Interrelated effects of age and parenthood on whole-brain controllability: protective effects of parenthood in mothers

Hamidreza Jamalabadi; Tim Hahn; Nils R Winter; Erfan Nozari; Jan Ernsting; Susanne Meinert; Elisabeth J Leehr; Katharina Dohm; Jochen Bauer; Julia-Katharina Pfarr; Frederike Stein; Florian Thomas-Odenthal; Katharina Brosch; Marco Mauritz; Marius Gruber; Jonathan Repple; Tobias Kaufmann; Axel Krug; Igor Nenadić; Tilo Kircher; Udo Dannlowski; Birgit Derntl

doi:10.3389/fnagi.2023.1085153

Interrelated effects of age and parenthood on whole-brain controllability: protective effects of parenthood in mothers

Front Aging Neurosci. 2023 Oct 18:15:1085153. doi: 10.3389/fnagi.2023.1085153. eCollection 2023.

Authors

Hamidreza Jamalabadi^#^{1

2}, Tim Hahn^#³, Nils R Winter³, Erfan Nozari^{4

5

6}, Jan Ernsting³, Susanne Meinert⁷, Elisabeth J Leehr³, Katharina Dohm³, Jochen Bauer⁸, Julia-Katharina Pfarr¹, Frederike Stein¹, Florian Thomas-Odenthal¹, Katharina Brosch¹, Marco Mauritz³, Marius Gruber³, Jonathan Repple³, Tobias Kaufmann^{2

9}, Axel Krug^{1

10}, Igor Nenadić^{1

11}, Tilo Kircher¹, Udo Dannlowski³, Birgit Derntl²

Affiliations

¹ Department of Psychiatry and Psychotherapy, Philipps University of Marburg, Marburg, Germany.
² Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
³ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁴ Department of Mechanical Engineering, University of California, Riverside, Riverside, CA, United States.
⁵ Department of Electrical and Computer Engineering, University of California, Riverside, Riverside, CA, United States.
⁶ Department of Bioengineering, University of California, Riverside, Riverside, CA, United States.
⁷ Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁸ Department of Clinical Radiology, University of Münster, Münster, Germany.
⁹ Norwegian Centre for Mental Disorders Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
¹⁰ Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
¹¹ Center for Mind, Brain, and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen, Marburg, Germany.

^# Contributed equally.

Abstract

Background: Controllability is a measure of the brain's ability to orchestrate neural activity which can be quantified in terms of properties of the brain's network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to long-lasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging.

Methods: In a sample of 814 healthy individuals (aged 33.9 ± 12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability).

Results and conclusion: In nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers.

Keywords: aging; brain; diffusion tensor imaging; network control theory; parenthood.

Copyright © 2023 Jamalabadi, Hahn, Winter, Nozari, Ernsting, Meinert, Leehr, Dohm, Bauer, Pfarr, Stein, Thomas-Odenthal, Brosch, Mauritz, Gruber, Repple, Kaufmann, Krug, Nenadić, Kircher, Dannlowski and Derntl.

Grants and funding

This work was supported by the Fortüne grant of Medical Faculty of University of Tübingen (No. 2487-1-0). This work was funded by the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4 to TH; DA1151/5-1 and DA1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grants Dan3/012/17 to UD and MzH 3/020/20 to TH), and the German Research Foundation (DFG grant FOR2107, KI588/14-1 and FOR2107, KI588/14-2 to TiK, Marburg, Germany). The MACS dataset used in this work is part of the German multicenter consortium Neurobiology of Affective Disorders. A translational perspective on brain structure and function funded by the German Research Foundation (Deutsche Forschungsgemeinschaft DFG; Forschungsgruppe/Research Unit FOR2107). Principal investigators (PIs) with respective areas of responsibility in the FOR2107 consortium are: Work Package WP1, FOR2107/MACS cohort and brain imaging: TiK (speaker FOR2107; DFG grant numbers KI 588/14-1, KI 588/14-2), UD (co-speaker FOR2107; DA 1151/5-1, DA 1151/5-2), AK (KR 3822/5-1, KR 3822/7-2), IN (NE 2254/1-2, NE 2254/3-1, and NE 2254/4-1), Carsten Konrad (KO 4291/3-1). WP2, animal phenotyping: Markus Wöhr (WO 1732/4-1, WO 1732/4-2), Rainer Schwarting (SCHW 559/14-1, SCHW 559/14-2). WP3, miRNA: Gerhard Schratt (SCHR 1136/3-1, 1136/3-2). WP4, immunology, mitochondriae: Judith Alferink (AL 1145/5-2), Carsten Culmsee (CU 43/9-1, CU 43/9-2), Holger Garn (GA 545/5-1, GA 545/7-2). WP5, genetics: Marcella Rietschel (RI 908/11-1, RI 908/11-2), Markus Nöthen (NO 246/10-1, NO 246/10-2), Stephanie Witt (WI 3439/3-1, WI 3439/3-2). WP6, multi method data analytics: Andreas Jansen (JA 1890/7-1, JA 1890/7-2), Tim Hahn (HA 7070/2-2), Bertram Müller-Myhsok (MU1315/8-2), Astrid Dempfle (DE 1614/3-1, DE 1614/3-2). CP1, biobank: Petra Pfefferle (PF 784/1-1, PF 784/1-2), Harald Renz (RE 737/20-1, 737/20-2). CP2, administration. TiK (KI 588/15-1, KI 588/17-1), UD (DA 1151/6-1), Carsten Konrad (KO 4291/4-1). Data access and responsibility: All PIs take responsibility for the integrity of the respective study data and their components. All authors and co-authors had full access to all study data. The FOR2107 cohort project (WP1) was approved by the Ethics Committees of the Medical Faculties, University of Marburg (AZ: 07/14) and University of Münster (AZ: 2014-422-b-S). BD and ToK are supported by the DFG (IRTG 2804). Open Access funding provided by the Open Access Publishing Fund of Philipps-Universität Marburg with support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).