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1. Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures

Author: Vladimir Belov, Tracy Erwin-Grabner, Moji Aghajani, Andre Aleman, Alyssa R. Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Robin Bülow, Christopher R. K. Ching, Colm G. Connolly, Kathryn Cullen, Christopher G. Davey, Danai Dima, Annemiek Dols, Jennifer W. Evans, Cynthia H. Y. Fu, Ali Saffet Gonul, Ian H. Gotlib, Hans J. Grabe, Nynke Groenewold, J Paul Hamilton, Ben J. Harrison, Tiffany C. Ho, Benson Mwangi, Natalia Jaworska, Neda Jahanshad, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Meng Li, David E. J. Linden, Frank P. MacMaster, David M. A. Mehler, Elisa Melloni, Bryon A. Mueller, Amar Ojha, Mardien L. Oudega, Brenda W. J. H. Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J. Portella, Elena Pozzi, Liesbeth Reneman, Matthew D. Sacchet, Philipp G. Sämann, Anouk Schrantee, Kang Sim, Jair C. Soares, Dan J. Stein, Sophia I. Thomopoulos, Aslihan Uyar-Demir, Nic J. A. van der Wee, Steven J. A. van der Werff, Henry Völzke, Sarah Whittle, Katharina Wittfeld, Margaret J. Wright, Mon-Ju Wu, Tony T. Yang, Carlos Zarate, Dick J. Veltman, Lianne Schmaal, Paul M. Thompson, Roberto Goya-Maldonado, and the ENIGMA Major Depressive Disorder working group
Subjects: Medicine, Science
Abstract: Abstract Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
Published: 2024
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2. No indications for altered EEG oscillatory activity in patients with chronic post-burn itch compared to healthy controls

Author: Samantha K. Millard, Klara Bokelmann, Rik Schalbroeck, Nic J. A. van der Wee, Nancy E. E. van Loey, and Antoinette I. M. van Laarhoven
Subjects: Medicine, Science
Abstract: Abstract A large proportion of patients with burn injuries develop chronic itch, which impacts quality of life. The underlying pathophysiological mechanisms are poorly understood. This cross-sectional pilot study investigates whether altered cortical oscillatory processes are involved in chronic post-burn itch. Continuous electroencephalography (EEG) data were recorded during rest and stimulation of non-injured skin, inducing itch (histamine and electrical) and cold-pressor task pain for 15 adults with chronic post-burn itch and 15 matched healthy controls. Quantitative metrics comprised oscillatory power and peak frequencies in theta, alpha, and beta bands. No statistical differences between patients and healthy controls were found in oscillatory activity during rest or stimulation, with Bayesian analysis suggesting equivocal evidence. However, post-traumatic stress symptoms and duration of chronic itch may be associated with changes in oscillatory activity. A lack of differences in cortical oscillatory processing and itch levels at non-injured sites, suggests that itch symptoms have a localised character in this sample of patients with post-burn itch. For future studies, a biopsychological approach with integration of peripheral and central nervous system techniques, linear and non-linear EEG analysis, injured and non-injured stimulation sites, and incorporation of individual characteristics is recommended. Insight into pathophysiological mechanisms underlying chronic post-burn itch could improve diagnostics and treatments.
Published: 2022
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3. Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group

Author: Anita Harrewijn, Elise M. Cardinale, Nynke A. Groenewold, Janna Marie Bas-Hoogendam, Moji Aghajani, Kevin Hilbert, Narcis Cardoner, Daniel Porta-Casteràs, Savannah Gosnell, Ramiro Salas, Andrea P. Jackowski, Pedro M. Pan, Giovanni A. Salum, Karina S. Blair, James R. Blair, Mira Z. Hammoud, Mohammed R. Milad, Katie L. Burkhouse, K. Luan Phan, Heidi K. Schroeder, Jeffrey R. Strawn, Katja Beesdo-Baum, Neda Jahanshad, Sophia I. Thomopoulos, Randy Buckner, Jared A. Nielsen, Jordan W. Smoller, Jair C. Soares, Benson Mwangi, Mon-Ju Wu, Giovana B. Zunta-Soares, Michal Assaf, Gretchen J. Diefenbach, Paolo Brambilla, Eleonora Maggioni, David Hofmann, Thomas Straube, Carmen Andreescu, Rachel Berta, Erica Tamburo, Rebecca B. Price, Gisele G. Manfro, Federica Agosta, Elisa Canu, Camilla Cividini, Massimo Filippi, Milutin Kostić, Ana Munjiza Jovanovic, Bianca A. V. Alberton, Brenda Benson, Gabrielle F. Freitag, Courtney A. Filippi, Andrea L. Gold, Ellen Leibenluft, Grace V. Ringlein, Kathryn E. Werwath, Hannah Zwiebel, André Zugman, Hans J. Grabe, Sandra Van der Auwera, Katharina Wittfeld, Henry Völzke, Robin Bülow, Nicholas L. Balderston, Monique Ernst, Christian Grillon, Lilianne R. Mujica-Parodi, Helena van Nieuwenhuizen, Hugo D. Critchley, Elena Makovac, Matteo Mancini, Frances Meeten, Cristina Ottaviani, Tali M. Ball, Gregory A. Fonzo, Martin P. Paulus, Murray B. Stein, Raquel E. Gur, Ruben C. Gur, Antonia N. Kaczkurkin, Bart Larsen, Theodore D. Satterthwaite, Jennifer Harper, Michael Myers, Michael T. Perino, Chad M. Sylvester, Qiongru Yu, Ulrike Lueken, Dick J. Veltman, Paul M. Thompson, Dan J. Stein, Nic J. A. Van der Wee, Anderson M. Winkler, and Daniel S. Pine
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.
Published: 2021
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4. The clinical and cost-effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: study protocol of a multicenter pragmatic randomized controlled trial

Author: Ericka C. Solis, Ingrid V. E. Carlier, Nic J. A. van der Wee, and Albert M. van Hemert
Subjects: Persistent depressive disorder, Chronic depression, Self-management, Psychiatric rehabilitation, Effectiveness, Partner/caregiver, Medicine (General), R5-920
Abstract: Abstract Background After regular treatment, patients with persistent depressive disorder (PDD) may remain in specialized psychiatric outpatient care without achieving remission. Lacking other options, these patients often receive long-term, non-protocolized care as usual (CAU) that does not involve the partner/caregiver of the patient. Although the revised depression treatment guidelines suggest focusing on psychiatric rehabilitation and self-management as the next treatment step for PDD, an evidence-based cost-effective self-management protocol for PDD is lacking. This study investigates the “Patient and Partner Education Program for All Chronic Illnesses” (PPEP4All) as a brief self-management protocol that could lead to lower costs, higher quality of life, and less disease burden in PDD patients and their partners/caregivers. Methods Presented is the rationale and methods of a multicenter pragmatic randomized controlled trial to evaluate the clinical efficacy and cost-effectiveness of PPEP4All for patients with PDD and their partners/caregivers. In accordance with current recommendations, a mixed methods research approach is used with both quantitative and qualitative data. A total of 178 eligible outpatients with PDD and their partners/caregivers are recruited and randomized to either PPEP4All or CAU. Those assigned to PPEP4All receive nine weekly self-management sessions with a trained PPEP4All therapist. Primary and secondary outcome measurements are at 0, 3, 6, and 12 months. Discussion This project will result in the implementation of a self-management intervention for patients with PDD, meeting an urgent need in mental healthcare. Using PPEP4All can optimize the quality and efficiency of care for both patients with PDD and their partners/caregivers. Trial registration Netherlands Trial Register Identifier NTR5973 . Registered on 20 July 2016.
Published: 2021
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5. Contributing factors to advanced brain aging in depression and anxiety disorders

Author: Laura K. M. Han, Hugo G. Schnack, Rachel M. Brouwer, Dick J. Veltman, Nic J. A. van der Wee, Marie-José van Tol, Moji Aghajani, and Brenda W. J. H. Penninx
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Depression and anxiety are common and often comorbid mental health disorders that represent risk factors for aging-related conditions. Brain aging has shown to be more advanced in patients with major depressive disorder (MDD). Here, we extend prior work by investigating multivariate brain aging in patients with MDD, anxiety disorders, or both, and examine which factors contribute to older-appearing brains. Adults aged 18–57 years from the Netherlands Study of Depression and Anxiety underwent structural MRI. A pretrained brain-age prediction model based on >2000 samples from the ENIGMA consortium was applied to obtain brain-predicted age differences (brain PAD, predicted brain age minus chronological age) in 65 controls and 220 patients with current MDD and/or anxiety. Brain-PAD estimates were associated with clinical, somatic, lifestyle, and biological factors. After correcting for antidepressant use, brain PAD was significantly higher in MDD (+2.78 years, Cohen’s d = 0.25, 95% CI −0.10-0.60) and anxiety patients (+2.91 years, Cohen’s d = 0.27, 95% CI −0.08-0.61), compared with controls. There were no significant associations with lifestyle or biological stress systems. A multivariable model indicated unique contributions of higher severity of somatic depression symptoms (b = 4.21 years per unit increase on average sum score) and antidepressant use (−2.53 years) to brain PAD. Advanced brain aging in patients with MDD and anxiety was most strongly associated with somatic depressive symptomatology. We also present clinically relevant evidence for a potential neuroprotective antidepressant effect on the brain-PAD metric that requires follow-up in future research.
Published: 2021
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6. Resting-State Functional Connectivity Characteristics of Resilience to Traumatic Stress in Dutch Police Officers

Author: Santoucha N. W. Setroikromo, Steven J. A. van der Werff, Annika S. Smit, Eric Vermetten, and Nic J. A. Van Der Wee
Subjects: MRI, stress, resilience, trauma, resting-state, police officers, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: BackgroundInsights into the neurobiological basis of resilience can have important implications for the prevention and treatment of stress-related disorders, especially in populations that are subjected to high-stress environments. Evaluating large-scale resting-state networks (RSNs) can provide information regarding resilient specific brain function which may be useful in understanding resilience. This study aimed to explore functional connectivity patterns specific for (high) resilience in Dutch policemen after exposure to multiple work-related traumatic events. We investigated resting-state functional connectivity (RSFC) of the salience network (SN), limbic network, and the default-mode network (DMN).MethodsResting-state functional MRI scans were obtained from trauma-exposed executive personnel of the Dutch police force and non-trauma-exposed recruits from the police academy. Participants were divided into three groups: a resilient group (n = 31; trauma exposure; no psychopathology), a vulnerable group (n = 32; trauma exposure, psychopathology), and a control group (n = 19; no trauma exposure, no psychopathology). RSFC of the three networks of interest was compared between these groups, using an independent component analysis and a dual regression approach.ResultsWe found decreased resilience-specific positive RSFC of the salience network with several prefrontal regions. The DMN and limbic network RFSC did not show resilience-specific patterns.ConclusionThis study shows a differential RSFC specific for resilient police officers. This differential RSFC may be related to a greater capacity for internal-focused thought and interoceptive awareness, allowing more effective higher-order responses to stress in highly resilient individuals.
Published: 2022
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7. Cross-disorder and disorder-specific deficits in social functioning among schizophrenia and alzheimer’s disease patients

