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Sexual scripts, that is, the mental representations of sexual behavior, are highly influenced by mating strategies and sexual experience. The relationship between these factors and sexual scripts is, however, poorly understood. Therefore, we assessed how long-term (e.g., "sex in a relationship") and short-term (e.g., "one-night stand") strategies, as well as experience with highly scripted sexual practices (BDSM: bondage-discipline, dominance-submission, sadism-masochism), influence verbalized sexual script composition and detailedness. To this end, 204 heterosexual men and women generated both a "sex in a relationship" and a "one-night stand" script. Regarding mating strategies, both men and women generated shorter "sex in a relationship" scripts than "one-night stand" scripts, due to a shorter approach (flirting) phase. In addition, in the "sex in a relationship" script, women generated longer foreplay phases than men. Regarding sexual experience, in the "sex in a relationship" script, individuals with high-BDSM experience generated longer foreplay phases than individuals with middle- or low-BDSM experience. This pattern was reversed in the "one-night stand" script. These results provide empirical support for interactions between mating strategies and individual experience with regard to the mental representations of sexual activity and gender behavior. Understanding this relationship may enable us to better predict sexual encounters and may help to prevent conflicting or abusive situations.

Prevalence of Internet use among adolescents is high, but little is known about the online sexual activities of German adolescents. This study aimed to describe the 12-month prevalence of German adolescents' online sexual experiences with a focus on Online Sexual Solicitation (OSS, subjectively negative online sexual experiences with a peer or any sexual online experience, positive or negative, with an adult). A sample of male and female adolescents aged 14-17 (N=2238) was recruited using online survey panel. The sample was representative for gender and education. Subjects completed an online survey reporting their online sexual activities (i.e., sexual conversation, exchanging pictures, and cybersex) with peers (14-17y.) and/or adults (≥18y.). Findings illustrated that 51.3% (n=1148) of adolescents had experienced online sexual activity, which mostly involved peers (n=969; 84.4%). In contrast, 23.2% (n=519) of the adolescents experienced OSS with 2.6% (n=57) reporting subjectively negative online sexual interactions with peers and 22.2% (n=490) reporting online sexual interactions with adults, of which 10.4% (n=51) were perceived as negative. The findings suggest that adolescents frequently engage in sexual interactions on the Internet with only a relatively small number perceiving such contacts as exploitative. In addition, females and adolescents with incomplete family situation, foreign nationality, higher education, homo- or bisexual orientation, and those without perceived social support reported OSS significantly more often., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Consistent evidence exists for sexual interest in children in nonclinical/nonforensic male populations. However, prevalences for community men's self-reported sexual interest in children have been based on indiscriminate definitions including postpubescent individuals, age-restricted samples, and/or small convenience samples. The present research assessed men's self-reported sexual interest in children (including child prostitution and child sex tourism) on the community level and examined the link between strictly defined sexual fantasies and behaviors involving prepubescent children. In an online survey of 8,718 German men, 4.1% reported sexual fantasies involving prepubescent children, 3.2% reported sexual offending against prepubescent children, and 0.1% reported a pedophilic sexual preference. Sexual fantasies involving prepubescent children were positively related to sexual offending against prepubescent children. Sexual interest in children was associated with subjectively perceived need for therapeutic help. In contrast to findings from forensic samples, men who reported child pornography use exclusively were identified as a subgroup differing from contact sexual offenders against prepubescent children and men who reported both child pornography use and contact sexual offenses against prepubescent children. The empirical link between child-related sexual fantasies and sexual victimization of prepubescent children and high levels of subjective distress from this inclination underscore the importance of evidence-based child sexual abuse prevention approaches in the community. Findings are discussed in terms of their relation to pedophilic disorder.

