The influence of pharmacological mineralocorticoid and glucocorticoid receptor blockade on the cortisol response to psychological stress.

The glucocorticoid cortisol is the end product of the hypothalamic-pituitary-adrenal (HPA) axis and crucial for the stress response in humans. Cortisol regulates numerous biological functions by binding to two different types of receptors: the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Both receptors are found in the brain where they are crucially involved in various mental functions and in feedback inhibition of cortisol release. The precise role of both receptors in the human stress response is not completely understood. In this study, we examined the effects of pharmacological blockade of the MR or the GR on stress-induced cortisol release in a sample of 318 healthy young men (M = 25.42, SD = 5.01). Participants received the MR antagonist spironolactone (300 mg), the GR antagonist mifepristone (600 mg), or a placebo and were subjected 90 min later to a social-evaluative stressor (Trier Social Stress Test) or a non-stressful control condition. We found significantly higher stress-induced cortisol release in the spironolactone group, whereas participants after mifepristone administration did not differ from the control groups. These results suggest that MR blockade results in attenuated fast negative feedback processes and emphasize the important role of the MR during the early phase of the stress response.

Non-instrumental information seeking is resistant to acute stress.

Previous research has shown that people intrinsically value non-instrumental information, which cannot be used to change the outcome of events, but only provides an early resolution of uncertainty. This is true even for information about rather inconsequential events, such as the outcomes of small lotteries. Here we investigated whether participants' willingness to pay for non-instrumental information about the outcome of simple coin-flip lotteries with guaranteed winnings was modulated by acute stress. Stress was induced using the Socially Evaluated Cold Pressor Test (SECPT), and information-seeking choices were compared to a warm water control group. Our results neither support the hypothesis that stress decreases information-seeking by directing cognitive resources away from the relevance of the lotteries, nor the opposite hypothesis that stress increases information-seeking by driving anxiety levels up. Instead, we found that despite successful stress induction, as evidenced by increased saliva cortisol levels in the SECPT group, information valuation was remarkably stable. This finding is in line with recent findings that experimentally increased state anxiety did not modulate non-instrumental information seeking. Together, these results suggest that the aversiveness of "not knowing" is a stable cognitive state and not easily modulated by situational context, such as acute stress.

Noradrenergic activation induced by yohimbine decreases interoceptive accuracy in healthy individuals with childhood adversity.

Acute stress affects interoception, but it remains unclear if this is due to activation of the sympatho-adreno-medullary (SAM) or hypothalamic-pituitary-adrenocortical axis. This study aimed to investigate the effect of SAM axis activation on interoceptive accuracy (IAcc). Central alpha2-adrenergic receptors represent a negative feedback mechanism of the SAM axis. Major depressive disorder and adverse childhood experiences (ACE) are associated with alterations in the biological stress systems, including central alpha2-adrenergic receptors. Here, healthy individuals with and without ACE as well as depressive patients with and without ACE (n = 114; all without antidepressant medication) were tested after yohimbine (alpha2-adrenergic antagonist) and placebo. We assessed IAcc and sensibility in a heartbeat counting task. Increases in systolic and diastolic blood pressure after yohimbine confirmed successful SAM axis activation. IAcc decreased after yohimbine only in the healthy group with ACE, but remained unchanged in all other groups (Group × Drug interaction). This effect may be due to selective upregulation of alpha2-adrenergic receptors after childhood trauma, which reduces capacity for attention focus on heartbeats. The sympathetic neural pathway including alpha2-adrenergic circuitries may be essential for mediating interoceptive signal transmission. Suppressed processing of physical sensations in stressful situations may represent an adaptive response in healthy individuals who experienced ACE.

Attentional bias in individuals with depression and adverse childhood experiences: influence of the noradrenergic system?

