Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder

Sah, Renu; Ekhator, Nosa N.; Strawn, Jeffrey R.; Sallee, Floyd R.; Baker, Dewleen G.; Horn, Paul S.; Geracioti, Thomas D.

doi:10.1016/j.biopsych.2009.04.037

Cited by 130 publications

(80 citation statements)

References 20 publications

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“…Both animal and human studies suggest that NPY is downregulated in response to traumatic stress (Morgan, Rasmusson, Winters, Hauger, & Hazlett, 2003), though perhaps less so among the stress resilient. This is consistent with findings of substantially decreased plasma (Rasmusson et al, 2000) and CSF (Sah et al, 2009) NPY levels in male veterans with PTSD, as well as blunted NPY responses to sympathetic system activation that correlate negatively with norepinephrine and blood pressure responses (Rasmusson et al, 2000). In addition, among male veterans with a lifetime history of PTSD, lower NPY levels are associated with less improvement in PTSD symptoms over time (Yehuda, Brand, & Yank, 2005).…”

Section: Neurobiological Risk Factorssupporting

confidence: 78%

Posttraumatic Stress Disorder

Bovin¹,

Wells²,

Rasmusson³

et al. 2014

The Wiley Handbook of Anxiety Disorders

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Section: Neurobiological Risk Factorssupporting

confidence: 78%

Posttraumatic Stress Disorder

Bovin¹,

Wells²,

Rasmusson³

et al. 2014

The Wiley Handbook of Anxiety Disorders

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“…Compared to healthy controls, PTSD patients displayed lower NPY levels in the plasma (Rasmusson et al, 2010;Yehuda et al, 2006) and CSF (Sah et al, 2009(Sah et al, , 2014 already under baseline conditions. Whether these changes are A C C E P T E D M A N U S C R I P T…”

Section: Response Of Npy Plasma Levels To Sympathetic Stimulation Stmentioning

confidence: 91%

The role of Neuropeptide Y in fear conditioning and extinction

et al. 2016

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While anxiety disorders are the brain disorders with the highest prevalence and constitute a major burden for society, a considerable number of affected people are still treated insufficiently. Thus, in an attempt to identify potential new anxiolytic drug targets, neuropeptides have gained considerable attention in recent years. Compared to classical neurotransmitters they often have a regionally restricted distribution and may bind to several distinct receptor subtypes. Neuropeptide Y (NPY) is a highly conserved neuropeptide that is specifically concentrated in limbic brain areas and signals via at least 5 different G-protein-coupled receptors. It is involved in a variety of physiological processes including the modulation of emotional-affective behaviors. An anxiolytic and stress-reducing property of NPY is supported by many preclinical studies. Whether NPY may also interact with processing of learned fear and fear extinction is comparatively unknown. However, this has considerable relevance since pathological, inappropriate and generalized fear expression and impaired fear extinction are hallmarks of human post-traumatic stress disorder and a major reason for its treatment-resistance. Recent evidence from different laboratories emphasizes a fear-reducing role of NPY, predominantly mediated by exogenous NPY acting on Y1 receptors. Since a reduction of fear expression was also observed in Y1 receptor knockout mice, other Y receptors may be equally important. By acting on Y2 receptors, NPY promotes fear extinction and generates a long-term suppression of fear, two important preconditions that could support cognitive behavioral therapies in human patients. A similar effect has been demonstrated for the closely related pancreatic polypeptide (PP) when acting on Y4 receptors. Preliminary evidence suggests that NPY modulates fear in particular by activation of Y1 and Y2 receptors in the basolateral and central amygdala, respectively. In the basolateral amygdala, NPY signaling activates inhibitory G protein-coupled inwardly-rectifying potassium channels or suppresses hyperpolarization-induced I(h) currents in a Y1 receptor-dependent fashion, favoring a general suppression of neuronal activity. A more complex situation has been described for the central extended amygdala, where NPY reduces the frequency of inhibitory and excitatory postsynaptic currents. In particular the inhibition of long-range central amygdala output neurons may result in a Y2 receptor-dependent suppression of fear. The role of NPY in processes of learned fear and fear extinction is, however, only beginning to emerge, and multiple questions regarding the relevance of endogenous NPY and different receptor subtypes remain elusive. Y2 receptors may be of particular interest for future studies, since they are the most prominent Y receptor subtype in the human brain and thus among the most promising therapeutic drug targets when translating preclinical evidence to potential new therapies for human anxiety disorders.

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“…44 Both cerebrospinal fluid and plasma NPY levels have been found to be low in male combat Veterans with PTSD. 45,46 Low plasma NPY levels, in turn, have been associated with increased noradrenergic system reactivity, as well as with increased PTSD symptoms and systolic blood pressure responses during sympathetic system activation, 45 whereas higher plasma NPY has been associated with greater in improvement in PTSD symptoms over time. 47 Chronic severe stress has been shown to reduce baseline plasma NPY levels in rodents.…”

Section: Npy As a Modulator Of Pain And The Effects Of Stressmentioning

confidence: 96%

The Shared Neuroanatomy and Neurobiology of Comorbid Chronic Pain and PTSD

Scioli-Salter¹,

Forman

Otis

et al. 2015

The Clinical Journal of Pain

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Chronic pain and posttraumatic stress disorder (PTSD) are disabling conditions that affect biological, psychological, and social domains of functioning. Clinical research demonstrates that patients who are affected by chronic pain and PTSD in combination experience greater pain, affective distress, and disability than patients with either condition alone. Additional research is needed to delineate the interrelated pathophysiology of chronic pain and PTSD, with the goal of facilitating more effective therapies to treat both conditions more effectively; current treatment strategies for chronic pain associated with PTSD have limited efficacy and place a heavy burden on patients, who must visit various specialists to manage these conditions separately. This article focuses on neurobiological factors that may contribute to the coprevalence and synergistic interactions of chronic pain and PTSD. First, we outline how circuits that mediate emotional distress and physiological threat, including pain, converge. Secondly, we discuss specific neurobiological mediators and modulators of these circuits that may contribute to chronic pain and PTSD symptoms. For example, neuropeptide Y, and the neuroactive steroids allopregnanolone and pregnanolone (together termed ALLO) have antistress and antinociceptive properties. Reduced levels of neuropeptide Y and ALLO have been implicated in the pathophysiology of both chronic pain and PTSD. The potential contribution of opioid and cannabinoid system factors also will be discussed. Finally, we address potential novel methods to restore the normal function of these systems. Such novel perspectives regarding disease and disease management are vital to the pursuit of relief for the many individuals who struggle with these disabling conditions.

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Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder

Cited by 130 publications

References 20 publications

Posttraumatic Stress Disorder

Posttraumatic Stress Disorder

The role of Neuropeptide Y in fear conditioning and extinction

The Shared Neuroanatomy and Neurobiology of Comorbid Chronic Pain and PTSD

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