Increased Neural Reactivity to Emotional Pictures in Men With High Hair Testosterone Concentrations

Sanja Klein; Onno Kruse; Isabell Tapia León; Tobias Stalder; Rudolf Stark; Tim Klucken

Disclosures

Soc Cogn Affect Neurosci. 2019;14(9):1009-1016. 

In This Article

Abstract and Introduction

Abstract

Testosterone has been linked to alterations in the activity of emotion neurocircuitry including amygdala, orbitofrontal cortex (OFC) and insula and diminished functional amygdala/prefrontal coupling. Such associations have only ever been studied using acute measures of testosterone, thus little is known about respective relationships with long-term testosterone secretion. Here, we examine associations between hair testosterone concentration (HTC), an index of long-term cumulative testosterone levels and neural reactivity during an emotional passive viewing task using functional magnetic resonance imaging (fMRI). Forty-six men viewed negative, positive and neutral pictures in the MRI. HTCs were assessed from 2 cm hair segments. The emotional paradigm elicited neural activation in the amygdala, insula and OFC. HTCs were associated with increased reactivity to negative pictures in the insula and increased reactivity to positive pictures in the OFC. We show an association of long-term testosterone levels with increased emotional reactivity in the brain. These results suggest a heightened emotional vigilance in individuals with high trait testosterone levels.

Introduction

Testosterone and other androgens have been shown to have neuroregulatory effects on serotonergic and dopaminergic systems by binding to androgen receptors in the amygdala, striatum and hypothalamus (Rubinow and Schmidt, 1996). These systems play an important role in emotion and behavior regulation as well as in general emotion processing in many mammals including humans. Therefore, testosterone is frequently examined as a modulator of these functions and associated psychopathologies (Rosell and Siever, 2015).

Such experimental works on the links between testosterone and human emotion processing has revealed exogenous testosterone to reduce skin conductance responses to negative pictures (Hermans et al., 2007) as well as fear potentiation of the startle reflex (Hermans et al., 2006). In line with this, Van Honk et al. (2005) found a lower fear-related attentional bias in a masked emotional Stroop task after testosterone administration. While many studies have focused on acute testosterone secretion or administration, little is known about the role of long-term cumulative testosterone. Testosterone measures aggregated over many saliva samples taken on multiple different days have been shown to be a good predictor of emotion regulation problems (Granger et al., 2003; van Bokhoven et al., 2006). Notably, Granger et al. (2003) found that these aggregated testosterone measures were superior in predicting emotion regulation problems compared to single-state measures. In a recent study, Grotzinger et al. (2018) utilized hair analyses to investigate long-term cumulative testosterone levels alongside short-term salivary testosterone data. Importantly, they found dysfunctional emotion regulation linked with hair testosterone concentrations (HTCs) but not with acute salivary testosterone levels, which corresponds to the notion that long-term endocrine data might be better suited for capturing associations with stable, trait-like behavioral dispositions. The method of hair steroid analysis, which was used in this research, has increasingly gained acceptance over the past decade for providing a reliable, valid and robust index of long-term hormone secretion patterns (reviews: Stalder et al., 2017; Stalder and Kirschbaum, 2012). While a lot of research exists using hair cortisol concentrations, so far, no comparable studies using hair testosterone analysis have been conducted to investigate links with general emotion processing.

Most studies concerned with acute testosterone have focused on fear-related stimuli, but more recently Bos et al. (2012) proposed a model featuring testosterone as important for helping to detect and cope with not only potentially threatening but also rewarding stimuli by simultaneously increasing salience perception and reducing fear to prepare for action. Thus, testosterone should be associated with increased activity in emotion processing regions when viewing negative as well as positive emotionally salient stimuli.

Accordingly, high acute testosterone levels have been linked with increased neural reactivity to emotional stimuli. In functional magnetic resonance imaging (fMRI) studies, endogenous and exogenous testosterone have been linked to increased activations in the amygdala (van Wingen et al., 2011; Heany et al., 2016) and the orbitofrontal cortex (OFC; van Wingen et al., 2011) in response to potentially threatening and rewarding stimuli. Specifically, increased amygdala activity correlating with high testosterone levels was found in response to negative (Hermans et al., 2008; Derntl et al., 2009; Manuck et al., 2010) as well as positive pictures (van Wingen et al., 2009; Bos et al., 2013) and emotional sounds (Bos et al., 2010). High testosterone levels have also been linked with increased reactivity to negative faces in prefrontal regions, in particular the OFC (Hermans et al., 2008) and the ventromedial prefrontal cortex ( Stanton et al., 2009). The insula as an important part of the salience network (Menon and Uddin, 2010; Uddin, 2015) has mostly been neglected in emotion processing studies concerned with testosterone. Bos et al. (2010) found that testosterone increased neural response of the insula to emotional sounds.

This study provides the first investigation of the relationship between HTC and emotion processing neuroimaging data. We hypothesized that subjects with higher HTC show increased salience perception of emotional pictures independent of valence compared to neutral pictures in all response systems measured. Thus, we hypothesized that subjects with higher HTC levels show higher subjective salience ratings, increased electrodermal activity and increased hemodynamic responses in emotion processing and saliency areas (amygdala, OFC and insula) when viewing emotional pictures compared to neutral.

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