Diagnoses of psychiatric diseases do not include criminal behavior. In schizophrenia, a non-negligible subgroup is incarcerated for capital and other crimes. Most studies that compared offender and non-offender patients with schizophrenia have only focused on male patients. With this study, we compared demographic and disease-related characteristics between 35 female incarcerated forensic patients (fSZ) and 35 female inpatients with schizophrenia (SZ). Basic clinical documentation and basic forensic clinical documentation revealed significant clinical and demographic differences between the two groups. Compared to SZ, fSZ were more severely clinically impaired, showing higher rates of comorbid alcohol and substance disorder, more suicide attempts, had more previous hospitalizations, and were younger at disease onset. Regarding demographic variables, fSZ showed a higher rate of unemployment and homelessness and had to rely more often on housing and legal guardianships compared to SZ. These results suggest that female forensic patients with schizophrenia are more severely affected by clinical and non-clinical variables requiring an adapted intervention program. These results may also indicate two developmental trajectories for criminal and non-criminal schizophrenia in females., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

The implicit assessment of pedophilic sexual interest through viewing-time methods necessitates visual stimuli. There are grave ethical and legal concerns against using pictures of real children, however. The present report is a summary of findings on a new set of 108 computer-generated stimuli. The images vary in terms of gender (female/male), explicitness (naked/clothed), and physical maturity (prepubescent, pubescent, and adult) of the persons depicted. A series of three studies tested the internal and external validity of the picture set. Studies 1 and 2 yielded good-to-high estimates of observer agreement with regard to stimulus maturity levels by two methods (categorization and paired comparison). Study 3 extended these findings with regard to judgments made by convicted child sexual offenders.

The phenomenon of sexual sadism was first scientifically described by Richard von Krafft-Ebing in 1999 as a sexual preference disorder that focuses on the infliction of suffering, pain, or humiliation to achieve sexual gratification. The present article reviews the historical development of the term sexual sadism, including the current descriptive nosology of psychiatric classification. Despite clear definitions that specify the sexual objects, duration, and distress necessary for a disorder, evidence for the diagnostic reliability for sexual sadism in the forensic domain is mixed. We argue that the reliance on the patient's willingness to divulge corresponding violent sexual fantasies is the Achilles' heel of the diagnosis. In an attempt to improve agreement across diagnosticians, we argue for the use of behavioral indicators. We summarize the extant research on the Severe Sexual Sadism Scale (SESAS), which is a file-based observer rating of pertinent crime-scene actions. We conclude that the analysis of crime-scene behavior, as achieved with the SESAS, can provide a useful complement for the clinical diagnosis in forensic psychiatry and psychology.

The causes of schizophrenia are still unknown. For the last 100 years, though, both "absent" and "perfect" vision have been associated with a lower risk for schizophrenia. Hence, vision itself and aberrations in visual functioning may be fundamental to the development and etiological explanations of the disorder. In this paper, we present the "Protection-Against-Schizophrenia" (PaSZ) model, which grades the risk for developing schizophrenia as a function of an individual's visual capacity. We review two vision perspectives: (1) "Absent" vision or how congenital blindness contributes to PaSZ and (2) "perfect" vision or how aberrations in visual functioning are associated with psychosis. First, we illustrate that, although congenitally blind and sighted individuals acquire similar world representations, blind individuals compensate for behavioral shortcomings through neurofunctional and multisensory reorganization. These reorganizations may indicate etiological explanations for their PaSZ. Second, we demonstrate that visuo-cognitive impairments are fundamental for the development of schizophrenia. Deteriorated visual information acquisition and processing contribute to higher-order cognitive dysfunctions and subsequently to schizophrenic symptoms. Finally, we provide different specific therapeutic recommendations for individuals who suffer from visual impairments (who never developed "normal" vision) and individuals who suffer from visual deterioration (who previously had "normal" visual skills). Rather than categorizing individuals as "normal" and "mentally disordered," the PaSZ model uses a continuous scale to represent psychiatrically relevant human behavior. This not only provides a scientific basis for more fine-grained diagnostic assessments, earlier detection, and more appropriate therapeutic assignments, but it also outlines a trajectory for unraveling the causes of abnormal psychotic human self- and world-perception.