RATIONALE: Major depressive disorder (MDD) is a severe mental disorder with affective, cognitive, and somatic symptoms. Mood congruent cognitive biases, including a negative attentional bias, are important for development, maintenance, and recurrence of depressive symptoms. MDD is associated with maladaptive changes in the biological stress systems such as dysregulations of central noradrenergic alpha2-receptors in the locus coeruleus-noradrenergic system, which can affect cognitive processes including attention. Patients with adverse childhood experiences (ACE), representing severe stress experiences in early life, might be particularly affected. OBJECTIVES: With an experimental design, we aimed to gain further knowledge about the role of noradrenergic activity for attentional bias in MDD patients with and without ACE. METHODS: We tested the effect of increased noradrenergic activity induced by the alpha2-receptor blocker yohimbine on attentional bias in a placebo-controlled repeated measures design. Four groups were included as follows: MDD patients with and without ACE, and healthy participants with and without ACE (total N = 128, all without antidepressant medication). RESULTS: A significant effect of MDD on attentional bias scores of sad face pictures (p = .037) indicated a facilitated attentional processing of sad face pictures in MDD patients (compared to non-MDD individuals). However, we found no such effect of ACE. For attentional bias of happy face pictures, we found no significant effects of MDD and ACE. Even though a higher increase of blood pressure and salivary alpha-amylase following yohimbine compared to placebo indicated successful noradrenergic stimulation, we found no significant effects of yohimbine on attentional bias of happy or sad face pictures. CONCLUSIONS: Our results are consistent with the hypothesis of a negative attentional bias in MDD patients. However, as we found no effect of ACE or yohimbine, further research is needed to understand the mechanisms by which ACE increases the risk of MDD and to understand the biological basis of the MDD-related negative attentional bias.

Effects of hydrocortisone and yohimbine on selective attention to emotional cues.

INTRODUCTION: Facial expressions contain important affective information, and selective attention to facial expression provides an advantage in the face of loss, stress and danger. In addition, the sympathetic nervous system and hypothalamus-pituitary-adrenal axis mediate the organism's response to loss and danger. Here, we aimed at investigating the influence of sympathetic nervous system and hypothalamus-pituitary-adrenal axis activation on selective attention to affective facial stimuli. METHODS AND MATERIALS: One hundred-and-four healthy men between 18-35 years old (mean (standard deviation) age: 24.1 (3.5) years) participated in the study. We used a randomised, double-blind, placebo-controlled design. Participants received either: (a) yohimbine, (b) hydrocortisone, (c) yohimbine and hydrocortisone or (d) placebo only and participated in a dot-probe task with sad, happy and neutral faces. We collected salivary samples to measure cortisol and alpha amylase activity in addition to measurements of blood pressure and heart rate. Salivary cortisol served as correlate of hypothalamus-pituitary-adrenal axis activation and salivary alpha amylase activity, blood pressure and heart rate as correlates of sympathetic nervous system activation. Measurements were carried out before and after drug administration. RESULTS: We did not find a main effect or interaction effect of hydrocortisone or yohimbine administration on selective attention to happy faces. However, we found an interaction of yohimbine and hydrocortisone on selective attention to sad faces. Post-hoc t-test revealed an attentional bias away from sad stimuli and towards neutral faces in the hydrocortisone-only group. DISCUSSION: Only hydrocortisone administration led to an attentional bias away from sad faces. Future studies should investigate these effects in major depression disorder, as this disorder is characterised by glucocorticoid resistance and increased processing of sad stimuli.

Psychosocial stress increases testosterone in patients with borderline personality disorder, post-traumatic stress disorder and healthy participants.

BACKGROUND: The gonadal hormone testosterone not only regulates sexual behavior but is also involved in social behavior and cognition in both sexes. Changes in testosterone secretion in response to stress have been reported. In addition, stress associated mental disorders such as borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) are characterized by alterations in basal testosterone metabolism. However, testosterone changes to stress have not been investigated in mental disorders such as BPD and PTSD so far. METHODS: In the study described, we investigated testosterone reactivity to an acute psychosocial stressor, the Trier Social Stress Test (TSST). Our sample consisted of young adult women with BPD (n = 28), PTSD (n = 22) or both disorders (n = 22), and healthy control (n = 51). Based on previous studies on basal testosterone secretion in these disorders, we expected the stress-associated testosterone reactivity to be higher in the BPD group and lower in the PTSD group, when compared to the healthy control group. RESULTS: The study could demonstrate an increase in testosterone after acute stress exposure across all groups and independent of BPD or PTSD status. Different possible explanations for the absence of a group effect are discussed. CONCLUSIONS: From the results of this study, we conclude that stress-related changes in testosterone release are not affected by BPD or PTSD status in a female patient population. This study expands the knowledge about changes in gonadal hormones and stress reactivity in these disorders.

