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

Abstract

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.

A three‐wave longitudinal study of subcortical–cortical resting‐state connectivity in adolescence: Testing age‐ and puberty‐related changes

“…For instance, animal work has observed a reduction in medial PFC volume and synapses in postpubertal rats, and neuronal losses during pubertal onset (Walker et al, ; Willing & Juraska, ). In humans, decreases in gray matter density in frontal regions (Peper et al, ), as well as hippocampus, amygdala, and caudate volumes (Goddings et al, ; Wierenga et al, ) have been related to pubertal development, but—to our knowledge—these findings are one of the first to test and compare effects of pubertal development on RS functional connectivity (but see also Ernst et al, ). Including pubertal development improved model fits for changes in specific subcortical–cortical connections, suggesting that the developing efficiency of the brain is a puberty‐driven maturational processes that may accelerate changes in modularity and plasticity in the developing brain.…”

“…These differences between sexes may suggest that pubertal development in boys and girls has differential influence on the development of subcortical–cortical connectivity. A recent study into RS connectivity in the cortical default network observed particularly sex × pubertal developmental interactions in which connectivity decreased across pubertal development in girls, whereas it increased in boys (Ernst et al, ). This was tentatively interpreted as relevant to the emergence of affective dysregulation in adolescence that affect girls more.…”

“…Goddings et al, 2014;Wierenga et al, 2018) have been related to pubertal development, but-to our knowledge-these findings are one of the first to test and compare effects of pubertal development on RS functional connectivity (but see alsoErnst et al, 2019). Including pubertal development improved model fits for changes in specific subcortical-cortical connections, suggesting that the developing efficiency of the brain is a puberty-driven maturational processes that may accelerate changes in modularity and plasticity in the developing brain.…”

Dysregulation of oxytocin and dopamine in the corticostriatal circuitry in bipolar II disorder

“…The ECN involves the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and posterior parietal cortex (PPC) 17 . Different activation patterns in these networks may contribute to mood dysregulation 18 and may distinguish BD from unipolar depression 15,19 . However, these patterns remain elusive in patients with BD II, because previous studies did not include BD II patients or distinguish them from BD I patients, even though BD II patients are as disabled as BD I patients 20,21 .…”

No evidence for a relationship between social closeness and similarity in resting-state functional brain connectivity in schoolchildren

“…Differences in DMN connectivity have been reported between adults and children 71 as well as within individuals throughout early adolescence 72 . In addition, researchers have found associations between pubertal development and strength of intrinsic functional connectivity 73 . Younger samples may therefore exhibit less intrinsic network homophily than more mature samples due to greater brain variability between subjects.…”