Table 4:
Summary of pre-clinical and clinical studies
| Pre-clinical studies | Clinical studies |
|---|---|
| Early life stress has long term effect on NPY levels and vulnerability to depression and stress (Husum and Mathe, 2002) | Insuflated NPY as antidepressant, a randomized controlled trial in MDD patients (Mathe et al., 2020) |
| Anxiolytic effect of intracerebroventircularly administered NPY in brain of rats of anxiety models (Heilig et al., 1989) | Intranasal administration of NPY as a novel treatment approach for the patients of PTSD (Sayed et al., 2018) |
| Anxiolytic effect of NPY is mediated through NPY1R (Broqua et al., 1995; Nakajima et al., 1998; Nwokafor et al., 2020; Sajdyk et al., 2002a) | Lower NPY levels in depressed patients which increased upon treatment with anti-depressants (Ozsoy et al., 2016) |
| NPY1R receptor antagonist treatment to Sprague-Dawley rats of chronic restraint stress model abolished the adaptation to stress (Yang et al., 2018) | Increased expression of NPY1 & 2R in postmortem brains of suicide victims (Caberlotto and Hurd, 2001) |
| NPY1R knockout induced anxiety and depression like behavior in FST rats (Karlsson et al., 2008) | Increased NPY levels in CSF and plasma of patients having MDD and other psychiatric illness (Lu et al., 2019; Soleimani et al., 2014) |
| Deletion/suppression of NPY2R is correlated with increased NPY levels and enhanced anxiolytic /anti-depressant like effect (Morales-Medina et al., 2010; Redrobe et al., 2003) | Reduced NPY levels in different brain regions of bipolar disorder patients (Kuromitsu et al., 2001; Sandberg et al., 2014) |
| Anxiolytic function of NPY1R and NPY5R, anxiogenic effect of NPY5R (Sajdyk et al., 2002a; Sajdyk et al., 2002b) | Higher CSF NPY levels in baseline depressed patients (Martinez et al., 2012) |
| Altered NPY levels in brain of different animal models of depression such as Flinders sensitive rats, maternal separation as genetic model of depression (Caberlotto et al., 1999; Jimenez-Vasquez et al., 2001; Miragaia et al., 2018) | Region specific NPY reduction in brain and reduced NPY levels in plasma and CSF of patients with history of depression and suicide attempts (Hashimoto et al., 1996; Heilig et al., 2004; Hou et al., 2006; Nilsson et al., 1996; Wahlestedt and Heilig, 1995; Widdowson et al., 1992) |
| NPY levels play important role in stress and depression treatment (Crespi, 2011) | CSF NPY reduced with anti-depressant treatment (Olsson et al., 2004) |
| Antidepressants desipramine and citalopram induced increase in NPY levels in brain of experimental animals (Heilig et al., 1988) | Decreased NPY levels correlated with suicide attempts (Westrin et al., 1999; Westrin et al., 1998; Widdowson et al., 1992) |
| No changes in anxiety or stress levels upon treatment with NPY5R antagonist (Kask et al., 2001) |
References for the Table 4:
Broqua, P., Wettstein, J.G., Rocher, M.N., Gauthier-Martin, B., Junien, J.L., 1995. Behavioral effects of neuropeptide Y receptor agonists in the elevated plus-maze and fear-potentiated startle procedures. Behav Pharmacol 6(3), 215-222.
Caberlotto, L., Hurd, Y.L., 2001. Neuropeptide Y Y(1) and Y(2) receptor mRNA expression in the prefrontal cortex of psychiatric subjects. Relationship of Y(2) subtype to suicidal behavior. Neuropsychopharmacology 25(1), 91-97.
Caberlotto, L., Jimenez, P., Overstreet, D.H., Hurd, Y.L., Mathe, A.A., Fuxe, K., 1999. Alterations in neuropeptide Y levels and Y1 binding sites in the Flinders Sensitive Line rats, a genetic animal model of depression. Neurosci Lett 265(3), 191-194.
Crespi, F., 2011. Influence of Neuropeptide Y and antidepressants upon cerebral monoamines involved in depression: an in vivo electrochemical study. Brain Res 1407, 27-37.
