Relevance of Neuropeptide Y (NPY) in Psychiatry

Abstract

Extensive preclinical studies suggest neuropeptide Y (NPY) to be involved in stress regulation and coping. NPY counteracts the behavioral consequences of stress and anxiety to maintain emotional homeostasis. NPY is also involved in learning, memory, and cognition, all of which are dysregulated in many psychiatric states. Dense localization of NPY and NPY receptors is found in brain areas implicated in psychopathology such as the amygdala, hippocampus, neocortex, septum, caudate-putamen, hypothalamus and locus coeruleus. Impaired central NPY signaling may therefore be involved in the pathophysiology of depression, anxiety, schizophrenia, alcoholism, and trauma-induced disorders like PTSD. Studies on the readily accessible plasma from psychiatric patients have provided some information on the relevance of NPY as a marker for sympathetic tone in certain conditions. Reports on cerebrospinal fluid (CSF) NPY in subjects with depression indicate a dysregulation of central NPY in this disorder, however, other conditions still need to be investigated.

Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

“…Recently significant interest has arisen in possible interactions between central mood substrates and circuitries involved in metabolism (Gomez-Pinilla, 2008;Krishnan and Nestler, 2008;Kuperman et al, 2010;McBriar, 2006;Shao et al, 2008). More specifically, several neuropeptides with a clear role in metabolism, such as leptin, ghrelin, orexin, neuropeptide Yand urocortin 3, produce clear anti-depressant-like responses (Eaton et al, 2007;Heilig, 2004;Kuperman et al, 2010;Lu, 2007;Lutter et al, 2008;Yamada et al, 2011), whereas e.g. melanin-concentrating hormone and cholecystokinin evoke a pro-depressant-like phenotype in several rodent models (Becker et al, 2008;Georgescu et al, 2005).…”

Plasma Neuropeptide Y Levels in Medication Naive Adolescents with Major Depressive Disorder

“…The hypothalamic paraventricular nucleus is the main site of accumulation of nerve terminals of NPY neurons, and electron microscopy revealed synapses between NPY and corticotrophinreleasing factor (CRF) neurons (2). It was proposed that NPY counteracts the corticotrophin-releasing factor (CRF)-mediated stress effects to maintain "emotional homeostasis" (3). High concentrations of NPY are particularly found in the limbic system, basal ganglia (caudate nucleus, putamen), cerebral cortex, and hypothalamus in the human brain (4).…”

“…It acts as a co-transmitter, neurohormone, and neuromodulator in the central and peripheral nervous systems (6). NPY and NPY receptors play an important role in the regulation of food intake (7), sexual behavior (8), information handling (9), cognition (10), learning and memory (11)(12)(13), control of blood pressure (14), sympathetic activity (15), modulation of emotional processing (3), and the regulation of stress and anxiety (13,16,17).…”

“…Many clinical studies have demonstrated decreased NPY levels in the CSF and plasma of depressed patients when compared to healthy control subjects (22)(23)(24)(25)(26). According to preclinical studies, three lines of evidence from animal work supported the relevance of NPY in depression: (1) animal models of depression and NPY levels; (2) potentiation of NPY expression by antidepressant treatments; (3) administration of NPY compounds reduce depressive behavior (3,27,28). All preclinical evidence discussed above supports a role of NPY and the Y1 receptor in the pathophysiology of depression (29).…”

“…The amygdala is known to be the brain region intimately involved in mediation and processing of emotion and emotional memory. Reduced central NPY may in turn contribute to CRF hyperactivity in the amygdala which may induce elevated anxiety in depressed patients (3).…”