Polygenic scores of subcortical brain volumes as possible modulators of treatment response in depression
Year: 2024
Type: article
Abstract: A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly hippocampal volume, as potential predictors of treatment response, as well as genetic factors. This study investigated the association of polygenic scores (PGSs) for seven subcortical brain volumes (including the hippocampus, nucleus accumbens, amygdala, and caudate nucleus) with treatment non-response and non-remission in MDD. Patients with MDD were recruited in the context of five clinical studies, including a total of 3637 individuals. PGSs were estimated using a Bayesian framework and continuous shrinkage priors (PRS-CS-auto) after standard genotype quality control and imputation. Logistic regressions were performed between PGSs and non-response or non-remission in each sample, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, using a random-effect model. No association was significant in the meta-analysis after Bonferroni correction. The top finding was found for the caudate volume PGS and non-remission (OR = 1.09, 95% CI = 1.01-1.19, p = 0.036), with no evidence of heterogeneity. Leave-one-out sensitivity analyses showed that this result was influenced by the two largest samples in the meta-analysis. This result should be considered as preliminary as it did not reach the Bonferroni-adjusted significance threshold. Future studies with greater statistical power may enhance the predictive performance of PGSs and contribute to the identification of polygenic predictors of treatment outcomes in MDD, contributing to precision psychiatry.
Source: Neuroscience Applied
Authors: Vincenzo Oliva, Alfonso Martone, Giuseppe Fanelli, Katharina Domschke, Alessandra Minelli, Massimo Gennarelli, Paolo Martini, Marco Bortolomasi, Eduard Maron, Alessio Squassina, Claudia Pisanu, Siegfried Kasper, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Diana De Ronchi, Bernhard T. Baune, Marie-Claude Potier, Roos van Westrhenen, Filip Rybakowski, Divya Mehta, Mara Dierssen, Joost G.E. Janzing, Pietro Liò, Alessandro Serretti, Chiara Fabbri
Institutions: Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, University of Bologna, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, University of Freiburg, University Medical Center Freiburg, Centro San Giovanni di Dio Fatebenefratelli, University of Brescia, Imperial College London, University of Tartu, University of Cagliari, Medical University of Vienna, Tel Aviv University, Sheba Medical Center, Université Libre de Bruxelles, Vrije Universiteit Brussel, Mario Negri Institute for Pharmacological Research, National and Kapodistrian University of Athens, The University of Melbourne, University of Münster, Florey Institute of Neuroscience and Mental Health, Institut des Sciences Moléculaires, Institut du Cerveau, Università degli Studi di Enna Kore
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
OpenAlex ID: W4391113167