Print  Close

Multivariate associations between psychiatric drug intake and GMV in psychosis and depression

Poster No:

457 

Submission Type:

Abstract Submission 

Authors:

Clara Weyer1,2, David Popovic3,1,4, Anne Ruef1, Lisa Hahn1, Elif Sarişik3,1,4, John Fanning1,4, Joseph Kambeitz5, Raimo K. Salokangas6, Jarmo Hietala6, Alessandro Bertolino7, Stefan Borgwardt8,9, Paolo Brambilla10,11, Rachel Upthegrove12,13, Stephen J. Wood14, Rebecca Lencer15, Eva Meisenzahl16, Nikolaos Koutsouleris1,3,17

Institutions:

1Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany, 2Graduate School of Systemic Neurosciences, LMU Munich, Planegg-Martinsried, Germany, 3Max-Planck Institute of Psychiatry, Munich, Germany, 4International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany, 5Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Bavaria, 6Department of Psychiatry, University of Turku, Turku, Finland, 7Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Bari, 8Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany, 9University of Basel, Department of Psychiatry (Psychiatric University Hospital, UPK), Basel, Switzerland, 10Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policli, Milan, Italy, 11Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy, 12Institute of Mental Health, University of Birmingham, Birmingham, United Kingdom, 13Early Intervention Service, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom, 14Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia, 15Institute for Translational Psychiatry, University Münster, Münster, Germany, 16Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany, 17Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom

First Author:

Clara Weyer  
Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich|Graduate School of Systemic Neurosciences, LMU Munich
Munich, Germany|Planegg-Martinsried, Germany

Co-Author(s):

David Popovic  
Max-Planck Institute of Psychiatry|Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich|International Max Planck Research School for Translational Psychiatry (IMPRS-TP)
Munich, Germany|Munich, Germany|Munich, Germany
Anne Ruef  
Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich
Munich, Germany
Lisa Hahn  
Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich
Munich, Germany
Elif Sarişik  
Max-Planck Institute of Psychiatry|Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich|International Max Planck Research School for Translational Psychiatry (IMPRS-TP)
Munich, Germany|Munich, Germany|Munich, Germany
John Fanning  
Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich|International Max Planck Research School for Translational Psychiatry (IMPRS-TP)
Munich, Germany|Munich, Germany
Joseph Kambeitz  
Department of Psychiatry and Psychotherapy, University of Cologne
Cologne, Bavaria
Raimo K. Salokangas  
Department of Psychiatry, University of Turku
Turku, Finland
Jarmo Hietala  
Department of Psychiatry, University of Turku
Turku, Finland
Alessandro Bertolino  
Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro
Bari, Bari
Stefan Borgwardt  
Department of Psychiatry and Psychotherapy, University of Lübeck|University of Basel, Department of Psychiatry (Psychiatric University Hospital, UPK)
Lübeck, Germany|Basel, Switzerland
Paolo Brambilla  
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policli|Department of Pathophysiology and Transplantation, University of Milan
Milan, Italy|Milan, Italy
Rachel Upthegrove  
Institute of Mental Health, University of Birmingham|Early Intervention Service, Birmingham Women’s and Children’s NHS Foundation Trust
Birmingham, United Kingdom|Birmingham, United Kingdom
Stephen J. Wood  
Centre for Youth Mental Health, University of Melbourne
Melbourne, Australia
Rebecca Lencer  
Institute for Translational Psychiatry, University Münster
Münster, Germany
Eva Meisenzahl  
Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University
Düsseldorf, Germany
Nikolaos Koutsouleris  
Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich|Max-Planck Institute of Psychiatry|Institute of Psychiatry, Psychology and Neuroscience, King's College London
Munich, Germany|Munich, Germany|London, United Kingdom

Introduction:

Psychiatric medication, including antipsychotics and antidepressants, is widely prescribed, even in young and adolescent populations at early or subthreshold disease stages. However, its impact on brain structure remains elusive. Elucidating the relationship between psychiatric medication and structural brain changes could enhance the understanding of the potential benefits and risks associated with such treatment. Therefore, the aim of this study is to investigate the associations between psychiatric medication intake and longitudinal grey matter volume (GMV) changes in a transdiagnostic sample of young individuals at early stages of psychosis or depression using an unbiased data-driven approach.

