Stress Controversies: Post-Traumatic Stress Disorder, Hippocampal Volume, Gastroduodenal Ulceration

What is it about?

Stress in mammals triggers a neuroendocrine response mediated by the (brain) hypothalamic–pituitary– adrenal axis and the autonomic nervous system. Increased activity of these two systems induces behavioural, cardiovascular, endocrine and metabolic cascades that enable the individual to fight or flee and cope with the stress. Our understanding of stress and stress-response mechanisms is generally robust. Here, however, we review three themes that remain controversial and deserve further scrutiny and investigation before they achieve canonical status. The themes are, first, reduced cortisol levels in post-traumatic stress disorder (PTSD). A reduction rather than a stress-induced increase in adrenal cortisol levels, as seen in major depressive disorder (MDD), is puzzling and furthermore is not a consistent feature of PTSD. The second theme concerns the reduction in volume of the hippocampus in MDD attributed to the neurotoxicity of increased cortisol. Reduced hippocampal volume in MDD has been found in some but not all studies. Third, the discovery of a causal association between the bacterium Helicobacter pylori and peptic ulcers apparently brought to an end the long-held view that peptic ulceration was caused predominantly by stress. However, recent studies suggest that stress can cause peptic ulceration in the absence of Helicobacter pylori. Predictably, the aetiological pendulum of gastric and duodenal ulceration has swung from ‘all stress’ to ‘all bacteria’ followed by a sober realisation that both factors alone or together may play a role. This raises the question as to whether stress and Helicobacter pylori interact, and if so how?

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Why is it important?

All three controversies are of clinical significance, pose fundamental questions about stress mechanisms and offer important areas for future research. Further studies on the three themes listed above suggest that: (i) in PTSD changes in the autonomic nervous system provide a more robust biological marker than cortisol levels; (ii) the hippocampus shows significant plasticity in major depression as well as in physiological states (e.g. increases in scatter-hoarding animals and London Taxi drivers); (iii) In about 30% - 40% of people with gastroduodenal ulcers psychogenic stress rather than Helicobacter pylori infection is the cause.

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