Enhanced noradrenergic activity by yohimbine and differential fear conditioning in patients with major depression with and without adverse childhood experiences.

Major depressive disorder (MDD) has been associated with changes in the biological stress systems, including the locus coeruleus-noradrenergic system. Accumulated evidence suggests an upregulation of central alpha2-receptors, leading to decreased noradrenergic activity on a central level in MDD patients. Adverse childhood experiences (ACE) such as physical or sexual abuse might contribute to those changes. Furthermore, noradrenaline can affect cognitive processes, e.g. learning and memory. Cognitive dysfunctions constitute an important symptom of MDD. We aimed to investigate the relationship of alpha2-receptor dysregulation with learning processes in MDD by conducting a differential fear conditioning paradigm after double-blind administration of the alpha2-receptor antagonist yohimbine versus placebo. To investigate the role of ACE systematically, we included four groups of healthy participants and MDD patients with and without ACE (MDD-/ACE-: N = 44, MDD-/ACE+: N = 26, MDD+/ACE-: N = 24, MDD+/ACE+: N = 24; without antidepressant medication). We found increased noradrenergic activity after yohimbine administration across groups as measured by alpha-amylase and blood pressure. Overall, fear responses were higher after yohimbine as indicated by skin conductance responses and fear-potentiated startle responses. While we found no significant MDD effect, ACE had significant impact on the ability to discriminate between both conditioned stimuli (CS+ predicting an aversive stimulus, CS- predicting none), depending on drug condition. After yohimbine, CS discrimination decreased in individuals without ACE, but not in individuals with ACE. Differences in the response to yohimbine might be explained by aberrant alpha2-receptor regulation in individuals with ACE. Impaired discrimination of threat and safety signals might contribute to enhanced vulnerability following ACE.

Stress effects on cognitive function in patients with major depressive disorder: Does childhood trauma play a role?

Impaired cognitive functioning constitutes an important symptom of major depressive disorder (MDD), potentially associated with elevated cortisol levels. Adverse childhood experiences (ACE) enhance the risk for MDD and can contribute to disturbances in the stress systems, including cortisol and cognitive functions. In healthy participants, cortisol administration as well as acute stress can affect cognitive performance. In the current study, we tested cognitive performance in MDD patients with (N = 32) and without (N = 52) ACE and healthy participants with (N = 22) and without (N = 37) ACE after psychosocial stress induction (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST). MDD predicted lower performance in verbal learning and both selective and sustained attention, while ACE predicted lower performance in psychomotoric speed and working memory. There were no interaction effects of MDD and ACE. After stress, MDD patients were more likely to show lower performance in working memory as well as in selective and sustained attention compared with participants without MDD. Individuals with ACE were more likely to show lower performance in verbal memory after stress compared with individuals without ACE. Our results indicate negative effects of MDD and ACE on distinct cognitive domains. Furthermore, MDD and/or ACE seem to enhance susceptibility for stress-related cognitive impairments.

Influence of glucocorticoid and mineralocorticoid receptor stimulation on task switching.

The influence of stress on executive functions has been demonstrated in numerous studies and is potentially mediated by the stress-induced cortisol release. Yet, the impact of cortisol on cognitive flexibility and task switching in particular remains equivocal. In this study, we investigated the influence of pharmacological glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) stimulation, two corticosteroid receptor types known to be responsible for cortisol effects on the brain. We conducted two experiments, each with 80 healthy participants (40 women and 40 men), and tested the effect of the unspecific MR/GR agonist hydrocortisone (Experiment I) and the more specific MR agonist fludrocortisone (Experiment II) on switch costs and task rule congruency in a bivalent, cued task switching paradigm. The results did not confirm our hypotheses; we found no significant effects of our manipulations on task switching capacity, although general switching and congruency effects were observed. We discuss the absence of MR/GR-mediated effects and propose alternative mechanisms that could explain stress induced effects on task switching.