Studies applying structural neuroimaging to pedophiles are scarce and have shown conflicting results. Although first findings suggested reduced volume of the amygdala, pronounced gray matter decreases in frontal regions were observed in another group of pedophilic offenders. When compared to non-sexual offenders instead of community controls, pedophiles revealed deficiencies in white matter only. The present study sought to test the hypotheses of structurally compromised prefrontal and limbic networks and whether structural brain abnormalities are related to phenotypic characteristics in pedophiles. We compared gray matter volume of male pedophilic offenders and non-sexual offenders from high-security forensic hospitals using voxel-based morphometry in cross-sectional and correlational whole-brain analyses. The significance threshold was set to p < .05, corrected for multiple comparisons. Compared to controls, pedophiles exhibited a volume reduction of the right amygdala (small volume corrected). Within the pedophilic group, pedosexual interest and sexual recidivism were correlated with gray matter decrease in the left dorsolateral prefrontal cortex (r = -.64) and insular cortex (r = -.45). Lower age of victims was strongly associated with gray matter reductions in the orbitofrontal cortex (r = .98) and angular gyri bilaterally (r = .70 and r = .93). Our findings of specifically impaired neural networks being related to certain phenotypic characteristics might account for the heterogeneous results in previous neuroimaging studies of pedophilia. The neuroanatomical abnormalities in pedophilia seem to be of a dimensional rather than a categorical nature, supporting the notion of a multifaceted disorder., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Sleep deprivation deteriorates mood, impairs the recognition of facial expressions, and affects the ability to regulate emotions. The present study investigated the effect of partial sleep deprivation on facial responses to emotional stimuli. Thirty-three healthy undergraduates were tested twice: after a night with (i) 8h and (ii) 4h sleep. Self-reported sleepiness and sustained attention (Psychomotor Vigilance Task) were assessed. Emotional reactivity was measured with facial Electromyogram (EMG) while participants were asked to respond with either compatible or incompatible facial muscles to emotional stimuli in order to study whether partial sleep deprivation caused slower reactions mainly in response to incompatible stimuli (due to an additional effort to suppress the compatible reaction caused by decreased inhibitory control) or in response to both compatible and incompatible stimuli. Self-reported sleepiness and reaction times in a sustained attention task significantly increased after one night of partial sleep deprivation. Facial reactions to emotional stimuli were decelerated. No significant interaction between sleep restriction and compatibility of the muscle to the picture valence could be observed. Hence, volitional facial reactions in response to emotional stimuli were slower after one night of reduced sleep, but affective inhibitory control was not significantly impaired. However, slowed facial responding to emotional stimuli may affect social interaction after sleep restriction., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A clear and structured approach to evidence-based and gender-specific risk assessment of violence in female offenders is high on political and mental health agendas. However, most data on the factors involved in risk-assessment instruments are based on data of male offenders. The aim of the present study was to validate the use of the Psychopathy Checklist Revised (PCL-R), the HCR-20 and the Violence Risk Appraisal Guide (VRAG) for the prediction of recidivism in German female offenders. This study is part of the Munich Prognosis Project (MPP). It focuses on a subsample of female delinquents (n = 80) who had been referred for forensic-psychiatric evaluation prior to sentencing. The mean time at risk was 8 years (SD = 5 years; range: 1-18 years). During this time, 31% (n = 25) of the female offenders were reconvicted, 5% (n = 4) for violent and 26% (n = 21) for non-violent re-offenses. The predictive validity of the PCL-R for general recidivism was calculated. Analysis with receiver-operating characteristics revealed that the PCL-R total score, the PCL-R antisocial lifestyle factor, the PCL-R lifestyle factor and the PCL-R impulsive and irresponsible behavioral style factor had a moderate predictive validity for general recidivism (area under the curve, AUC = 0.66, p = 0.02). The VRAG has also demonstrated predictive validity (AUC = 0.72, p = 0.02), whereas the HCR-20 showed no predictive validity. These results appear to provide the first evidence that the PCL-R total score and the antisocial lifestyle factor are predictive for general female recidivism, as has been shown consistently for male recidivists. The implications of these findings for crime prevention, prognosis in women, and future research are discussed., (Copyright © 2012 John Wiley & Sons, Ltd.)

