Pubertal maturation and sex effects on the default-mode network connectivity implicated in mood dysregulation

Monique Ernst, , Brenda Benson, Eric Artiges, Adam X. Gorka, Herve Lemaitre, Tiffany Lago, Ruben Miranda, Tobias Banaschewski, Arun L. W. Bokde, Uli Bromberg, Rüdiger Brühl, Christian Büchel, Anna Cattrell, Patricia Conrod, Sylvane Desrivières, Tahmine Fadai, Herta Flor, Antoine Grigis, Juergen Gallinat, Hugh Garavan, Penny Gowland, Yvonne Grimmer, Andreas Heinz, Viola Kappel, Frauke Nees, Dimitri Papadopoulos-Orfanos, Jani Penttilä, Luise Poustka, Michael N. Smolka, Argyris Stringaris, Maren Struve, Betteke M. van Noort, Henrik Walter, Robert Whelan, Gunter Schumann, Christian Grillon, Marie-Laure Paillère Martinot, Jean-Luc Martinot
Transl Psychiatry. 2019-02-25; 9(1):
DOI: 10.1038/s41398-019-0433-6

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Collaborators: Dalley J, Subramaniam N, Theobald D, Bach C, Barker GJ,
Fauth-Bühler M, Millenet S, Spanagel R, Albrecht L, Ivanov N, Rapp M, Reuter J,
Strache N, Ströhle A, Poline JB, Schwartz Y, Thyreau B, Ireland J, Rogers J,
Bordas N, Bricaud Z, Filippi I, Galinowski A, Gollier-Briant F, Hall D, Havatzias
S, Jia T, Mallik C, Nymberg C, Ruggeri B, Smith L, Stueber K, Topper L, Werts H,
Brühl R R, Ihlenfeld A, Walaszek B, Hübner T, Müller K, Paus T, Ripke S, Mennigen
E, Schmidt D, Vetter NC, Ziesch V, Carter D, Connolly C, Nugent S, Jones J,
Yacubian J, Schneider S, Head K, Heym N, Newman C, Pausova Z, Tahmasebi A,
Stephens D.

This study examines the effects of puberty and sex on the intrinsic functional
connectivity (iFC) of brain networks, with a focus on the default-mode network
(DMN). Consistently implicated in depressive disorders, the DMN’s function may
interact with puberty and sex in the development of these disorders, whose onsets
peak in adolescence, and which show strong sex disproportionality
(females > males). The main question concerns how the DMN evolves with puberty as
a function of sex. These effects are expected to involve within- and
between-network iFC, particularly, the salience and the central-executive
networks, consistent with the Triple-Network Model. Resting-state scans of an
adolescent community sample (n = 304, male/female: 157/147; mean/std age:
14.6/0.41 years), from the IMAGEN database, were analyzed using the AFNI software
suite and a data reduction strategy for the effects of puberty and sex. Three
midline regions (medial prefrontal, pregenual anterior cingulate, and posterior
cingulate), within the DMN and consistently implicated in mood disorders, were
selected as seeds. Within- and between-network clusters of the DMN iFC changed
with pubertal maturation differently in boys and girls (puberty-X-sex).
Specifically, pubertal maturation predicted weaker iFC in girls and stronger iFC
in boys. Finally, iFC was stronger in boys than girls independently of puberty.
Brain-behavior associations indicated that lower connectivity of the anterior
cingulate seed predicted higher internalizing symptoms at 2-year follow-up. In
conclusion, weaker iFC of the anterior DMN may signal disconnections among
circuits supporting mood regulation, conferring risk for internalizing disorders.

Auteurs Bordeaux Neurocampus