Decision making in response to physiological and combined physiological and psychosocial stress.

Individuals tend to make riskier decisions in response to stress. The magnitude of the stress effect on decision-making under risk seems to depend on the stressor type and the decision situation. We examined the effects of physiological and combined physiological and psychosocial stress on decision-making under risk and whether risk taking differs between women and men. Ninety female (n = 45) and male (n = 45) students completed a decision-making under risk task with explicit probabilities and without feedback after exposure to physiological (Cold Pressor Test, CPT), combined physiological and psychosocial (Socially Evaluated Cold Pressor Test, SECPT), or no stress (Warm Water Test, WWT). Subjective stress ratings, salivary cortisol, blood pressure, and heart rate indicated increased stress reactions to the CPT and SECPT compared with the WWT. We found no effect of condition, indicating no difference in risk taking between the CPT, SECPT, and WWT. We did find a sex effect, showing that men made riskier decisions compared with women. Unexpectedly, a Condition × Sex interaction indicated increased risk taking in men compared with women in reaction to the CPT and in women in reaction to the SECPT compared with the WWT. In summary, our results suggest that the sex of the individuum making the decision in combination with the stressor type influence decisions made under risk. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Inflammatory Measures in Depressed Patients With and Without a History of Adverse Childhood Experiences.

Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels. Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 ± 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse. Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93). Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of "inflammatory depression". Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies.

The role of physiological arousal for self-reported emotional empathy.

The capacity to represent the emotional and mental states of others is referred to by the concept of empathy. Empathy further differentiates into an emotional and a cognitive subcomponent, which in turn is known to require a tacit perspective-taking process. However, whether the empathizer by himself needs to enter an affective state as a necessary precondition for emotional empathy remains a matter of debate. If empathy would require a vicarious emotional reaction, specific physiological markers of affective responding should be detectable in the empathizing person. In the present study, we investigated the relationship between self-reported empathy and psychophysiological responses in young, healthy participants. We assessed emotional and cognitive empathy with the Multifaceted Empathy Test on the one hand and the corresponding heart rate and skin conductance responses (SCR), affective startle modulation and heart rate variability on the other. We found a negative relationship between SCR and self-reported emotional empathy: higher SCR to emotional stimuli predicted lower empathy ratings. We conclude that physiological arousal is not necessary and might even diminish empathy for others.

The time course of pupil dilation evoked by visual sexual stimuli: Exploring the underlying ANS mechanisms.

The early processing of visual sexual stimuli shows signs of automaticity. Moreover, there is evidence for sex-specific patterns in cognitive and physiological responding to erotica. However, little is known about the time course of rapid pupillary responses to sexual stimuli and their correspondence with other measures of autonomic activity in women and men. To study pupil dilation as an implicit measure of sexual arousal at various stages of picture processing, we presented 35 heterosexual participants with pictures showing either erotic couples or single (male/female) erotic nudes, contrasted with people involved in everyday situations. Brightness-adjusted grayscale pictures were shown for a duration of 2,500 ms within the central visual field, alternating with perceptually matched patches. Left pupil diameter was recorded at 500 Hz using a video-based eye tracker. Skin conductance and heart rate were coregistered and correlated with latent components of pupil dilation (dissociated by temporal PCA). Whereas stimulus-evoked changes in pupil size indicated virtually no initial constriction, a rapid effect of appetence emerged (dilation to erotica within 500 ms). Responses at early stages of processing were remarkably consistent across both sexes. In contrast, later phases of pupil dilation, subjective ratings, and skin conductance responses showed a sex-specific pattern. Moreover, evidence for an association of early-onset pupil dilation and heart rate acceleration was found, suggestive of parasympathetic inhibition, whereas the late component was mainly related to sympathetically mediated skin conductance. Taken together, our results indicate that different temporal components of pupil responses to erotic stimuli may reflect divergent underlying neural mechanisms.

Selective attention to emotional cues and emotion recognition in healthy subjects: the role of mineralocorticoid receptor stimulation.

