Specialization of amygdala subregions in emotion processing.

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies.

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Effects of intranasal oxytocin and positive couple interaction on immune factors in skin wounds.

BACKGROUND: Intimate social relationships improve individual health and longevity, an effect which is supposed to be mediated through stress-sensitive endocrine and immune mechanisms in response to positive interaction behavior. On a neuroendocrine level, oxytocin (OT) buffers stress responses, modulates social attachment behavior and has been associated with cytokine expression. Consequently, the aim of the present study was to investigate instructed positive couple interaction, observed behavior, and OT in their effect on immune function. METHODS: In a 4-group design, 80 healthy couples (N = 160 individuals) received four standard dermal suction blister wounds and were randomized to instructed positive interaction/control and intranasal OT/placebo. Unstimulated cytokines (IL-1ß, IL-6, TNF-α) were assessed from wound liquid at 40 min, 105 min and 24 hrs after wounding. RESULTS: Overall, group assignment did not affect friendly or dominant behavior during the interaction sequence. IL-1ß and IL-6 levels, however, were moderated by group assignment with lowest levels in women in the positive interaction and OT condition in IL-1 and highest levels in IL-6. TNF-α responses to wounding were not affected from group assignment, however observed friendliness in women was associated with lower TNF-α levels. DISCUSSION: These findings support the immune-regulating role of friendly behavior in romantic couples. Above this, the data provide the first empirical evidence that an intervention that simultaneously targets neuroendocrine mediators and behavior could affect immune function in a sex specific manner and with potential long-term health relevance.

Resting-state neuroimaging in social anxiety disorder: a systematic review.

There has been a growing interest in resting-state brain alterations in people with social anxiety disorder. However, the evidence has been mixed and contested and further understanding of the neurobiology of this disorder may aid in informing methods to increase diagnostic accuracy and treatment targets. With this systematic review, we aimed to synthesize the findings of the neuroimaging literature on resting-state functional activity and connectivity in social anxiety disorder, and to summarize associations between brain and social anxiety symptoms to further characterize the neurobiology of the disorder. We systematically searched seven databases for empirical research studies. Thirty-five studies met the inclusion criteria, with a total of 1611 participants (795 people with social anxiety disorder and 816 controls). Studies involving resting-state seed-based functional connectivity analyses were the most common. Individuals with social anxiety disorder (vs. controls) displayed both higher and lower connectivity between frontal-amygdala and frontal-parietal regions. Frontal regions were the most consistently implicated across other analysis methods, and most associated with social anxiety symptoms. Small sample sizes and variation in the types of analyses used across studies may have contributed to the inconsistencies in the findings of this review. This review provides novel insights into established neurobiological models of social anxiety disorder and provides an update on what is known about the neurobiology of this disorder in the absence of any overt tasks (i.e., resting state). The knowledge gained from this body of research enabled us to also provide recommendations for a more standardized imaging pre-processing approach to examine resting-state brain activity and connectivity that could help advance knowledge in this field. We believe this is warranted to take the next step toward clinical translation in social anxiety disorder that may lead to better treatment outcomes by informing the identification of neurobiological targets for treatment.

The Effect of Intranasal Oxytocin on the Association Between Couple Interaction and Sleep: A Placebo-Controlled Study.

OBJECTIVE: Although most people in romantic relationships cosleep, biosocial modulators of sleep quality have only recently come into focus. Oxytocin (OT) might be one such modulator, as it had been shown to increase social attachment and safety. We investigated the association between everyday life couple interaction and sleep quality, as well as the effects of OT on this association. METHODS: Eighty heterosexual couples ( N = 160 individuals, mean [standard deviation] age = 28 [5] years) were randomized to self-administer a) 32 international units of intranasal OT or b) placebo during 5 consecutive days. Each morning, they reported on sleep quality, and on subjective feelings of closeness and valence of couple interaction at a maximum of four times a day. Data were analyzed using hierarchical linear models. RESULTS: Subjective closeness ( B = 0.43, t (73) = 3.80, p < .001) and valence (negative - positive) of couple interaction ( B = 0.50, t (73) = 3.91, p < .001) were positively associated with sleep quality. Persons with OT reported higher levels of sleep quality than those without ( B = 0.47, t (74) = 2.32, p = .023). The association between closeness and sleep quality was stronger with OT than without (OT by closeness: B = 0.31, t (72) = 2.29, p = .025; OT by valence of interaction: B = 0.27, t (72) = 1.77, p = .081). Whereas the effect of couple interaction on sleep quality was strong in men, the OT effects were especially pronounced in women. CONCLUSIONS: Our results suggest that enhancing closeness and positive couple interaction in cosleeping partners might be a way to improve sleep quality. The moderating effects of OT and sex on the association between couple interaction and sleep quality can have important implications for sleep therapy.Trial Registration: The study was preregistered at ClinicalTrials.gov ("Oxytocin, Couple Interaction, and Wound Healing" study, identifier NCT01594775). The present analyses were not preregistered.