Author: Ilja M. J. Saris, Moji Aghajani, Niels Jongs, Lianne M. Reus, Nic J. A. van der Wee, Amy C. Bilderbeck, Inge Winter van Rossum, Celso Arango, Alejandro de la Torre-Luque, Asad Malik, Andreea Raslescu, Gerard R. Dawson, José L. Ayuso-Mateos, Martien J. Kas, and Brenda W. J. H. Penninx
Subjects: Medicine, Science
Abstract: Background Social functioning is often impaired in schizophrenia (SZ) and Alzheimer’s disease (AD). However, commonalities and differences in social dysfunction among these patient groups remain elusive. Materials and methods Using data from the PRISM study, behavioral (all subscales and total score of the Social Functioning Scale) and affective (perceived social disability and loneliness) indicators of social functioning were measured in patients with SZ (N = 56), probable AD (N = 50) and age-matched healthy controls groups (HC, N = 29 and N = 28). We examined to what extent social functioning differed between disease and age-matched HC groups, as well as between patient groups. Furthermore, we examined how severity of disease and mood were correlated with social functioning, irrespective of diagnosis. Results As compared to HC, both behavioral and affective social functioning seemed impaired in SZ patients (Cohen’s d’s 0.81–1.69), whereas AD patients mainly showed impaired behavioral social function (Cohen’s d’s 0.65–1.14). While behavioral indices of social functioning were similar across patient groups, SZ patients reported more perceived social disability than AD patients (Cohen’s d’s 0.65). Across patient groups, positive mood, lower depression and anxiety levels were strong determinants of better social functioning (p’s Conclusions AD and SZ patients both exhibit poor social functioning in comparison to age- and sex matched HC participants. Social dysfunction in SZ patients may be more severe than in AD patients, though this may be due to underreporting by AD patients. Across patients, social functioning appeared as more influenced by mood states than by severity of disease.
Published: 2022

8. Unresolved–disorganized attachment adjusted for a general psychopathology factor associated with atypical amygdala resting-state functional connectivity

Author: Marie-José van Hoof, Madelon M. E. Riem, Amy S. Garrett, Nic J. A. van der Wee, Marinus H. van IJzendoorn, and Robert R. J. M Vermeiren
Subjects: general psychopathology factor, unresolved–disorganized attachment, amygdala, resting-state functional connectivity, dorsal anterior cingulate cortex, medial prefrontal cortex, psychopathology, adolescents, Psychiatry, RC435-571
Abstract: Background: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved–disorganized attachment (Ud) is another transdiagnostic risk factor that may be relevant to explain differences in patient characteristics within diagnostic classifications. Objective: In the current study, we examined unique relations of resting-state functional connectivity (RSFC) with Ud and GPF. Method: RSFC data were collected from a mixed group of adolescents (N = 74) with and without psychiatric disorder, as part of the Emotional Pathways’ Imaging Study in Clinical Adolescents (EPISCA) study. Ud was measured using the Adult Attachment Interview (AAI). Associations between Ud, GPF, and RSFC of the amygdala and dorsal anterior cingulate cortex (dACC) and with amygdala–medial frontal connectivity were examined. Results: Ud was positively associated with greater functional connectivity between the left amygdala and the left lateral occipital cortex, precuneus, and superior parietal lobule. Furthermore, Ud was negatively associated with left amygdala–medial frontal cortex connectivity. GPF was not significantly associated with dACC or amygdala connectivity. Conclusions: Atypical amygdala connectivity may reflect a vulnerability factor rather than a biomarker of psychopathology. The unique association of Ud and amygdala RSFC, adjusted for a GPF, across participants with and without various classifications of psychopathology illustrates that dimensional approaches based on the AAI may complement psychiatric classifications in clinical research and practice.
Published: 2019
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9. Novel genetic loci associated with hippocampal volume

Author: Derrek P. Hibar, Hieab H. H. Adams, Neda Jahanshad, Ganesh Chauhan, Jason L. Stein, Edith Hofer, Miguel E. Renteria, Joshua C. Bis, Alejandro Arias-Vasquez, M. Kamran Ikram, Sylvane Desrivières, Meike W. Vernooij, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Ashley H. Beecham, Alexa Beiser, Manon Bernard, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Vincent Chouraki, Gabriel Cuellar-Partida, Fabrice Crivello, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, Oliver Grimm, Michael E. Griswold, Tulio Guadalupe, Boris A. Gutman, Johanna Hass, Unn K. Haukvik, David Hoehn, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Kjetil N. Jørgensen, Nazanin Karbalai, Dalia Kasperaviciute, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, David C. M. Liewald, Lorna M. Lopez, Michelle Luciano, Christine Macare, Andre F. Marquand, Mar Matarin, Karen A. Mather, Manuel Mattheisen, David R. McKay, Yuri Milaneschi, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Paul Nyquist, Loes M. Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Lukas Pirpamer, Benno Pütz, Adaikalavan Ramasamy, Jennifer S. Richards, Shannon L. Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Stefan Ropele, Emma J. Rose, Natalie A. Royle, Tatjana Rundek, Philipp G. Sämann, Arvin Saremi, Claudia L. Satizabal, Lianne Schmaal, Andrew J. Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V. Smith, Emma Sprooten, Lachlan T. Strike, Alexander Teumer, Diana Tordesillas-Gutierrez, Roberto Toro, Daniah Trabzuni, Stella Trompet, Dhananjay Vaidya, Jeroen Van der Grond, Sven J. Van der Lee, Dennis Van der Meer, Marjolein M. J. Van Donkelaar, Kristel R. Van Eijk, Theo G. M. Van Erp, Daan Van Rooij, Esther Walton, Lars T. Westlye, Christopher D. Whelan, Beverly G. Windham, Anderson M. Winkler, Katharina Wittfeld, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Lisa R. Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P. Zwiers, Ingrid Agartz, Laura Almasy, David Ames, Philippe Amouyel, Ole A. Andreassen, Sampath Arepalli, Amelia A. Assareh, Sandra Barral, Mark E. Bastin, Diane M. Becker, James T. Becker, David A. Bennett, John Blangero, Hans van Bokhoven, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Kazima B. Bulayeva, Wiepke Cahn, Vince D. Calhoun, Dara M. Cannon, Gianpiero L. Cavalleri, Ching-Yu Cheng, Sven Cichon, Mark R. Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Anton J. M. De Craen, Eco J. C. De Geus, Philip L. De Jager, Greig I. De Zubicaray, Ian J. Deary, Stéphanie Debette, Charles DeCarli, Norman Delanty, Chantal Depondt, Anita DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Christian Enzinger, Susanne Erk, Thomas Espeseth, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra A. Fleischman, Ian Ford, Myriam Fornage, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H. H. Göring, Robert C. Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Asta K. Håberg, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G. Hernandez, Dirk J. Heslenfeld, Beng-Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Matthew Huentelman, Hilleke E. Hulshoff Pol, Masashi Ikeda, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kloszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Francis J. McMahon, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Steven G. Potkin, Bruce M. Psaty, Simone Reppermund, Marcella Rietschel, Joshua L. Roffman, Nina Romanczuk-Seiferth, Jerome I. Rotter, Mina Ryten, Ralph L. Sacco, Perminder S. Sachdev, Andrew J. Saykin, Reinhold Schmidt, Helena Schmidt, Peter R. Schofield, Sigurdur Sigursson, Andrew Simmons, Andrew Singleton, Sanjay M. Sisodiya, Colin Smith, Jordan W. Smoller, Hilkka Soininen, Vidar M. Steen, David J. Stott, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Magda Tsolaki, Christophe Tzourio, Andre G. Uitterlinden, Maria C. Valdés Hernández, Marcel Van der Brug, Aad van der Lugt, Nic J. A. van der Wee, Neeltje E. M. Van Haren, Dennis van ’t Ent, Marie-Jose Van Tol, Badri N. Vardarajan, Bruno Vellas, Dick J. Veltman, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Thomas H. Wassink, Michael E. Weale, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y. Wong, Clinton B. Wright, Ronald H. Zielke, Alan B. Zonderman, Nicholas G. Martin, Cornelia M. Van Duijn, Margaret J. Wright, W. T. Longstreth, Gunter Schumann, Hans J. Grabe, Barbara Franke, Lenore J. Launer, Sarah E. Medland, Sudha Seshadri, Paul M. Thompson, and M. Arfan Ikram
Subjects: Science
Abstract: The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.
Published: 2017
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10. Clinical and Physiological Correlates of Irritability in Depression: Results from the Netherlands Study of Depression and Anxiety

Author: Floor E. A. Verhoeven, Linda Booij, Nic J. A. Van der Wee, Brenda W. H. J. Penninx, and A. J. Willem Van der Does
Subjects: Psychiatry, RC435-571, Psychology, BF1-990
Abstract: Objective. Irritable and nonirritable depressed patients differ on demographic and clinical characteristics. We investigated whether this extends to psychological and physiological measures. Method. We compared irritable and nonirritable unipolar depressed patients on symptomatology, personality, and (psycho)physiological measures (cortisol, cholesterol, and heart rate variability). Symptomatology was reassessed after one year, and we also compared depressed patients who were irritable or non-irritable at both time points (Irr++ versus Irr−−). Results. Almost half (46%; N=420) of the sample was classified as irritable. These patients scored higher on depression severity, anxiety, hypomanic symptoms, and psychological variables. No differences were observed on physiological markers after correction for depression severity. The same pattern was found when comparing Irr++ and Irr−− groups. Conclusion. Irritable and non-irritable depressed patients differ on clinical and psychological variables, but not on the currently investigated physiological markers. The clinical relevance of the distinction and the significance of the hypomanic symptoms remain to be demonstrated.
Published: 2011
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11. Clinical outcome in patients with suspected inflammatory neuropsychiatric lupus treated with immunosuppression

Author: Rory C Monahan, Liesbeth J J Beaart-van de Voorde, Rolf Fronczek, Jeroen de Bresser, Jeroen Eikenboom, Margreet Kloppenburg, Huub A M Middelkoop, Gisela M Terwindt, Nic J A van der Wee, Tom W J Huizinga, and Gerda M Steup-Beekman
Subjects: Rheumatology, treatment, healthcare, General Medicine, systemic, outcome assessment, lupus erythematosus
Abstract: BackgroundThe short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral centre for NPSLE to investigate the type of inflammatory NPSLE manifestations, type of immunosuppressive treatment prescribed for these manifestations and clinical outcomes.MethodsAll patients with SLE visiting the Leiden University Medical Centre NPSLE clinic between 2007 and 2021 receiving immunosuppressive therapy for neuropsychiatric symptoms were included. Clinical, immunological and radiological information was collected in as standardised way during a 1-day multidisciplinary assessment. In a multidisciplinary consensus meeting, the presence of NPSLE and the type of NPSLE manifestations and treatment were determined. For this study, short-term (0–6 months) and long-term outcomes (7–24 months) of the NP symptoms were assessed by two independent readers and scored on a 7-point Likert scale, ranging from death to resolved.ResultsIn total, 95 out of 398 (24%) patients visiting the NPSLE clinic between 2007 and 2021 received any form of immunosuppressive treatment for 101 separate NPSLE events. The most common NP manifestation was cognitive dysfunction (50%) as identified by formal cognitive assessment, often present in combination with other NPSLE manifestations. Treatment modalities were induction (24%), induction and maintenance (73%) and other therapy (3%). The treatments mostly consisted of (combinations of) prednisone (97%), methylprednisolone (53%), azathioprine (generally 2 mg/kg daily) (49%) and cyclophosphamide (generally induction 750 mg/m2every 4 weeks for 24 weeks or 500mg biweekly for 12 weeks) (42%). Short-term outcome showed improvement on the Likert scale in 73% (improved: 22%, much improved: 29%, resolved: 22%), no change in 21% and worsening in 6% of patients. Long-term outcome was available for 78 out of 101 events and showed improvement in 70% (improved: 14%, much improved: 28%, resolved: 28%), no change in 17%, worsening in 10% and death in 3% of patients (none directly NPSLE-related).ConclusionThe outcome of inflammatory NPSLE after immunosuppressive treatment is generally good, with improvement of neuropsychiatric symptoms occuring in approximately 70% of events.
Published: 2023

