Skip to main content

The healing power of well-being

  • Jobin Mathew (a1) and Cheramadathikudyl Scariya Paulose (a2)

Neuroendocrine system plays an important role in modulating our body functions and emotions. At the same time, emotions implicate a pivotal role in the regulation of brain function and neuroendocrine system. Negative affective states such as depression and stress are associated with premature mortality and increase the risk of various fatal diseases. It has been suggested that positive affective states are protective and improve our health and productiveness. Several potential mechanisms have been posited to account for these associations including improved health behaviour, direct physiological benefits, enhanced resistance and recovery from stress among individuals with high versus low positive emotional resources. This review summarises information concerning the neuronal and hormonal systems in mood, impact of negative and positive affective states on the level of cortisol, epinephrine, serotonin, dopamine and endorphins. The functional correlation of neuronal and hormonal systems in the development of diseases and their ability to enhance health-relevant biological processes are also evaluated.

Corresponding author
Dr C. S. Paulose, Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala 682 022, India. Tel: +91 484 2575588; Fax: +91 484 2575588; E-mail:
Hide All
1.Smith, TW.Hostility and health: current status of a psychosomatic hypothesis. Health Psychol 1992;11:139150.
2.Argyle, M.The psychology of happiness, 2nd edn.New York: Routledge, 2001.
3.Steptoe, A, Gibson, EL, Hamer, M, Wardle, J.Neuroendocrine and cardiovascular correlates of positive affect measured by ecological momentary assessment and by questionnaire. Psychoneuroendocrinology 2007;32:5664.
4.Richman, LS, Kubzansky, L, Maselko, J, Kawachi, I, Choo, P, Bauer, M.Positive emotion and health: going beyond the negative. Health Psychol 2005;24:422429.
5.Brummett, BH, Boyle, SH, Siegler, IC, Williams, RB, Mark, DB, Barefoot, JC.Ratings of positive and depressive emotion as predictors of mortality in coronary patients. Int J Cardiol 2005;20:213216.
6.Linden, W, Earle, TL, Gerin, W, Christenfeld, N.Physiological stress reactivity and recovery: conceptual siblings separated at birth? J Psychosom Res 1997;42:117135.
7.Newmann, SA, Waldstein, SR.Similar patterns of cardiovascular response during emotional activation as a function of affective valence and arousal and gender. J Psychosom Res 2001;50:245253.
8.Ong, AD, Allaire, JC.Cardiovascular intraindividual variability in later life: the influence of social connectedness and positive emotions. Psychol Aging 2005;20:476485.
9.Jacobs, GD.The physiology of mind-body interactions: the stress response and the relaxation response. J Altern Complement Med 2001;7:8392.
10.Fraser, R, Ingram, MC, Anderson, NH, Morrison, C, Davies, E, Connell, JM.Cortisol effects on body mass, blood pressure, and cholesterol in the general population. Hypertension 1999;33:13641368.
11.Epel, ES, Burke, HM, Wolkowitz, OM. The psychoneuroendocrinology of aging: anabolic and catabolic hormones. In: Aldwin, CM, Park, CL, Spiro, A, eds. Handbook of health psychology and aging. New York: Guilford Press, 2007: 119141.
12.McEwen, BS, Biron, CA, Brunson, KW et al. The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Brain Res Rev 1997;23:79133.
13.Gold, SM, Zakowski, SG, Valdimarsdottir, HB, Bovbjerg, DH.Higher Beck depression scores predict delayed epinephrine recovery after acute psychological stress independent of baseline levels of stress and mood. Biol Psychol 2004;67:261273.
14.Lindfors, P, Lundberg, U.Is low cortisol release an indicator of positive health? Stress Health 2002;18:153160.
15.Weitzman, ED, Czeisler, CA, Zimmerman, JC, Moore-Ede, MC.Biological rhythms in man: relationship of sleep-wake, cortisol, growth hormone, and temperature during temporal isolation. Adv Biochem Psychopharmacol 1981;28:475499.
16.Manji, HK, Drevets, WC, Charney, DS.The cellular neurobiology of depression. Nat Med 2001;7:541547.
17.Herman, JP, Figueiredo, H, Mueller, NK et al. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol 2003;24:151180.
18.Chappell, PB, Smith, MA, Kilts, CD et al. Alterations in corticotropin-releasing factor-like immunoreactivity in discrete brain regions after acute and chronic stress. J Neurosci 1986;6:29082914.
19.Mizoguchi, K, Ishige, A, Aburada, M, Tabira, T.Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus. Neuroscience 2003;119:887897.
20.Millan, MJ.Multi-target strategies for the improved treatment of depressive states: conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther 2006;110:135370.