Methods:

The study sample comprised 247 participants (mean [SD] age = 25.06 [6.13] years, 50.61% male), consisting of young, minimally medicated individuals at clinical high-risk states for psychosis, individuals with recent-onset depression or psychosis, and healthy control individuals. Participants were recruited as part of the multicentric PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Structural magnetic resonance imaging was used to obtain whole-brain voxel-wise GMV for all participants at two timepoints (mean [SD] time between scans = 11.15 [4.93] months). The multivariate sparse partial least squares (SPLS) algorithm was embedded in a nested cross-validation framework to identify parsimonious associations between the cumulative intake of psychiatric medication, including commonly prescribed antipsychotics and antidepressants, and change in GMV between both timepoints, while additionally factoring in age, sex, and diagnosis. Furthermore, we correlated the retrieved SPLS results to personality domains (NEO-FFI) and childhood trauma (CTQ).

Results:

SPLS analysis revealed significant associations between the antipsychotic classes of benzamides, butyrophenones and thioxanthenes and longitudinal GMV decreases in cortical regions including the insula, posterior superior temporal sulcus as well as cingulate, postcentral, precentral, orbital and frontal gyri. These brain regions corresponded most closely to the dorsal and ventral attention, somatomotor, salience and default network. Furthermore, the medication signature was negatively associated with the personality domains extraversion, agreeableness and conscientiousness and positively associated with the CTQ domains emotional and physical neglect.

Conclusions:

Antipsychotic treatment over a period of one year was linked to distinct GMV reductions in key cortical hubs. These patterns were already visible in young individuals at early or subthreshold stages of mental illness and were further linked to childhood neglect and personality traits. Hence, a better and more in-depth understanding of the structural brain implications of medicating young and adolescent individuals might lead to more cautious, sustainable and targeted treatment strategies.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Modeling and Analysis Methods:

Multivariate Approaches 2

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Anatomy and Functional Systems

Novel Imaging Acquisition Methods:

Anatomical MRI

Physiology, Metabolism and Neurotransmission :

Pharmacology and Neurotransmission

Keywords:

Multivariate
Pharmacotherapy
Psychiatric Disorders
STRUCTURAL MRI
Other - Antipsychotics

1|2Indicates the priority used for review
Supporting Image: LV1.png
   ·Behavioral and brain pattern of the medication-brain signature
 

Provide references using author date format

Koutsouleris, N., Kambeitz-Ilankovic, L., Ruhrmann, S., Rosen, M., Ruef, A., Dwyer, D. B., Paolini, M., Chisholm, K., Kambeitz, J., Haidl, T., Schmidt, A., Gillam, J., Schultze-Lutter, F., Falkai, P., Reiser, M., Riecher-Rössler, A., Upthegrove, R., Hietala, J., Salokangas, R. K. R., Pantelis, C., … PRONIA Consortium (2018). Prediction Models of Functional Outcomes for Individuals in the Clinical High-Risk State for Psychosis or With Recent-Onset Depression: A Multimodal, Multisite Machine Learning Analysis. JAMA psychiatry, 75(11), 1156–1172. https://doi.org/10.1001/jamapsychiatry.2018.2165

Monteiro, J. M., Rao, A., Shawe-Taylor, J., Mourão-Miranda, J., & Alzheimer's Disease Initiative (2016). A multiple hold-out framework for Sparse Partial Least Squares. Journal of neuroscience methods, 271, 182–194. https://doi.org/10.1016/j.jneumeth.2016.06.011

Popovic, D., Ruef, A., Dwyer, D. B., Antonucci, L. A., Eder, J., Sanfelici, R., Kambeitz-Ilankovic, L., Oztuerk, O. F., Dong, M. S., Paul, R., Paolini, M., Hedderich, D., Haidl, T., Kambeitz, J., Ruhrmann, S., Chisholm, K., Schultze-Lutter, F., Falkai, P., Pergola, G., Blasi, G., … PRONIA Consortium (2020). Traces of Trauma: A Multivariate Pattern Analysis of Childhood Trauma, Brain Structure, and Clinical Phenotypes. Biological psychiatry, 88(11), 829–842. https://doi.org/10.1016/j.biopsych.2020.05.020