neuropeptide-y and Mood-Disorders

Obesity and mood disorders are often overlapping pathologies that are prevalent public health concerns. Many studies have indicated a positive correlation between depression and obesity, although weight loss and decreased appetite are also recognized as features of depression. Accordingly, DSM-5 defines two subtypes of depression associated with changes in feeding: melancholic depression, characterized by anhedonia and associated with decreased feeding and appetite; and atypical depression, characterized by fatigue, sleepiness, hyperphagia, and weight gain. The central nervous system plays a key role in the regulation of feeding and mood, thus suggesting that overlapping neuronal circuits may be involved in their modulation. However, these circuits have yet to be completely characterized. The central melanocortin system, a circuitry characterized by the expression of specific peptides (pro-opiomelanocortins, agouti-related protein, and neuropeptide Y) and their melanocortin receptors, has been shown to be a key player in the regulation of feeding. In addition, the melanocortin system has also been shown to affect anxiety and depressive-like behavior, thus suggesting a possible role of the melanocortin system as a biological substrate linking feeding and depression. However, more studies are needed to fully understand this complex system and its role in regulating metabolic and mood disorders. In this review, we will discuss the current literature on the role of the melanocortin system in human and animal models in feeding and mood regulation, providing evidence of the biological interplay between anxiety, major depressive disorders, appetite, and body weight regulation.

Topics: Animals; Depressive Disorder, Major; Energy Metabolism; Melanocortins; Mood Disorders; Neuropeptide Y; Obesity

Neuropeptide Y (NPY) is abundant in the extended amygdala, a conceptual macrostructure in the basal forebrain important for regulation of negative affective states. NPY has been attributed a central role in anxiety-like behavior, fear, nociception, and reward in rodents. Deletion of the NPY gene in mice produces a high-anxiety high-alcohol-drinking phenotype. NPY infused into the brains of rats selectively bred to consume high quantities of alcohol suppresses alcohol drinking by those animals, an effect that is mediated by central amygdala (CeA). Likewise, alcohol-preferring rats exhibit basal NPY deficits in CeA. NPY infused into the brains of alcohol-dependent rats blocks excessive alcohol drinking by those animals, an effect that also has been localized to the CeA. NPY in CeA may rescue dependence-induced increases in anxiety and alcohol drinking via inhibition of downstream effector regions that receive GABAergic inputs from CeA. It is hypothesized here that NPY modulates anxiety-like behavior via Y2R regulation of NPY release, whereas NPY modulation of alcohol-drinking behavior in alcohol-dependent animals occurs via Y2R regulation of GABA release.

Topics: Alcoholism; Amygdala; Animals; Disease Models, Animal; Humans; Mood Disorders; Neuropeptide Y; Recruitment, Neurophysiological

Emotion is critical to most aspects of human behavior, and individual differences in systems recruited to process emotional stimuli, expressed as variation in emotionality, are characteristic of several neuropsychiatric disorders. We examine the genetic origins of individual differences in emotion processing by focusing on functional variants at five genes: catechol-O-methyltransferase (COMT), serotonin transporter (SLC6A4), neuropeptide Y (NPY), a glucocorticoid receptor-regulating co-chaperone of stress proteins (FKBP5) and pituitary adenylate cyclase-activating polypeptide receptor (ADCYAP1R1). These represent a range of effects of genes on emotion as well as the variety of mechanisms and factors, such as stress, that modify these effects. The new genomic era of genome-wide association studies (GWAS) and deep sequencing may yield a wealth of new loci modulating emotion. The effects of these genes can be validated by neuroimaging, neuroendocrine and other studies accessing intermediate phenotypes, deepening our understanding of mechanisms of emotion and variation in emotionality.