RATIONALE: Selective attention toward emotional cues and emotion recognition of facial expressions are important aspects of social cognition. Stress modulates social cognition through cortisol, which acts on glucocorticoid (GR) and mineralocorticoid receptors (MR) in the brain. OBJECTIVES: We examined the role of MR activation on attentional bias toward emotional cues and on emotion recognition. METHODS: We included 40 healthy young women and 40 healthy young men (mean age 23.9 ± 3.3), who either received 0.4 mg of the MR agonist fludrocortisone or placebo. A dot-probe paradigm was used to test for attentional biases toward emotional cues (happy and sad faces). Moreover, we used a facial emotion recognition task to investigate the ability to recognize emotional valence (anger and sadness) from facial expression in four graded categories of emotional intensity (20, 30, 40, and 80 %). RESULTS: In the emotional dot-probe task, we found a main effect of treatment and a treatment × valence interaction. Post hoc analyses revealed an attentional bias away from sad faces after placebo intake and a shift in selective attention toward sad faces compared to placebo. We found no attentional bias toward happy faces after fludrocortisone or placebo intake. In the facial emotion recognition task, there was no main effect of treatment. CONCLUSIONS: MR stimulation seems to be important in modulating quick, automatic emotional processing, i.e., a shift in selective attention toward negative emotional cues. Our results confirm and extend previous findings of MR function. However, we did not find an effect of MR stimulation on emotion recognition.

Two separable mechanisms are responsible for mental stress effects on high frequency heart rate variability: an intra-individual approach in a healthy and a diabetic sample.

Central withdrawal of parasympathetic cardiac control and increased respiratory frequency represent two important determinants of reduced respiratory-related heart rate variability (HRV). However, studies are missing to disentangle their relative contribution during mental stress. Healthy subjects (n=10) and type 2 diabetic patients (n=8), the latter with evidence of cardiac autonomic neuropathy, participated in this study. Using an intra-individual approach, high-frequency (hf) HRV was assessed for spontaneous (during rest and mental stress) and paced breathing (0.15, 0.2, 0.25, 0.3, 0.35, 0.4 and 0.45 Hz; randomized sequence). Mental stress was induced by a challenging reaction time task. Effects of respiratory frequency on hf HRV were individually predicted by paced breathing data. Mental stress decreased hf HRV (p<.001), and increased respiratory frequency (p=.01). Individual prediction of hf HRV by stress respiratory frequency resulted in lower values (p=.02) than observed during rest, indicating that respiratory stress effects were sufficient to reduce hf HRV. However, observed hf HRV values during stress were even lower (p<.001). These results indicate that hf HRV reductions during stress can only partly be explained by concomitant respiratory frequency changes. This effect is detectable in healthy subjects and in patients with evidence of diabetic cardiac autonomic neuropathy.

Rapid cortisol enhancement of psychomotor and startle reactions to side-congruent stimuli in a focused cross-modal choice reaction time paradigm.

The stress hormone cortisol has been shown to affect hemodynamic activity of human brain structures, presumably via a nongenomic mechanism. However, behavioral implications of this finding remain unknown. In a placebo-controlled, blinded, cross-over design the rapid effects of IV hydrocortisone (5mg) on cross-modal integration of simultaneous, unilateral visual and acoustic signals in a challenging startle and reaction time (RT) paradigm were studied. On two separate days 1 week apart, 24 male volunteers responded by button push to either up- or down pointing triangles presented in random sequence in the periphery of one of the visual hemi-fields. Visual targets were accompanied by unilateral acoustic startle noise bursts, presented at the same or opposite side. Saccadic latency, manual RT, and startle eye blink responses were recorded. Faster manual reactions and increased startle eye blink responses were observed 11-20 min after hydrocortisone administration when visual targets and unilateral acoustic startle noises were presented in the same sensory hemi-field, but not when presented in opposite sensory hemi-fields. Our results suggest that a nongenomic, cortisol-sensitive mechanism enhances psychomotor and startle reactions when stimuli occur in the same sensory hemi-field. Such basic cognitive effects of cortisol may serve rapid adaptation and protection against danger stimuli in stressful contexts.

