A neurobiological model of posttraumatic stress disorder (PTSD) associates its specific symptoms with a memory network that is mainly composed of amygdala, hippocampus and medial prefrontal cortex. According to that framework, a core problem in PTSD consists in the excessive formation of amygdaloid fear networks that cannot be sufficiently inhibited by hippocampus and prefrontal cortex. A reason for this disturbed inhibition was suggested in the cortisol-mediated atrophy of hippocampal tissue. However, there is still no entirely unambiguous empirical support for this theory. Particularly methodological differences between studies have been discussed as potential reason for existing inconsistencies.Study 1: Potential PTSD-associated differences in basal cortisol levels were elucidated within an investigation of the diurnal cortisol release of highly traumatized, Rwandese refugees. Both, the study design and the choice of the population allowed a maximal control of methodological confounds. Notwithstanding, no PTSD-related alterations in cortisol profiles were revealed. Study 2: Potential brain structural alterations of regions associated with episodic memory networks were investigated in a sample of traumatized refugees with and without PTSD. Specific volume changes were revealed in the right inferior parietal cortex, the bilateral later prefrontal cortex and the bilateral isthmus of the cingulate. Study 3: The specific role of hippocampus and insula in the pathophysiology of PTSD was clarified in a combined volumetry/spectroscopy investigation of the same sample. In both structures neither volume reductions nor changes in neuronal density were revealed. An association between left hippocampal metabolite concentration and the occurrence of negative childhood experiences suggests that these experiences might have a particular influence on hippocampal integrity.In light of the present results, it seems unlikely that PTSD-related alterations in cortisol release might result in atrophies within hippocampal tissue. Morphological alterations in this structure might rather be the consequence of negative childhood experiences or develop secondary to other factors, as e.g. excessive alcohol abuse. Moreover, an extension of the conventional neurobiological model of PTSD seems reasonable. Particularly cortical regions that have been associated with the volitional control of memory processes and the regulation of emotional conditions showed PTSD-specific structural volume reductions. The contribution of these structures in the pathophysiology of PTSD should be the focus of future research