Introduction: Pedophiles show sexual interest in prepubescent children but not in adults. Research into the neurofunctional mechanisms of paraphilias has gathered momentum over the last years., Aim: To elucidate the underlying neural processing of sexual interest among pedophiles and to highlight the differences in comparison with nonparaphilic sexual interest in adults., Methods: Nine pedophilic patients and 11 nonpedophilic control subjects underwent functional magnetic resonance imaging (fMRI) while viewing pictures of nude (prepubescents, pubescents, and adults) and neutral content, as well as performing a concomitant choice reaction time task (CRTT)., Main Outcome Measures: Brain blood oxygen level-dependent (BOLD) signals and response latencies in the CRTT during exposure to each picture category., Results: Analysis of behavioral data showed group differences in reaction times regarding prepubescent and adult but not pubescent stimuli. During stimulation with pictures displaying nude prepubescents, pedophiles showed increased BOLD response in brain areas known to be involved in processing of visual sexual stimuli. Comparison of pedophilic patients with the control group discovered differences in BOLD responses with respect to prepubescent and adult but not to pubescent stimuli. Differential effects in particular occurred in the cingulate gyrus and insular region., Conclusions: The brain response of pedophiles to visual sexual stimulation by images of nude prepubescents is comparable with previously described neural patterns of sexual processing in nonpedophilic human males evoked by visual stimuli depicting nude adults. Nevertheless, group differences found in the cingulate gyrus and the insular region suggest an important role of these brain areas in pedophilic sexual interest. Furthermore, combining attention-based methods like CRTT with fMRI may be a viable option for future diagnostic procedures regarding pedophilia., (© 2011 International Society for Sexual Medicine.)

Psychopathic personality disorder and sexual sadism share several common characteristics, such as emotional detachment from the suffering of others or the preparedness to inflict pain or injuries. Based on a sample of 100 male forensic patients (all of them sex offenders, half of them sadistic), the concept of psychopathy and sexual sadism as a unified construct was tested empirically. Pooling indicator variables for psychopathic and sexually sadistic disorders showed that a two-factorial solution yielded a better fit than a single-factor model. The two factors identified psychopathy and sexual sadism as separate latent variables. More specifically, the data were compatible with a path model in which affective deficits and behavioral disinhibition of the psychopathy domain are precursors to sexually sadistic conduct.

Cross-cultural research on psychopathy necessitates assessment methods that are generalizable across linguistic and cultural differences. Multiple-group confirmatory factor analysis was used to compare the factorial structure of Psychopathy Checklist-Revised (PCL-R) assessments obtained from file reviews of North-American (N=2622) and German (N=443) male offenders. The analyses indicated that the 18 item, 4-factor model of the PCL-R obtained with the standard PCL-R protocol (interview and file review) also holds for file review data. On a factor-by-factor level, the data are commensurate with strong factorial invariance of factor loadings and item thresholds for the Interpersonal and Lifestyle factors, and with likely metric invariance for the Affective factor. The Antisocial factor showed structural differences between the two samples. The results imply that cultural or environmental factors more strongly influence the judgment and/or expression of antisociality. Based on the results, cross-cultural comparisons between North-American and German offenders in terms of PCL-R psychopathy should be limited to the Interpersonal and Lifestyle factors. Further research using data obtained through the standard protocol (i.e., interview plus file information) is encouraged., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Choice-reaction time (CRT) is an experimental information-processing paradigm. Based on an interference effect in visual attention, the CRT method has been shown to be suitable for measuring sexual orientation in men and women. The present study assessed the potential of the CRT to identify deviant (i.e., pedophilic) sexual interest. Participants were patients from forensic-psychiatric hospitals: 21 child molesters and 21 non-sex offenders. The dependent variable was reaction time in an ostensible seek-and-locate task (i.e., identifying the position of a dot superimposed on a picture of a person). There was an interaction effect between stimulus age category and participant group status: Child molesters took longer to respond to pictures of children relative to pictures of adults. Non-sex offenders showed an opposite pattern (i.e., longer reaction times with pictures of adults than with pictures of children). In addition, the data supported the notion of sexual content induced delay: Subjects took longer for the task with nude stimuli than with clothed ones. A subtractive preference index, derived from the reaction times for child and adult stimulus material, allowed distinguishing participants from both groups almost perfectly (ROC-AUC = .998). We conclude that a match of sexual interest with properties of visual stimuli led to a cognitive interference effect: Attentional resources were drawn from the ostensible task of locating the dot towards exploring the picture. This opens up the possibility of using this interference effect (i.e., the delay of response times) for diagnostic purposes.

Severe sexual sadism is a disorder of sexual preference that focuses on humiliation and subjugation of the victim, sometimes causing grievous injury or death. Sexual sadists pose a particular risk. However, the diagnosis as such is unreliable and prevalence estimates vary. In a sample of male high-security forensic inpatients who had committed sexual offenses, we found two-thirds of sexual sadists had not been identified as such prior to commitment. Possible reasons for missing the diagnosis are many fold. Present data support the notion that unrecognized sexual sadists more closely resembled non-sadistic sex offenders than accurately diagnosed sadists. In particular, initially unrecognized sexual sadists had less severe previous convictions, less vocational training, and experienced a less supportive upbringing than their correctly identified sadistic counterparts. The latter, in contrast, more often reached media coverage through their offense(s). We conclude that severe sexual sadism is likely an underdiagnosed, yet forensically highly relevant disorder.