21.Anisman, H, Merali, Z, Hayley, S.Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders. Prog Neurobiol 2008;85:174.'Absi, M, Lovallo, WR. Caffeine effects on the human stress axis. In: Nehlig, A, ed. Coffee, tea, chocolate and the brain. Boca Raton: CRC Press, 2004: 113131.
23.Carsten, W, Gregory, EM, Richard, S.Cortisol secretion and functional disabilities in old age: importance of using adaptive control strategies. Psychosom Med 2009;71:9961003.
24.Berk, L, Tan, S, Napier, B, Evy, W.Eustress of mirthful laughter modifies natural killer cell activity. Clin Res 1989;37:115A.
25.Berk, L, Tan, S, Nehlsen-Cannarella, S et al. Humor associated laughter decreases cortisol and increases spontaneous lymphocyte blastogenesis. Clin Res 1988;36:435A.
26.Abercrombie, ED, Zigmond, MJ.Partial injury to central noradrenergic neurons: reduction of tissue norepinephrine content is greater than reduction of extracellular norepinephrine measured by microdialysis. J Neurosci 1989;9:40624067.
27.Arnsten, AF, Li, BM.Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 2005;57:13771384.
28.Carney, RM, Freedland, KE.Depression, mortality, and medical morbidity in patients with coronary heart disease. Biol Psychiatry 2003;54:241247.
29.Coccaro, EF, Kavoussi, RJ.Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Arch Gen Psychiatry 1997;54:10811088.
30.Delamothe, T.Happiness. BMJ 2005;331:14891490.
31.Levett, C.Wellbeing and happiness – worth striving for. Aust Nurs J 2010;10:1821.
32.Adamsen, L, Stage, M, Laursen, J, Rørth, M, Quist, M.Exercise and relaxation intervention for patients with advanced lung cancer: a qualitative feasibility study. Scand J Med Sci Sports 2011. DOI: 10.1111/j.1600-0838.2011.01323.x.
33.Weiss, A, Costa, PT Jr.Domain and facet personality predictors of all-cause mortality among medicare patients aged 65 to 100. Psychosom Med 2005;67:724733.
34.Peirson, AR, Heuchert, JW.Correlations for serotonin levels and measures of mood in a nonclinical sample. Psychol Rep 2000;87:707716.
35.Williams, E, Stewart-Knox, B, Helander, A et al. Associations between whole-blood serotonin and subjective mood in healthy male volunteers. Biol Psychol 2006;71:171174.
36.Zald, DH, Depue, RA.Serotonergic functioning correlates with positive and negative affect in psychiatrically healthy males. Pers Individ Dif 2001;30:7186.
37.Flory, JD, Manuck, SB, Matthews, KA, Muldoon, MF.Serotonergic function in the central nervous system is associated with daily ratings of positive mood. Psychiatry Res 2004;129:1119.
38.aan het Rot, M, Moskowitz, DS, Pinard, G, Young, SN.Social behaviour and mood in everyday life: effects of tryptophan in quarrelsome individuals. J Psychiatry Neurosci 2006;31:253262.
39.Muldoon, MF, Mackey, RH, Williams, KV, Korytkowski, MT, Flory, JD, Manuck, SB.Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity. J Clin Endocrinol Metab 2004;89:266271.
40.Perreau-Linck, E, Beauregard, M, Gravel, P et al. In vivo measurements of brain trapping of α-[11C]methyl-L-tryptophan during acute changes in mood states. J Psychiatry Neurosci 2007;32:430434.
41.Kjaer, TW, Bertelsen, C, Piccini, P, Brooks, D, Alving, J, Lou, HC.Increased dopamine tone during meditation-induced change of consciousness. Brain Res Cogn Brain Res 2002;13:255259.
42.Fisher, HE, Aron, A, Brown, LL.Romantic love: a mammalian brain system for mate choice. Philos Trans R Soc Lond B Biol Sci 2006;361:21732186.
43.Hussain, T, Lokhandwala, MF.Renal dopamine receptors and hypertension. Exp Biol Med (Maywood) 2003;228:134142.
44.Fan, X, Ellen, HJ.D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD. Neurobiol Dis 2007;26:201211.
45.Yasunari, K, Kohno, M, Kano, H, Hanehira, T, Minami, M, Yoshikawa, J.Anti-atherosclerotic action of vascular D1 receptors. Clin Exp Pharmacol Physiol Suppl 1999;26:S36S40.
46.Luo, Y, Kokkonen, GC, Wang, X, Neve, KA, Roth, GS.D2 dopamine receptors stimulate mitogenesis through pertussis toxin-sensitive G proteins and Ras-involved ERK and SAP/JNK pathways in rat C6-D2L glioma cells. J Neurochem 1998;71:980989.
