In a large sample of adults, no significant relationships were observed between psychopathy and baseline testosterone or cortisol, or cortisol reactivity to a stressor. Furthermore, there were no significant interactions between these variables. Although we did not observe a relationship between psychopathy and the ratio of baseline testosterone to cortisol, predicted by Terburg et al. (2009)
, we did observe a significant relationship between psychopathy and the ratio of baseline testosterone to cortisol reactivity. Individuals scoring higher in psychopathy had a higher ratio of baseline testosterone to cortisol reactivity; this accounted for 5% of the variance in psychopathic traits. This effect was only true for individuals with high baseline levels of testosterone. These findings highlight the importance of a multi-system approach in hormone research.
The fact that we observed a significant relationship with the ratio score (at high levels of testosterone), but not with levels of the individual hormones or their interactions, may be indicative of the interconnected nature of the hormone systems. The ratio score indicates the level of testosterone relative to cortisol reactivity within an individual
. This score could be viewed as a general index of the imbalance between the HPA and HPG axes within that individual. In contrast, the interaction term for cortisol × testosterone treats the hormones as two distinct variables, with the individual’s score on each hormone being relative to the scores of the group. For example, an individual may have high testosterone (relative to the group) and low cortisol reactivity (relative to the group), but the important question seems to be ‘how high is the individual’s testosterone relative to his own
cortisol reactivity?’ This makes sense given the high degree of interconnectedness between the HPA and HPG axes. High HPG axis activity relative to HPA axis activity may affect the sensitivity of brain regions such as the amygdala. Both testosterone and cortisol regulate and facilitate neuropeptide gene expression in the amygdala, and their influence on the probability of approach versus withdrawal is in opposing directions (Schulkin, 2003
; Szot & Dorsa, 1994
) – cortisol facilitates withdrawal and fearfulness, whereas testosterone facilitates approach and reward-seeking. Therefore, the relative contribution of each hormone is important in determining the reactivity of the amygdala to environmental stimuli. Similarly, the HPA and HPG axes act in opposite directions in their influence on the connectivity between subcortical and cortical regions. Increased levels of cortisol have been associated with enhanced functional connectivity between subcortical and cortical regions (Schutter & van Honk, 2005
), whereas injections of testosterone have been found to reduce this communication (Schutter & van Honk, 2004
; van Wingen, et al., 2010
). Therefore, the activity of these two systems relative to each other seems have a significant effect on brain systems that are relevant to psychopathy.
A high ratio of testosterone relative to cortisol reactivity may mean that amygdala functioning is driven more by testosterone than cortisol, so the individual becomes more likely to engage in approach-related or aggressive behavior, is more sensitive to reward, and is less fearful and less sensitive to cues of punishment or threat (Terburg, et al., 2009
; van Honk & Schutter, 2006
). This may contribute to the fearlessness, reward-seeking, impulsiveness, and poor decision-making observed in psychopathy. Furthermore, the decoupling between subcortical and cortical regions that results from increased testosterone relative to cortisol may have effects in two ways: 1) During decision-making, emotion-related information from the amygdala that signals cues of threat, risk, or harm to others may not be able to reach cortical areas in order to inform the decision. This may result in the callousness, lack of empathy, risk-taking, and instrumental aggression observed in psychopathy. 2) Cortical regions may be less able to send inhibitory signals to subcortical regions, resulting in deficits in emotion regulation and inhibition (van Honk & Schutter, 2006
), which contribute to reactive aggression and labile affect observed in psychopathy. Thus, through these processes, a high ratio between testosterone and cortisol reactivity may contribute to a variety of psychopathic traits, including both instrumental and reactive forms of aggression.
An additional finding of the present study was that psychopathy was only related to the ratio score at high levels of testosterone. This may mean that at lower levels of testosterone, the effect of testosterone on the amygdala and its connectivity to cortical regions is minimal, and the ratio of testosterone to cortisol becomes less relevant to behavior. Low testosterone levels have previously been described as a protective factor against antisocial behavior (Farrington & Coid, 2003
). In contrast, at higher levels, testosterone may have a pronounced effect on amygdala functioning and connectivity; without sufficient cortisol responding to counterbalance these effects and to promote withdrawal behavior and fearfulness, psychopathic traits may develop.
