Plasma neuropeptide Y in anxiety disorders: findings in panic disorder and social phobia

doi:10.1016/0165-1781(95)02776-9

Psychiatry Research

Volume 59, Issue 3, 31 January 1996, Pages 183-188

https://doi.org/10.1016/0165-1781(95)02776-9 Get rights and content

Abstract

The demonstration in preclinical studies that centrally administered neuropeptide Y (NPY) has anxiolytic effects had led to speculation that NPY may play a role in human anxiety disorders. We therefore decided to study plasma NPY levels in 22 patients with DSm-III-R anxiety disorders (11 with panic disorder and 11 with social phobia, generalized type) and 12 never psychiatrically ill comparison subjects. Under resting conditions, plasma NPY levels did not differ among the three diagnostic groups. Following hand immersion in ice water, plasma NE levels — but not NPY levels — increased immediately, but there were no significant differential diagnostic effects. These results are convergent with prior reports of normal sympathetic nerve activity in patients with anxiety disorders.

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Targeting the neuropeptide Y system in stress-related psychiatric disorders
2015, Neurobiology of Stress
Citation Excerpt :
Elevated plasma NPY was detected in a study of individuals with panic disorder, in which the authors suggest that an increase in NPY may be compensatory to buffer enhanced sympathetic activation in this disorder (Boulenger et al., 1996). Other studies have not detected differences in NPY levels between healthy controls and persons with obsessive compulsive, social anxiety, or panic disorders (Stein et al., 1996; Altemus et al., 1999), or have failed to identify genetic associations between NPY and anxiety disorders (Lindberg et al., 2006). Clinical investigations have revealed that the plasma and CSF of depressed individuals contain decreased concentrations of NPY compared to healthy controls (Hashimoto et al., 1996; Heilig et al., 2004; Hou et al., 2006; Nilsson et al., 1996; Widerlov et al., 1988).
Repeated, extreme, or traumatic stressors can elicit pathological effects leading to many negative physical and psychological outcomes. Stressors can precipitate the onset of psychiatric diseases, or exacerbate pre-existing disorders including various anxiety and mood disorders. As stressors can negatively impact human psychiatric health, it is essential to identify neurochemicals that may confer protection from the negative sequelae of repeated or extreme stress exposure. Elucidating the neurobiological underpinnings of stress resilience will enhance our ability to promote resilience to, or recovery from, stress-related psychiatric disease. Herein, we will review the evidence for neuropeptide Y as an endogenous mediator of resilience and its potential relevance for the treatment of stress-related psychiatric diseases.
Neuroregulatory peptides of central nervous system origin: From laboratory to clinic
2009, Hormones, Brain and Behavior Online
Neuropeptides synthesized in the central nervous system are potent and specific neuromodulators with the capacity to diffuse or travel to relatively distant sites within the brain. These short chains of amino acids retain potency in small concentrations – a property that permits them to entrain mass-sustained functions, such as regulation of mood, appetite, anxiety level, and libido. In addition, many neuropeptides have been pathophysiologically implicated in neuropsychiatric diseases. This chapter reviews the major neuropeptides of brain origin whose clinical relevance is established (growth hormone-releasing hormone, gonadotropin-releasing hormone, somatostatin, corticotropin-releasing hormone, thyrotropin-releasing hormone, vasopressin, oxytocin, the opioids, the melanocortins, and cholecystokinin) and a few that are of emerging or expanding clinical neuropsychiatric interest (substance P, neuropeptide Y, and orexins). Particular attention is paid to recent findings from behavioral studies, clinical physiology, and pharmacology which are furthering our understanding of the pathophysiology of numerous psychiatric and neurological disorders. An overview of the clinical approach to each neuropeptide is provided.
Chapter 4.1 Peptide receptor ligands to treat anxiety disorders
2008, Handbook of Behavioral Neuroscience
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Interestingly, NPY acts as a co-transmitter in the sympathetic nervous system and may be released from cardiac sympathetic nerve endings during a panic attack (Esler et al., 2004). However, unaltered plasma levels of NPY were reported in panic, as well as in GAD and social phobia in another study (Stein et al., 1996). Thus, clinical studies investigating changes in the NPY system in anxiety disorders must be considered inconclusive at the moment.
Neuropeptides seem to play critical roles in the modulation of anxiety and in the pathophysiology of anxiety disorders. Specific, small-molecule, non-peptide receptor ligands targeting these peptide systems have been developed and are at various stages of the drug development process, such as antagonists acting at the corticotropin-releasing factor, cholecystokinin, neurokinin, neuropeptide Y, vasopressin, melanocortin, angiotensin, galanin, bombesin, or melanin-stimulating hormone receptors. Furthermore, oxytocin, δ-opiate, and orphanin FQ/nociceptin receptor agonists have been developed and shown to have anxiolytic-like properties in preclinical models. Some of these compounds are currently in clinical testing. This review provides an update of the preclinical and clinical status of the field. Although a number of obstacles need to be overcome in this area, it can be concluded that compounds acting at neuropeptide targets represents a highly promising approach for the development of the next generation drugs to treat anxiety disorders.
Sympathetic reactivity in agoraphobic patients with and without personality disorders
2003, Journal of Psychosomatic Research
Objective: To compare sympathetic activity in agoraphobic patients with and without personality disorders before and after 11 weeks inpatient treatment. Methods: Agoraphobic patients (n=38), 84% with panic disorder and 47% with personality disorders underwent cold pressure test (CPT), mental stress test (MST), and a specific anxiety test (SAT). Psychological assessments were done by the Bodily Sensations Questionnaire (BSQ), the Agoraphobic Cognitions Questionnaire (ACQ), Spielberger STAI-1 and -2, and a Stress Test Anxiety (STA) questionnaire. Sympathetic activity was measured by blood pressure, heart rate, epinephrine, and norepinephrine. Results: The sympathetic activity did not differ significantly between patient groups, and the reactivity to stress was very low. The sympathetic reactivity remained unchanged after treatment, whereas psychiatric symptoms decreased. Correlations between sympathetic activity and psychological distress were not significant. Conclusion: Interpretation of bodily signals seems to be more important than the actual sympathetic activity in agoraphobic patients.