47.Morgadinho, MT, Fontes Ribeiro, CA, Macedo, TR.Presynaptic dopamine receptors involved in the inhibition of noradrenaline and dopamine release in the human gastric and uterine arteries. Fundam Clin Pharmacol 1999;13:662670.
48.Hertel, P, Fagerquist, MV, Svensson, TH.Enhanced cortical dopamine output and antipsychotic-like effects of raclopride by alpha2 adrenoceptor blockade. Science 1999;286:105107.
49.Daw, ND, Kakade, S, Dayan, P.Opponent interactions between serotonin and dopamine. Neural Netw 2002;15:603616.
50.De Simoni, MG, Dal Toso, G, Fodritto, F, Sokola, A, Algeri, S.Modulation of striatal dopamine metabolism by the activity of dorsal raphe serotonergic afferences. Brain Res 1987;411:8188.
51.Ikemoto, S, Panksepp, J.The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res Brain Res Rev 1999;31:641.
52.Höllt, V, Tulunay, FC, Woo, SK, Loh, HH, Herz, A.Opioid peptides derived from pro-enkephalin A but not that from pro-enkephalin B are substantial analgesics after administration into brain of mice. Eur J Pharmacol 1982;85:355356.
53.Kieffer, BL, Gaveriaux-Ruff, C.Exploring the opioid system by gene knockout. Prog Neurobiol 2002;66:285306.
54.Clarke, S, Zimmer, A, Zimmer, AM, Hill, RG, Kitchen, I.Region selective up-regulation of micro-, delta- and kappa-opioid receptors but not opioid receptor-like 1 receptors in the brains of enkephalin and dynorphin knockout mice. Neuroscience 2003;122:479489.
55.Kosterlitz, HW, Hughes, J.Some thoughts on the significance of enkephalin, the endogenous ligand. Life Sci 1975;17:9196.
56.Peciña, S, Berridge, KC.Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci 2005;25:1177711786.
57.Gonzales, RA, Weiss, F.Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens. J Neurosci 1998;18:1066310671.
58.Gianoulakis, C.Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholism. J Psychiatry Neurosci 2001;26:304318.
59.Simmons, D, Self, DW.Role of mu- and delta-opioid receptors in the nucleus accumbens in cocaine-seeking behavior. Neuropsychopharmacology 2009;34:19461957.
60.Hawkes, CH.Endorphins: the basis of pleasure? J Neurol Neurosurg Psychiatry 1992;55:247250.
61.Bidlack, JM, Khimich, M, Parkhill, AL, Sumagin, S, Sun, B, Tipton, CM.Opioid receptors and signaling on cells from the immune system. J Neuroimmune Pharmacol 2006;1:260269.
62.Rang, HP, Urban, L.New molecules in analgesia. Br J Anaesth 1995;75:145156.
63.Irvine, L, Elliott, L, Wallace, H, Crombie, IK.A review of major influences on current public health policy in developed countries in the second half of the 20th century. J R Soc Promot Health 2006;126:7378.
64.Danner, DD, Snowdon, DA, Friesen, WV.Positive emotions in early life and longevity: findings from the Nun Study. J Pers Soc Psychol 2001;80:804813.
65.Koivumaa-Honkanen, H, Koskenvuo, M, Honkanen, RJ, Viinamäki, H, Heikkilä, K, Kaprio, J.Life dissatisfaction and subsequent work disability in an 11-year follow-up. Psychol Med 2004;34:221228.
66.Koivumaa-Honkanen, H, Kaprio, J, Honkanen, R, Viinamäki, H, Koskenvuo, M.Life satisfaction and depression in a 15-year follow-up of healthy adults. Soc Psychiatry Psychiatr Epidemiol 2004;39:994999.
67.Koivumaa-Honkanen, H, Honkanen, R, Koskenvuo, M, Kaprio, J.Self-reported happiness in life and suicide in ensuing 20 years. Soc Psychiatry Psychiatr Epidemiol 2003;38:244248.
68.Koivumaa-Honkanen, H, Honkanen, R, Viinamäki, H, Heikkilä, K, Kaprio, J, Koskenvuo, M.Self-reported life satisfaction and 20-year mortality in healthy Finnish adults. Am J Epidemiol 2000;152:983991.
69.Lyubomirsky, S, King, L, Diener, E.The benefits of frequent positive affect: does happiness lead to success? Psychol Bull 2005;131:803855.
70.Southwick, SM, Vythilingam, M, Charney, DS.The psychobiology of depression and resilience to stress: implications for prevention and treatment. Annu Rev Clin Psychol 2005;1:255291.
71.Arborelius, L, Owens, M, Plotsky, P, Nemeroff, C.The role of corticotropin-releasing factor in depression and anxiety. J Endocrinol 1999;160:112.