12. Volume of subcortical brain regions in social anxiety disorder: Mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author: Nynke A. Groenewold, Janna Marie Bas-Hoogendam, Alyssa R. Amod, Max A. Laansma, Laura S. Van Velzen, Moji Aghajani, Kevin Hilbert, Hyuntaek Oh, Ramiro Salas, Andrea P. Jackowski, Pedro M. Pan, Giovanni A. Salum, James R. Blair, Karina S. Blair, Joy Hirsch, Spiro P. Pantazatos, Franklin R. Schneier, Ardesheer Talati, Karin Roelofs, Inge Volman, Laura Blanco-Hinojo, Narcís Cardoner, Jesus Pujol, Katja Beesdo-Baum, Christopher R. K. Ching, Sophia I. Thomopoulos, Andreas Jansen, Tilo Kircher, Axel Krug, Igor Nenadić, Frederike Stein, Udo Dannlowski, Dominik Grotegerd, Hannah Lemke, Susanne Meinert, Alexandra Winter, Michael Erb, Benjamin Kreifelts, Qiyong Gong, Su Lui, Fei Zhu, Benson Mwangi, Jair C. Soares, Mon-Ju Wu, Ali Bayram, Mesut Canli, Raşit Tükel, P. Michiel Westenberg, Alexandre Heeren, Henk R. Cremers, David Hofmann, Thomas Straube, Alexander G. G. Doruyter, Christine Lochner, Jutta Peterburs, Marie-José Van Tol, Raquel E. Gur, Antonia N. Kaczkurkin, Bart Larsen, Theodore D. Satterthwaite, Courtney A. Filippi, Andrea L. Gold, Anita Harrewijn, André Zugman, Robin Bülow, Hans J. Grabe, Henry Völzke, Katharina Wittfeld, Joscha Böhnlein, Katharina Dohm, Harald Kugel, Elisabeth Schrammen, Peter Zwanzger, Elisabeth J. Leehr, Lisa Sindermann, Tali M. Ball, Gregory A. Fonzo, Martin P. Paulus, Alan Simmons, Murray B. Stein, Heide Klumpp, K. Luan Phan, Tomas Furmark, Kristoffer N. T. Månsson, Amirhossein Manzouri, Suzanne N. Avery, Jennifer Urbano Blackford, Jacqueline A. Clauss, Brandee Feola, Jennifer C. Harper, Chad M. Sylvester, Ulrike Lueken, Dick J. Veltman, Anderson M. Winkler, Neda Jahanshad, Daniel S. Pine, Paul M. Thompson, Dan J. Stein, Nic J. A. Van der Wee, Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Clinical Psychology, UCL - SSH/IPSY - Psychological Sciences Research Institute, and UCL - SSS/IONS/NEUR - Clinical Neuroscience
Subjects: Adult, Adolescent, 230 Affective Neuroscience, Brain, Phobia, Social, Anxiety, Experimental Psychopathology and Treatment, Cellular and Molecular Neuroscience, Psychiatry and Mental health, methods [Magnetic Resonance Imaging], Humans, ddc:610, methods [Neuroimaging], Molecular Biology
Abstract: Contains fulltext : 288062.pdf (Publisher’s version ) (Closed access) There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE
Published: 2023
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13. Neural correlates of anxious distress in depression:A neuroimaging study of reactivity to emotional faces and resting-state functional connectivity

Author: Laura Nawijn, Richard Dinga, Moji Aghajani, Marie‐José van Tol, Nic J. A. van der Wee, Andreas Wunder, Dick J. Veltman, Brenda W. H. J. Penninx, Adult Psychiatry, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Complex Trait Genetics, APH - Personalized Medicine, APH - Global Health, and APH - Digital Health
Subjects: Depressive Disorder, Major, neuroimaging, 220 Statistical Imaging Neuroscience, anxious distress specifier, salience, amygdala, anxiety, Anxiety Disorders, Magnetic Resonance Imaging, behavioral disciplines and activities, Psychiatry and Mental health, Clinical Psychology, depression, mental disorders, Humans
Abstract: Background: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. However, little is known about the neurobiological correlates of anxious distress in MDD.Methods: We probed the relation between the DSM-5 ADS and task-related reactivity to emotional faces, as well as resting-state functional connectivity patterns of intrinsic salience and basal ganglia networks in unmedicated MDD patients with (MDD/ADS+, N = 24) and without ADS (MDD/ADS−, N = 48) and healthy controls (HC, N = 59). Both categorical and dimensional measures of ADS were investigated.Results: MDD/ADS+ patients had higher left amygdala responses to emotional faces compared to MDD/ADS− patients (p =.015)—part of a larger striato-limbic cluster. MDD/ADS+ did not differ from MDD/ADS− or controls in resting-state functional connectivity of the salience or basal ganglia networks.Conclusions: Current findings suggest that amygdala and striato-limbic hyperactivity to emotional faces may be a neurobiological hallmark specific to MDD with anxious distress, relative to MDD without anxious distress. This may provide preliminary indications of the underlying mechanisms of anxious distress in depression, and underline the importance to account for heterogeneity in depression research.
Published: 2022
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14. Suspected Transverse Myelitis with Normal MRI and CSF Findings in a Patient with Lupus: What to Do? A Case Series and Systematic Review

Author: Nic J A van der Wee, H.J.L. Beaart, Rolf Fronczek, Gisela M Terwindt, Gerda M Steup-Beekman, Tom W J Huizinga, Rory C Monahan, Margreet Kloppenburg, Liesbeth J J Beaart-van de Voorde, and Jeroen de Bresser
Subjects: medicine.medical_specialty, Neuropsychiatric Disease and Treatment, Systemic lupus erythematosus, business.industry, Medical record, Individual participant data, CSF, lupus, Neurological disorder, medicine.disease, Functional disorder, Normal MRI, Transverse myelitis, 030227 psychiatry, 03 medical and health sciences, transverse myelitis, 0302 clinical medicine, Systematic review, neuropsychiatric, Internal medicine, medicine, business, 030217 neurology & neurosurgery, Original Research, MRI
Abstract: Rory C Monahan,1 Hannelore JL Beaart,1 Rolf Fronczek,2,3 Gisela M Terwindt,2 Liesbeth JJ Beaart-van de Voorde,1 Jeroen de Bresser,4 Margreet Kloppenburg,1,5 Nic JA van der Wee,6 Tom WJ Huizinga,1 Gerda M Steup-Beekman1,7 1Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, the Netherlands; 2Department of Neurology, LUMC, Leiden, the Netherlands; 3Sleep-Wake Center SEIN, Heemstede, the Netherlands; 4Department of Radiology, LUMC, Leiden, the Netherlands; 5Department of Clinical Epidemiology, LUMC, Leiden, the Netherlands; 6Department of Psychiatry, LUMC, Leiden, the Netherlands; 7Department of Rheumatology, Haaglanden Medical Center, The Hague, the NetherlandsCorrespondence: Rory C MonahanDepartment of Rheumatology, Leiden University Medical Center (LUMC), Leiden 2333 ZA, the NetherlandsTel +3171-5265762Fax +3171-5266752Email r.c.monahan@lumc.nlPurpose: To evaluate the use of immunosuppressive treatment, clinical outcome and diagnostic strategy in patients with systemic lupus erythematosus (SLE) presenting with clinical features of transverse myelitis (TM), but normal MRI of the spinal cord (sMRI) and normal cerebrospinal fluid (CSF) assessment, and to suggest a clinical guideline.Patients and Methods: All patients with SLE and clinical features compatible with (sub)acute TM visiting the NPSLE clinic of the LUMC between 2007 and 2020 were included. Information on baseline characteristics, investigations, treatment and outcomes was collected from electronic medical records. In addition, a systematic review of individual participant data was performed up to April 2020 in PubMed, Embase and Web of Science, identifying all patients with TM, SLE and sMRI assessment. Data regarding sMRI, CSF analysis, treatment and outcome were extracted, and outcome was compared between patients with normal sMRI and CSF (sMRI-/CSF-) and patients with abnormalities.Results: Twelve SLE patients with a clinical diagnosis of TM were identified: four sMRI-/CSF- and one sMRI- with CSF not available. All patients received immunosuppressive treatment, but outcome in sMRI-/CSF- patients was worse: no recovery (n=1) or partial recovery (n=3) compared to partial recovery (n=4) and (nearly) complete recovery (n=3) in MRI+ patients. The systematic literature review yielded 146 articles eligible for inclusion, 90% case reports. A total of 427 SLE patients with TM were identified, of which only four cases were sMRI-/CSF- (1%), showing no improvement (n=1), partial improvement (n=2) and complete recovery (n=1) after immunosuppressive treatment.Conclusion: Outcome in SLE patients presenting with clinically suspected TM with normal sMRI and CSF is less favorable, despite treatment with immunosuppressive therapy. Taking a functional neurological disorder into consideration may be helpful in order to start other therapeutic strategies. We suggest prescribing immunosuppressive treatment for a restricted period of time to evaluate its effect in cases where a functional disorder initially is considered unlikely.Keywords: lupus, neuropsychiatric, transverse myelitis, MRI, CSF
Published: 2020
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15. Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults

Author: John H. Krystal, Lee A. Baugh, Laura Nawijn, Mieke Verfaellie, Sinead Kelly, Lauren E. Salminen, E. Geuze, Paul M. Thompson, Yuval Neria, Chadi G. Abdallah, Sanne J.H. van Rooij, Judith K. Daniels, Courtney C. Haswell, Murray B. Stein, Milissa L. Kaufman, Benjamin Wade, Nic J A van der Wee, Kyle Choi, Ruth A. Lanius, Martha E. Shenton, Ye Zhu, Jonathan C Ipser, Richard A. Bryant, Benjamin Suarez-Jimenez, Mayuresh S. Korgaonkar, Carol E. Franz, Danielle R. Sullivan, Emily L. Dennis, Sheri Koopowitz, Richard J. Davidson, Christopher L. Averill, Jessica Bomyea, Rajendra A. Morey, Jim Lagopoulos, Jonathan D. Wolff, Kerry J. Ressler, Li Wang, Anika Sierk, Evan M. Gordon, Stefan S. du Plessis, Jessie L. Frijling, Mirjam van Zuiden, Inga K. Koerte, Sherry Winternitz, David Hofmann, Annerine Roos, Tor D. Wager, Jasmeet P. Hayes, Margaret A. Sheridan, Dan J. Stein, Jeffrey P. Guenette, Daniel O’Doherty, Jean Théberge, Geoff J May, Tanja Jovanovic, Vincent A. Magnotta, Stephen R. McCauley, Robert Vermeiren, Xi Zhu, Regina E. McGlinchey, Soraya Seedat, Antje Manthey, Gerald E. York, Scott R. Sponheim, Steven J. A. van der Werff, Seth G. Disner, William P. Milberg, Carmen S. Velez, Jana K Tran, Kelene A. Fercho, Steven M. Nelson, Richard W J Neufeld, William S. Kremen, Elisabeth A. Wilde, Jack B. Nitschke, Mitzy Kennis, Thomas Straube, Lauren A.M. Lebois, Steven E. Bruce, Jennifer S. Stevens, Atilla Gonenc, Neda Jahanshad, Mark W. Logue, Leigh van den Heuvel, Raluca M. Simons, Negar Fani, David F. Tate, Deleene S. Menefee, Katie A. McLaughlin, Peter Kochunov, Gina L. Forster, Maria Densmore, Gen Li, Matthew Peverill, Daniel W. Grupe, Jeffrey S. Simons, Michael J. Lyons, Henrik Walter, Staci A. Gruber, Saskia B. J. Koch, Nicholas D. Davenport, Alan N. Simmons, Jiook Cha, Miranda Olff, Philipp Kinzel, Dick J. Veltman, Emily K Clarke, Clinical Psychology and Experimental Psychopathology, Adult Psychiatry, ANS - Amsterdam Neuroscience, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Global Health, APH - Mental Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, and APH - Personalized Medicine
Subjects: Adult, Male, Adolescent, Traumatic brain injury, Alcohol abuse, Corpus callosum, Article, Stress Disorders, Post-Traumatic, White matter, Young Adult, Cellular and Molecular Neuroscience, Fractional anisotropy, medicine, Humans, Molecular Biology, Depression (differential diagnoses), Aged, Aged, 80 and over, business.industry, Confounding, Brain, Middle Aged, medicine.disease, White Matter, Psychiatry and Mental health, Diffusion Tensor Imaging, medicine.anatomical_structure, Anisotropy, Female, business, Clinical psychology, Diffusion MRI
Abstract: A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed, which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3,047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1,426 individuals with PTSD and 1,621 controls (2174 males/873 females) between ages 18–83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen’s d=−0.11, p=0.0055). The tapetum connects the left and right hippocampus, structures for which structure and function have been consistently implicated in PTSD. Results remained significant/similar after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.
Published: 2021
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16. No indications for altered EEG oscillatory activity in patients with chronic post-burn itch compared to healthy controls

Author: Samantha K, Millard, Klara, Bokelmann, Rik, Schalbroeck, Nic J A, van der Wee, Nancy E E, van Loey, and Antoinette I M, van Laarhoven
Subjects: Adult, Cross-Sectional Studies, Pruritus, Quality of Life, Humans, Bayes Theorem, Electroencephalography, Pilot Projects
Abstract: A large proportion of patients with burn injuries develop chronic itch, which impacts quality of life. The underlying pathophysiological mechanisms are poorly understood. This cross-sectional pilot study investigates whether altered cortical oscillatory processes are involved in chronic post-burn itch. Continuous electroencephalography (EEG) data were recorded during rest and stimulation of non-injured skin, inducing itch (histamine and electrical) and cold-pressor task pain for 15 adults with chronic post-burn itch and 15 matched healthy controls. Quantitative metrics comprised oscillatory power and peak frequencies in theta, alpha, and beta bands. No statistical differences between patients and healthy controls were found in oscillatory activity during rest or stimulation, with Bayesian analysis suggesting equivocal evidence. However, post-traumatic stress symptoms and duration of chronic itch may be associated with changes in oscillatory activity. A lack of differences in cortical oscillatory processing and itch levels at non-injured sites, suggests that itch symptoms have a localised character in this sample of patients with post-burn itch. For future studies, a biopsychological approach with integration of peripheral and central nervous system techniques, linear and non-linear EEG analysis, injured and non-injured stimulation sites, and incorporation of individual characteristics is recommended. Insight into pathophysiological mechanisms underlying chronic post-burn itch could improve diagnostics and treatments.
Published: 2021

17. Exploring the course of adolescent anxiety and depression: associations with white matter tract microstructure

Author: Eline F, Roelofs, Janna Marie, Bas-Hoogendam, Steven J A, van der Werff, Saskia D, Valstar, Nic J A, van der Wee, and Robert R J M, Vermeiren
Subjects: Cross-Sectional Studies, Diffusion Tensor Imaging, Adolescent, Depression, Anisotropy, Brain, Humans, Anxiety, Child, White Matter
Abstract: Cross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies investigating the course of WM microstructure are lacking. This study explored WM alterations and its relation to clinical symptoms over time in adolescents with internalizing disorders. DTI scans were acquired at baseline and after three months in 22 adolescents with clinical depression and comorbid anxiety (INT), and 21 healthy peers (HC) (age: 12-18). Tract-based spatial statistics was used for three voxelwise analyses: i) changes in WM microstructure between and within the INT and HC group; ii) associations between changes in symptom severity and changes in WM microstructure within youths with INT; and iii) associations between baseline WM parameters with changes in symptom severity within youths with INT. Data did not reveal changes in WM microstructure between or within groups over three months' time nor associations between changes in WM microstructure and changes in self-reported symptoms (analyses corrected for age, gender and puberty stage). Lower baseline levels of fractional anisotropy (FA) in the right posterior corona radiata (PCR) and right cingulum were associated with a higher decrease of depressive symptoms within the INT group. Post hoc analysis of additional WM parameters in the significant FA clusters showed that higher levels of baseline mean diffusivity and radial diffusivity in the PCR were associated with a lower decrease in depressive symptoms. Baseline WM microstructure characteristics were associated with a higher decrease in depressive symptoms over time. These findings increase our understanding of neurobiological mechanisms underlying the course of internalizing disorders in adolescents.
Published: 2021

18. Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group

Author: Judith K. Daniels, Chadi G. Abdallah, Nic J A van der Wee, Michael D. DeBellis, Ifat Levy, Jeremy A. Elman, Mayuresh S. Korgaonkar, Sheri Koopowitz, Jeffrey P. Guenette, Paul M. Thompson, Lee A. Baugh, Laura Nawijn, Daniel O’Doherty, Anna R. Hudson, Dan J. Stein, Alan N. Simmons, Kelene A. Fercho, Carol E. Franz, Emily L. Dennis, Robert H. Paul, Jonathan C Ipser, Benjamin Suarez-Jimenez, Richard J. Davidson, Ilan Harpaz-Rotem, Jack B. Nitschke, Lauren A.M. Lebois, Elbert Geuze, Neda Jahanshad, Yuanchao Zheng, Lauren E. Salminen, Anika Sierk, Tor D. Wager, Antje Manthey, Thomas Straube, Kerry J. Ressler, Atilla Gonenc, Ingrid Agartz, Jessica Bomyea, Margaret A. Sheridan, Steven E. Bruce, Staci A. Gruber, Yuval Neria, William S. Kremen, Christian Schmahl, Mitzy Kennis, Mark W. Logue, Miranda Olff, Faisal Rashid, Kyle Choi, Jean Théberge, Tanja Jovanovic, Seth G. Disner, K. Luan Phan, Steven J. A. van der Werff, Theo G.M. van Erp, Katie A. McLaughlin, Richard A. Bryant, Jennifer S. Stevens, Emily K. Clarke-Rubright, Vincent A. Magnotta, Christopher R.K. Ching, Sherry Winternitz, Nicholas D. Davenport, Matthew Peverill, Tiril P. Gurholt, Juan Eugenio Iglesias, Soraya Seedat, Inga K. Koerte, Amy Kennedy-Krage, Babok Hosseini, Raluca M. Simons, John H. Krystal, Michael Hollifield, Christopher L. Averill, Philipp Kinzel, Dick J. Veltman, Martha E. Shenton, Negar Fani, Murray B. Stein, Kathleen Thomaes, Ruth A. Lanius, Joanna Bright, Anthony P. King, Soichiro Nakahara, Xi Zhu, Jessie L. Frijling, Mirjam van Zuiden, Tim Varkevisser, Chanelle Buckle, David Hofmann, Gina L. Forster, Annerine Roos, Sanne J.H. van Rooij, Jasmeet P. Hayes, Unn K. Haukvik, Maria Densmore, Richard W. J. Neufeld, Courtney C. Haswell, Sophia I. Thomopoulos, Jeffrey S. Simons, Daniel W. Grupe, Xin Wang, Robert Vermeiren, Leigh van den Heuvel, Michael J. Lyons, Henrik Walter, Saskia B. J. Koch, Scott R. Sponheim, Philipp G. Sämann, Christopher D. Whelan, Julia Herzog, Stefan S. du Plessis, Jonathan D. Wolff, Sven C. Mueller, Kristen M. Wrocklage, Rajendra A. Morey, Jim Lagopoulos, and Milissa L. Kaufman
Subjects: Oncology, medicine.medical_specialty, business.industry, Traumatic brain injury, Hippocampus, Alcohol use disorder, Hippocampal formation, medicine.disease, behavioral disciplines and activities, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Internal medicine, mental disorders, medicine, business, Beta (finance), 030217 neurology & neurosurgery, Depression (differential diagnoses)
Abstract: BackgroundPTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression.MethodsWe used random effects regressions and a harmonized neuroimaging protocol based on FreeSurfer (v6.0) to identify sub-structural hippocampal markers of current PTSD (C-PTSD), depression, and the interaction of these conditions across 31 cohorts worldwide (N=3,115;Mage=38.9±13.9 years). Secondary analyses tested these associations by sex and after modeling the simultaneous effects of remitted PTSD, childhood trauma, mild traumatic brain injury, and alcohol use disorder.ResultsA significant negative main effect of depression (n=800, vs. no depression, n=1456) was observed in the hippocampal tail (ß=−0.13) and CA1 (ß=−0.09) after adjusting for covariates and multiple testing (adjusted p’s (q)=0.028). A main effect of C-PTSD (n=1042 vs. control, n=1359) was not significant, but an interaction between C-PTSD and depression was significant in the CA1 (ß=−0.24, q=0.044). Pairwise comparisons revealed significantly smaller CA1 volumes in individuals with C-PTSD+Depression than controls (ß=−0.12, q=0.012), C-PTSD-only (ß=−0.17, q=0.001), and Depression-only (ß=−0.18, q=0.023). Follow-up analyses revealed sex effects in the hippocampal tail of depressed females, and an interaction effect of C-PTSD and depression in the fimbria of males.ConclusionsCollectively our results suggest that depression is a stronger predictor of hippocampal volumetry than PTSD, particularly in the CA1, and provide compelling evidence of more pronounced hippocampal phenotypes in comorbid PTSD and depression compared to either condition alone.
Published: 2019
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19. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: G. Bruce Pike, Marcel P. Zwiers, Andreas Meyer-Lindenberg, Jeroen van der Grond, Randy L. Gollub, Karen A. Mather, Andrew J. Schork, Vidar M. Steen, Marc M. Bohlken, Nhat Trung Doan, Derek W. Morris, John B.J. Kwok, Emma J. Rose, Johanna Hass, Andrew Simmons, Tian Ge, Reinhold Schmidt, Micael Andersson, Ian J. Deary, Christopher Chen, Derrek P. Hibar, Simon E. Fisher, Lucija Abramovic, Marcella Rietschel, Edith Hofer, Simon Lovestone, Clyde Francks, Christopher R.K. Ching, Srdjan Djurovic, Lachlan T. Strike, Lorna M. Lopez, Rene L. Olvera, Owen Carmichael, M. Arfan Ikram, Andre F. Marquand, Christine Macare, W.T. Longstreth, Philippe Amouyel, Aaron L. Goldman, Wolfgang Hoffmann, Philip L. De Jager, David C. Liewald, Harald H H Göring, Aad van der Lugt, David Ames, Neeltje E.M. van Haren, Lars Nyberg, Nina Romanczuk-Seiferth, Lukas Pirpamer, Stefan Ehrlich, Alexa S. Beiser, Lianne Schmaal, Hilkka Soininen, Mark Jenkinson, Kazima B. Bulayeva, Anderson M. Winkler, Mike A. Nalls, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lars T. Westlye, Loes M. Olde Loohuis, Andrew Singleton, Gabriel Cuellar-Partida, Randy L. Buckner, Dorret I. Boomsma, Dena G. Hernandez, Steven G. Potkin, Sudha Seshadri, Bertram Müller-Myhsok, D. Hoehn, Gareth E. Davies, Chantal Depondt, Henrik Walter, Michael E. Weale, Deborah Janowitz, Susanne Erk, Iryna O. Fedko, Daniel R. Weinberger, Nic J A van der Wee, Jean-Luc Martinot, Jessica A. Turner, Marieke Klein, Sandra Barral, Sebastian Mohnke, Albert Hofman, Ingrid Melle, Saud Alhusaini, Vincent Chouraki, Stephen M. Lawrie, Mark E. Bastin, Juan C. Troncoso, Jean Shin, Wiro J. Niessen, Diane M. Becker, Laura Almasy, Anders M. Dale, Benjamin S. Aribisala, Dennis van 't Ent, Marco P. Boks, M. Mallar Chakravarty, Paul M. Thompson, David Reese McKay, Michael Griswold, John Blangero, Narelle K. Hansell, Eco J. C. de Geus, Paul A. Nyquist, Susana Muñoz Maniega, Sampath Arepalli, Tatjana Rundek, Dan L. Longo, Anton J. M. de Craen, Rebekah McWhirter, Nazanin Mirza-Schreiber, Henning Tiemeier, Girma Woldehawariat, Sven Cichon, Irene Pappa, Amelia A. Assareh, Sudheer Giddaluru, Pieter J. Hoekstra, Hieab H.H. Adams, Hilleke E. Hulshoff Pol, Grant W. Montgomery, Roel A. Ophoff, Markus M. Nöthen, Sara Pudas, Sigurdur Sigurdsson, Arthur W. Toga, Tien Yin Wong, Massimo Pandolfo, Corina U. Greven, Esther Walton, Tianye Jia, David J. Stott, Gunter Schumann, Marie-José van Tol, Dalia Kasperaviciute, Thomas Wolfers, Henry Völzke, Ian Ford, Shannon L. Risacher, Jessika E. Sussmann, Nicholas G. Martin, Wei Wen, Daniah Trabzuni, Iwona Kłoszewska, Kwangsik Nho, Gianpiero L. Cavalleri, Adam M. Brickman, Sungeun Kim, Andreas Heinz, Ralph L. Sacco, Neda Jahanshad, Velandai Srikanth, Elena Shumskaya, Susan H. Blanton, Katharina Wittfeld, Badri N. Vardarajan, Joshua C. Bis, Joanne E. Curran, Helena Schmidt, Peter T. Fox, Clifford R. Jack, Jason L. Stein, Laura M. E. Blanken, Thomas Espeseth, Dick J. Veltman, Sebastian Guelfi, Margaret J. Wright, Norman Delanty, Michael Czisch, Martina Papmeyer, Oscar L. Lopez, Marjolein M. J. Van Donkelaar, Bruce M. Psaty, Jan K. Buitelaar, Sven J. van der Lee, David A. Bennett, Beng-Choon Ho, Oliver Martinez, Wiepke Cahn, Li Shen, J. Wouter Jukema, Janita Bralten, Peter Kochunov, Greig I. Zubicaray, Marcel P. van der Brug, Ching-Yu Cheng, Philipp G. Sämann, Stella Trompet, Roberto Roiz-Santiañez, David C. Glahn, Allissa Dillman, Venkata S. Mattay, Dara M. Cannon, Michael W. Weiner, Christopher D. Whelan, Alexander Teumer, Sylvane Desrivières, Ole A. Andreassen, Thomas E. Nichols, Manuel Mattheisen, Matthias Nauck, René S. Kahn, Albert V. Smith, Colin Smith, Vilmundur Gudnason, Denis A. Evans, Anouk den Braber, Katie L. McMahon, Han G. Brunner, Florian Holsboer, Yuri Milaneschi, Andrew J. Saykin, Jiemin Liao, Vince D. Calhoun, Neelum T. Aggarwal, Dennis van der Meer, Hans J. Grabe, Anita L. DeStefano, Claudia L. Satizabal, Alan B. Zonderman, Alex P. Zijdenbos, Tulio Guadalupe, Ingrid Agartz, Jordan W. Smoller, Allison C. Nugent, Alejandro Arias-Vasquez, Masashi Ikeda, Avram J. Holmes, Brenda W.J.H. Penninx, John Hardy, Herve Lemaitre, Charles DeCarli, Patrizia Mecocci, Catharina A. Hartman, Tomas Axelsson, Oliver Grimm, Irina Filippi, Wayne C. Drevets, Hans van Bokhoven, Miguel E. Rentería, Aiden Corvin, Ryota Kanai, Kristel R. van Eijk, Andrew M. McIntosh, Jouke-Jan Hottenga, Roberto Toro, Lavinia Athanasiu, Joanna M. Wardlaw, Thomas H. Mosley, Mina Ryten, Meike W. Vernooij, Michelle Luciano, Joshua L. Roffman, Rebecca F. Gottesman, Dhananjay Vaidya, Ryota Hashimoto, Mar Matarin, Adaikalavan Ramasamy, Jerome I. Rotter, Ryan L. Muetzel, Konstantinos Arfanakis, Theo G.M. van Erp, Ganesh Chauhan, Xinmin Liu, Tomáš Paus, Emma Sprooten, Christiane Wolf, David S. Knopman, Manon Bernard, Zdenka Pausova, Bryan J. Traynor, Maria C. Valdés Hernández, Robert C. Green, Russell Thomson, Ravi Duggirala, Lisa R. Yanek, Luigi Ferrucci, Bing Xu, Thomas D. Dyer, Thomas H. Wassink, Eric Westman, Jennifer S. Richards, Phil H. Lee, Benno Pütz, Mark R. Cookson, Benedicto Crespo-Facorro, Natalie A. Royle, Bernd Kraemer, Katrin Hegenscheid, Francis J. McMahon, Tatiana Foroud, M. Kamran Ikram, Myriam Fornage, Nanda Rommelse, Saima Hilal, Perminder S. Sachdev, Qiang Chen, Najaf Amin, Lenore J. Launer, Norbert Hosten, Guillén Fernández, Simone Reppermund, Ashley Beecham, Dirk J. Heslenfeld, Masaki Fukunaga, Cornelia M. van Duijn, Clinton B. Wright, Erik G. Jönsson, Sanjay M. Sisodiya, Oliver Gruber, Christophe Tzourio, André G. Uitterlinden, Robert Johnson, Jaap Oosterlaan, Bernard Mazoyer, H. Ronald Zielke, Stephanie Le Hellard, Jingyun Yang, Georg Homuth, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Henry Brodaty, Beverly G Windham, Gary Donohoe, Rachel M. Brouwer, James T. Becker, Kumar B. Rajan, Daan van Rooij, Thomas W. Mühleisen, Kazutaka Ohi, Peter R. Schofield, Tonya White, Barbara Franke, Unn K. Haukvik, Debra A. Fleischman, J. Raphael Gibbs, Colm McDonald, Anbupalam Thalamuthu, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Keck School of Medicine [Los Angeles], University of Southern California (USC), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Johns Hopkins University (JHU), QIMR Berghofer Medical Research Institute, Leiden University Medical Center (LUMC), Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Miami Leonard M. Miller School of Medicine (UMMSM), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Royal College of Surgeons in Ireland (RCSI), Umeå University, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), University of New South Wales [Sydney] (UNSW), Murdoch University, University of Oslo (UiO), Uppsala University, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Toronto, University of Washington [Seattle], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Columbia University Medical Center (CUMC), Columbia University [New York], Pennington Biomedical Research Center, Louisiana State University (LSU), McGill University = Université McGill [Montréal, Canada], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lieber Institute for Brain Development [Baltimore] (LIBD), University of California [Los Angeles] (UCLA), University of California, Vrije Universiteit Amsterdam [Amsterdam] (VU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Massachusetts General Hospital [Boston], Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Bergen (UiB), Haukeland University Hospital, Johns Hopkins University School of Medicine [Baltimore], Universität Heidelberg [Heidelberg], University of Mississippi Medical Center (UMMC), International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], National University of Singapore (NUS), Medical University Graz, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Yale University [New Haven], University College of London [London] (UCL), Imperial College London, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Institute of Human Genetics, University of Bonn, Department of Genomics, Life and Brain Center, Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dpt of Psychiatry [New Haven], Yale University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Department of Psychology [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Department of Neurosciences [San Diego], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Queensland Institute of Medical Research, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, King Faisal Specialist Hospital and Research Centre, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Depts of Radiology, University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, National Institutes of Health [Bethesda] (NIH), General Internal Medicine, Johns Hopkins School of Medicine, Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], 849 Department of Human Genetics, Dementia Collaborative Research Centre, Centre for Healthy Brain Ageing, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Université de Lausanne (UNIL), Department of Psychiatry [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Metacohorts Consortium, Division of Medical Genetics, University of Basel (Unibas), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], VU University Amsterdam, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Psychology, University of Queensland, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Molecular and Cellular Therapeutics, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Department of Radiology, Mayo Clinic, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Department of Physics, Okayama University, Okayama University, National Institute of Aging, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Department of Molecular Neurosciences, Institute of Neurology, UCL, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Tohoku University [Sendai], Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Centre for Allergy Research, Karolinska Institutet [Stockholm], Interuniversity Cardiology Institute Netherlands, Institute of Cognitive Neuroscience, School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Laboratoire de Statistique Théorique et Appliquée (LSTA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Psychiatry Institute, Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Université de Toulon - UFR Lettres et Sciences Humaines (UTLN UFR LSH), Université de Toulon (UTLN), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Warwick Manufacturing Group [Coventry] (WMG), University of Warwick [Coventry], Department of Statistics [Warwick], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Group Health Research Institute, Group Health Cooperative, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Centre for Healthy Brain Ageing [Sydney], The University of Sydney, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Department of Clinical and Experimental Epilepsy, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Department of Epidemiology, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of York [York, UK], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genentech, Inc. [San Francisco], Departments of Radiology and of Epidemiology [Rotterdam], Psychiatry and Leiden Institute for Brain and Cognition, Department of Neurology [Rotterdam], Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Neurobiology, Care Sciences and Society, Research Laboratory for Archaeology & the History of Art, Singapore Eye Research Institute, Singapore National Eye Centre, School of Life Sciences, Arizona State University [Tempe] (ASU), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], University of Missouri [Columbia] (Mizzou), University of Missouri System, Göttingen Zentrum Geowissenschaften, Georg-August-University [Göttingen], Human Genetics Center, Psychiatry, EMGO - Mental health, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, Klinische Genetica, MUMC+: DA Klinische Genetica (5), RS: FHML non-thematic output, RS: GROW - School for Oncology and Reproduction, RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Universidad de Cantabria, Universiteit Leiden, Radboud University [Nijmegen], University of California (UC), Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Bonn = University of Bonn, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Yale School of Medicine [New Haven, Connecticut] (YSM), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of California (UC)-University of California (UC), Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Radboud University [Nijmegen]-Radboud University [Nijmegen], Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Harvard University-Massachusetts Institute of Technology (MIT), University of Eastern Finland, Humboldt University Of Berlin, Georg-August-University = Georg-August-Universität Göttingen, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Epidemiology, Child and Adolescent Psychiatry / Psychology, Ophthalmology, Radiology & Nuclear Medicine, Internal Medicine, Neurosciences, Obstetrics & Gynecology, Neurology, EMGO+ - Mental Health, Biological Psychology, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), McGill University-McGill University, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), McGill University, Technische Universität Dresden (TUD), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], University of Bergen (UIB), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Minnesota [Twin Cities], Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], University of Tasmania (UTAS), Humboldt Universität zu Berlin, Department of Physics [Kowloon], University of Missouri [Columbia], Georg-August-Universität Göttingen, and the Alzheimer's Disease Neuroimaging Initiative, EPIGEN, IMAGEN, SYS
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Genome-wide association study, Disease, methods [Genome-Wide Association Study], Genome-wide association studies, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Cognition, PARKINSONS-DISEASE, pathology [Brain], genetics [Parkinson Disease], 610 Medicine & health, General Neuroscience, growth & development [Brain], physiology [Cognition], 220 Statistical Imaging Neuroscience, COMMON VARIANTS, Brain, Parkinson Disease, Phenotype, 17Q21.31 MICRODELETION, IGF-I, genetics [Oncogene Protein v-akt], Oncogene Protein v-akt, ALZHEIMERS-DISEASE, HEAD CIRCUMFERENCE, Brain size, genetics [Polymorphism, Single Nucleotide], Medical genetics, GROWTH, Neuroinformatics, medicine.medical_specialty, Neuroscience(all), European Continental Ancestry Group, genetics [Genetic Loci], Biology, Genetic correlation, Polymorphism, Single Nucleotide, 150 000 MR Techniques in Brain Function, Article, White People, 03 medical and health sciences, Image processing, SDG 3 - Good Health and Well-being, ddc:570, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Gene, METAANALYSIS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurology & Neurosurgery, Neuroscience (all), Height, [SCCO.NEUR]Cognitive science/Neuroscience, CONSORTIUM, Development of the nervous system, 1702 Cognitive Science, 030104 developmental biology, Genetic Loci, Human genome, BRAIN SIZE, 1109 Neurosciences, genetics [Phosphatidylinositol 3-Kinases], Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 165723pub.pdf (Publisher’s version ) (Closed access) Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rhogenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
Published: 2016
Full Text: View/download PDF