A Self-Controlled Mind Is Reflected by Stable Mental Processing.

Self-control-the ability to inhibit inappropriate impulses-predicts economic, physical, and psychological well-being. However, recent findings demonstrate low correlations among self-control measures, raising the question of what self-control actually is. Here, we examined the idea that people high in self-control show more stable mental processing, characterized by processing steps that are fewer in number but longer lasting because of fewer interruptions by distracting impulses. To test this hypothesis, we relied on resting electroencephalography microstate analysis, a method that provides access to the stream of mental processing by assessing the sequential activation of neural networks. Across two samples (Study 1: N = 58 male adults from Germany; Study 2: N = 101 adults from Canada, 58 females), the temporal stability of resting networks (i.e., longer durations and fewer occurrences) was positively associated with self-reported self-control and a neural index of inhibitory control, and it was negatively associated with risk-taking behavior. These findings suggest that stable mental processing represents a core feature of a self-controlled mind.

Oxytocin Receptor Gene DNA Methylation: A Biomarker of Treatment Response in Obsessive-Compulsive Disorder?

INTRODUCTION: Obsessive-compulsive disorder (OCD) is associated with high chronicity and treatment resistance, indicating the need for early therapy response markers enabling fast and personalized treatment adaptations. Although epigenetic mechanisms such as DNA methylation of the oxytocin receptor (OXTR) gene have previously been linked to OCD pathogenesis, epigenetic markers as predictors of treatment success have not yet been investigated in OCD. OBJECTIVE: For the first time, this therapyepigenetic study aimed to investigate the role of OXTR methylation as a treatment response marker in OCD. METHODS: In total, 113 inpatients with OCD (57 females) were compared to 113 age- and sex-matched healthy controls. Patients were investigated over a 10-week course of standardized, OCD-specific cognitive-behavioral psychotherapy. Clinical response was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, before in vivo exposure, and after therapy. OXTR exon III methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. RESULTS: Relative OXTR hypermethylation was observed in OCD patients compared to healthy controls. In OCD, higher baseline OXTR methylation was found to predict impaired treatment response at both categorical (responders vs. nonresponders) and dimensional (relative Y-BOCS reduction) levels, whereas lower baseline methylation was related to treatment response and greater symptom improvements. Analysis of Y-BOCS subdimensions revealed that the association between OXTR hypermethylation with impaired treatment response applied especially to symptoms related to obsessions, but not compulsions. CONCLUSIONS: OXTR hypermethylation may constitute a predictive marker of impaired treatment response in OCD and thus carries great potential for future personalized treatment efforts in OCD.

Acute alcohol intoxication modulates the temporal dynamics of resting electroencephalography networks.

This study aimed to provide a currently missing link between general intoxication-induced changes in overall brain activity and the multiple cognitive control deficits typically observed during acute alcohol intoxication. For that purpose, we analyzed the effects of acute alcohol intoxication (1.1‰) on the four archetypal electroencephalography (EEG) resting networks (i.e., microstates A-D) and their temporal dynamics (e.g., coverage and transitions from one microstate to another), as well as on self-reported resting-state cognition in n = 22 healthy young males using a counterbalanced within-subject design. Our microstate analyses indicated that alcohol increased the coverage of the visual processing-related microstate B at the expense of the autonomic processing-related microstate C. Add-on exploratory analyses revealed that alcohol increased transitions from microstate C to microstate B and decreased bidirectional transitions between microstate C and the attention-related microstate D. In line with the observed alcohol-induced decrease of the autonomic processing-related microstate C, participants reported decreases of their somatic awareness during intoxication, which were positively associated with more transitions from microstate C to microstate B. In sum, the observed effects provide mechanistic insights into how alcohol might hamper cognitive processing by generally prioritizing the bottom-up processing of visual stimuli over top-down internal information processing. The fact that this was found during the resting state further proves that alcohol-induced changes in brain activity are continuously present and do not only emerge during demanding situations or tasks.

