DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

Abstract

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects.

An exploratory pilot investigation of neurosteroids and self-reported pain in female Iraq/Afghanistan-era Veterans

“…Identification of biomarkers associated with pain symptoms could help detect risk factors for the development of pain symptoms and guide the development of novel neurosteroid therapeutics for pain disorders. Based on these current findings and prior reports [30,38,40,48], DHEA administration could have therapeutic utility considering it markedly increases DHEAS levels [45][46]48], and quantifying these neurosteroids may have biomarker potential. For example, although the associations found in this study cannot elucidate causation, it is possible that individuals with low DHEAS levels at baseline may be more vulnerable to the development of chronic pain-and that pain symptoms could be ameliorated by restoring DHEAS and/or enhancing DHEAS levels through exogenous administration of DHEA or other neurosteroids.…”

“…In addition, an examination of DHEA and DHEAS levels in male Iraq/ Afghanistan-era Veterans and possible relationships to pain symptoms will be important; considering pronounced sex differences in DHEA and DHEAS levels, the investigation of these molecules in both males and females could contribute to the understanding of sex differences in the neurobiology of pain. Given recent promising neuroimaging findings following DHEA administration [45][46], the use of neuroimaging approaches in the future could also yield new insights into the possible mechanistic contributions of DHEA and DHEAS to the physiology and therapeutics of pain and provide potential biomarker data for the prediction of therapeutic response to neurosteroid interventions. In addition, examining the genetic underpinnings of neurosteroid synthesis and metabolism will be critical.…”

“…For example, reduced levels of DHEA are associated with depression-like symptoms in animal models [41], and reductions in DHEA [42] and DHEAS [43][44] are also associated with depression and anxiety symptoms in clinical populations. Furthermore, two recent functional magnetic resonance imaging studies in healthy adult men suggest that a single dose of DHEA modulates neurocircuitry involved in anxiety and depression [45][46]. In addition, a randomized, double-blind placebo-controlled trial of DHEA resulted in improvement for negative symptoms, depression, and anxiety symptoms in patients with schizophrenia [47]an effect that was more pronounced in females than in males.…”

DHEAS and cortisol/DHEAS-ratio in recurrent depression: State, or trait predicting 10-year recurrence?

“…The effect was in the expected direction in the CT-group: low cortisol/DHEAS-ratio was associated with longer time till recurrence. This could be caused by enhancing effects of DHEAS on memory and cognition, which make patients with a relatively lower cortisol/DHEAS-ratio more receptive for CT's recurrence preventing effects (Maninger et al, 2009;Sripada et al, 2013). Analogically, lower cortisol (and higher DHEAS) prospectively predicted post-traumatic stress disorder (PTSD)-symptoms in trauma center patients (Mouthaan et al, 2014).…”

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) and emotional processing — A behavioral and electrophysiological approach

“…In this regard, a study using LORETA showed that DHEA administration increased the activity in the anterior cingulate cortex (Alhaj et al, 2006). Another recent study using functional Magnetic Resonance Imaging (fMRI) found that DHEA reduces the activity in regions associated with the generation of negative emotion and enhances activity in regions linked to regulatory processes (Sripada et al, 2013).…”