neuropeptide-y and Combat-Disorders

This article reviews the role of neuropeptide Y (NPY) in the pathophysiology of post-traumatic stress disorder (PTSD) and gastrointestinal disorders such as irritable bowel syndrome (IBS) with which PTSD is highly comorbid. NPY is low in the cerebrospinal fluid and plasma of male combat veterans with PTSD and correlates negatively with sympathetic nervous system (SNS) hyperreactivity, PTSD symptoms and time to recovery. NPY regulation has not yet been evaluated in women with PTSD.. NPY levels in bowel tissue are low in IBS with diarrhea (IBS-D) versus IBS with constipation. The density of ghrelin containing cells of the gastric oxyntic mucosa is markedly increased in IBS-D. PTSD-related SNS hyperreactivity may interact with this substrate to increase ghrelin release, which activates receptors in the lumbosacral spinal cord and basolateral amygdala to increase colonic motility and amygdala hyperreactivity, respectively. Loss of function gene polymorphisms in adrenergic α2-autoreceptors and increased corticotropin-releasing hormone, as observed in PTSD, are also thought to contribute to IBS-D.. Knowledge of shared underlying NPY system-related neurobiological factors that contribute to the comorbidity of PTSD and gastrointestinal disorders may help guide research, development and prescription of targeted and more effective individualized therapeutic interventions.

Topics: Combat Disorders; Comorbidity; Constipation; Diarrhea; Female; Gastric Mucosa; Ghrelin; Humans; Irritable Bowel Syndrome; Male; Neuropeptide Y; Stress Disorders, Post-Traumatic; Veterans

War veterans are at increased risk of suicide that may be related to deployment and/or post-deployment stressors and to adjustment-related factors. The aim of this study was to examine whether levels of plasma neuropeptide Y (NPY) might distinguish combat veterans who have made a post-deployment suicide attempt from those who have never made a suicide attempt. We focused on NPY because of prior findings linking NPY with the neurobiology of resilience, stress-related and other disorders, and suicidal behavior. Demographic and clinical parameters of suicide attempters and non-attempters were assessed and plasma NPY was determined by radioimmunoassay. NPY levels were higher among attempters in comparison to non-attempters, controlling for sex and body-mass index. Suicide attempters had higher Scale for Suicidal Ideation (SSI) scores than non-attempters. There was a positive correlation between NPY levels and SSI scores among non-attempters but not among attempters. Likewise, NPY levels positively correlated with Brown-Goodwin Aggression Scale scores among suicide attempters but not among non-attempters. This is the first demonstration of altered plasma NPY levels in association with suicide attempt history and suicidal ideation in veterans. Our findings suggest that clinical differences between combat veterans with or without a history of suicide attempt may have a neurobiological origin.

Topics: Adult; Biomarkers; Combat Disorders; Female; Humans; Male; Middle Aged; Neuropeptide Y; Suicidal Ideation; Suicide, Attempted; Veterans

In order to decrease the risk of developing stress-related disorders after military deployment, biological vulnerability factors should be identified. Neuropeptide Y (NPY) is a peptide neurotransmitter that is associated with modulation of the stress response. Using the data of two longitudinal prospective cohort studies (N = 892 and N = 2427), plasma NPY (pNPY) was assessed as a possible susceptibility biomarker for the development of PTSD symptoms over time. Data collection started prior to deployment and follow-up assessments were completed up to two years after deployment. In pNPY levels, measured before and shortly after deployment, three distinct trajectories were identified. In both cohorts, these trajectories were not related to the level of reported PTSD symptoms over time and neither were pre-deployment pNPY levels. Whereas previous research suggested that high NPY levels might be a marker for resilience, the current findings suggest limited usefulness of peripherally measured NPY in the development of PTSD.

Topics: Adolescent; Adult; Afghan Campaign 2001-; Combat Disorders; Humans; Longitudinal Studies; Male; Middle Aged; Military Personnel; Neuropeptide Y; Prospective Studies; Psychiatric Status Rating Scales; Resilience, Psychological; Stress Disorders, Post-Traumatic; Surveys and Questionnaires; Young Adult

