Arnsten AFT. Stress signaling pathways that impair prefrontal cortex structure and function. Nat Res Neurosci 10: 410-422

Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nature Reviews Neuroscience (Impact Factor: 31.43). 07/2009; 10(6):410-22. DOI: 10.1038/nrn2648
Source: PubMed


The prefrontal cortex (PFC) - the most evolved brain region - subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness.

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    • "On the one hand, neuroticism and related traits (e.g., anxiety) seem to generally diminish processing efficiency through disadvantageous arousal level as well as emotional and cognitive resource-demanding interferences , such as worrisome thoughts or negative emotions. On the other hand, in accordance with many studies showing the effect of distress on aggravated operations in the prefrontal cortex (for a review, see Arnsten, 2009), neuroticism-related characteristics seem to mainly reduce resources available to control attention by impairing processes in the central executive of WM (e.g., Bishop, 2009; Derakshan & Eysenck, 2009; Eysenck & Calvo, 1992; Eysenck, Derakshan, Santos, & Calvo, 2007; Gray et al., 2005; Schmeichel, Volokhov, & Demaree, 2008; Shackman et al., 2006). These assumptions were confirmed in neuroimaging studies revealing that neuroticism is associated with reduced neuronal efficiency and impoverished recruitment of prefrontal attention control mechanisms during a WM task (Bishop, 2009; Gray et al., 2005). "
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    ABSTRACT: Studies revealing transfer effects of working memory (WM) training on non-trained cognitive performance of children hold promising implications for scholastic learning. However, the results of existing training studies are not consistent and provoke debates about the potential and limitations of cognitive enhancement. To examine the influence of individual differences on training outcomes is a promising approach to find causes for such inconsistencies. In this study, we implemented WM training in an elementary school setting. The aim was to investigate near and far transfer effects on cognitive abilities and academic achievement and to examine the moderating effects of a dispositional and a regulative temperament factor, neuroticism and effortful control. Ninety-nine second graders were randomly assigned to either 20 sessions of computer-based adaptive WM training, computer-based reading training or a no-contact control group. For the WM training group, our analyses reveal near transfer on a visual WM task, far transfer on a vocabulary task as a proxy for crystallized intelligence, and increased academic achievement in reading and math by trend. Considering individual differences in temperament, we found that effortful control predicts larger training mean and gain scores and that there is a moderation effect of both temperament factors on post-training improvement: WM training condition predicted higher post-training gains compared to both control conditions only in children with high effortful control or low neuroticism. Our results suggest that a short but intensive WM training program can enhance cognitive abilities in children, but that sufficient self-regulative abilities and emotional stability are necessary for WM training to be effective.
    Memory & Cognition 10/2015; DOI:10.3758/s13421-015-0548-9 · 1.92 Impact Factor
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    • "• Researchers could develop treatments that target withdrawal symptoms and stress-related pathology, such as stress-induced craving and alcohol seeking, implicated by the alcohol-related neuroadaptations in the PSL circuit. For instance, alpha1-adrenergic antagonists, such as Prazosin, show promise for improving stress-induced deficits and impaired PFC function from chronic stress (for a review, see Arnsten 2009). This drug also reduces alcohol withdrawal symptoms and stress-related alcohol seeking in animals (Kukolja et al. 2011; Walker et al. 2008) and improves stress and alcohol cue– induced craving and alcohol use outcomes in humans (Fox et al. 2012; Simpson et al. 2009). "
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    ABSTRACT: Chronic alcohol-related neuroadaptations in key neural circuits of emotional and cognitive control play a critical role in the development of, and recovery from, alcoholism. Converging evidence in the neurobiological literature indicates that neuroplastic changes in the prefrontal-striatal-limbic circuit, which governs emotion regulation and decisionmaking and controls physiological responses in the autonomic nervous system and hypothalamic-pituitary-adrenal axis system, contribute to chronic alcoholism and also are significant predictors of relapse and recovery. This paper reviews recent evidence on the neuroplasticity associated with alcoholism in humans, including acute and chronic effects, and how these neurobiological adaptations contribute to alcohol recovery, along with the discussion of relevant clinical implications and future research directions.
    Alcohol research : current reviews 09/2015; 37(1):143-152.
    • "The present results are also in line with previous research on psychological stressors. It has been shown that a psychological stressor increases cortisol levels (Dickerson and Kemeny, 2004), impairs prefrontal cortex function (Arnsten, 2009) and increases the sensitivity of the amygdala towards threatening stimuli (van Marle et al., 2009). This could lead to a facilitation of emotion recognition for these stimuli. "
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    ABSTRACT: Chronic or repeated cocaine use has been linked to impairments in social skills. It is not clear whether cocaine is responsible for this impairment or whether other factors, like polydrug use, distort the observed relation. We aimed to investigate this relation by means of a placebo-controlled experimental study. Additionally, associations between stressor-related activity (cortisol, cardiovascular parameters) induced by the biological stressor cocaine, and potential cocaine effects on emotion recognition were studied. Twenty-four healthy recreational cocaine users participated in this placebo-controlled within-subject study. Participants were tested between 1 and 2h after treatment with oral cocaine (300mg) or placebo. Emotion recognition of low and high intensity expressions of basic emotions (fear, anger, disgust, sadness, and happiness) was tested. Findings show that cocaine impaired recognition of negative emotions; this was mediated by the intensity of the presented emotions. When high intensity expressions of Anger and Disgust were shown, performance under influence of cocaine 'normalized' to placebo-like levels while it made identification of Sadness more difficult. The normalization of performance was most notable for participants with the largest cortisol responses in the cocaine condition compared to placebo. It was demonstrated that cocaine impairs recognition of negative emotions, depending on the intensity of emotion expression and cortisol response. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2015; 25. DOI:10.1016/j.euroneuro.2015.08.012 · 4.37 Impact Factor
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