72.Rosen, J, Schulkin, J. Adaptive fear, allostasis, and the pathology of anxiety. In: Schulkin, J, ed. Allostasis, homeostasis, and the cost of physiological adaptation. Cambridge: Cambridge University Press, 2004: 164227.
73.Rauch, S, Whalen, P, Shin, L, McInerney, S, Macklin, M, Lasko, N.Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder. A functional MRI study. Biol Psychiatry 2000;47:769–766.
74.Sheline, YI, Wang, PW, Gado, MH, Csernansky, JG, Vannier, MW.Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A 1996;93:39083913.
75.Drevets, WC, Videen, TO, Price, JL, Preskorn, SH, Carmichael, ST, Raichle, ME.A functional anatomical study of unipolar depression. J Neurosci 1992;12:36283641.
76.Thomas, KM, Drevets, WC, Dahl, RE et al. Amygdala response to fearful faces in anxious and depressed children. Arch Gen Psychiatry 2001;58:10571063.
77.Glaser, R, Kiecolt-Glaser, JK, Malarkey, WB, Sheridan, JF.The influence of psychological stress on the immune response to vaccines. Ann N Y Acad Sci 1998;840:649655.
78.Lupien, SJ, McEwen, B.The acute effects of corticosteroids on cognition: integration of animal and human model studies. Brain Res Brain Res Rev 1997;24:127.
79.Sterling, P. Principles of allostasis: optimal design, predictive regulation, pathophysiology, and rational therapeutics. In: Schulkin, J, ed. Allostasis, homeostasis, and the costs of physiological adaptation. Cambridge: Cambridge University Press, 2004: 1764.
80.Kubzansky, LD, Thurston, RC.Emotional vitality and incident coronary heart disease: benefits of healthy psychological functioning. Arch Gen Psychiatry 2007;64:13931401.
81.Steptoe, A, Wardle, J, Marmot, M.Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes. Proc Natl Acad Sci U S A 2005; 102:65086512.
82.Cohen, S, Alper, CM, Doyle, WJ, Treanor, JJ, Turner, RB.Positive emotional style predicts resistance to illness after experimental exposure to rhinovirus or influenza a virus. Psychosom Med 2006;68:809815.
83.Ironson, G, Hayward, H.Do positive psychosocial factors predict disease progression in HIV-1? A review of the evidence. Psychosom Med 2008;70:546554.
84.Björntorp, P.Do stress reactions cause abdominal obesity and comorbidities? Obes Rev 2001;2:7386.
85.Brown, ES, Varghese, FP, McEwen, BS.Association of depression with medical illness: does cortisol play a role? Biol Psychiatry 2004;55:19.
86.Lundberg, U, Lindfors, P.Psychophysiological reactions to telework in female and male white-collar workers. J Occup Health Psychol 2002;7:354364.
87.Schulz, P, Kirschbaum, C, Prüssner, J, Hellhammer, D.Increased free cortisol secretion after awakening in chronically stressed individuals due to work overload. Stress Med 1998;14:9197.
88.Pruessner, M, Hellhammer, DH, Pruessner, JC, Lupien, SJ.Self-reported depressive symptoms and stress levels in healthy young men: associations with the cortisol response to awakening. Psychosom Med 2003;65:9299.
89.Luecken, LJ, Dausch, B, Gulla, V, Hong, R, Compas, BE.Alterations in morning cortisol associated with PTSD in women with breast cancer. J Psychosom Res 2004;56:1315.
90.Girod, JP, Brotman, JD.Does altered glucocorticoid homeostasis increase cardiovascular risk? Cardiovasc Res 2004;64:217226.
91.Levi, L.The urinary output of adrenalin and noradrenalin during pleasant and unpleasant emotional states. Psychosom Med 1965;27:403419.
92.Fry, W.Mirth and oxygen saturation levels of peripheral blood. Psychother Psychosom 1971;19:7684.
93.Aapm, APS et al. The use of opioids for the treatment of chronic pain. A consensus statement from the American Academy of Pain Medicine and the American Pain Society. Clin J Pain 1997;13:68.
94.Angst, MS, Clark, JD.Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology 2006;104:570587.
95.Paskind, J.Effects of laughter on muscle tone. Arch Neurol Psychiatry 1932;28:623628.
96.Overeem, S, Taal, W, Ocal Gezici, E, Lammers, G, Van Dijk, J.Is motor inhibition during laughter due to emotional or respiratory influences? Psychophysiology 2004;41:254258.
97.Steinberg, H, Sykes, EA.Introduction to symposium on endorphins and behavioural processes: review of literature on endorphins and exercise. Pharmacol Biochem Behav 1985;23:857862.
98.Vale, W, Spiess, J, Rivier, C, Rivier, J.Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 1981;213:13941397.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed