H. P. F. Koppeschaar

Testosterone shifts the balance between sensitivity for punishment and reward in healthy young women

Animal research has demonstrated reductions in punishment sensitivity and enhanced reward dependency after testosterone administration. In humans, elevated levels of testosterone have been associated with violent and antisocial behavior. Interestingly, extreme forms of violent and antisocial behavior can be observed in the psychopath. Moreover, it has been argued that reduced punishment sensitivity and heightened reward dependency are crucially involved in the etiology and maintenance of psychopathy. A task that has been proven to be capable of simulating punishment-reward contingencies is the IOWA gambling task. Decisions to choose from decks of cards become motivated by punishment and reward schedules inherent in the task. Importantly, clinical and subclinical psychopaths demonstrate a risky, disadvantageous pattern of decision-making in the task, indicating motivational imbalance (insensitivity for punishment and enhanced reward dependency). Here, in a double-blind placebo-controlled crossover design (n = 12), whether a single administration of testosterone would shift the motivational balance between the sensitivity for punishment and reward towards this tendency to choose disadvantageously was investigated. As hypothesized, subjects showed a more disadvantageous pattern of decision-making after testosterone compared to placebo administration. These findings not only provide the first direct evidence for the effects of testosterone on punishment-reward contingencies in humans, but they also give further insights into the hypothetical link between testosterone and psychopathy.

Correlations among Salivary Testosterone, Mood, and Selective Attention to Threat in Humans

An experiment was designed to investigate the relation among salivary testosterone, mood, and selective attention to threat. The participant group consisted of 32 nonclinical subjects (16 men and 16 women). Individuals completed the Profile Of Mood States (POMS) and performed a pictorial emotional Stroop task measuring selective attention to angry faces. Anticipating a time lag between testosterone (as measured in saliva) and cognitive emotional behavior, multiple time-coursed saliva samples were taken preceding the assessment of questionnaire and task for every subject. In both sexes, salivary testosterone was significantly related to mood (i.e., anger and tension) and selective attention to angry faces when saliva samples were taken 6 h before questionnaire and task assessment. Research on the relation between testosterone and human behavior might benefit by taking into account time lags between the behavioral manifestations and the continuously changing levels of testosterone.

GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults.

BACKGROUND The diagnosis of growth hormone (GH) deficiency in adults is based on provocative testing of GH secretion. The insulin tolerance test (ITT), currently the favoured test for this diagnosis, has been criticised for poor reproducibility and inconvenience. Since the combined administration of GH-releasing hormone (GHRH) plus GH-releasing peptide-6 (GHRP-6) is the most potent stimulus of GH secretion, we did a multicentre study comparing GH peaks elicited by ITT with those elicited by the GHRH/GHRP-6 test in healthy controls and GH-deficient individuals (cases). METHODS 125 adult patients with organic pituitary disease and 125 healthy individuals were studied. All cases and controls were given GHRH 1 microg per kg bodyweight intravenously plus GHRP-6 1 microg per kg intravenously at 0 min and blood samples were obtained during a subsequent 120 min period. 27 controls and all cases had an ITT. Inclusion criteria were severe GH deficiency--ie, a GH peak after ITT of < or = 3 microg/L. Results of the GHRH/GHRP-6 test were analysed by receiver-operating characteristic curve methodology. FINDINGS GH peaks seen after the GHRH/GHRP-6 test did not result in any side-effects and were not affected by age, sex, amount of adipose tissue, or by the GH assay system used. The GH mean peak after the GHRH/GHRP-6 test was 59.2 microg/L (SD 2.2) for controls and 4.1 microg/L (0.3) for cases, whereas after ITT the mean peak was 14.3 microg/L (1.7) and 0.5 microg/L (0.06), respectively. The differential peak responses of controls and cases was greater (p<0.001), for GHRH/GHRP-6 test than for ITT. When individually analysed GH peaks were a continuum, from 139.0 microg/L to 0.01 microg/L, with a cut-off point of 15.0 microg/L. The GHRH/GHRP-6 test performed well under the ROC curve analysis. For clinical utility, it is then proposed that values > or = 20.00 microg/L be considered normal and < or = 10.00 microg/L as GH deficient. INTERPRETATION The GHRH/GHRP-6 test is a convenient, safe and reliable test for adult GH deficiency and is not confounded by clinical factors known to alter GH secretory patterns. An evoked GH concentration of > or = 15.0 microg/L accurately distinguishes between healthy and GH-deficient adults.

A single administration of testosterone reduces fear-potentiated startle in humans

BACKGROUND Ample evidence from animal research indicates that the gonadal steroid hormone testosterone has fear-reducing properties. Human data on this topic, however, are scarce and far less unequivocal. The present study therefore aimed to scrutinize anxiolytic effects of a single dose of testosterone, using a direct physiological index of fear in humans. METHODS Twenty healthy female participants were tested in a double-blind, placebo-controlled crossover design involving sublingual administration of a single dose of testosterone. Four hours after intake, we assessed effects on baseline startle and fear-potentiated startle in a verbal threat-of-shock paradigm. RESULTS In accordance with predictions, testosterone administration resulted in reduced fear-potentiated startle, without affecting baseline startle. CONCLUSIONS This study provides direct evidence that a single dose of testosterone reduces fear in humans. The relationship of this effect to previous research on anxiolytic effects of benzodiazepines, as well as possible mechanisms of action, is discussed.

A single administration of testosterone improves visuospatial ability in young women

Previous research has documented correlations between endogenous testosterone levels and visuospatial cognitive function. Some causal relations have also been established in treatment designs in which testosterone was administered to elderly subjects for a number of weeks. Particularly, one study reported a selective effect of a single administration of testosterone on some aspects of spatial memory in 15 women. The present study tested the hypothesis whether a single administration of 0.5 mg of sublingual testosterone would improve visuospatial ability in healthy young women on a test that has consistently been associated with male superiority. Twenty-six women participated in a double-blind placebo-controlled cross-over trial of single administration of testosterone and placebo. Subjects were tested in the same phase of the menstrual-cycle. Four to five hours after both administrations, subjects completed a standardized measure of visuospatial ability (3-D Mental Rotations Test). Visuospatial ability improved significantly after testosterone administration compared to placebo, after controlling for learning effects due to repeated testing. Testosterone is suggested to be causally related to visuospatial ability in young women.

A single administration of testosterone induces cardiac accelerative responses to angry faces in healthy young women.

Recently, it was demonstrated how individuals with high levels of testosterone selectively attend toward angry faces. It was argued that this suggests that high levels of testosterone are associated with an aggressive, dominating personality style. In this study, the authors used a double-blind, placebo-controlled design to examine whether exogenous testosterone would induce cardiac acceleration in response to angry faces. Participants (healthy young women) were exposed to neutral, happy, or angry faces. Administration of a single dosage of testosterone (0.5 mg) induced an accelerative cardiac response to angry faces. It is argued that this effect is due to the encouragement of dominance behavior and the inclination toward aggression. Possible mechanisms behind testosterone-driven changes in behavior are discussed with relevance to steroid-responsive networks in the limbic system that drive and control motivational and physiological aspects of social behavior.

Sex differences for selective forms of spatial memory

In the present study, a systematic comparison of sex differences for several tests of spatial memory was conducted. Clear evidence for more accurate male performance was obtained for precise metric positional information in a wayfinding task and in an object location memory task. In contrast, no sex difference characterized topological information processing (object-to-position assignment). Together, these findings provide further insight in the specificity of sex differences in spatial memory and in the functional architecture of spatial memory. Implications for the relevant evolutionary basis are discussed.

Conscious and preconscious selective attention to social threat: different neuroendocrine response patterns

This study was designed to investigate the relationship between selective attention to social threat and neuroendocrine activity. Selective attention to social threat was measured using a supraliminal (unmasked) and a subliminal (masked) version of a pictorial emotional Stroop task, comparing color-naming latencies of neutral and angry faces. Neuroendocrine activity was assessed as (pre-task to post-task) increases in salivary cortisol and testosterone. Forty subjects were randomly assigned to the unmasked or masked version of the task. Analyses for the unmasked task revealed that post-task cortisol levels were significantly increased in subjects showing selective attention to angry faces. Results for the masked task indicated that post-task cortisol and testosterone levels were significantly increased in subjects showing preconscious selective attention to angry faces. The difference in neuroendocrine activity between tasks is suggested to depend on cortical (i.e. prefrontal) control in the unmasked task. Thus, psychological affective regulatory processes were involved in the unmasked task, whereas the neuroendocrine response patterns in the masked task indicates a biologically prepared mechanism.

Growth hormone, insulin-like growthfactor I and cognitive function in adults

This review focuses on the possible contribution of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis to cognitive function. Binding sites for GH and IGF-I are found in various areas of the brain. Their distribution suggests that GH and IGF-I contribute to the function of the hippocampus, a brain structure important for the maintenance of cognitive functions such as learning and memory. Evidence for cognitive deficits in GH-deficient individuals has been found in various studies, some of which have shown that these deficits can be reversed by GH substitution therapy. In addition to examining conditions of GH deficiency, this article reviews studies evaluating the correlation between the cognitive deficits associated with ageing and age-related decreases in GH or IGF-I secretion. Based on the available data, one might hypothesize that relative GH or IGF-I deficiency could contribute to the deterioration of cognitive functions observed in the elderly.

BASELINE SALIVARY CORTISOL LEVELS AND PRECONSCIOUS SELECTIVE ATTENTION FOR THREAT: A Pilot Study

This study was conducted to examine the relationship between baseline salivary cortisol (CORT) levels and selective attention for displays of angry faces. Selective attention was investigated using a pictorial emotional Stroop task, comparing colournaming-speed of angry and neutral faces. The task was assessed in supraliminal (unmasked) and subliminal (masked) conditions to 28 non-clinical subjects (14 male and 14 female). Repeated measures analysis of variance revealed a significant interaction between median split CORT levels (low vs. high) and masked face valence (angry vs. neutral). The latter effect was mainly due to significant facilitation in the high CORT subject-group; these subjects seemed to allocate their attention away from the masked angry face. A relation between baseline CORT levels and fast withdrawal behavior is suggested.