Gonadal hormone regulation of the emotion circuitry in humans

doi:10.1016/j.neuroscience.2011.04.042

Neuroscience

Volume 191, 15 September 2011, Pages 38-45

https://doi.org/10.1016/j.neuroscience.2011.04.042 Get rights and content

Abstract

Gonadal hormones are known to influence the regulation of emotional responses and affective states. Whereas fluctuations in progesterone and estradiol are associated with increased vulnerability for mood disorders, testosterone is mainly associated with social dominance, aggressive, and antisocial behavior. Here, we review recent functional neuroimaging studies that have started to elucidate how these hormones modulate the neural circuitry that is important for emotion regulation, which includes the amygdala and the medial prefrontal (mPFC) and orbitofrontal cortex (OFC). The amygdala is thought to generate emotional responses, and the prefrontal brain regions to regulate those responses. Overall, studies that have investigated women during different phases of the menstrual cycle suggest that progesterone and estradiol may have opposing actions on the amygdala and prefrontal cortex. In addition, the influence of exogenous progesterone appears to be dose-dependent. Endogenous testosterone concentrations are generally positively correlated to amygdala and OFC responses, and exogenous testosterone increases amygdala reactivity. Whereas the administration of progesterone increases amygdala reactivity and its connectivity with the mPFC, testosterone administration increases amygdala reactivity but decreases its connectivity with the OFC. We propose that this opposing influence on amygdala-prefrontal coupling may contribute to the divergent effects of progesterone and testosterone on emotion regulation and behavioral inhibition, respectively, which may promote the differential vulnerability to various psychiatric disorders between women and men.

This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Highlights

▶Gonadal hormones are known to influence the regulation of emotion and affect. ▶We review functional neuroimaging studies that have investigated gonadal hormone effects. ▶Endogenous hormones regulate amygdala and prefrontal cortex activity. ▶Exogenous progesterone and testosterone influence amygdala reactivity. ▶Progesterone and testosterone have divergent effects on amygdala coupling.

Section snippets

Gonadal hormones and psychiatric disorders

The sex difference in the prevalence of mood disorders starts during puberty and reduces in the years after menopause (Steiner et al., 2003, Weissman and Olfson, 1995). This suggests that fluctuations in the female gonadal hormones such as progesterone and estradiol have a major impact on the susceptibility to mood disorders in women. Indeed, the hormonal changes during the menstrual cycle induce depressive symptoms in women with premenstrual syndrome (Schmidt et al., 1998), which is discussed

The menstrual cycle and affect

The natural hormone fluctuations during the menstrual cycle offer an opportunity to investigate the influence of female gonadal hormones on the brain and behavior, as different phases of the menstrual cycle are characterized by different concentrations of progesterone and estradiol (see Fig. 1). On the basis of these hormone levels, the menstrual cycle can be divided into at least four distinct phases: the menstrual or early follicular phase during the first week, with the lowest levels of

The emotion regulation circuitry

The association of male and female gonadal hormones with various emotion regulation disorders suggests a possible common underlying neural circuitry. Indeed, a similar neurocircuitry underlies mood and anxiety disorders as well as impulse-control and substance abuse disorders. A key brain structure involved in emotion processing is the amygdala, which is located within the medial temporal lobe (see Fig. 2). It consists of several nuclei that appear to form distinct anatomical and functional

Sex, gonadal hormones, and brain structure

Sex differences in brain structures suggest that gonadal hormones have organizational effects during development on the emotion circuitry. Sexual dimorphisms in brain structure have been reported in both the amygdala and PFC, with relatively larger amygdala volumes in men than women, and variable sex differences within different regions of the PFC (Goldstein et al., 2001, Witte et al., 2010). Although hormonal concentrations are correlated with regional brain volume in these brain regions

The menstrual cycle

Most studies have compared neural responses to emotional stimuli between the follicular phase and luteal phase, reflecting phases with relatively low versus high estradiol and progesterone concentrations, respectively (see above). One study specifically focused on the mid-cycle phase that is characterized by high estradiol but low progesterone concentrations (Goldstein et al., 2005), and is therefore discussed separately.

The majority of studies that have investigated neural responsivity during

Common and divergent gonadal hormone effects

The studies reviewed above demonstrate that gonadal hormones regulate the activity within the emotion circuitry. Menstrual cycle studies suggest that progesterone increases amygdala and mPFC reactivity to emotional stimuli. Although confirmatory evidence remains limited, this conclusion is supported by a placebo-controlled study in which a single dose of progesterone increased amygdala reactivity and its connectivity to the mPFC (van Wingen et al., 2008b). Evidence about the influence of

Conclusion

The neuroimaging studies that are discussed in this review highlight the activational effects of gonadal hormones on the amygdala and PFC. In addition to the organizational effects of these hormones, these studies strongly suggest that activational effects contribute to sex differences in this neurocircuitry underlying the regulation of emotion and affect (Cahill, 2006, Goldstein et al., 2010, Sergerie et al., 2008). Recent studies indicate that progesterone and testosterone have diverging

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NeuroimagingReviewGonadal hormone regulation of the emotion circuitry in humans

Abstract

Highlights

Section snippets

Gonadal hormones and psychiatric disorders

The menstrual cycle and affect

The emotion regulation circuitry

Sex, gonadal hormones, and brain structure

The menstrual cycle

Common and divergent gonadal hormone effects

Conclusion

Neuroimage

Neuroimage

Psychoneuroendocrinology

Trends Neurosci

Aggress Violent Behav

Psychoneuroendocrinology

Biol Psychiatry

Psychoneuroendocrinology

Psychoneuroendocrinology

Trends Cogn Sci

Front Neuroendocrinol

Biol Psychiatry

Fertil Steril

Psychoneuroendocrinology

Psychoneuroendocrinology

Trends Cogn Sci

Psychoneuroendocrinology

Psychoneuroendocrinology

Biol Psychiatry

Brain Res

J Affect Disord

Curr Opin Neurobiol

Psychoneuroendocrinology

Int J Psychophysiol

Neurosci Biobehav Rev

Curr Opin Neurobiol

Biol Psychol

J Affect Disord

Trends Neurosci

Neuroimage

Psychoneuroendocrinology

Neuroimage

The amygdala: a functional analysis

Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men

Arch Gen Psychiatry

Allopregnanolone concentration and mood: a bimodal association in postmenopausal women treated with oral progesterone

Psychopharmacology

The influence of testosterone on human aggression

Br J Psychol

Mood, sexuality, hormones, and the menstrual cycleII. Hormone levels and their relationship to the premenstrual syndrome

Psychosom Med

Neuroimaging
Review
Gonadal hormone regulation of the emotion circuitry in humans