Time-Dependent Effects of Corticosteroids on Human Amygdala Processing

Abstract

Acute stress is associated with a sensitized amygdala. Corticosteroids, released in response to stress, are suggested to restore homeostasis by normalizing/desensitizing brain processing in the aftermath of stress. Here, we investigated the effects of corticosteroids on amygdala processing using functional magnetic resonance imaging. Since corticosteroids exert rapid nongenomic and slow genomic effects, we administered hydrocortisone either 75 min (rapid effects) or 285 min (slow effects) before scanning in a randomized, double-blind, placebo-controlled design. Seventy-two healthy males were scanned while viewing faces morphing from a neutral facial expression into fearful or happy expressions. Imaging results revealed that hydrocortisone desensitizes amygdala responsivity rapidly, while it selectively normalizes responses to negative stimuli slowly. Psychophysiological interaction analyses suggested that this slow normalization is related to an altered coupling of the amygdala with the medial prefrontal cortex. These results reveal a temporarily fine-tuned mechanism that is critical for avoiding amygdala overshoot during stress and enabling adequate recovery thereafter.

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

“…This might suggest that the stress-induced enhancement of amygdala activity might take about twenty minutes to arise which would be in line with in-vitro findings of enhanced amygdala excitability after corticosterone applications of 20 min (Karst et al, 2010) and a delayed rise of brain corticosterone levels after stress (Qian et al, 2011). Furthermore, the stress-induced increase in amygdala activity and connectivity may be transient as amygdala activity was found to be reduced one hour after hydrocortisone administration (Henckens et al, 2010) and no connectivity increase with the striatum could be detected one hour after stress onset (van Marle et al, 2010) or hydrocortisone administration (Henckens et al, 2012). These results highlight the striking time-dependency of stress effects on neural activity and memory (Henckens et al, 2010;Joëls et al, 2011;van Ast et al, 2013).…”

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

“…In line with this suggestion, increased amygdala-OFC coupling has been associated with higher levels of depression in this genotype. Likewise, evidence has been provided of the coupling between amygdala and a regulatory prefrontal region (mPFC) as being meditated by cortisol during resting state (Veer et al 2012) and fearful face processing (Henckens et al 2010), highlighting the influence of glucocorticoids on regulatory emotion networks. Previous research has emphasized the role of the anterior cingulate (ACC) in anxiety (Etkin and Wager 2007) and mood disorders (Drevets et al 2008).…”

“…Depressive symptoms were assessed with the Beck Depression Inventory [BDI, German version by Hautzinger et al (1994)] at age 25 years. In addition, to obtain a more stable measure of depression a composite score of the BDI levels during adulthood (ages 19, 22, 23 and 25 years) was formed.…”

Traumatic Experiences Disrupt Amygdala – Prefrontal Connectivity

“…Several lines of evidence have indicated that cortisol could be implicated (Henckens et There is an adaptive mechanism of time-dependent modulation of the amygdala by corticosteroids: rapid nongenomic effects of corticosteroids suppress overall amygdala activity in a nonspecific manner, whereas slow genomic actions of corticosteroids normalize responses to negative input by specifically altering prefrontal control (Henckens et al, 2010). It has been suggested that serotonin (5-hydroxytryptamine) also plays a role in regulating functional interactions between the amygdala and the prefrontal cortex (Davidson et al, 2000, Siever, 2008.…”