It is unclear why the ratio involving cortisol reactivity
was significant whereas the ratio involving baseline cortisol levels was not – it is unknown whether this discrepancy is a result of measurement factors, or whether there is a neurobiological explanation. With regards to measurement, it has been suggested that the degree of cortisol reactivity to a stressor is a more robust indicator than baseline cortisol of how an individual responds to cues of threat or punishment; baseline cortisol may be a less reliable and valid indicator of stress reactivity, as it is influenced by a multitude of daily living factors that can impact cortisol levels (Loney, et al., 2006
). Stress induced changes in cortisol may provide a more precise measure of the functioning of the HPA axis and may be less susceptible to the influence of confounding factors (O’Leary, et al., 2007
). In the current study, the correlation between baseline cortisol and cortisol reactivity (AUC) was 0.47, suggesting that the two variables are clearly related, but that having high baseline cortisol levels does not directly translate into increased cortisol reactivity – other factors are involved in this process.
A possible neurobiological explanation is based on the idea that testosterone has more of an influence on cortisol reactivity than on baseline cortisol levels. In animals, castration and androgen replacement studies have found that androgens inhibit stress-stimulated cortisol release, but not baseline cortisol concentrations (Handa, et al., 1994
; Papadopoulos & Wardlaw, 2000
). Similarly, in humans, testosterone was found to decrease cortisol reactivity (as measured by area under the curve) to stress-stimulation, but not baseline cortisol levels (Rubinow, et al., 2005
). Therefore, the association between testosterone and cortisol reactivity may be the most relevant indicator of how the HPA and HPG axes interact. As we see in the present study, not all individuals with high testosterone levels had a high testosterone to cortisol reactivity ratio, indicating that there are individual differences in the degree to which testosterone suppresses the cortisol response. Individuals with high testosterone levels in which testosterone suppresses cortisol reactivity to a greater extent, may have the most pronounced alterations in amygdala functioning. In these individuals, the amygdala may be tuned to the testosterone-driven reward-seeking and approach-related behavior (Daitzman & Zuckerman, 1980
), and much less responsive to cues of fear or threat that are facilitated by the HPA axis (Schulkin, et al., 1998
), which would predispose for psychopathic traits. Furthermore, the higher levels of testosterone may reduce the connectivity between the amygdala and orbitofrontal cortex, thus impairing decision-making and inhibitory mechanisms (discussed above).
Analyses of the subfactors of psychopathy revealed that Factor 2 (Lifestyle-Antisocial) of psychopathy was a unique predictor of the testosterone-cortisol reactivity ratio. When entered together neither of its subfactors (Lifestyle or Antisocial) were significant, suggesting that it is the common variance that is shared between the two factors that is most associated with the ratio score. The altered imbalance between the HPA and HPG axis that may generally increase the probability of approach over withdrawal behavior and increase sensitivity to reward versus punishment (discussed above) may be associated with a latent factor that contributes to the specific features of Facets 3 and 4. Increased sensitivity to reward versus punishment, as well as an inclination toward approach behavior would likely result in the development of the more specific traits and behavior such as impulsivity, stimulation-seeking, irresponsibility (Facet 3), poor behavioral controls, and aggressive and deviant behavior (Facet 4).
Zero-order correlations also revealed a significant correlation between the ratio score and Facet 2 (Affective), suggesting that this factor may be related despite a lack of significance with the overall Interpersonal – Affective factor. This result may be potentially explained by reduced communication between the amygdala and cortical regions – if emotional input from the amygdala is unable to influence cognitive processes such as decision-making, the result may be that decision-making becomes cold and calculated, and the individual is described as callous and unemotional.
Limitations of this study include the fact that the sample was predominantly male, so findings cannot be generalized to psychopathic women, particularly considering the large gender differences in hormones between males and females. Many participants did not respond to the stressor task, which may be due to the fact that this temporary employment agency is a high-risk sample that attracts disproportionately high numbers of antisocial individuals. We do not have inter-rater reliability information for the PCL-R assessments, which were conducted by three raters. Finally, due to practical considerations, baseline saliva samples were acquired when participants came into the lab, rather than at waking, so it is possible that effects may not have been detected. However, all correlations with baseline cortisol and testosterone were .1 or less, so it is likely that any effects would have been small.
Although the present findings did not support the exact hypothesis of Terburg et al. (2009)
, the significant relationship between psychopathy and the testosterone/cortisol reactivity ratio provides support for the idea that the HPA and HPG axes may work in concert to predispose toward psychopathic traits, and highlights the importance of a multi-system approach. The interconnected nature of these systems may help to explain the mixed findings in previous studies examining individual hormones, as well as the lack of main effects of individual hormones in the present study. Future research will be necessary to elucidate the mechanisms of hormone action outlined by Terburg et al. (2009)
and van Honk & Schutter (2006)
. Research on hormones may be a key element in aiding our understanding of the how brain abnormalities associated with psychopathy may arise.