Kogevinas, Michael Boehnke, Rosa Bosch, Gerome Breen, Benjamin M. Neale, Jessica S. Johnson, Katherine Gordon-Smith, Cristina Sánchez-Mora, Alexander W. Charney, Henry R. Kranzler, Digby Quested, René S. Kahn, Lili Milani, Merete Nordentoft, Nathalie Brunkhorst-Kanaan, Laura M. Huckins, James T.R. Walters, Sigrid Børte, Antonio F. Pardiñas, Kristian Hveem, Julie Garnham, Jacob Lawrence, Vassily Trubetskoy, Rodney J. Scott, Nicholas Bass, Carlos N. Pato, Andrea Pfennig, Wei Xu, Calwing Liao, Nicholas John Craddock, Thomas Damm Als, Christina M. Hultman, Fernando S. Goes, Adebayo Anjorin, Evgenia Porichi, Frans Henskens, Nelson B. Freimer, Janice M. Fullerton, Cathryn M. Lewis, Srdjan Djurovic, Roel A. Ophoff, Phil Lee, Peter McGuffin, Gunnar Morken, George P. Patrinos, Alessandro Serretti, Cynthia Shannon Weickert, Pablo Cervantes, Bendik S. Winsvold, Tatiana Foroud, Tõnu Esko, Ulrich Schall, Michele T. Pato, Ji Hyun Baek, John R. Kelsoe, Olav B. Smeland, Janos Kalman, Eva C. Schulte, Joanna Hauser, Urs Heilbronner, Magnús Haraldsson, Martin Hautzinger, Lea Zillich, Eline J. Regeer, Douglas Blackwood, Laura J. Scott, Jordan W. Smoller, Michael J. Gandal, Marquis P. Vawter, Philip B. Mitchell, Ole Kristian Drange, Peter R. Schofield, Susanne Bengesser, Stefan Herms, George Kirov, Markus Leber, Louise Frisén, Thomas W. Mühleisen, Susan L. McElroy, Irwin D. Waldman, Wade H. Berrettini, Sally I. Sharp, Minsoo Kim, Lisa Jones, Eli A. Stahl, Hreinn Stefansson, Esben Agerbo, Dolores Malaspina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman J.R.I., Qiao Z., Als T.D., Bigdeli T.B., Borte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Baekvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Bocker Pedersen C., Boen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.-K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsashagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Giortz Pedersen M., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.-J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McCarroll S.A., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sanchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Soholm Hansen C., Soler Artigas M., Spijker A.T., Stein D.J., Strauss J.S., Swiatkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Walters J.T.R., Witt S.H., Xi S., Xu W., Yang J.M.K., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood D.H.R., Boehnke M., Borglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Muller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribases M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Shannon Weickert C., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.-A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etain, Bruno

Subjects
Multifactorial Inheritance, Bipolar Disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Genome-wide association study, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH: Bipolar Disorder, Chromosomes, Human, Spectrum disorder, Genetics, 0303 health sciences, Bipolar Disorder/genetics, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Schizophrenia, Synaptic signaling, Case-Control Studie, Human, Quantitative Trait Loci, Biology, MESH: Phenotype, MESH: Chromosomes, Human, Article, 03 medical and health sciences, MESH: Major Histocompatibility Complex, SDG 3 - Good Health and Well-being, ddc:570, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, Multifactorial Inheritance/genetics, MESH: Genome, Human, 030304 developmental biology, MESH: Humans, Genome, Human, Risk Factor, Chromosomes, Human/genetics, Mental illness, medicine.disease, MESH: Quantitative Trait Loci, Human genetics, Psychologie, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, Expression quantitative trait loci, MESH: Multifactorial Inheritance, Quantitative Trait Loci/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2021

49. Research domain criteria (Rdoc): A perspective to probe the biological background behind treatment efficacy in depression

Author

Daniel Souery, Chiara Fabbri, Stuart Montgomery, Roberto Colombo, Joseph Zohar, Diego Albani, Diana De Ronchi, Concetta Crisafulli, Marco Calabrò, Dan Rujescu, Panagiotis Ferentinos, Gianluigi Forloni, Alessandro Serretti, Julien Mendlewicz, Siegfried Kasper, Calabro M., Fabbri C., Kasper S., Zohar J., Souery D., Montgomery S., Albani D., Forloni G., Ferentinos P., Rujescu D., Mendlewicz J., Colombo R., De Ronchi D., Serretti A., and Crisafulli C.

Subjects
Nosology, United State, Drug target, Research domain criteria, Antidepressant, Major depressive disorder, 01 natural sciences, Biochemistry, RDoC Construct, 03 medical and health sciences, Drug Discovery, medicine, Humans, 0101 mathematics, Depression (differential diagnoses), National Institute of Mental Health (U.S.), 030304 developmental biology, Pharmacology, 0303 health sciences, Depressive Disorder, Major, Depression, Mental Disorders, Organic Chemistry, Perspective (graphical), RDoC Constructs, antidepressant, behavioral paradigm, drugs targets, major depressive disorder, medicine.disease, Mental health, Behavioral paradigm, Treatment efficacy, United States, 010101 applied mathematics, Treatment Outcome, Molecular Medicine, Psychology, Research Domain Criteria, Clinical psychology, Human
Abstract

Background: Major Depressive Disorder(MDD) and its frequent partial response to antidepressants are a major health concern and therefore an important focus of research. Despite the efforts, MDD pathogenesis and the mechanisms of antidepressant action are only partially understood. In the last few years, the need of rethinking the classification of depressive disorders and psychiatric disorders, in general, has been suggested, in order to provide a nosology that reflects more closely the biological background associated with disease pathogenesis and its role/significance in treatment. The classification proposed by the National Institute of Mental Health (NIMH), namely the research domain criteria (RDoC), may represent a key framework to guide research in this direction. Methods: A literature search was performed on PubMed and Google Scholar databases in order to retrieve data regarding Antidepressants effects on specific RDoC constructs. Further, the targets of drugs of interest were identified through the Drug bank database, and their possible function within RDoC constructs was discussed. Discussion: In this review, we summarize and discuss the significance of the results of pre-clinical and clinical studies investigating specific RDoC paradigms relevant to depressive phenotypes and antidepressant effects. Conclusion: The RDoC framework may facilitate a more specific use of antidepressants based on the individual’s spectrum of symptoms and the development of new compounds that target specific depressive symptoms.

Published
2021

50. A polygenic predictor of treatment-resistant depression using whole exome sequencing and genome-wide genotyping

Author

Alessandro Serretti, Julien Mendlewicz, Alexander Kautzky, Gianluigi Forloni, Diego Albani, Panagiotis Ferentinos, Siegfried Kasper, Daniel Souery, Chiara Fabbri, Joseph Zohar, Dan Rujescu, Stuart Montgomery, Rudolf Uher, Cathryn M. Lewis, Fabbri C., Kasper S., Kautzky A., Zohar J., Souery D., Montgomery S., Albani D., Forloni G., Ferentinos P., Rujescu D., Mendlewicz J., Uher R., Lewis C.M., and Serretti A.

Subjects
Exome sequencing, Oncology, DISORDER, Genome-wide association study, Antidepressant, VARIANTS, Genome, Depressive Disorder, Treatment-Resistant, 0302 clinical medicine, RARE, Physiopsychologie et psychologie biologique [psychiatrie], IMPUTATION, Exome, 0303 health sciences, Depression, treatment-resistant depression, exome sequencing, genome-wide association study, pathway, antidepressant, polygenic prediction, predictive modeling, ASSOCIATION, 3. Good health, Psychiatry and Mental health, TREATMENT-RESISTANT DEPRESSION, Major depressive disorder, BURDEN, medicine.medical_specialty, Genotype, Predictive markers, Article, lcsh:RC321-571, Pharmacological treatment, Cellular and Molecular Neuroscience, 03 medical and health sciences, Internal medicine, Genetic model, Exome Sequencing, medicine, Humans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Gene, Genotyping, Biological Psychiatry, 030304 developmental biology, Depressive Disorder, Major, business.industry, Physique, Astronomie, medicine.disease, TAR-ASTERISK-D, 030227 psychiatry, ANTIDEPRESSANT RESPONSE, business, Pharmacogenomics, Treatment-resistant depression, 030217 neurology & neurosurgery, Imputation (genetics), Psychiatrie
Abstract

Treatment-resistant depression (TRD) occurs in ~30% of patients with major depressive disorder (MDD) but the genetics of TRD was previously poorly investigated. Whole exome sequencing and genome-wide genotyping were available in 1209 MDD patients after quality control. Antidepressant response was compared to non-response to one treatment and non-response to two or more treatments (TRD). Differences in the risk of carrying damaging variants were tested. A score expressing the burden of variants in genes and pathways was calculated weighting each variant for its functional (Eigen) score and frequency. Gene-based and pathway-based scores were used to develop predictive models of TRD and non-response using gradient boosting in 70% of the sample (training) which were tested in the remaining 30% (testing), evaluating also the addition of clinical predictors. Independent replication was tested in STAR*D and GENDEP using exome array-based data. TRD and non-responders did not show higher risk to carry damaging variants compared to responders. Genes/pathways associated with TRD included those modulating cell survival and proliferation, neurodegeneration, and immune response. Genetic models showed significant prediction of TRD vs. response and they were improved by the addition of clinical predictors, but they were not significantly better than clinical predictors alone. Replication results were driven by clinical factors, except for a model developed in subjects treated with serotonergic antidepressants, which showed a clear improvement in prediction at the extremes of the genetic score distribution in STAR*D. These results suggested relevant biological mechanisms implicated in TRD and a new methodological approach to the prediction of TRD., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

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