neuropeptide-y and Sleep-Wake-Disorders

The need for addressing posttraumatic stress disorder (PTSD) among combat veterans returning from Afghanistan and Iraq is a growing public health concern. Current PTSD management addresses psychiatric parameters of this condition. However, PTSD is not simply a psychiatric disorder. Traumatic stress increases the risk for inflammation-related somatic diseases and early mortality. The metabolic syndrome reflects the increased health risk associated with combat stress and PTSD. Obesity, dyslipidemia, hypertension, diabetes mellitus, and cardiovascular disease are prevalent among PTSD patients. However, there has been little appreciation for the need to address these somatic PTSD comorbidities. Medical professionals treating this vulnerable population should screen patients for cardiometabolic risk factors and avail themselves of existing preventive diet, exercise, and pharmacologic modalities that will reduce such risk factors and improve overall long-term health outcomes and quality of life. There is the promise that cardiometabolic preventive therapy complementing psychiatric intervention may, in turn, help improve the posttraumatic stress system dysregulation and favorably impact psychiatric and neurologic function. © 2013 S. Karger AG, Basel.

Topics: Arousal; Autonomic Nervous System Diseases; Blood Coagulation Disorders; Coronary Disease; Diabetes Complications; Dyslipidemias; Endoplasmic Reticulum Stress; Health Status; Humans; Inflammation; Insulin Resistance; Mental Healing; Mental Health; Metabolic Syndrome; Mortality, Premature; Neuropeptide Y; Neurosecretory Systems; Neurotransmitter Agents; Obesity; Risk Factors; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Suicide; Weight Gain

The aims of this study were to validate the efficacy of progressive muscle relaxation (PMR) in patients with atopic dermatitis and to evaluate the serological parameters that may serve as objective measures of the efficacy of PMR. A total of 25 patients with atopic dermatitis were randomly assigned to either a PMR group (n = 15) or a control group (n = 10). Serum levels of nerve growth, neuropeptide Y, and Th2 cytokines (IL-4, IL-5, and IL-13) were measured at baseline and after one month. At baseline, only anxiety was positively correlated with pruritus score (state anxiety: R = 0.496, p = 0.014; trait anxiety: R = 0.423, p = 0.04). Serum levels of neuropeptide Y were inversely related to the State-Trait Anxiety Inventory (STAI) (state anxiety: R = -0.475, p = 0.019; trait anxiety: R = -0.418, p = 0.042) and pruritus scores (R = -0.451, p = 0.035). After one month of PMR therapy, the degree of pruritus and loss of sleep was significantly decreased in the PMR group (p < 0.001), but not among controls. State anxiety scores showed significant improvement after treatment only in the PMR group (p = 0.005). There were no significant changes in the serological parameters in either group. Reductions in Eczema Area and Severity Index (EASI) scores were significant, but similar, in both groups. PMR may be a useful adjunctive modality for the management of atopic dermatitis through the reduction of anxiety. No change was found in biological parameters, but it was observed that neuropeptide Y may be related to high levels of anxiety in atopic dermatitis at baseline.

Topics: Adolescent; Adult; Anxiety; Child; Dermatitis, Atopic; Female; Humans; Interleukin-13; Interleukin-4; Interleukin-5; Male; Muscle Relaxation; Nerve Growth Factor; Neuropeptide Y; Pruritus; Relaxation Therapy; Severity of Illness Index; Sleep Wake Disorders; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome; Young Adult

Hyperarousal and sleep disturbances are common, debilitating symptoms of post-traumatic stress disorder (PTSD). PTSD patients also exhibit abnormalities in quantitative electroencephalography (qEEG) power spectra during wake as well as rapid eye movement (REM) and non-REM (NREM) sleep. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for PTSD, provide modest remediation of the hyperarousal symptoms in PTSD patients, but have little to no effect on the sleep-wake architecture deficits. Development of novel therapeutics for these sleep-wake architecture deficits is limited by a lack of relevant animal models. Thus, the present study investigated whether single prolonged stress (SPS), a rodent model of traumatic stress, induces PTSD-like sleep-wake and qEEG spectral power abnormalities that correlate with changes in central serotonin (5-HT) and neuropeptide Y (NPY) signaling in rats. Rats were implanted with telemetric recording devices to continuously measure EEG before and after SPS treatment. A second cohort of rats was used to measure SPS-induced changes in plasma corticosterone, 5-HT utilization, and NPY expression in brain regions that comprise the neural fear circuitry. SPS caused sustained dysregulation of NREM and REM sleep, accompanied by state-dependent alterations in qEEG power spectra indicative of cortical hyperarousal. These changes corresponded with acute induction of the corticosterone receptor co-chaperone FK506-binding protein 51 and delayed reductions in 5-HT utilization and NPY expression in the amygdala. SPS represents a preclinical model of PTSD-related sleep-wake and qEEG disturbances with underlying alterations in neurotransmitter systems known to modulate both sleep-wake architecture and the neural fear circuitry.