A Protective Mechanism against Illusory Perceptions Is Amygdala-Dependent.

Most people have a clear sense of body ownership, preserving them from physical harm. However, perceptual body illusions - famously the rubber hand illusion (RHI) - can be elicited experimentally in healthy individuals. We hypothesize that the amygdala, a core component of neural circuits of threat processing, is involved in protective mechanisms against disturbed body perceptions. To test this hypothesis, we started by investigating two monozygotic human twin sisters with focal bilateral amygdala damage due to Urbach-Wiethe disease. Relative to 20 healthy women, the twins exhibited, on two occasions 1 year apart, augmented RHI responses in form of faster illusion onset and increased vividness ratings. Following up on these findings, we conducted a volumetric brain morphometry study involving an independent, gender-mixed sample of 57 healthy human volunteers (36 female, 21 male). Our results revealed a positive correlation between amygdala volume and RHI onset, i.e., the smaller the amygdala, the less time it took the RHI to emerge. This raised the question of whether a similar phenotype would result from experimental amygdala inhibition. To dampen amygdala reactivity, we intranasally administered the peptide hormone oxytocin to the same 57 individuals in a randomized trial before conducting the RHI. Compared with placebo, oxytocin treatment yielded enhanced RHI responses, again evident in accelerated illusion onset and increased vividness ratings. Together, the present series of experiments provides converging evidence for the amygdala's unprecedented role in reducing susceptibility to the RHI, thus protecting the organism from the potentially fatal threats of a distorted bodily self.SIGNIFICANCE STATEMENT Compelling evidence indicates that the amygdala is of vital importance for danger detection and fear processing. However, lethal threats can arise not only from menacing external stimuli but also from distortions in bodily self-perception. Intriguingly, the amygdala's modulatory role in such illusory body perceptions is still elusive. To probe the amygdala's involvement in illusory body experiences, we conducted a multi-methodological series of experiments in a rare human amygdala lesion model, complemented by a morphological and pharmaco-modulatory experiment in healthy volunteers. Our findings convergently suggest that the amygdala's integrity is indispensable for maintaining an unbiased, precise perception of our bodily self. Hence, the amygdala might shield us against distortions in self-perception and the resultant loss of behavioral control of our organism.

Intimacy as Related to Cortisol Reactivity and Recovery in Couples Undergoing Psychosocial Stress.

OBJECTIVE: The importance of recovery from stress is evident in times of high prevalence of stress-related diseases. Intimacy has been found to buffer psychobiological stress reactivity, suggesting that emotional and physical closeness might trigger biological mechanisms that underlie the health-beneficial effects of couple relationships. Here, we investigated whether couples' spontaneous expression of intimacy before and after psychosocial stress exposure in the laboratory reduced cortisol reactivity and accelerated recovery. METHODS: Data from 183 couples (366 individuals) were analyzed. Couples were randomly assigned to one of the following three experimental conditions: only the female partner (n = 62), only the male partner (n = 61), or both partners were stressed in parallel (n = 60) with the Trier Social Stress Test. Couples' behavior was videotaped and coded for expressions of intimacy, and saliva samples were taken repeatedly (nine times) to analyze cortisol levels before and after stress. Data were analyzed using hierarchical linear modeling. RESULTS: Observed partner intimacy reduced cortisol responses to stress in women (B = -0.016, SE = 0.006, p = .008), although this effect was eliminated among women using oral contraceptives. Observed partner intimacy also reliably accelerated cortisol recovery in men (B = -0.002, SE = 0.001, p = .023) and women (B = -0.002, SE = 0.001, p = .016). CONCLUSIONS: Spontaneous nonverbal expressions of intimacy seem to regulate the effects of acute environmental demands on established biological indices of stress response.

Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.

PURPOSE: The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women. METHODS: In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography. FINDINGS: Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT. IMPLICATIONS: Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.

Glucocorticoid administration restores salience network activity in patients with spider phobia.

BACKGROUND: Glucocorticoids reduce phobic fear in patients with anxiety disorders. Although the neurobiology of anxiety disorders is not fully understood, convergent structural and functional neuroimaging studies have identified abnormalities in various brain regions, including those in the salience network (SN) and default mode network (DMN). Here, we examine the effects of glucocorticoid administration on SN and DMN activity during the processing of phobic stimuli. METHODS: We use functional magnetic resonance imaging to record brain activity in 24 female patients with spider phobia who were administered either 20 mg of cortisol or placebo while viewing pictures of spiders. Fourteen healthy female participants were tested with the same task but without substance administration. Independent component analysis (ICA) performed during stimulus encoding identified the SN and DMN as exhibiting synchronized activation in diverse brain regions; thus, we examined the effects of cortisol on these networks. Furthermore, participants had to rate their level of fear at various time points. RESULTS: Glucocorticoids reduced phobic fear in patients with spider phobia. The ICA performed during stimulus encoding revealed that activity in the SN and DMN was reduced in placebo-treated patients versus healthy controls. Brain activity in the SN, but not the DMN, was altered in cortisol- versus placebo-treated patients to a level that was similar to that observed in healthy controls. CONCLUSIONS: Activity in both the SN and DMN was reduced in patients with spider phobia. Cortisol administration altered the SN activity to a level that was comparable to that found in healthy controls. This alteration in SN activity might reflect the fear-reducing effects of glucocorticoids in phobia.

Testosterone and androgen receptor gene polymorphism are associated with confidence and competitiveness in men.

A contribution to a special issue on Hormones and Human Competition. Studies in non-human animals and humans have demonstrated the important role of testosterone in competitive interactions. Here, we investigated whether endogenous testosterone levels predict the decision to compete, in a design excluding spite as a motive underlying competitiveness. In a laboratory experiment with real monetary incentives, 181 men solved arithmetic problems, first under a noncompetitive piece rate, followed by a competition incentive scheme. We also assessed several parameters relevant to competition, such as risk taking, performance, and confidence in one's own performance. Salivary testosterone levels were measured before and 20min after the competition task using mass spectrometry. Participants were also genotyped for the CAG repeat polymorphism of the androgen receptor gene, known to influence the efficacy of testosterone signaling in a reciprocal relationship to the number of CAG repeats. We observed a significant positive association between basal testosterone levels and the decision to compete, and that higher testosterone levels were related to greater confidence in one's own performance. Whereas the number of CAG repeats was not associated with the choice to compete, a lower number of CAG repeats was related to greater confidence in those who chose to compete, but this effect was attributable to the polymorphism's effect on actual performance. An increase in testosterone levels was observed following the experiment, and this increase varied with self-reported high-school math grades. We expand upon the latest research by documenting effects of the androgen system in confidence in one's own ability, and conclude that testosterone promotes competitiveness without spite.

Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine.

The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are evolutionarily highly conserved mediators in the regulation of complex social cognition and behaviour. Recent studies have investigated the effects of OXT and AVP on human social interaction, the genetic mechanisms of inter-individual variation in social neuropeptide signalling and the actions of OXT and AVP in the human brain as revealed by neuroimaging. These data have advanced our understanding of the mechanisms by which these neuropeptides contribute to human social behaviour. OXT and AVP are emerging as targets for novel treatment approaches--particularly in synergistic combination with psychotherapy--for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.

The effect of oxytocin on attention to angry and happy faces in chronic depression.

BACKGROUND: Chronic depression is characterized by a high degree of early life trauma, psychosocial impairment, and deficits in social cognition. Undisturbed recognition and processing of facial emotions are basic prerequisites for smooth social interactions. Intranasal application of the neuropeptide oxytocin has been reported to enhance emotion recognition in neuropsychiatric disorders and healthy individuals. We therefore investigated whether oxytocin modulates attention to emotional faces in patients with chronic depression. METHODS: In this double-blind, randomized, controlled study, 43 patients received a single dose of oxytocin or placebo nasal spray and were tested while fulfilling a facial dot probe task. We assessed reaction times to neutral probes presented at the location of one of two faces depicting happy, angry, or neutral expressions as a prime. RESULTS: When comparing reaction times to the congruent (prime and probe at the same location) with incongruent presentation of facial emotions, neither the placebo nor oxytocin group showed an attentional preference for emotional facial expressions in terms of a threat bias. However, oxytocin treatment did reveal two specific effects: it generally reduced the allocation of attention towards angry facial expressions, and it increased sustained attention towards happy faces, specifically under conditions of heightened awareness, i.e. trials with longer primes. CONCLUSIONS: We investigated a heterogeneous group of medicated male and female patients. We conclude that oxytocin does modulate basic factors of facial emotion processing in chronic depression. Our findings encourage further investigations assessing the therapeutic potential of oxytocin in chronic depression. TRIAL REGISTRATION: EUDRA-CT 2010-020956-69 . Date registered: 23 February 2011.

Effects of Stress on the Social Support Provided by Men and Women in Intimate Relationships.

