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The effects of sex and stress hormones on classical fear conditioning have been subject of recent experimental studies. A correlation approach between basal cortisol concentrations and neuronal activation in fear-related structures seems to be a promising alternative approach in order to foster our understanding of how cortisol influences emotional learning. In this functional magnetic resonance imaging study, participants with varying sex hormone status (20 men, 15 women taking oral contraceptives, 15 women tested in the luteal phase) underwent an instructed fear conditioning protocol with geometrical figures as conditioned stimuli and an electrical stimulation as unconditioned stimulus. Salivary cortisol concentrations were measured and afterwards correlated with fear conditioned brain responses. Results revealed a positive correlation between basal cortisol levels and differential activation in the amygdala in men and OC women only. These results suggest that elevated endogenous cortisol levels are associated with enhanced fear anticipation depending on current sex hormone availability.
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Stress and fear conditioning processes are both important vulnerability factors in the development of psychiatric disorders. In behavioral studies considerable sex differences in fear learning have been observed after increases of the stress hormone cortisol. But neuroimaging experiments, which give insights into the neurobiological correlates of stress × sex interactions in fear conditioning, are lacking so far. In the current functional magnetic resonance imaging (fMRI) study, we tested whether a psychosocial stressor (Trier Social Stress Test) compared to a control condition influenced subsequent fear conditioning in 48 men and 48 women taking oral contraceptives (OCs). One of two pictures of a geometrical figure was always paired (conditioned stimulus, CS+) or never paired (CS-) with an electrical stimulation (unconditioned stimulus). BOLD responses as well as skin conductance responses were assessed. Sex-independently, stress enhanced the CS+/CS- differentiation in the hippocampus in early acquisition but attenuated conditioned responses in the medial frontal cortex in late acquisition. In early acquisition, stress reduced the CS+/CS- differentiation in the nucleus accumbens in men, but enhanced it in OC women. In late acquisition, the same pattern (reduction in men, enhancement in OC women) was found in the amygdala as well as in the anterior cingulate. Thus, psychosocial stress impaired the neuronal correlates of fear learning and expression in men, but facilitated them in OC women. A sex-specific modulation of fear conditioning after stress might contribute to the divergent prevalence of men and women in developing psychiatric disorders.
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An important feature of the human defense system comprises fear learning, which stress hormones can crucially modulate. However, stress hormones might influence men and women differently, in part because of interactions with sex hormones. In women, distinct stages of the menstrual cycle or the intake of oral contraceptives (OC) affect sex hormone levels. In this study, we used a differential fear conditioning paradigm with electrical stimulation as unconditioned stimulus (UCS) following one neutral stimulus (conditioned stimulus, CS+), but not another (CS-).To investigate implicit fear learning, participants were distracted from detecting the contingencies between CS and UCS. To address interaction effects of sex and stress hormones, 32 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women received either 30 mg cortisol or a placebo. In the contrast CS+ minus CS-, an interaction between cortisol administration and sex hormone status emerged in the anterior parahippocampal gyrus and the hippocampus. Cortisol reduced fear learning in men, FO, and LU women, but enhanced it in OC women. Additionally, cortisol attenuated differential amygdala activation in the entire group. These results demonstrate that OC usage substantially modifies cortisol effects on emotional learning in women, particularly in memory-related medial temporal lobe regions. Further, a high dose of cortisol reduces amygdala differentiation pointing to a lowered learning ability of the defense system under high cortisol concentrations, irrespective of current sex hormone availability.
Erkunden
Team
- Vaitl (3)
Eintragsart
Sprache
- Englisch (3)
Thema
- Adolescent (1)
- Adult (3)
- alpha-Amylases/metabolism (1)
- Amygdala (1)
- Analysis of Variance (1)
- Anterior cingulate (1)
- Brain/blood supply/*physiology (1)
- Brain Mapping (1)
- *Brain Mapping (1)
- Brain/physiology (1)
- Conditioning, Classical/*physiology (2)
- Conditioning, Operant/*physiology (1)
- Conditioning, Psychological/*drug effects/physiology (1)
- Contraception Behavior/psychology (1)
- Contraceptives, Oral/*pharmacology/therapeutic use (1)
- Cortisol (1)
- Double-Blind Method (1)
- Electric Stimulation (2)
- Fear/*drug effects/physiology (1)
- Fear learning (1)
- Fear/*physiology/*psychology (1)
- Fear/*psychology (1)
- Female (3)
- fMRI (1)
- Galvanic Skin Response/physiology (2)
- Gonadal Steroid Hormones/*blood (1)
- Humans (3)
- Hydrocortisone/metabolism (1)
- Hydrocortisone/*pharmacology (1)
- Learning/*drug effects/physiology (1)
- Magnetic Resonance Imaging/methods (1)
- Male (3)
- Nucleus accumbens (1)
- Oral contraceptives (1)
- Photic Stimulation (1)
- Placebos (1)
- Saliva/metabolism (1)
- *Sex Characteristics (1)
- Sex differences (1)
- Stress hormones (1)
- Stress, Psychological/*physiopathology/*psychology (1)
- TSST (1)
- Young Adult (2)