Hashimoto, H., Onishi, H., Koide, S., Kai, T., Yamagami, S., 1996. Plasma neuropeptide Y in patients with major depressive disorder. Neurosci Lett 216(1), 57-60.
Heilig, M., Soderpalm, B., Engel, J.A., Widerlov, E., 1989. Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology (Berl) 98(4), 524-529.
Heilig, M., Wahlestedt, C., Ekman, R., Widerlov, E., 1988. Antidepressant drugs increase the concentration of neuropeptide Y (NPY)-like immunoreactivity in the rat brain. Eur J Pharmacol 147(3), 465-467.
Heilig, M., Zachrisson, O., Thorsell, A., Ehnvall, A., Mottagui-Tabar, S., Sjogren, M., Asberg, M., Ekman, R., Wahlestedt, C., Agren, H., 2004. Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J Psychiatr Res 38(2), 113-121.
Hou, C., Jia, F., Liu, Y., Li, L., 2006. CSF serotonin, 5-hydroxyindolacetic acid and neuropeptide Y levels in severe major depressive disorder. Brain Res 1095(1), 154-158.
Husum, H., Mathe, A.A., 2002. Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes. Neuropsychopharmacology 27(5), 756-764.
Jimenez-Vasquez, P.A., Mathe, A.A., Thomas, J.D., Riley, E.P., Ehlers, C.L., 2001. Early maternal separation alters neuropeptide Y concentrations in selected brain regions in adult rats. Brain Res Dev Brain Res 131(1-2), 149-152.
Karlsson, R.M., Choe, J.S., Cameron, H.A., Thorsell, A., Crawley, J.N., Holmes, A., Heilig, M., 2008. The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice. Psychopharmacology (Berl) 195(4), 547-557.
Kask, A., Vasar, E., Heidmets, L.T., Allikmets, L., Wikberg, J.E., 2001. Neuropeptide Y Y(5) receptor antagonist CGP71683A: the effects on food intake and anxiety-related behavior in the rat. Eur J Pharmacol 414(2-3), 215-224.
Kuromitsu, J., Yokoi, A., Kawai, T., Nagasu, T., Aizawa, T., Haga, S., Ikeda, K., 2001. Reduced neuropeptide Y mRNA levels in the frontal cortex of people with schizophrenia and bipolar disorder. Brain Res Gene Expr Patterns 1(1), 17-21.
Lu, J., Li, S., Li, H., Mou, T., Zhou, L., Huang, B., Huang, M., Xu, Y., 2019. Changes In Plasma NPY, IL-1beta And Hypocretin In People Who Died By Suicide. Neuropsychiatr Dis Treat 15, 2893-2900.
Martinez, J.M., Garakani, A., Yehuda, R., Gorman, J.M., 2012. Proinflammatory and “resiliency” proteins in the CSF of patients with major depression. Depress Anxiety 29(1), 32-38.
Mathe, A.A., Michaneck, M., Berg, E., Charney, D.S., Murrough, J.W., 2020. A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder. Int J Neuropsychopharmacol 23(12), 783-790.
Miragaia, A.S., de Oliveira Wertheimer, G.S., Consoli, A.C., Cabbia, R., Longo, B.M., Girardi, C.E.N., Suchecki, D., 2018. Maternal Deprivation Increases Anxiety- and Depressive-Like Behaviors in an Age-Dependent Fashion and Reduces Neuropeptide Y Expression in the Amygdala and Hippocampus of Male and Female Young Adult Rats. Front Behav Neurosci 12, 159.
Morales-Medina, J.C., Dumont, Y., Quirion, R., 2010. A possible role of neuropeptide Y in depression and stress. Brain Res 1314, 194-205.
Nakajima, M., Inui, A., Asakawa, A., Momose, K., Ueno, N., Teranishi, A., Baba, S., Kasuga, M., 1998. Neuropeptide Y produces anxiety via Y2-type receptors. Peptides 19(2), 359-363.