Molecular targets in the treatment of anxiety
2002, Biological Psychiatry
Citation Excerpt :
There have been conflicting reports regarding NPY in anxiety disorder subjects. Stein and colleagues found no difference in NPY levels in patients with panic disorder and social phobia, versus healthy volunteers, either at baseline or after stress exposure (Stein et al 1996). Boulenger and colleagues, however, found that NPY-like immunoreactivity was elevated in 12 patients with panic disorder compared with healthy control subjects (Boulenger et al 1996).
Although the cathecholamine systems have long been the focus of drug therapy in anxiety and depression, the development of novel drugs specifically aimed at new targets within these traditional neurotransmitter systems and at targets outside of these systems is now propelling the field of drug development in anxiety. A greater understanding of regional brain networks implicated in stress, anxiety, and anxious behaviors has provided localized targets for anxiolytics. Within the serotonin and norepinephrine systems, increased understanding of postsynaptic receptor regulation with chronic treatment and cross-system effects of drug therapy have been critical in furthering our understanding of effective pharmacological interventions. Receptors within the glutamate, γ-aminobutyric acid, and neuropeptide systems provide a rich diversity of drug targets, both in localization and function. While acknowledging significant clinical and biological differences between the various anxiety disorders, an important aspect of modern neurobiological research is to look for similarities among these disorders, given that they are highly comorbid with each other and often respond to the same spectrum of treatments. Here we review current views on both traditional and new molecular targets in the treatment of anxiety, realizing that the ultimate challenge in effective anxiolytic drug development may be achieving specificity in brain regions important in generating and sustaining anxiety.
Neurobiology of generalized anxiety disorder
2001, Psychiatric Clinics of North America
Citation Excerpt :
For example, one study119 found that the lowest CSF concentrations of NPY in depressed patients were among those who had the most severe anxiety; another study13 showed higher plasma NPY-like immunoreactivity in patients with panic disorder compared with healthy controls. Other investigators,107 however, did not find significant differences between controls and subjects with panic disorder or social phobia at basal and during stress stimulation. The reasons for these discrepancies are unknown but underscore the need for additional study of NPY in anxiety disorders in general.
Generalized anxiety disorder (GAD) is a relatively new diagnostic entity first defined as a distinct category in the DSM-III.⁷ Two major epidemiologic studies, the National Survey of Mental Health and Well-Being² and the National Comorbidity Survey¹²⁰ have shown an incidence of 3.6% and 3.1% per year, respectively. Based on the National Comorbidity Survey data in the United States alone, more than 9 million people are afflicted with GAD at some point during their lifetimes. Also, GAD is one of the most common psychiatric disorders seen by primary care physicians.
GAD was once considered by many clinicians to be a relatively mild condition, but new scientific data have challenged the perception that GAD is mild and minimally disabling. GAD has been found to be associated with various adverse social consequences, such as being more prevalent in lower socioeconomic groups, being poorly paid, being on disability, and experiencing more marital instability and divorce than the general population.¹² GAD has a lifetime comorbidity rate of 62% with major depressive disorder (MDD), 39.5% with dysthymia, 37.6% with alcoholism, and 34.4% with social phobia. Comorbid GAD seems to be associated with an even greater level of functional impairment than GAD alone. Follow-up studies have shown a substantial impairment and even poorer outcome among people with GAD than among those with panic disorder.121, 125 Thus, it is evident that GAD is neither an infrequent nor mild condition but an important public health problem that merits additional research on treatment and mechanism of illness.
The diagnostic concept of GAD, however, is somewhat controversial. Some investigators have suggested that GAD is a residual or prodromal phase of MDD,92, 98 or a “forme fruste” of MDD.⁶¹ Other investigators have observed that it is attributable to other anxiety disorders, such as social phobia⁸¹ or panic disorder.¹¹⁴ Still others have conceptualized GAD as a dimension of personality function, a generalized anxious temperament that, when pronounced, constitutes psychopathology,⁴ whereas other investigators have conceptualized GAD as a part of a general neurotic syndrome.¹¹³ A well-designed 5-year longitudinal follow-up study, however, showed significant diagnostic stability for GAD, supporting the reliability of the diagnosis.¹²¹ Thus additional research must be carried out to clarify the diagnostic boundaries of GAD so that meaningful conclusions may be drawn from research studies.
This article provides a concise picture of preclinical and clinical research pertinent to the neurobiology of GAD. Research on functional neuroanatomy and fear circuitry; animal models relevant to GAD; research on the genetics of GAD; and neurochemistry, neurophysiology, and functional imaging studies relevant to GAD are discussed. Finally, a crucial discussion of several biological models of GAD is presented, and paths for future research are suggested.

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ArticlePlasma neuropeptide Y in anxiety disorders: findings in panic disorder and social phobia

Abstract

Psychiatry Res

Reg Pept

Life Sci

Life Sci

Peptides

Neuroscience

Life Sci

Biol Psychiatry

J Affect Disord

Peptides

Psychosomatics

Neuropeptide Y radioimmunoassay: characterization and application

Clin Exp Pharmacol Physiol

An inventory for measuring depression

Arch Gen Psychiatry

Article
Plasma neuropeptide Y in anxiety disorders: findings in panic disorder and social phobia