Topics: Catechol O-Methyltransferase; Emotions; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Humans; Mood Disorders; Neuroimaging; Neuropeptide Y; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Serotonin Plasma Membrane Transport Proteins; Tacrolimus Binding Proteins

Neuropeptide Y (NPY) is a highly conserved neuropeptide belonging to the pancreatic polypeptide family. Its potential role in the etiology and pathophysiology of mood and anxiety disorders has been extensively studied. NPY also has effects on feeding behavior, ethanol intake, sleep regulation, tissue growth and remodeling. Findings from animal studies have delineated the physiological and behavioral effects mediated by specific NPY receptor subtypes, of which Y1 and Y2 are the best understood.. Physiological roles and alterations of the NPYergic system in anxiety disorders, depression, posttraumatic stress disorder (PTSD), alcohol dependence and epilepsy. For each disorder, studies in animal models and human investigations are outlined and discussed, focusing on behavior, neurophysiology, genetics and potential for novel treatment targets.. The wide implications of NPY in psychiatric disorders such as depression and PTSD make the NPYergic system a promising target for the development of novel therapeutic interventions. These include intranasal NPY administration, currently under study, and the development of agonists and antagonists targeting NPY receptors. Therefore, we are proposing that via this mode of administration, NPY might exert CNS therapeutic actions without untoward systemic effects. Future work will show if this is a feasible approach.

Topics: Alcoholism; Animals; Anxiety Disorders; Drug Delivery Systems; Drug Design; Epilepsy; Humans; Mood Disorders; Neuropeptide Y; Receptors, Neuropeptide Y

Neuropeptide Y (NPY) is considered to be an important neuromodulator in the regulation of emotional behavior. For example, NPY is consistently involved in anxiety-related behaviors and there is increasing support for a role of this peptide in mood disorders such as depression. Furthermore, recent evidence suggests that NPY has a significant role in the neurobiological response to alcohol, including alcohol consumption, dependence, and withdrawal. In addition, NPY is beginning to emerge as an important modulator in the etiology of alcoholism that is independent from the addictive and reinforcing properties of the traditional system commonly associated with dopamine and instead, is strongly associated with innate emotionality. The recent developments elucidating the role of NPY in emotion and alcohol dependence are reviewed and the potential of the NPY system as a novel therapeutic strategy in the treatment of anxiety, depression and alcohol-related disorders is examined.

Topics: Alcohol-Induced Disorders, Nervous System; Alcoholism; Animals; Anxiety Disorders; Brain; Depressive Disorder; Emotions; Humans; Mood Disorders; Neuropeptide Y; Receptors, Neuropeptide; Stress, Psychological

The functional role of sigma receptors in the central nervous system has been investigated extensively. Sigma1-receptors have been shown to play an important role in antidepressive effects since selective sigma1-receptor agonists, as well as typical antidepressants, reduced the immobility time in the forced swimming and tail suspension tests. The reduction of immobility by sigma1-receptor agonists is antagonized by NE-100, a sigma1-receptor antagonist. It has been suggested that sigma receptors are involved in anxiety since Lu 28-179, a sigma2-receptor agonist, has anxiolytic properties in rodents. In addition to the depressive animal model, phenytoin-sensitive sigma1-receptor agonists such as (+)-SKF-10,047 and dextromethorphan attenuate the conditioned fear stress (CFS) response (which is not influenced by typical anxiolytics and antidepressants) in rodents, the attenuating effects being mediated through phenytoin-sensitive sigma1 receptors, which are closely connected to the mesolimbic dopaminergic systems. Furthermore, neurosteroids such as dehydroepiandrosterone sulfate also attenuate the CFS response, the effect being mediated via sigma1 receptors. These findings suggest that sigma receptors are involved in stress-induced pathophysiological changes such as depression and anxiety and that phenytoin-sensitive sigma1-receptor ligands are useful for the treatment of affective disorders, particularly those considered to be treatment-resistant.

Topics: Animals; Dehydroepiandrosterone; Dextromethorphan; Humans; Ligands; Mood Disorders; Neuropeptide Y; Phenazocine; Receptors, sigma; Sigma-1 Receptor; Stress, Physiological

In order to receive a further understanding of stress-regulation in depressed suicide attempters, peptides that are supposed to be related to the stress system (the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system) were studied in plasma. When compared with healthy controls, cortisol was high (p<0.001) and corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) appeared to be low (p<0.001) in patients who had recently attempted suicide. Patients who had repeatedly attempted suicide had the lowest NPY. A correlation between NPY and cortisol (p<0.05) was found in suicidal patients with depression NOS, whereas beta-endorphins correlated with cortisol (p<0.01) in suicidal patients with major depressive disorder. A postdexamethasone decrease of NPY was noted in the controls but not in the patients. These results suggest stress system alterations in suicidal patients with mood disorders.