20. Noradrenergic and cholinergic modulation of late ERP responses to deviant stimuli

Author: Stephen B R E, Brown, Nic J A, van der Wee, Martijn S, van Noorden, Erik J, Giltay, and Sander, Nieuwenhuis
Subjects: Adult, Male, Brain Mapping, Principal Component Analysis, Adolescent, Scopolamine, Brain, Electroencephalography, Event-Related Potentials, P300, Cholinergic Antagonists, Clonidine, Young Adult, Adrenergic alpha-2 Receptor Agonists, Reaction Time, Humans, Female, Psychomotor Performance
Abstract: Researchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo-controlled crossover study in which we investigated how the late positive ERP response to deviant stimuli is modulated by (a) clonidine, an α2 agonist that attenuates baseline noradrenergic activity; and (b) scopolamine, a muscarinic antagonist of acetylcholine receptors. We collected EEG data from 18 healthy volunteers during the performance of an auditory oddball task with several active and passive task conditions. We then used temporospatial principal component analysis (PCA) to decompose the ERP waveforms. The PCA revealed two distinct late positive ERP components: the classic parietal P300 and the frontal novelty P3. Statistical analysis of the temporospatial factor scores indicated that in most conditions the amplitude of the classic P300 was increased by clonidine and scopolamine. In contrast, the amplitude of the novelty P3 was decreased by both drugs. The similar pattern of results for clonidine and scopolamine probably reflects the strong interactions between the noradrenergic and cholinergic systems. The results, in combination with previous pharmacological studies, suggest a critical role for both neuromodulator systems in the generation of the P300 and the novelty P3.
Published: 2015

21. CHANGES IN REGIONAL BRAIN ACTIVATION RELATED TO DEPRESSIVE STATE: A 2-YEAR LONGITUDINAL FUNCTIONAL MRI STUDY

Author: Esther M, Opmeer, Rudie, Kortekaas, Marie-José, van Tol, Remco J, Renken, Liliana R, Demenescu, Saskia, Woudstra, Gert J, Ter Horst, Mark A, van Buchem, Nic J A, van der Wee, Dick J, Veltman, and André, Aleman
Subjects: Adult, Facial Expression, Male, Brain Mapping, Depressive Disorder, Emotions, Brain, Humans, Female, Longitudinal Studies, Magnetic Resonance Imaging, Netherlands
Abstract: Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology.A 2-year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning.Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed.Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2-year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states.
Published: 2014

22. Amygdala activation during emotional face processing in adolescents with affective disorders: the role of underlying depression and anxiety symptoms

Author: Bianca G Van Den Bulk, Paul H.F. Meens, Natasja D.J. van Lang, Leone ede Voogd, Nic J A Van Der Wee, Serge A R Rombouts, Eveline A Crone, Robert R.J.M. Vermeiren, Pediatric surgery, and EMGO - Mental health
Subjects: medicine.medical_specialty, Future studies, Emotional processing, Anxiety, Amygdala, lcsh:RC321-571, Behavioral Neuroscience, Neuroimaging, medicine, Original Research Article, Psychiatry, individual differences, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Depression (differential diagnoses), Depression, face processing, medicine.disease, Comorbidity, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, medicine.anatomical_structure, Neurology, Clinical diagnosis, adolescence, medicine.symptom, Psychology, Clinical psychology, Neuroscience
Abstract: Depressive and anxiety disorders are often first diagnosed during adolescence and it is known that they persist into adulthood. Previous studies often tried to dissociate depressive and anxiety disorders, but high comorbidity makes this difficult and maybe even impossible. The goal of this study was to use neuroimaging to test what the unique contribution is of depression and anxiety symptomatology on emotional processing and amygdala activation, and to compare the results with a healthy control group. We included 25 adolescents with depressive and/or anxiety disorders and 26 healthy adolescents. Participants performed an emotional face processing task while in the MRI scanner. We were particularly interested in the relation between depression/anxiety symptomatology and patterns of amygdala activation. There were no significant differences in activation patterns between the control group and the clinical group on whole brain level and ROI level. However, we found that dimensional scores on an anxiety but not a depression subscale significantly predicted brain activation in the right amygdala when processing fearful, happy and neutral faces. These results suggest that anxiety symptoms are a better predictor for differentiating activation patterns in the amygdala than depression symptoms. Although the current study includes a relatively large sample of treatment naive adolescents with depression/anxiety disorders, results might be influenced by differences between studies in recruitment strategies or methodology. Future research should include larger samples with a more equal distribution of adolescents with a clinical diagnosis of depression and/or anxiety. To conclude, this study shows that abnormal amygdala responses to emotional faces in depression and anxiety seems to be more dependent on anxiety symptoms than on depression symptoms, and thereby highlights the need for more research to better characterize clinical groups in future studies.
Published: 2014
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23. Advances in the neuroimaging of panic disorder

Author: Justine Nienke, Pannekoek, Steven J A, van der Werff, Dan J, Stein, and Nic J A, van der Wee
Subjects: Animals, Brain, Humans, Panic Disorder, Neuroimaging, Fear, Magnetic Resonance Imaging
Abstract: Models of the neuroanatomy of panic disorder (PD) have relied on both animal work on fear and on clinical data from neuroimaging. Early work hypothesised a network of brain regions involved in fear processing (e.g. the amygdala), but more recent work has also pointed to the involvement of other cortical areas and other brain circuitry (e.g. the insula and anterior cingulate cortex). Studies investigating functional and structural brain connectivity in PD may ultimately shed light on the extent to which the neuroanatomy of PD is localised versus distributed, and on how current treatments alter this neuroanatomy.
Published: 2013

24. Neuroimaging of resilience to stress: current state of affairs

Author: Steven J A, van der Werff, J Nienke, Pannekoek, Dan J, Stein, and Nic J A, van der Wee
Subjects: Functional Neuroimaging, Adaptation, Psychological, Animals, Brain, Humans, Stress, Psychological
Abstract: Resilience is defined as a dynamic, multidimensional process encompassing positive adaptation within the context of significant adversity. The complex nature of this construct makes it a difficult topic to study in neuroimaging research; however, in this article, we propose ways to operationalize resilience. The limited amount of structural and functional neuroimaging studies specifically designed to examine resilience have mainly focused on investigating alterations in regions of the brain involved in emotion and stress regulation circuitry. In the future, neuroimaging of resilience is expected to benefit from functional and structural connectivity approaches and the use of novel imaging task paradigms.
Published: 2013

25. Neuroimaging resilience to stress: a review

Author: Steven J A van der Werff, Susan M. van den Berg, Justine Nienke Pannekoek, Bernet M. Elzinga, and Nic J A Van Der Wee
Subjects: neuroimaging, Cognitive Neuroscience, Context (language use), PTSD, Review Article, lcsh:RC321-571, 030227 psychiatry, 03 medical and health sciences, Behavioral Neuroscience, stress, 0302 clinical medicine, Neuropsychology and Physiological Psychology, trauma, Neuroimaging, Stress (linguistics), Resilience (network), Psychology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, resilience, 030217 neurology & neurosurgery, Clinical psychology, Neuroscience, MRI
Abstract: There is a high degree of intra-individual variation in how individuals respond to stress. This becomes evident when exploring the development of posttraumatic symptoms or stress-related disorders after exposure to trauma. Whether or not an individual develops posttraumatic symptoms after experiencing a traumatic event is partly dependent on a person's resilience. Resilience can be broadly defined as the dynamic process encompassing positive adaptation within the context of significant adversity. Even though research into the neurobiological basis of resilience is still in its early stages, these insights can have important implications for the prevention and treatment of stress-related disorders. Neuroimaging studies contribute to our knowledge of intra-individual variability in resilience and the development of posttraumatic symptoms or other stress-related disorders. This review provides an overview of neuroimaging findings related to resilience. Structural, resting-state, and task-related neuroimaging results associated with resilience are discussed. There are a limited number of studies available and neuroimaging research of resilience is still in its infancy. The available studies point at brain circuitries involved in stress and emotion regulation, with more efficient processing and regulation associated with resilience.
Published: 2013

26. Reference values for mental health assessment instruments: objectives and methods of the Leiden Routine Outcome Monitoring Study

Author: Yvonne W M, Schulte-van Maaren, Ingrid V E, Carlier, Erik J, Giltay, Martijn S, van Noorden, Margot W M, de Waal, Nic J A, van der Wee, and Frans G, Zitman
Subjects: Adult, Male, Adolescent, Mental Disorders, Middle Aged, Young Adult, Cross-Sectional Studies, Reference Values, Outcome Assessment, Health Care, Humans, Female, Sex Distribution, Qualitative Research, Aged, Netherlands
Abstract: Routine outcome monitoring (ROM) was developed to establish the outcome of psychotherapeutic and pharmacological treatments through repeated assessments before, during and after treatment. Although standardization of psychiatric assessments and their reference values are essential for patient care, for various ROM instruments reference values are not available. The aim of the Leiden ROM Study is to generate reference values for 22 ROM instruments, covering generic and specific mood, anxiety and somatoform (MAS) disorders, for the general population. This article describes the extensive process of recruitment, as well as baseline characteristics of patient versus non-patient groups.Cross-sectional study in randomly selected participants aged 18-65 years from the Dutch population, included through general practitioners.Extensive demographic, psychosocial, mental health, and biological data from 1302 participants, recruited via general practitioners, were collected during a two-hour standardized assessment including observer-rated and self-report scales. These data will be compared with corresponding data from 7840 patients with psychopathology who were referred to secondary care. On-going quality control and calibration ensured maintenance of high quality during data collection.This reference group study for mental health assessments is the first study of this size carried out in the Netherlands. The results of this study are expected to be of value to secondary psychiatric care because they allow the indication of progress in health, treatment effect and possible termination of treatment. Additionally, the reference values can be used by primary care physicians as decision threshold for referral to specialized mental health care and vice versa.
Published: 2012

27. Predicting outcome of depression using the depressive symptom profile: the Leiden Routine Outcome Monitoring Study

Author: Martijn S, van Noorden, Esther M, van Fenema, Nic J A, van der Wee, Frans G, Zitman, and Erik J, Giltay
Subjects: Adult, Male, Psychiatric Status Rating Scales, Depressive Disorder, Adolescent, Middle Aged, Cohort Studies, Young Adult, Outcome and Process Assessment, Health Care, Predictive Value of Tests, Humans, Female, Aged, Follow-Up Studies, Proportional Hazards Models
Abstract: To investigate the predictive value of items for individual depressive symptoms measured with the self-rated Beck Depression Inventory-Revised (BDI-II) self-report scale on outcome in a large naturalistic cohort of depressive outpatients.We used a cohort of 1,489 adult patients aged 18-65 years with major depressive disorder or dysthymic disorder established with the MINI-Plus diagnostic interview. All patients had a routine outcome monitoring baseline measurement in 2004-2009, with a maximum of 2 years follow-up. We used multivariable Cox regression models to predict remission (MADRS10; where MADRS stands for Montgomery-Åsberg Depression Rating Scale) and response (≥50% improvement), and adjusted for clinical and demographic characteristics (i.e. marital status, level of education, working status, comorbid anxiety, avoidant and borderline personality traits, and suicidality) that were identified as predictors in earlier studies.Of the 21 BDI-II items, the items "pessimism" and "loss of energy" independently predicted for both remission and response. For pessimism, the hazard ratio (HR) for remission was 0.81 (95% confidence interval [CI]: 0.73-0.89, P.001) and for loss of energy, the HR was 0.81 (95% CI: 0.72-0.92, P = .001).These findings of robust prediction of poor outcome by baseline items of "pessimism" and "loss of energy" in a naturalistic treatment setting may help clinicians to identify depressive patients in need for additional or alternative therapeutic approaches.
Published: 2012

28. Orbitofrontal gray matter relates to early morning awakening: a neural correlate of insomnia complaints?

Author: Diederick eStoffers, Sarah eMoens, Jeroen eBenjamins, Marie-José evan Tol, Brenda W.H.J. Penninx, Dick J Veltman, Nic J A Van Der Wee, E J W VanSomeren, Psychiatry, Anatomy and neurosciences, EMGO - Mental health, NCA - Attention & Cognition, Other departments, Netherlands Institute for Neuroscience (NIN), Integrative Neurophysiology, Neuroscience Campus Amsterdam - Attention & Cognition, Clinical Neuropsychology, and EMGO+ - Mental Health
Subjects: medicine.medical_specialty, insomnia, Audiology, Structural magnetic resonance imaging, lcsh:RC346-429, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, mental disorders, Insomnia, medicine, Elderly people, voxel-based morphometry, Psychiatry, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Original Research, 0303 health sciences, Neural correlates of consciousness, business.industry, early morning awakening, Early morning awakening, aging, Voxel-based morphometry, Neurology, Orbitofrontal cortex, Neurology (clinical), medicine.symptom, structural magnetic resonance imaging, business, orbitofrontal cortex, Insula, 030217 neurology & neurosurgery, Neuroscience
Abstract: Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%.The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences inGMdensity are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean ageD41 years, range 18-56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA.Whole-brain voxel-based morphometrywas used to investigate their association withGMdensity. Results showthat participants with lowerGMdensity in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS.This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated. © 2012 Stoffers, Moens, Ben-jamins, vanTol, Penninx, Veltman, Van der Wee and Van Someren.
Published: 2012
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29. Reliability and validity of the Global Assessment of Functioning Scale in clinical outpatients with depressive disorders

Author: Esther M V, Grootenboer, Erik J, Giltay, Rosalind, van der Lem, Tineke, van Veen, Nic J A, van der Wee, and Frans G, Zitman
Subjects: Adult, Male, Psychiatric Status Rating Scales, Depressive Disorder, Psychometrics, Outpatients, Humans, Mass Screening, Regression Analysis, Reproducibility of Results, Female, Netherlands
Abstract: The Global Assessment of Functioning Scale (GAF) is widely used to assess psychological, social and occupational functioning. The validity and reliability of the GAF in clinical practice have only scarcely been studied in naturalistic samples.A total of 432 outpatients with a current major depressive disorder (MDD) were evaluated with routine outcome monitoring (ROM). At baseline the GAF score was assessed by the treating clinician and at ROM baseline and follow-up sessions also by a trained test nurse. Sociodemographic data, the Mini International Neuropsychiatric Interview Plus and scores on the Montgomery-Äsberg Depression Rating Scale, Beck Depression Inventory-revised, Brief Symptom Inventory and Short Form-36 were assessed.At baseline, the mean GAF score by the clinician was 54.8 (range 35-85), and this was systematically lower than the mean GAF score by the test nurse of 57.5 (range 31-88). GAF scores by the clinician and test nurse correlated weakly (r = 0.26). The GAF scores of the clinicians correlated strongly with disease severity, and social and physical functioning.The GAF showed rather poor inter-rater reliability as well as poor discriminant validity with disease severity and physical limitations in a large naturalistic sample of outpatients with MDD.
Published: 2011

30. Vitality predicts level of guideline-concordant care in routine treatment of mood, anxiety and somatoform disorders

Author: Esther M, van Fenema, Nic J A, van der Wee, Erik J, Giltay, Margien E, den Hollander-Gijsman, and Frans G, Zitman
Subjects: Adult, Male, Evidence-Based Medicine, Mood Disorders, Comorbidity, Anxiety Disorders, Logistic Models, Practice Guidelines as Topic, Health Status Indicators, Humans, Female, Guideline Adherence, Somatoform Disorders, Netherlands, Retrospective Studies
Abstract: To examine the clinical and psychosocial correlates of adherence to treatment guidelines among outpatients with common mental disorders in a routine clinical setting.In this retrospective cohort study, we analysed 192 patients who were treated for a mood, anxiety or somatoform disorder with pharmacotherapy, psychotherapy or a combination of both treatment modalities. Guideline adherence was assessed with a disorder independent set of quality indicators during up to 3 years of follow-up. At baseline, a standardized diagnostic interview, the Brief Symptom Inventory (BSI), the Short Form 36 (SF-36) and demographic variables were assessed. Using multivariable regression analysis we identified independent predictors associated with guideline adherence.Patients were aged 36.8 years (SD 11.6) on average. The majority of patients were treated with psychotherapy (47.4%), followed by pharmacotherapy (37.5%) and a combination of pharmacotherapy and psychotherapy (15.1%). Three adherence groups were defined: low (29.7%), intermediate (43.2%) and high (27.1%). Univariate predictors of low adherence were low scores on the subscales vitality and social functioning of the SF-36. In the multivariable model, low adherence was independently predicted by a score lower than 50 on the subscale vitality of the SF-36 (odds ratio per 10 units increase in vitality = 1.34, 95% confidence interval: 1.06-1.71). No significant differences were found within socio-demographic variables, co-morbidity and the scores on the BSI subscales between the adherence groups.We found that patients with low scores on the vitality subscale of the SF-36 were at the highest risk to receive low guideline-concordant care. Understanding factors that affect treatment adherence may help to prevent non-adherence and increase the quality of care as well as cost-effectiveness.
Published: 2010

31. Routine outcome monitoring and feedback on physical or mental health status: evidence and theory

Author: Ingrid V E, Carlier, Denise, Meuldijk, Irene M, Van Vliet, Esther, Van Fenema, Nic J A, Van der Wee, and Frans G, Zitman
Subjects: Adult, Male, Young Adult, Mental Health, Health Status, Outcome Assessment, Health Care, Humans, Female, Middle Aged, Models, Theoretical, Aged, Feedback, Randomized Controlled Trials as Topic
Abstract: Routine Outcome Monitoring (ROM) is an important quality tool for measuring outcome of treatment in health care. The objective of this article is to summarize the evidence base that supports the provision of feedback on ROM results to (mental) health care professionals and patients. Also, some relevant theoretical aspects are considered.Literature study (Pubmed, Medline, PsychINFO, Embase Psychiatry, 1975-2009) concerning randomized controlled trials (RTC's) of ROM and feedback on physical or mental health status of patients of all ages. Main search terms were routine outcome monitoring/measurement, feedback, health status measurement, patient reported outcome measures.Included were 52 RCT's concerning ROM and feedback with adult or older patients: of these seven RCT's were exclusively focused on physical health and 45 RCT's (also) on the mental health of the patient, although not always in a mental health care setting or as primary outcome measure. There appears to be a positive impact of ROM on diagnosis and monitoring of treatment, and on communication between patient and therapist. Other results were less clear. There were no published RCT's on this topic with children or adolescents.ROM appears especially effective for the monitoring of patients who are not doing well in therapy. Further research into this topic and the clinical-and cost-effectiveness of ROM is recommended, especially in mental health care for both adults and children. Also, more theory-driven research is needed with relevant conceptualizations such as Feedback Intervention Theory, Therapeutic Assessment.
Published: 2010

32. Whole Brain Resting-State Analysis Reveals Decreased Functional Connectivity in Major Depression

Author: Ilya M. Veer, Christian Beckmann, Marie-Jose Van Tol, Luca Ferrarini, Julien Milles, Dick Veltman, Andre Aleman, Mark A Van Buchem, Nic J A Van Der Wee, Serge A R Rombouts, Psychiatry, NCA - Brain Imaging, Heymans Institute for Psychological Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Other departments
Subjects: Cognitive Neuroscience, resting-state functional magnetic resonance imaging, Neuroscience (miscellaneous), Expression, Amygdala, lcsh:RC321-571, Lingual gyrus, Cellular and Molecular Neuroscience, Text mining, Developmental Neuroscience, medicine, Resting-state fMRI, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, Resting state fMRI, business.industry, Working memory, Functional connectivity, functional connectivity, Cognition, amygdala, group ICA, medicine.disease, Comorbidity, medicine.anatomical_structure, independent component analysis, business, Psychology, major depression, Neuroscience
Abstract: Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.
Published: 2010
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33. A case of mania after long-term use of quinagolide

Author: David J. Vinkers and Nic J A van der Wee
Subjects: Psychiatry and Mental health, medicine.medical_specialty, business.industry, Quinagolide, Medicine, medicine.symptom, business, Psychiatry, Mania, Term (time)
Published: 2007
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34. Clinical outcome in patients with suspected inflammatory neuropsychiatric lupus treated with immunosuppression: an observational cohort study

Author: Margreet Kloppenburg, Tom W J Huizinga, Jeroen Eikenboom, Gisela M Terwindt, Liesbeth J J Beaart-van de Voorde, Gerda M Steup-Beekman, Jeroen de Bresser, Rory C Monahan, Huub A M Middelkoop, Nic J A van der Wee, and Rolf Fronczek
Subjects: Immunologic diseases. Allergy, RC581-607
Abstract: Background The short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral centre for NPSLE to investigate the type of inflammatory NPSLE manifestations, type of immunosuppressive treatment prescribed for these manifestations and clinical outcomes.Methods All patients with SLE visiting the Leiden University Medical Centre NPSLE clinic between 2007 and 2021 receiving immunosuppressive therapy for neuropsychiatric symptoms were included. Clinical, immunological and radiological information was collected in as standardised way during a 1-day multidisciplinary assessment. In a multidisciplinary consensus meeting, the presence of NPSLE and the type of NPSLE manifestations and treatment were determined. For this study, short-term (0–6 months) and long-term outcomes (7–24 months) of the NP symptoms were assessed by two independent readers and scored on a 7-point Likert scale, ranging from death to resolved.Results In total, 95 out of 398 (24%) patients visiting the NPSLE clinic between 2007 and 2021 received any form of immunosuppressive treatment for 101 separate NPSLE events. The most common NP manifestation was cognitive dysfunction (50%) as identified by formal cognitive assessment, often present in combination with other NPSLE manifestations. Treatment modalities were induction (24%), induction and maintenance (73%) and other therapy (3%). The treatments mostly consisted of (combinations of) prednisone (97%), methylprednisolone (53%), azathioprine (generally 2 mg/kg daily) (49%) and cyclophosphamide (generally induction 750 mg/m2 every 4 weeks for 24 weeks or 500mg biweekly for 12 weeks) (42%). Short-term outcome showed improvement on the Likert scale in 73% (improved: 22%, much improved: 29%, resolved: 22%), no change in 21% and worsening in 6% of patients. Long-term outcome was available for 78 out of 101 events and showed improvement in 70% (improved: 14%, much improved: 28%, resolved: 28%), no change in 17%, worsening in 10% and death in 3% of patients (none directly NPSLE-related).Conclusion The outcome of inflammatory NPSLE after immunosuppressive treatment is generally good, with improvement of neuropsychiatric symptoms occuring in approximately 70% of events.
Published: 2023
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35. To treat or not to treat with immunosuppressive therapy: psychiatric disorders in patients with systemic lupus erythematosus

Author: Margreet Kloppenburg, Tom WJ Huizinga, Gerda M Steup-Beekman, Rory C Monahan, Anne M E Blonk, Huub A M Middelkoop, and Nic J A van der Wee
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2022
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36. How embarrassing! The behavioral and neural correlates of processing social norm violations.

Author: Janna Marie Bas-Hoogendam, Henk van Steenbergen, Tanja Kreuk, Nic J A van der Wee, and P Michiel Westenberg
Subjects: Medicine, Science
Abstract: Social norms are important for human social interactions, and violations of these norms are evaluated partly on the intention of the actor. Here, we describe the revised Social Norm Processing Task (SNPT-R), a paradigm enabling the study of behavioral and neural responses to intended and unintended social norm violations among both adults and adolescents. We investigated how participants (adolescents and adults, n = 87) rate intentional and unintentional social norm violations with respect to inappropriateness and embarrassment, and we examined the brain activation patterns underlying the processing of these transgressions in an independent sample of 21 adults using functional Magnetic Resonance Imaging (fMRI). We hypothesized to find activation within the medial prefrontal cortex, temporo-parietal cortex and orbitofrontal cortex in response to both intentional and unintentional social norm violations, with more pronounced activation for the intentional social norm violations in these regions and in the amygdala. Participants' ratings confirmed the hypothesis that the three types of stories are evaluated differently with respect to intentionality: intentional social norm violations were rated as the most inappropriate and most embarrassing. Furthermore, fMRI results showed that reading stories on intentional and unintentional social norm violations evoked activation within the frontal pole, the paracingulate gyrus and the superior frontal gyrus. In addition, processing unintentional social norm violations was associated with activation in, among others, the orbitofrontal cortex, middle frontal gyrus and superior parietal lobule, while reading intentional social norm violations was related to activation in the left amygdala. These regions have been previously implicated in thinking about one's self, thinking about others and moral reasoning. Together, these findings indicate that the SNPT-R could serve as a useful paradigm for examining social norm processing, both at the behavioral and the neural level.
Published: 2017
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37. On the connection between level of education and the neural circuitry of emotion perception

Author: Liliana Ramona Demenescu, Adrian eStan, Rudie eKortekaas, Nic J A Van Der Wee, Dick eVeltman, and Andre eAleman
Subjects: emotion, facial expressions, Neural Response, psychophysiological interaction, Educational attainment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Through education, a social group transmits accumulated knowledge, skills, customs, and values to its members. So far, to the best of our knowledge, the association between educational attainment and neural correlates of emotion processing has been left unexplored. In a retrospective analysis of the NESDA fMRI study, we compared two groups of fourteen healthy volunteers with intermediate and high educational attainment, matched for age and gender. The data concerned event-related functional magnetic resonance imaging of brain activation during perception of facial emotional expressions. The region of interest analysis showed stronger right amygdala activation to facial expressions in participants with lower relative to higher educational attainment. The psychophysiological interaction analysis revealed that participants with higher educational attainment exhibited stronger right amygdala – right insula connectivity during perception of emotional and neutral facial expressions. This exploratory study suggests the relevance of educational attainment on the neural mechanism of facial expression processing.
Published: 2014
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38. Influence of COMT val158met genotype on the depressed brain during emotional processing and working memory.

Author: Esther M Opmeer, Rudie Kortekaas, Marie-José van Tol, Nic J A van der Wee, Saskia Woudstra, Mark A van Buchem, Brenda W Penninx, Dick J Veltman, and André Aleman
Subjects: Medicine, Science
Abstract: Major depressive disorder (MDD) has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the catechol-O-methyltransferase (COMT) gene has been shown to influence prefrontal cortex (PFC) activation during both emotional processing and working memory (WM). Although COMT-genotype is not directly associated with MDD, it may affect MDD pathology by altering PFC activation, an endophenotype associated with both COMT and MDD. 125 participants, including healthy controls (HC, n=28) and MDD patients were genotyped for the COMT val158met polymorphism and underwent functional magnetic resonance imaging (fMRI-neuroimaging) during emotion processing (viewing of emotional facial expressions) and a WM task (visuospatial planning). Within HC, we observed a positive correlation between the number of met-alleles and right inferior frontal gyrus activation during emotional processing, whereas within patients the number of met-alleles was not correlated with PFC activation. During WM a negative correlation between the number of met-alleles and middle frontal gyrus activation was present in the total sample. In addition, during emotional processing there was an effect of genotype in a cluster including the amygdala and hippocampus. These results demonstrate that COMT genotype is associated with relevant endophenotypes for MDD. In addition, presence of MDD only interacts with genotype during emotional processing and not working memory.
Published: 2013
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39. Extraversion is linked to volume of the orbitofrontal cortex and amygdala.

Author: Henk Cremers, Marie-José van Tol, Karin Roelofs, Andre Aleman, Frans G Zitman, Mark A van Buchem, Dick J Veltman, and Nic J A van der Wee
Subjects: Medicine, Science
Abstract: Neuroticism and extraversion are personality factors associated with the vulnerability for developing depression and anxiety disorders, and are possibly differentially related to brain structures implicated in the processing of emotional information and the generation of mood states. To date, studies on brain morphology mainly focused on neuroticism, a dimension primarily related to negative affect, yielding conflicting findings concerning the association with personality, partially due to methodological issues and variable population samples under study. Recently, extraversion, a dimension primarily related to positive affect, has been repeatedly inversely related to with symptoms of depression and anxiety disorders. In the present study, high resolution structural T1-weighted MR images of 65 healthy adults were processed using an optimized Voxel Based Morphometry (VBM) approach. Multiple regression analyses were performed to test for associations of neuroticism and extraversion with prefrontal and subcortical volumes. Orbitofrontal and right amygdala volume were both positively related to extraversion. Extraversion was differentially related to volume of the anterior cingulate cortex in males (positive) and females (negative). Neuroticism scores did not significantly correlate with these brain regions. As extraversion is regarded a protective factor for developing anxiety disorders and depression and has been related to the generation of positive affect, the present results indicate that the reduced likelihood of developing affective disorders in individuals high on extraversion is related to modulation of emotion processing through the orbitofrontal cortex and the amygdala.
Published: 2011
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