Although evolutionary and social-structural models predict that women will be more supportive than men in relationships, behavioral studies fail to confirm this difference. We predicted instead that gender differences in support will be moderated by stress, and that men will provide lower-quality support primarily when their stress is high. We predicted further that the detrimental effects of stress on men's support will be more evident when men are responding to women's emotionally toned expressions of stress than when men are responding to women's affectively neutral expressions of stress. Stressed and unstressed men and women were observed providing support to a stressed relationship partner. While unstressed, men and women generally provided similar support to the stressed partner. While stressed, men provided lower-quality support than did comparably stressed women, but only in response to emotionally toned expressions of stress. Thus, gender differences in support may arise because women are better able than men to regulate other people's emotional distress while managing stresses of their own.

Menstrual cycle phase affects discrimination of infant cuteness.

Recent studies have shown that women are more sensitive than men to subtle cuteness differences in infant faces. It has been suggested that raised levels in estradiol and progesterone may be responsible for this advantage. We compared young women's sensitivity to computer-manipulated baby faces varying in cuteness. Thirty-six women were tested once during ovulation and once during the luteal phase of their menstrual cycle. In a two alternative forced-choice experiment, participants chose the baby which they thought was cuter (Task 1), younger (Task 2), or the baby that they would prefer to babysit (Task 3). Saliva samples to assess levels of estradiol, progesterone and testosterone were collected at each test session. During ovulation, women were more likely to choose the cuter baby than during the luteal phase, in all three tasks. These results suggest that cuteness discrimination may be driven by cyclic hormonal shifts. However none of the measured hormones were related to increased cuteness sensitivity. We speculate that other hormones than the ones measured here might be responsible for the increased sensitivity to subtle cuteness differences during ovulation.

Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples.

Knowledge about the effects of the neuropeptide oxytocin (OXT) on human sexual behaviors and partner interactions remains limited. Based on our previous studies, we hypothesize that OXT should be able to positively influence parameters of sexual function and couple interactions. Employing a naturalistic setting involving 29 healthy heterosexual couples (n=58 participants), we analyzed the acute effects of intranasally administered OXT (24IU) on sexual drive, arousal, orgasm and refractory aspects of sexual behavior together with partner interactions. Data were assessed by psychometric instruments (Acute Sexual Experiences Scale, Arizona Sexual Experience Scale) as well as biomarkers, such as cortisol, α-amylase and heart rate. Intranasal OXT administration did not alter "classical" parameters of sexual function, such as sexual drive, arousal or penile erection and lubrication. However, analysis of variance and a hierarchical linear model (HLM) revealed specific effects related to the orgasmic/post-orgasmic interval as well as parameters of partner interactions. According to HLM analysis, OXT increased the intensity of orgasm, contentment after sexual intercourse and the effect of study participation. According to ANOVA analysis, these effects were more pronounced in men. Men additionally indicated higher levels of sexual satiety after sexual intercourse with OXT administration. Women felt more relaxed and subgroups indicated better abilities to share sexual desires or to empathize with their partners. The effect sizes were small to moderate. Biomarkers indicated moderate psychophysiological activation but were not affected by OXT, gender or method of contraception. Using a naturalistic setting, intranasal OXT administration in couples exerted differential effects on parameters of sexual function and partner interactions. These results warrant further investigations, including subjects with sexual and relationship problems.

Glucocorticoids enhance in vivo exposure-based therapy of spider phobia.

BACKGROUND: Preclinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes. In particular, it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights. Here, we investigate whether glucocorticoids enhance the outcome of in vivo exposure-based group therapy of spider phobia. METHODS: In a double blind, block-randomized, placebo-controlled, between-subject study design, 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure-based group therapy. Cortisol (20 mg) or placebo was orally administered 1 hr before each therapy session. Patients returned for a follow-up assessment one month after therapy. RESULTS: Exposure-based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Questionnaire (FSQ) from pretreatment to immediate posttreatment and to follow-up. The administration of cortisol to exposure therapy resulted in increased salivary cortisol concentrations and a significantly greater reduction in fear of spiders (FSQ) as compared to placebo at follow-up, but not immediately posttreatment. Furthermore, cortisol-treated patients reported significantly less anxiety during standardized exposure to living spiders at follow-up than placebo-treated subjects. Notably, groups did not differ in phobia-unrelated state-anxiety before and after the exposure sessions and at follow-up. CONCLUSIONS: These findings indicate that adding cortisol to in vivo exposure-based group therapy of spider phobia enhances treatment outcome.