Topics: Adult; Age Factors; Anti-Inflammatory Agents; beta-Endorphin; Corticotropin-Releasing Hormone; Dexamethasone; Female; Humans; Male; Mood Disorders; Neuropeptide Y; Psychiatric Status Rating Scales; Sex Factors; Stress, Psychological; Suicide, Attempted

In recent decades, the role of genetic factors in the predisposition to suicidal behavior has attracted considerable attention. Although each genetic investigation appears to be valuable, no one study on its own can comprehensively explain the etiology of suicidal behavior.. In this study, using a broad literature review, we found the suicide-associated gene coexpression network. In addition, cytoband, molecular function, biological process, cellular component, tissue-based expression, and disease/disorder enrichment analyses were carried out to determine the most central cellular and molecular infrastructures involved in suicidal behavior.. The reconstructed network consisted of 104 genes, including 91 previously known genes and 13 novel genes, and 354 interactions. Topological analysis showed that in total, CCK, INPP1, DDC, and NPY genes are the most fundamental hubs in the network. We found that suicide genes are significantly concentrated within chromosomes 11 and 6. Further analysis showed that monoaminergic signal transduction, especially through GPCRs, in the cingulate gyrus, superior prefrontal gyrus, dorsal striatum, and the cerebellum are the main, deficient routes in suicide. Moreover, it turned out that genetically, suicidal behavior is more likely in patients with mood and affective disorders.. Like other behavioral disorders, suicide has a complex and multifactorial basis and at present, the only approaches to the integrated study of such disorders are computer-based methods. The results of such studies, although subject to a degree of uncertainty, however, can pave the way for future basic and clinical studies.

Topics: Aromatic-L-Amino-Acid Decarboxylases; Cholecystokinin; Databases, Genetic; Humans; Mental Disorders; Mood Disorders; Neuropeptide Y; Phosphoric Monoester Hydrolases; Risk Factors; Suicidal Ideation; Suicide; Suicide, Attempted

Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From The Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional magnetic resonance imaging while making gender decisions of emotional facial expressions. Results showed interactions between genotype and CEM, within carriers of the risk genotype, CEM was associated with higher amygdala activation, whereas CEM did not influence activation in non-risk carriers. In the posterior cingulate cortex (PCC), less activation was seen in those with CEM and the risk genotype, whereas genotype did not influence PCC activation in those without CEM. In addition, those carrying the risk genotype and with experience of CEM made a faster gender decision than those without CEM. Thus, the combined effect of carrying NPY risk genotype and a history of CEM affected amygdala and PCC reactivity, areas related to emotion, self-relevance processing and autobiographical memory. These results are consistent with the notion that the combination of risk genotype and CEM may cause hypervigilance.

Topics: Adult; Amygdala; Brain; Brain Mapping; Child; Child Abuse; Emotions; Facial Expression; Female; Genotype; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Male; Mood Disorders; Neuropeptide Y; Pattern Recognition, Visual; Risk; Stress, Psychological

It has been hypothesized that the neuropeptide Y (NPY) system is involved in the pathogenesis of mood disorder. In this study, Y(1) and Y(2) receptor mRNA expression levels were analyzed in the dorsolateral prefrontal cortex of subjects affected with major depression, bipolar disorder, or schizophrenia and compared to normal controls. No significant alterations in Y(1) or Y(2) mRNA expression levels were observed between the groups. However, the Y(2) mRNA expression was elevated in layer IV in subjects with suicide as a cause of death. For the Y(1) mRNA expression, there was a negative correlation with increasing subject age in the prefrontal cortex. Analysis of covariance revealed a significant elevation of the Y(1) mRNA expression levels in individuals with a current history of marijuana use but no other drug. In summary, the current results suggest distinct alterations of the prefrontal Y(1) and Y(2) neuronal populations in aging and suicide.

Topics: Adult; Aged; Aging; Bipolar Disorder; Depressive Disorder, Major; Female; Gene Expression; Humans; Male; Middle Aged; Mood Disorders; Neurons; Neuropeptide Y; Prefrontal Cortex; Receptors, Neuropeptide Y; RNA, Messenger; Schizophrenia; Suicide