Accruing evidence indicates that neuropeptide Y (NPY), a peptide neurotransmitter, is a resilience-to-stress factor in humans. We previously reported reduced cerebrospinal fluid (CSF) NPY concentrations in combat-related posttraumatic stress disorder (PTSD) subjects as compared with healthy, non-combat-exposed volunteers. Here we report CSF NPY in combat-exposed veterans with and without PTSD. We quantified NPY concentrations in morning CSF from 11 male subjects with PTSD from combat in Iraq and/or Afghanistan and from 14 combat-exposed subjects without PTSD. NPY-like immunoreactivity (NPY-LI) was measured by EIA. The relationship between CSF NPY and clinical symptoms, as measured by the Clinician-Administered PTSD Scale (CAPS) and Beck Depression Inventory (BDI), was assessed, as was the relationship between combat exposure scale (CES) scores and CSF NPY. As compared with the combat-exposed comparison subjects without PTSD, individuals with PTSD had significantly lower concentrations of CSF NPY [mean CSF NPY was 258. 6 ± 21.64 pg/mL in the combat trauma-no PTSD group but only 180.5 ± 12.62 pg/mL in PTSD patients (p=0.008)]. After adjusting for CES and BDI scores the two groups were still significantly different with respect to NPY. Importantly, CSF NPY was negatively correlated with composite CAPS score and intrusive (re-experiencing) subscale scores, but did not significantly correlate with CES or BDI scores. Our current findings further suggest that NPY may regulate the manifestation of PTSD symptomatology, and extend previous observations of low CSF NPY concentrations in the disorder. Central nervous system NPY may be a clinically important pharmacotherapeutic target, and/or diagnostic measure, for PTSD.

Topics: Adult; Afghan Campaign 2001-; Case-Control Studies; Combat Disorders; Humans; Iraq War, 2003-2011; Male; Neuropeptide Y; Stress Disorders, Post-Traumatic; Veterans; Young Adult

Neuropeptide Y (NPY), a peptide neurotransmitter that regulates stress and anxiety, has been proposed to be a stress resilience factor in humans. Posttraumatic stress disorder (PTSD) is a stress-related anxiety disorder. We hypothesized that central nervous system NPY is dysregulated in PTSD and sought to redress the absence of central NPY data in the disorder.. We determined morning NPY concentrations in cerebrospinal fluid (CSF) from 10 male subjects with chronic combat-related PTSD and from 13 healthy men. Neuropeptide Y-like immunoreactivity was measured by enzyme immunoassay (EIA).. As compared with the normal comparison subjects, PTSD patients had significantly lower concentrations of CSF neuropeptide Y (mean CSF NPY was 360.0 +/- 17.7 pg/mL in control subjects but only 233.6 +/- 28.7 pg/mL in PTSD patients [p = .0008]). Adjustments for age and body mass index (BMI) still revealed a highly significant reduction in CSF NPY in the PTSD group (p = .003).. Men with combat-related PTSD have low CSF concentrations of the putative resiliency hormone NPY, possibly related to the disorder or to extreme stress exposure per se.

Topics: Adult; Combat Disorders; Hospitals, Veterans; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neuropeptide Y

Risk and resilience factors presumably explain the individual differences in the response to adversity. However, little is known about how such factors are related. Risk and protective factors may reflect a quantitative difference along a single dimension (e.g., low IQ might be associated with risk and high IQ with resilience); however, they may also refer to orthogonal constructs that interact and/or moderate stress effects to increase or diminish the probability of developing trauma-related psychopathology (e.g., good coping could offset low IQ). The authors illustrate experimental strategies for distinguishing between these possibilities for any putative measure relating to symptom development, using a database that includes published and unpublished psychological and biological variables from a relatively homogenous cohort of exposed and nonexposed veterans.

Topics: Adaptation, Psychological; Aged; Aged, 80 and over; Combat Disorders; Dehydroepiandrosterone; Hippocampus; Humans; Male; Middle Aged; Neuropeptide Y; Prognosis; Psychopathology; Receptors, Glucocorticoid; Risk Factors; Stress Disorders, Post-Traumatic

Exposure to uncontrollable stress reduces baseline plasma neuropeptide-Y levels in animals. We previously reported that baseline plasma neuropeptide-Y levels, as well as neuropeptide-Y responses to yohimbine, were lower in combat veterans with posttraumatic stress disorder, but we were unable to determine whether this was attributable to posttraumatic stress disorder or trauma exposure. The current report addresses this issue.. A) Baseline plasma neuropeptide-Y levels were measured in 8 healthy combat veterans compared to 18 combat veterans with posttraumatic stress disorder and 8 healthy nontraumatized subjects; and B) Baseline plasma neuropeptide-Y levels, trauma exposure, and posttraumatic stress disorder symptoms were assessed in 41 active military personnel.. Plasma neuropeptide-Y was negatively associated with trauma exposure but not posttraumatic stress disorder symptoms in active duty personnel. Baseline neuropeptide-Y was reduced in combat veterans with and without posttraumatic stress disorder.. Trauma exposure rather than posttraumatic stress disorder is associated with reduced baseline plasma neuropeptide-Y levels. Future studies must determine if neuropeptide-Y reactivity differentiates trauma-exposed individuals with and without posttraumatic stress disorder.

Topics: Adult; Analysis of Variance; Combat Disorders; Humans; Male; Neuropeptide Y; Personality Inventory; Placebos; Psychiatric Status Rating Scales; Stress Disorders, Post-Traumatic; Veterans; Wounds and Injuries; Yohimbine