The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder

Abstract

Research on the neurobiology of the stress response in animals has led to successful new treatments for Post-Traumatic Stress Disorder (PTSD) in humans. Basic research has found that high levels of catecholamine release during stress rapidly impair the top-down cognitive functions of the prefrontal cortex (PFC), while strengthening the emotional and habitual responses of the amygdala and basal ganglia. Chronic stress exposure leads to dendritic atrophy in PFC, dendritic extension in the amygdala, and strengthening of the noradrenergic (NE) system. High levels of NE release during stress engage low affinity alpha-1 adrenoceptors, (and likely beta-1 adrenoceptors), which rapidly reduce the firing of PFC neurons, but strengthen amygdala function. In contrast, moderate levels of NE release during nonstress conditions engage higher affinity alpha-2A receptors, which strengthen PFC, weaken amygdala, and regulate NE cell firing. Thus, either alpha-1 receptor blockade or alpha-2A receptor stimulation can protect PFC function during stress. Patients with PTSD have signs of PFC dysfunction. Clinical studies have found that blocking alpha-1 receptors with prazosin, or stimulating alpha-2A receptors with guanfacine or clonidine can be useful in reducing the symptoms of PTSD. Placebo-controlled trials have shown that prazosin is helpful in veterans, active duty soldiers and civilians with PTSD, including improvement of PFC symptoms such as impaired concentration and impulse control. Open label studies suggest that guanfacine may be especially helpful in treating children and adolescents who have experienced trauma. Thus, understanding the neurobiology of the stress response has begun to help patients with stress disorders.

Assessment of mental stress effects on prefrontal cortical activities using canonical correlation analysis: an fNIRS-EEG study

“…Interestingly, the reduction in the oxygenated hemoglobin concentration at the PFC subregions in our study is consistent with previous fMRI human and animals stress studies [4,[47][48][49]. Furthermore, similar reduction in the oxygenated hemoglobin at the DLPFC was observed in subjects with post-traumatic stress disorder [50,51]. The reduction in cortical activities has also been reported at the ventromedial PFC while inhibiting fear response [52].…”

Stress weakens prefrontal networks: molecular insults to higher cognition

“…For example, increases in REDD1 have been found in the dlPFC of depressed patients, which is similar to what is seen in the stressed rat PFC 74 . Notably, there is evidence that treatment strategies arising from basic research are effective in stress-related disorders 111 . The α1-AR antagonist prazosin is now in widespread use to treat PTSD in veterans, active duty soldiers and civilians (reviewed in ref.…”

Exposure to and recall of violence reduce short-term memory and cognitive control

“…Support for these hypotheses comes from extensive neurobiological and clinical research documenting the effects of traumatizing stress (29,30) and PTSD (4-6) on the neuroendocrine network underlying cognitive control. In particular, the release of catecholamine induced by acute stressors impairs cognitive control of the prefrontal cortex (PFC) (31), while at the same time enhancing the emotional and habitual responses of the amygdala, which also regulates fear conditioning, and the tonic firing of the noradrenergic locus coeruleus (32,33). The dopamine system is also involved, because acute stress triggers enhanced dopamine efflux in the medial PFC.…”