173 research outputs found

    Neuropsychology of trauma-exposure: emotional learning, stress responsivity and the glucocorticoid receptor

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    In the present dissertation the aim was to identify correlates of trauma-exposure in persons who developed symptoms of a posttraumatic stress disorder and in those who were trauma-exposed but do not suffer from PTSD as well as in persons without trauma-exposure. In the first part of the dissertation, mechanisms of context conditioning and the release of glucocorticoids by the Hypothalamus-pituitary-adrenocortical axis were investigated in trauma-exposed and non-exposed persons. In the second part of the dissertation, receptor sensitivity was investigated by comparing the glucocorticoid receptor expression on lymphocyte subpopulations in PTSD patients, trauma-exposed and non-traumatized controls. In addition, potential factors predicting the number of glucocorticoid receptors were identified

    Posttraumatic Stress Disorder: A Theoretical Model of the Hyperarousal Subtype

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    Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framewor

    Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression

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    The neural networks that putatively modulate aspects of normal emotional behavior have been implicated in the pathophysiology of mood disorders by converging evidence from neuroimaging, neuropathological and lesion analysis studies. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular evidence from lesion analysis studies suggests that the MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The MPFC is part of a larger “default system” of cortical areas that include the dorsal PFC, mid- and posterior cingulate cortex, anterior temporal cortex, and entorhinal and parahippocampal cortex, which has been implicated in self-referential functions. Dysfunction within and between structures in this circuit may induce disturbances in emotional behavior and other cognitive aspects of depressive syndromes in humans. Further, because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders. This paper discusses these systems together with the neurochemical systems that impinge on them and form the basis for most pharmacological therapies

    Relationship between respiratory, endocrine, and cognitive-emotional factors in response to a pharmacological panicogen

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    Background : The cholecystokinin agonist pentagastrin has been used to study panic attacks in the laboratory and to investigate hypothalamic–pituitary–adrenal axis activity. Its mechanism of panicogenesis remains unclear. Data from other models suggest that respiratory stimulation itself may induce panic, but pentagastrin's effects on respiration are not well established. Data from another model also suggest links between respiratory and HPA axis reactivity and cognitive modulation of both. To further explore these phenomena, we added respiratory measures to a study of cognitive modulation of HPA and anxiety responses to pentagastrin. Methods : Healthy subjects received pentagastrin and placebo injections, with measurement of cortisol and subjective responses, on two different laboratory visits. They were randomly assigned to receive standard instructions or one of two versions of previously studied cognitive interventions (to either facilitate coping or increase sense of control), given before each visit. Capnograph measures of heart rate (HR), respiratory rate (RR), and end-tidal pCO 2 were obtained on 24 subjects. Results : Relative to placebo, pentagastrin induced a significant decline in pCO 2 with no change in RR. Cortisol and HR increased, as expected. Cognitive intervention reduced the hyperventilatory response to pentagastrin. Conclusions : Pentagastrin stimulates respiration, likely via increases in tidal volume. Respiratory stimulation could play a role in its panicogenic potency, though perhaps indirectly. As with HPA axis responses, higher-level brain processes may be capable of modulating pentagastrin-induced hyperventilation. This model may be useful for further study of cortical/cognitive control of interacting emotional, respiratory, and neuroendocrine sensitivities, with potential relevance to panic pathophysiology. Depression and Anxiety, 2010.  © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78296/1/20725_ftp.pd

    The Neurosteroids Allopregnanolone and DHEA Modulate Neurocircuits implicated in Emotion Regulation and Posttraumatic Stress Disorder.

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    The neurosteroids dehydroepiandrosterone (DHEA) and allopregnanolone are integral components of the stress response and exert positive modulatory effects on emotion in human and animal studies. Though these antidepressant and anxiolytic effects have been well established, little research to date has examined their neural correlates. In particular, brain imaging techniques have not yet been used to assess the impact of neurosteroid administration on emotion regulation neurocircuitry. In a parallel line of research, growing evidence supports that intrinsic connectivity networks involved in emotion regulation are disrupted in anxiety disorders. However, the impact of neurosteroids on these intrinsic connectivity networks is unknown. Thus, the current studies aim to describe the impact of neurosteroids on emotion regulation neurocircuits and amygdala intrinsic connectivity by measuring the effects of neurosteroid administration on the Shifted-Attention Emotional Appraisal Task and on resting-state fMRI. We demonstrate that during emotion regulation, DHEA and allopregnanolone reduce activity in regions associated with generation of negative emotion and enhance activity in regions linked to regulatory processes. Further, we demonstrate that these neurosteroids modulate amygdala intrinsic connectivity in ways that run counter to aberrations observed in posttraumatic stress disorder. Thus, our results provide initial neuroimaging evidence that DHEA and allopregnanolone may be useful as pharmacological interventions for anxiety disorders and invite further investigation into the brain basis of neurosteroid emotion regulatory effects.PHDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/100064/1/rekaufma_1.pd

    The neuroscience of fear and anxiety: a primer for clinicians

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    Over the last few decades, research in affective neuroscience has led to considerable insights into the biology of fear and anxiety. For those in the practice of psychotherapy, these advances hold the potential for explaining the evolutionary utility of these emotions and targeting psychotherapeutic interventions to neurobiological correlates when these emotions go awry. The conversation of neuroscience, however, has yet to find a comfortable place in the therapy room. Translational and conceptual disparities owing to the historical split between psychology and neuroscience, continue to present challenges to their integration. The present study seeks to reframe clinicians’ understanding of the biological underpinnings of fear and anxiety from a static model governed by genetic predisposition and chemical imbalances, to a dynamic process that focuses on the environment’s impact on biology. The following topics will be addressed: What are the neurobiological processes of fear and anxiety? Why did they evolve to serve adaptive purposes? What are the conditions in which disorders of anxiety and fear emerge? To answer these questions, this review of the literature discusses how fear and anxiety centers in the mammalian brain were shaped through phylogenetic development to respond to physical and interpersonal threat, and how fear and anxiety continue to benefit in learning and defensive action. An updated view of the neuroscience of fear and anxiety is also reviewed detailing the functions of known structures and involved pathways. Risk factors for panic and anxiety disorders, the neurological impacts of failure of coping with fear and anxiety are explored, and the application of psychotherapy are discussed. These findings will be applied towards a concise handbook on the neuroscience of fear and anxiety to provide a narrative of an adaptive model for use in the therapy room
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