Defy or ally : Neuroendocrine regulation of human socio-emotional behavior

Abstract

Evolution has created a human brain that is characterized by a layered, hierarchical organization. These superimposed layers have gradually evolved to generate ever more complex forms of socio-emotional behavior. The present thesis centers on the neurobiological substrates that generate this behavior, with a particular focus on the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) neuroendocrine axes, and the autonomic nervous system. A multidisciplinary approach is taken that combines theory and methods from cognitive psychology, cognitive neuroscience, and psychopharmacology. The first part of the thesis concerns social aggression. In a series of studies, first, the feasibility of employing cognitive and physiological responses to facial expressions displaying social aggression is validated. Subsequently, these methods are used to provide evidence that within the well-established framework of lateralization of the prefrontal cortex, anger is lateralized to the left instead of the right hemisphere. This finding is consistent with recent theories based on an approach-avoidance framework of prefrontal lateralization. A subsequent study applied functional MRI to study the role of steroid hormones in regulating social aggression. It is shown that a profile of low basal levels of HPA axis regulated stress hormones, in combination with and high levels of the HPG axis regulated hormone testosterone, is predictive of a strong amygdala response to socially threatening facial expressions. Moreover, after elevation of testosterone levels through oral administration, this response increased. These findings provide one of the very few demonstrations of the putative relation between testosterone and reactive aggression in humans. The second part of the thesis centers on neuroendocrine regulation of fear circuits in humans using psychophysiological methods such as fear potentiated startle and electrodermal activity. In three studies, it is shown that testosterone has fear-reducing properties. Recent notions that the HPA axis may similarly exert negative feedback upon central fear circuitry through cortisol could not be supported. In the third part of the thesis two studies are reported that investigate empathy from the viewpoint that this socio-emotional capacity is rooted in perspective taking through imitation. The first of these demonstrates that volunteers that score high on a questionnaire assessing autistic traits have a reduced tendency to spontaneously mimic facial expressions. The final study again uses a manipulation of testosterone to show that spontaneous mimicry is decreased after administration, arguably due to a reduced tendency to empathize. In conclusion, this thesis endorses the view that an integrated account of functioning of the HPA and HPG axes and their influence upon socio-emotional processes, likely through altering neuropeptidergic transmission in limbic brain circuits, may contribute to finding new and more specific treatments of psychopathologies in the socio-emotional domain.