Startle effects on saccadic responses to emotional target stimuli.

Startle stimuli elicit various physiological and cognitive responses. This study investigated whether acoustic startle stimuli affect saccadic reactions in an emotional pro- or antisaccade task. Startle probes were presented either 500 ms before or simultaneous with an imperative stimulus that indicated whether a saccade towards or away from positive, neutral, or negative peripheral target pictures had to be performed. Valence interacted with saccade direction according to an approach-avoidance pattern of gaze behavior, with delayed prosaccades to negative targets and antisaccades away from positive targets. Acoustic startle stimuli preceding the presentation of peripheral target pictures speeded up the initiation saccades, irrespective of stimulus valence. Results indicate a speeding of cognitive-motor processing by preceding startle stimuli.

Effects of cold pressor stress on the human startle response.

Both emotion and attention are known to influence the startle response. Stress influences emotion and attention, but the impact of stress on the human startle response remains unclear. We used an established physiological stressor, the Cold Pressor Test (CPT), to induce stress in a non-clinical human sample (24 student participants) in a within-subjects design. Autonomic (heart rate and skin conductance) and somatic (eye blink) responses to acoustic startle probes were measured during a pre-stress baseline, during a three minutes stress intervention, and during the subsequent recovery period. Startle skin conductance and heart rate responses were facilitated during stress. Compared to baseline, startle eye blink responses were not affected during the intervention but were diminished afterwards. These data describe a new and unique startle response pattern during stress: facilitation of autonomic stress responses but no such facilitation of somatic startle eye blink responses. The absence of an effect of stress on startle eye blink responsiveness may illustrate the importance of guaranteeing uninterrupted visual input during periods of stress.

Effect of facial self-resemblance on the startle response and subjective ratings of erotic stimuli in heterosexual men.

Cues of kinship are predicted to increase prosocial behavior due to the benefits of inclusive fitness, but to decrease approach motivation due to the potential costs of inbreeding. Previous studies have shown that facial resemblance, a putative cue of kinship, increases prosocial behavior. However, the effects of facial resemblance on mating preferences are equivocal, with some studies finding that facial resemblance decreases sexual attractiveness ratings, while other studies show that individuals choose mates partly on the basis of similarity. To further investigate this issue, a psychophysiological measure of affective processing, the startle response, was used in this study, assuming that differences in approach motivation to erotic pictures will modulate startle. Male volunteers (n = 30) viewed 30 pictures of erotic female nudes while startle eyeblink responses were elicited by acoustic noise probes. The female nude pictures were digitally altered so that the face either resembled the male participant or another participant, or were not altered. Non-nude neutral pictures were also included. Importantly, the digital alteration was undetected by the participants. Erotic pictures were rated as being pleasant and clearly reduced startle eyeblink magnitude as compared to neutral pictures. Participants showed greater startle inhibition to self-resembling than to other-resembling or non-manipulated female nude pictures, but subjective pleasure and arousal ratings did not differ among the three erotic picture categories. Our data suggest that visual facial resemblance of opposite-sex nudes increases approach motivation in men, and that this effect was not due to their conscious evaluation of the erotic stimuli.

Effects of stress on human mating preferences: stressed individuals prefer dissimilar mates.

Although humans usually prefer mates that resemble themselves, mating preferences can vary with context. Stress has been shown to alter mating preferences in animals, but the effects of stress on human mating preferences are unknown. Here, we investigated whether stress alters men's preference for self-resembling mates. Participants first underwent a cold-pressor test (stress induction) or a control procedure. Then, participants viewed either neutral pictures or pictures of erotic female nudes whose facial characteristics were computer-modified to resemble either the participant or another participant, or were not modified, while startle eyeblink responses were elicited by noise probes. Erotic pictures were rated as being pleasant, and reduced startle magnitude compared with neutral pictures. In the control group, startle magnitude was smaller during foreground presentation of photographs of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to self-resembling mates. In the stress group, startle magnitude was larger during foreground presentation of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to dissimilar mates. Our findings show that stress affects human mating preferences: unstressed individuals showed the expected preference for similar mates, but stressed individuals seem to prefer dissimilar mates.