Topics: Analysis of Variance; Animals; Brain Waves; Corticosterone; Disease Models, Animal; Electroencephalography; Electromyography; Fourier Analysis; Indoles; Male; Neuropeptide Y; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Serotonin; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Tacrolimus Binding Proteins; Time Factors

Sleep and feeding rhythms are highly coordinated across the circadian cycle, but the brain sites responsible for this coordination are unknown. We examined the role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially hyperphagic, became obese, exhibited sustained disruption of circadian feeding patterns, and had abnormal circadian distribution of sleep-wake patterns. Total amounts of rapid eye movement sleep (REMS) and non-REMS (NREMS) were not altered by NPY-SAP lesions, but a peak amount of REMS was permanently displaced to the dark period, and circadian variation in NREMS was eliminated. The phase reversal of REMS to the dark period by the lesion suggests that REMS timing is independently linked to the function of MBH NPY receptor-expressing neurons and is not dependent on NREMS pattern, which was altered but not phase reversed by the lesion. Sleep-wake patterns were altered in controls by restricting feeding to the light period, but were not altered in NPY-SAP rats by restricting feeding to either the light or dark period, indicating that disturbed sleep-wake patterns in lesioned rats were not secondary to changes in food intake. Sleep abnormalities persisted even after hyperphagia abated during the static phase of the lesion. Results suggest that the MBH is required for the essential task of integrating sleep-wake and feeding rhythms, a function that allows animals to accommodate changeable patterns of food availability. NPY receptor-expressing neurons are key components of this integrative function.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Caloric Restriction; Circadian Rhythm; Corticosterone; Eating; Feeding Behavior; Hyperphagia; In Situ Hybridization; Male; Neurons; Neuropeptide Y; Obesity; Photoperiod; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Saponins; Sleep; Sleep Wake Disorders; Sleep, REM; Time Factors; Wakefulness

Neuropeptide Y (NPY) has neuromodulatory actions on multiple brain functions including endocrine, behavioral, and circadian processes and has been implicated in the pathophysiology of both anxiety and depression. Behavioral studies suggest that NPY is a potent anxiolytic, whereas CRF is anxiogenic, thus it seems that a balance of these two peptides may exert important influences on behavioral state regulation. However, little is known about how the NPY/CRF balance affects general arousal, attention, and/or sleep states. The present study evaluated the effects of CRF alone, and co-administered with NPY, on spontaneous brain activity as well as on auditory processing using electrophysiological measures. Electroencephalographic (EEG) and event-related potentials (ERPs) were obtained in rats following intracerebroventricular administration of CRF (0.5 microgram) and CRF (0.5 microgram)/NPY (5.0 or 15 micrograms). Auditory processing, as assessed by ERPs, was affected most significantly in the frontal cortex where CRF produced increases in the N1 and P3 components of the ERP, and NPY/CRF co-administration produced significant decreases. These data are consistent with a role for CRF in hyperarousal, and further suggest that NPY may be capable of reversing such states. Administration of CRF also produced a significant increase in the time to sleep onset and a decrease in the amount of time spent in non-rapid eye movement (NREM) sleep as quantified by scoring the EEG paper records. Co-administration of NPY with CRF reversed the effects of CRF on sleep duration and sleep onset in a dose-dependent fashion. Spectral analysis revealed that CRF produced quantitative changes in the EEG that were similar to what has previously been reported. CRF-induced increases in fast frequency activity were found to be reversed by co-administration of NPY. Taken together these data suggest that "dysregulation" of sleep and arousal states in depression and anxiety may be consistent with an upset of the balance between hypothalamic neuropeptide systems.

Topics: Animals; Anxiety Disorders; Corticotropin-Releasing Hormone; Depressive Disorder; Dose-Response Relationship, Drug; Electroencephalography; Evoked Potentials, Auditory; Frontal Lobe; Hypothalamus; Injections, Intraventricular; Male; Neuropeptide Y; Rats; Rats, Wistar; Sleep Wake Disorders