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. 2022 Jan 18:12:807839.
doi: 10.3389/fpsyt.2021.807839. eCollection 2021.

Focusing on Comorbidity-A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders

Lydia Fortea  1   2   3 , Anton Albajes-Eizagirre  1 , Yuan-Wei Yao  4   5   6 , Edu Soler  1 , Norma Verdolini  1   2   3   7 , Alexander O Hauson  8   9 , Adriana Fortea  1   2   3   10   11 , Santiago Madero  1   12 , Aleix Solanes  1   13 , Scott C Wollman  8 , Maria Serra-Blasco  2   14   15 , Toby Wise  16 , Steve Lukito  17 , Maria Picó-Pérez  18   19   20 , Christina Carlisi  17   21 , JinTao Zhang  22 , PingLei Pan  23 , Álvar Farré-Colomés  1   24 , Danilo Arnone  25   26 , Matthew J Kempton  16   27 , Carles Soriano-Mas  2   28   29 , Katya Rubia  17 , Luke Norman  17   30   31 , Paolo Fusar-Poli  27   32   33   34 , David Mataix-Cols  35   36 , Marc Valentí  1   2   3   7   11 , Esther Via  37   38 , Narcis Cardoner  2   13   39 , Marco Solmi  32   40   41   42 , Jae I Shin  43 , Eduard Vieta  1   2   3   7   11 , Joaquim Radua  1   2   27   35
Affiliations

Focusing on Comorbidity-A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders

Lydia Fortea et al. Front Psychiatry. .

Abstract

Background: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information.

Objectives: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities.

Methods: The novel approach consists of a modification of Seed-based d Mapping-with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults.

Discussion: The novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools.

Keywords: comorbidity; gray matter (GM); magnetic resonance imaging (MRI); medication; mental disorder; meta-analysis; seed-based d mapping (SDM).

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Conflict of interest statement

NV has received financial support for CME activities and travel funds from the following entities (unrelated to the present work): Angelini, Janssen-Cilag, Lundbeck, Otsuka. EVia is a co-investigator in a Janssen-Cilag, S.A., clinical trial with the esketamine molecule (unrelated to the present work). KR received a grant from TAKEDA pharmaceutical for another project and consulting fees from Lundbeck and Supernus (unrelated to the present work). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Rules for creating the gray matter maps of a simulated patient. After creating a map using white noise, we added or subtracted 0.5 in the colored brain regions of interest (ROI) depending on the disorders he/she had.
Figure 2
Figure 2
Regions showing statistically significant effects using the novel SDM-PSI approach. ROI, region of interest.
Figure 3
Figure 3
Regions showing statistically significant effects using the previous SDM-PSI approach (separate results for meta-analysis of studies on disorder A, meta-analysis of studies on disorder B, and meta-analysis of studies on disorder C). ROI, region of interest.
See this image and copyright information in PMC

References

    1. DeLisi LE, Goldin LR, Hamovit JR, Maxwell ME, Kurtz D, Nurnberger JI, et al. . Cerebral ventricular enlargement as a possible genetic marker for schizophrenia. Psychopharmacol Bull. (1985) 21:365–7. - PubMed
    1. Brühl AB, Delsignore A, Komossa K, Weidt S. Neuroimaging in social anxiety disorder—a meta-analytic review resulting in a new neurofunctional model. Neurosci Biobehav Rev. (2014) 47:260–80. 10.1016/j.neubiorev.2014.08.003 - DOI - PubMed
    1. Brühl AB, Hänggi J, Baur V, Rufer M, Delsignore A, Weidt S, et al. . Increased cortical thickness in a frontoparietal network in social anxiety disorder: increased cortical thickness in SAD. Hum Brain Mapp. (2014) 35:2966–77. 10.1002/hbm.22378 - DOI - PMC - PubMed
    1. Irle E. Reduced amygdalar and hippocampal size in adults with generalized social phobia. J Psychiatry Neurosci. (2010) 35:126–31. 10.1503/jpn.090041 - DOI - PMC - PubMed
    1. Irle E, Barke A, Lange C, Ruhleder M. Parietal abnormalities are related to avoidance in social anxiety disorder: a study using voxel-based morphometry and manual volumetry. Psychiatry Res Neuroimaging. (2014) 224:175–83. 10.1016/j.pscychresns.2014.08.013 - DOI - PubMed