Serotonin and early life stress interact to shape brain architecture and anxious avoidant behavior – a TPH2 imaging genetics approach

Abstract

Serotonin regulates developmental and experience-dependent neuroplasticity in limbicprefrontal systems engaged in emotional reactivity and regulation. Tryptophan hydroxylase 2 (TPH2) regulates central serotonergic biosynthesis rates and transgenic animal models suggest that TPH2-associated changes in serotonergic signaling mediate the impact of early life stress (ELS) shaping a phenotype characterized by anxious avoidance. The present study employed an imaging genomics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of ELS on brain structure and function and punishment sensitivity in humans (n = 252). Higher ELS exposure was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. On the phenotype level, the genotype moderated the association between higher ELS exposure and higher punishment sensitivity. In TT carriers, the association between higher ELS exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. The present findings suggest that ELS shapes the neural organization of the thalamic-limbic-prefrontal circuits in interaction with individual variations in TPH2 to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.

Putamen volume predicts real‐time fMRI neurofeedback learning success across paradigms and neurofeedback target regions

“…Briefly, the rs‐FC data were initially subjected to standard preprocessing steps including slice timing and head movement corrections, normalization to MNI space, removal of physiological noise and global signal intensity and finally, band‐pass filtering. The functional connectivity analysis employed the identified cluster associated with NF learning success from the VBM analysis as seed region to calculate whole brain resting state FC (details of the sample, preprocessing and analysis are additionally provided in the SI; for the further sample description see also [Liu et al, 2020]).…”

Opposing and emotion-specific frontal alterations during facial emotion processing in generalized anxiety and depression

“…To control for previously reported effects of early life stress on the brain (e.g. Liu et al, 2020; Teicher et al, 2016) the Childhood Trauma Questionnaire (CTQ) was administered. All subjects underwent a previously evaluated facial emotion processing paradigm during fMRI (see Domes et al, 2007; Knyazev et al, 2009; Kou et al, 2020).…”

Oxytocinergic modulation of stress-associated amygdala-hippocampus pathways in humans is mediated by serotonergic mechanisms

“…Anxiety and depression have been associated with amygdala functional networks (Spengler et al, 2017a; Zhao et al, 2019b; Xu et al, 2021; Liu et al, 2021b) and therefore corresponding indices were assessed to control for pre-treatment differences between the groups. To this end the State-Trait Anxiety Inventory (STAI) (Spielberger et al, 1970) and Beck Depression Inventory (BDI-II) (Beck et al, 1996) were applied.…”