Nilsson, C., Karlsson, G., Blennow, K., Heilig, M., Ekman, R., 1996. Differences in the neuropeptide Y-like immunoreactivity of the plasma and platelets of human volunteers and depressed patients. Peptides 17(3), 359-362.
Nwokafor, C., Serova, L.I., Nahvi, R.J., McCloskey, J., Sabban, E.L., 2020. Activation of NPY receptor subtype 1 by [D-His(26)]NPY is sufficient to prevent development of anxiety and depressive like effects in the single prolonged stress rodent model of PTSD. Neuropeptides 80, 102001.
Olsson, A., Regnell, G., Traskman-Bendz, L., Ekman, R., Westrin, A., 2004. Cerebrospinal neuropeptide Y and substance P in suicide attempters during long-term antidepressant treatment. Eur Neuropsychopharmacol 14(6), 479-485.
Ozsoy, S., Olguner Eker, O., Abdulrezzak, U., 2016. The Effects of Antidepressants on Neuropeptide Y in Patients with Depression and Anxiety. Pharmacopsychiatry 49(1), 26-31.
Redrobe, J.P., Dumont, Y., Herzog, H., Quirion, R., 2003. Neuropeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety: evidence from Y2 receptor knockout mice. Behav Brain Res 141(2), 251-255.
Sajdyk, T.J., Schober, D.A., Gehlert, D.R., 2002a. Neuropeptide Y receptor subtypes in the basolateral nucleus of the amygdala modulate anxiogenic responses in rats. Neuropharmacology 43(7), 1165-1172.
Sajdyk, T.J., Schober, D.A., Smiley, D.L., Gehlert, D.R., 2002b. Neuropeptide Y-Y2 receptors mediate anxiety in the amygdala. Pharmacol Biochem Behav 71(3), 419-423.
Sandberg, J.V., Jakobsson, J., Palsson, E., Landen, M., Mathe, A.A., 2014. Low neuropeptide Y in cerebrospinal fluid in bipolar patients is associated with previous and prospective suicide attempts. Eur Neuropsychopharmacol 24(12), 1907-1915.
Sayed, S., Van Dam, N.T., Horn, S.R., Kautz, M.M., Parides, M., Costi, S., Collins, K.A., Iacoviello, B., Iosifescu, D.V., Mathe, A.A., Southwick, S.M., Feder, A., Charney, D.S., Murrough, J.W., 2018. A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder. Int J Neuropsychopharmacol 21(1), 3-11.
Soleimani, L., Oquendo, M.A., Sullivan, G.M., Mathe, A.A., Mann, J.J., 2014. Cerebrospinal fluid neuropeptide Y levels in major depression and reported childhood trauma. Int J Neuropsychopharmacol 18(1).
Wahlestedt, C., Heilig, M., 1995. Neuropeptide Y and related peptides, in: Bloom, F.E., Kupfer, D.J. (Eds.), Psychopharmacology: A fourth Generation of Progress. Raven Press, New York, pp. 543-552.
Westrin, A., Ekman, R., Traskman-Bendz, L., 1999. Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) plasma levels in mood disorder patients with a recent suicide attempt. Eur Neuropsychopharmacol 9(3), 205-211.
Westrin, A., Engstom, G., Ekman, R., Traskman-Bendz, L., 1998. Correlations between plasma-neuropeptides and temperament dimensions differ between suicidal patients and healthy controls. J Affect Disord 49(1), 45-54.
Widdowson, P.S., Ordway, G.A., Halaris, A.E., 1992. Reduced neuropeptide Y concentrations in suicide brain. J Neurochem 59(1), 73-80.
Yang, Z., Han, S., Keller, M., Kaiser, A., Bender, B.J., Bosse, M., Burkert, K., Kogler, L.M., Wifling, D., Bernhardt, G., Plank, N., Littmann, T., Schmidt, P., Yi, C., Li, B., Ye, S., Zhang, R., Xu, B., Larhammar, D., Stevens, R.C., Huster, D., Meiler, J., Zhao, Q., Beck-Sickinger, A.G., Buschauer, A., Wu, B., 2018. Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor. Nature 556(7702), 520-524.