Stress, time and the brain

Microphone in depression congress
Stressful life events can be major risk factors for the development of neuropsychiatric disorders – but what is stress and what exactly does it do to the brain? Scientists are exploring the profound and divergent impact of stress on cognition, emotion and mental health. We report from a symposium at CINP 2016 in Seoul, Korea, where global experts shared their research insights.

Acute stress, chronic stress and the stress neuromatrix.  In the opening lecture of a CINP 2016 entitled  “Stress, time and the brain. A dynamic role in neuropsychiatric pathophysiology and treatment”  Dr Nuno Sousa of the Life and Health Sciences Research Institute, School of Health Sciences, University of Minho in Portugal, explained how the brain can shift back and forth from a healthy to a stressed pattern.

The stress neuromatrix

It is well known that a degree of stress can be a positive and motivating force, essential to survival and inevitable and unavoidable at times. However acute or chronic stress and a shift towards stressed states can lead to instability. Dr Nuno Sousa has recently published a seminal paper on the dynamics of the stress neuromatrix (see References and Further Reading), and shared his views with the CINP symposium audience. He said that new models are needed when thinking about stress and the independent yet inter-related effects of acute and chronic stress.

From simple threat to pathological threat

Dr Sousa said that faced with chronic stress exposure, there is an activation of many brain regions outside of those involved with dealing normal stressor encountered by healthy subjects. Furthermore, there may be susceptibilities that affect the dynamics of the chronic brain stress construct. The stage of chronic stress, perceptions of stress, and the salience ascribed to a stressor, modify emotional and hedonic constructs that incorporate threat and value assessment and memory of stressful experiences. There may then be an ‘altered mode’ that permits acute stressors to turn from simple threats to pathological constructs.

Gender stresses

Professor Zhen Yan of the Department of Physiology and Biophysics at The State University of New York at Buffalo, USA had some insights to add.  She reminded delegates of the well-known role of glucocorticoids in stress pathways and stress pathology.  She described basic research highlighting the importance of normal glucocorticoid receptor activation in the facilitation of working memory which has to balanced against the part that glucocorticoids play in stress reactions. She noted that males and females show different cognitive and emotional responses to repeated stress, highlighting that oestrogen can play a part in preventing the detrimental effects of repeated stress on glutaminergic transmission and cognition.

Stress weakens excitatory transmission

Turning to the impact of stress on brain neurotransmission, Professor Scott Thompson, Professor and Chair of the Department of at the University of Maryland School of Medicine in the USA said that chronic stress leads to a weakening of excitatory synaptic transmission within and between multiple brain regions. This results in potentially depressive-like behavioural changes, reflected in decreased dopamine release from the ventral tegmental area, which lowers the value of rewarding stimuli and promotes anhedonia.

Professor Thompson described studies in animal models that show there are changes in glutamatergic signaling that may be amenable to modifications by antidepressant therapies, supporting an excitatory synapse hypothesis model in which depressive-like behaviour is caused by dysfunctional cortico-mesolimbic circuitry.

Some more vulnerable

Stress, it seems, can be very damaging

The final presenter in the symposium was Professor Maurizio Popoli of the Center of Neuropharmacology, at the University of Milan, Italy. He described how vulnerable individuals faced with repeated stress or even single stressful events can sustain and experience alteration in brain function. Research involving brain imaging suggests there may be volumetric reduction and remodelling of the neuroarchitecture in limbic and cortical brain regions in depressed subjects. He described data from animal models which suggest that chronic stress reduces synaptic spines and causes atrophy and maladaptive remodelling changes implicated in a chain of events leading to development of psychopathology. He also said that basic scientific research suggests that even a single exposure to stress can exert complex and remarkable effects on the architecture of the prefrontal cortex that are rapid and sustained.

Stress, it seems, can be very damaging.

References
  1. Sousa N. The dynamics of the stress neuromatrix. Mol Psychiatry 2016;21:302-12.
  2. Wei J, Yuen EY, Liu W, et al. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Mol Psychiatry 2014;19:588-98.
  3. Popoli M, Yan Z, McEwen BS, Sanacora G. The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 2012;13:22-37.
  4. Musazzi L, Treccani G, Popoli M. Functional and structural remodeling of glutamate synapses in prefrontal and frontal cortex induced by behavioral stress. Front Psychiatry 2015;6:60.
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