Maladaptive social behavior is one of the defining characteristics of psychopathic personality disorder. Nevertheless, maladaptive social behavior has only rarely been observed among psychopaths in experimentally controlled situations. The authors assessed the behavior of criminal psychopaths from high-security psychiatric hospitals in a computer simulation of a social dilemma situation. The psychopaths showed a markedly higher proneness to competitive (i.e., noncooperative) behavior than did healthy adults from the general population. The odds ratio between defection and being a psychopath was estimated at 7.86 in the sample. The probability to choose selfish instead of cooperative behavior was significantly linked to the following subscales of the Psychopathy Personality Inventory-Revised (S. O. Lilienfeld & M. R. Widows, 2005): rebellious nonconformity, Machiavellian egocentricity, and the total score. On average, the psychopathic participants accumulated higher gain and more strongly exploited their counterpart than did the healthy participants.

Background: Several pharmacotherapeutic approaches have confirmed the influence of neuroendocrine parameters on sexual desire, function, and fantasies in men; however, the relevance of acute neuroendocrine changes in mediating heightened sexual drive remains unknown. We recently demonstrated that plasma prolactin substantially increases following orgasm in healthy men, suggesting a feedback mechanism for peripheral prolactin in the control of acute sexual arousal. Because prolactin appears to play a regulatory role in acute sexual drive, we initiated this study to see whether sexual offenders with a high sexual drive have a different neuroendocrine response to sexual arousal. This study compares the prolactin response to orgasm of sexual offenders with high sexual drive and that of healthy subjects with average sexual drive., Methods: From a subject pool of 150 inpatients held because of sexual crimes, we recruited 10 volunteers, based on their high sexual drive according to an intensive, semistructured clinical interview. We defined sexual drive by a short refractory period and strong sexualization, or a high frequency of sexual stimulation. We analyzed the acute psychoneuroendocrine response to sexual arousal and orgasm continuously before, during, and after masturbation-induced orgasm in patients and control subjects., Results: Sexual offenders demonstrated higher sexual desire (P < 0.001) and function (P < 0.001) and a more positively perceived refractory period (P < 0.05). Both groups displayed a prolonged, significant increase in prolactin plasma levels after orgasm (P < 0.001). Sexual offenders did not differ from control subjects in neuroendocrine response to sexual arousal and orgasm., Conclusions: These data demonstrate that sexual offenders with a high sexual drive do not differ from control subjects in the postorgasmic neuroendocrine response, particularly in prolactin release. This study confirms that factors other than peripheral hormones influence deviant sexual behaviour.

Background: Criminal offenders with a diagnosis of psychopathy or borderline personality disorder (BPD) share an impulsive nature but tend to differ in their style of emotional response. This study aims to use multiple psychophysiologic measures to compare emotional responses to unpleasant and pleasant stimuli., Methods: Twenty-five psychopaths as defined by the Hare Psychopathy Checklist and 18 subjects with BPD from 2 high-security forensic treatment facilities were included in the study along with 24 control subjects. Electrodermal response was used as an indicator of emotional arousal, modulation of the startle reflex as a measure of valence, and electromyographic activity of the corrugator muscle as an index of emotional expression., Results: Compared with controls, psychopaths were characterized by decreased electrodermal responsiveness, less facial expression, and the absence of affective startle modulation. A higher percentage of psychopaths showed no startle reflex. Subjects with BPD showed a response pattern very similar to that of controls, ie, they showed comparable autonomic arousal, and their startle responses were strongest to unpleasant slides and weakest to pleasant slides. However, corrugator electromyographic activity in subjects with BPD demonstrated little facial modulation when they viewed either pleasant or unpleasant slides., Conclusions: The results support the theory that psychopaths are characterized by a pronounced lack of fear in response to aversive events. Furthermore, the results suggest a general deficit in processing affective information, regardless of whether stimuli are negative or positive. Emotional hyporesponsiveness was specific to psychopaths, since results for offenders with BPD indicate a widely adequate processing of emotional stimuli.

Background: Based on findings of stress-induced neural disturbances in animals and smaller hippocampal volumes in humans with posttraumatic stress disorder), we hypothesized that patients with borderline personality disorders (BPD), who often are victims of early traumatization, have smaller volumes of the hippocampus and the amygdala. We assumed that volumes of these brain regions are negatively correlated with traumatic experiences and with neuropsychological deficits., Methods: We studied 21 female patients with BPD and a similar group of healthy controls. We performed clinical assessments, a modified version of the Childhood Trauma Questionnaire, and magnetic resonance imaging volumetric measurements of the hippocampus, amygdala, temporal lobes, and prosencephalon. Neuropsychological testing included scales on which disturbances in BPD were previously reported., Results: The patients with BPD had nearly 16% smaller volumes of the hippocampus (P<.001) and 8% smaller volumes of the amygdala (P<.05) than the healthy controls. The results for both hemispheres were nearly identical and were controlled for the volume of the prosencephalon and for head tilts. The volumes of the hippocampus were negatively correlated with the extent and the duration of self-reported early traumatization only when BPD and control subjects were considered together. Levels of neuropsychological functioning were associated with the severity of depression but not with the volumes of the hippocampus., Conclusion: In female patients with BPD, we found reduction of the volumes of the hippocampus (and perhaps of the amygdala), but the association of volume reduction and traumatic experiences remains unclear. Arch Gen Psychiatry. 2000;57:1115-1122.

Attentional factors are thought to affect eye-tracking patterns. The present study examined the hypothesis that specific quantitative features of eye tracking would be correlated with the amplitude of a component of the auditory evoked potential, the N100, which is known to be enhanced by arousal and selective attention. We studied 12 clinically stable schizophrenic patients by means of DC-electro-oculography. The frequency and amplitude of different types of saccades (catchup, backup, anticipatory saccades, and square wave jerks) were assessed. The results suggest that small and large saccades, as classified by a simple amplitude criterion (4 degrees), have differential meanings and indicate that enhanced amplitudes of small saccades are an effect of arousal.

To evaluate 5-hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder, we examined hypothermic, neuroendocrine, and behavioral responses to the selective 5-hydroxytryptamine1A receptor ligand ipsapirone in patients with primary obsessive-compulsive disorder and healthy controls. Twelve patients and 22 controls received a single dose of ipsapirone, 0.3 mg/kg, or placebo under double-blind, random assignment conditions. Ipsapirone induced hypothermia and release of corticotropin and cortisol but had no effect on behavior, including obsessive or compulsive symptoms. Thermoregulatory and neuroendocrine responses to ipsapirone were not consistently different between healthy controls and patients with obsessive-compulsive disorder. These results provide no direct support for the hypothesis that a serotonergic dysfunction related to 5-hydroxytryptamine1A receptors may be linked to the pathophysiologic characteristics of obsessive-compulsive disorder and point to the need for the evaluation of other 5-hydroxytryptamine receptor subtypes. Future studies of the responsivity of 5-hydroxytryptamine1A receptors to direct-acting ligands, such as ipsapirone, should facilitate assessment of the integrity of the 5-hydroxytryptamine system and its involvement in antiobsessional drug effects.

The selective 5-HT1A receptor ligand ipsapirone (IPS) induces corticotropin (ACTH) and cortisol secretion in humans. To explore 5-HT1A receptor-mediated hypothalamic-pituitary-adrenal (HPA) system activation in depression, 24 subjects (12 patients with unipolar depression and 12 individually matched controls) were given 0.3 mg/kg IPS or placebo in random order. Compared with controls, the depressed patients exhibited significantly decreased ACTH and cortisol responses to IPS in association with increased basal cortisol secretion. The impaired HPA response following 5-HT1A receptor challenge in unipolar depression could have resulted from glucocorticoid-dependent subsensitivity of the (post-synaptic) 5-HT1A receptor itself and/or from a defective postreceptor signaling pathway [inhibitory guanine nucleotide-binding protein (Gi)-adenylate cyclase complex function], thus supporting the hypothesis that a disintegrated 5-HT and HPA system interaction may be present in depression. Future studies of the HPA response to direct-acting 5-HT1A ligands, such as IPS, should facilitate the assessment of 5-HT/HPA system integrity in various affective disorders and its involvement in psychotropic drug effects.