Neuronal and hormonal systems in mood

The nervous and endocrine systems are related in three main areas: structure, chemical and function. The endocrine and nervous systems work in parallel and in conjunction in maintaining homeostasis. Chemically, both the endocrine and nervous systems function in communication by means of the same transmitters. Studies evaluating mechanisms that may account for associations between positive emotion and health have examined measures of neuroendocrine function (Reference Steptoe, Gibson, Hamer and Wardle3). Norepinephrine, epinephrine and cortisol are stress-related neuroendocrine hormones that influence numerous bodily processes. Norepinephrine in the central nervous system (CNS) acts to regulate behavioural and physiologic responses to the environment, including alerting, attention and autonomic nervous system regulation. Norepinephrine and epinephrine are the peripheral mediators of sympathoadrenal response that increases heart rate and mobilises other bodily responses (Reference Jacobs9). Similarly, release of cortisol increases blood pressure and blood sugar levels in response to stress (Reference Fraser, Ingram, Anderson, Morrison, Davies and Connell10). Chronically elevated levels of cortisol have been associated with negative health outcomes such as reduced bone density, lean mass, atrophy of hippocampal cells (Reference Epel, Burke, Wolkowitz, Aldwin, Park and Spiro11), obesity, type 2 diabetes, hypertension and autoimmune conditions (Reference McEwen, Biron and Brunson12). Prolonged neuroendocrine response to stress has also been associated with depressed mood (Reference Gold, Zakowski, Valdimarsdottir and Bovbjerg13). Lower levels of salivary cortisol have been associated with measures of well-being (Reference Lindfors and Lundberg14). Thus, the association between neuroendocrine function and emotional responding is also a potential mechanism linking positive emotion to physical health outcomes. Considerable evidence points to a role for stressor-provoked neurochemical changes in the provocation, exacerbation and recurrence of illness. Major depressive disorder has been associated with variations in levels and turnover of serotonin [5-hydroxytryptamine (5-HT)], alterations of the 5-HT transporter and several 5-HT receptors (5-HT_1A, 5-HT_1B, 5-HT_2A and 5-HT_2C), DA and norepinephrine function (Reference Weitzman, Czeisler, Zimmerman and Moore-Ede15). Moreover, depression has been associated with alterations in peptidergic function, including corticotropin-releasing hormone (CRH), arginine vasopressin, neuromedin B and substance P, and growth factors (Reference Manji, Drevets and Charney16).

The hypothalamo–pituitary–adrenocortical (HPA) axis is a critical adaptive system that maximises survival potential in the face of physical or psychological challenge (Reference Herman, Figueiredo and Mueller17). The principal end products of the HPA axis, glucocorticoid hormones, act on multiple organ systems including the brain to maintain homeostatic balance. While glucocorticoids are beneficial for short-term survival, prolonged exposure can lead to serious metabolic, immunological and psychological dysfunctions (Reference Herman, Figueiredo and Mueller17), requiring that glucocorticoid secretion be a tightly regulated process. Therefore, termination of the glucocorticoid response is well controlled by efficient feedback inhibition mechanisms. Activation of the HPA axis can occur reflexively in response to physical challenge. These ‘reactive' responses are driven by ascending brain systems or circumventricular organs, which send direct projections to the hypothalamic paraventricular nucleus (PVN) (Reference Chappell, Smith and Kilts18). Neurons of the PVN produce CRH, the primary ACTH secretagogue and thereby control ACTH release and subsequent glucocorticoid secretion (Reference Chappell, Smith and Kilts18). Reactive responses are initiated by stimuli that signal a direct threat to homeostasis or survival. Activation of the HPA axis and glucocorticoid secretion may also occur in the absence of frank threat, perhaps serving to prepare the organism for potential homeostatic challenge (Reference Mizoguchi, Ishige, Aburada and Tabira19). Such ‘anticipatory' responses are initiated through comparison of environmental stimuli to either innate programmes (e.g. instinctual fear of predators) or memories (e.g. prior experience with a painful stimulus). As would be expected, anticipatory responses rely heavily on limbic and associational systems capable of integrating the significance of observed external events and rely on indirect connections with the PVN (Reference Millan20). Studies show that limbic mechanisms are responsible for regulation of the HPA axis during acute and chronic stress. Also, the key central circuits hippocampus, amygdala and prefrontal cortex are (a) involved in regulation of anticipatory stress responses and (b) implicated in pathologies associated with chronic stress (Reference Anisman, Merali and Hayley21).

Cortisol and norepinephrine

Cortisol is usually referred to as the ‘stress hormone' as it is involved in response to stress and anxiety, controlled by CRH. It increases blood pressure and blood sugar, and reduces immune responses. Under basal conditions, cortisol release is regulated by the hypothalamic PVN, responding to a combination of diurnal and metabolic inputs (Reference Weitzman, Czeisler, Zimmerman and Moore-Ede15). These signals are responsible for the typical peak of cortisol secretion at awakening and for its gradual decline through the day, with a nadir in the early morning hours during the human sleep period. This pattern can be altered by a variety of homeostatic challenges. Exercise, for example, may evoke a rise in cortisol resulting in the liberation of glucose and storage of fatty acids (Reference al'Absi, Lovallo and Nehlig22).

Studies show that older adults who secreted relatively high levels of diurnal cortisol experience an increase in their functional disabilities, but only if they endorsed low levels of health-related control strategies (Reference Carsten, Gregory and Richard23). By contrast, high cortisol level is not associated with an increase in functional disabilities among older adults who reported using high levels of these control strategies. In addition, the findings show that there is a relatively smaller increase in functional disabilities among older adults who secrete low level of cortisol, and the use of control strategies are not significantly associated with changes in functional disabilities among these individuals. Furthermore, individual differences in health-engagement control strategies may contribute to obtaining critical information about illness, receiving adequate professional advice and help, and adhering to difficult treatment regimes, medication or beneficial health behaviours. In a similar vein, the emotional benefits derived from the use of secondary control strategies may attenuate the downstream biological consequences of a persistently high cortisol level, and the motivational advantages of these strategies may foster investments in overcoming emerging threats to a person's well-being and physical health. These consequences of using adaptive control strategies can counteract potential adverse effects of high cortisol level on the development of older adults' physical health problems (Reference Carsten, Gregory and Richard23).

A recent study examined the effect of viewing a humorous film on a wide variety of stress hormones, using direct testing of hormone levels in serum (Reference Berk, Tan, Napier and Evy24). Subjects in the treatment group viewed a humorous video, while those in control group were kept in a quiet room for the same amount of time. Endocrine testing was performed before, during and post stimuli. The results showed that serum cortisol, growth hormone and plasma dopac, a metabolite of DA, all decreased with laughter. The control group showed no significant changes in any of the endocrine measures used. Laughter decreases stress hormones, and could theoretically act to buffer the effects of stress on the immune system. Because cortisol is immunosuppressive, the study theorised that laughter could act as an immunoenhancer by decreasing levels of this particular stress hormone (Reference Berk, Tan, Napier and Evy24,Reference Berk, Tan and Nehlsen-Cannarella25). Instead of taking medication to reduce stress, alternative stress busters can be used. Body and mind can be calmed by listening to music, meditating, practicing yoga and exercising. Something as simple as playing with children can also reduce stress.

Norepinephrine is a stress hormone and affects the sections of the brain that control attention and responsive actions. Along with the bodily chemical epinephrine, it underlies the action of fight-or-flight. A lack of this chemical will lead to poor concentration, restlessness and irritability. Norepinephrine or noradrenaline is produced in the adrenal medulla and can also be released by neurons in the CNS and sympathetic nervous system (Reference Jacobs9). As a neurotransmitter, norepinephrine has a role in alertness, emotions, sleeping, dreaming and learning (Reference Abercrombie and Zigmond26). Along with epinephrine, it increases heart rate and blood flow to the heart, brain and muscles, and prepares the body for the fight-or-flight response (Reference Abercrombie and Zigmond26). Norepinephrine is a well-established neurotransmitter in the CNS with widespread distribution throughout the brain and has hypothesised functions in arousal, attention, stress, anxiety and affective disorders. Cell bodies for the norepinephrine systems in the brain originate in the dorsal pons and brainstem (Reference Arnsten and Li27). The locus coeruleus in the dorsal pons is the source of the dorsal noradrenergic pathway to the cortices and hippocampus and the brainstem projections converge in the ventral noradrenergic bundle to innervate the basal forebrain and hypothalamus (Reference Arnsten and Li27). At very low or very high concentrations of norepinephrine, postsynaptic effects as well as behavioural performance tend to be disrupted (Reference Carney and Freedland28).

Serotonin and DA

Serotonin is a neurotransmitter and is linked to aggression, anger, body temperature, mood, sleep, sexuality, appetite and even vomiting. With this in mind, this article looks at mood. Mood and serotonin levels affect emotion, behaviour and thought; therefore, low levels of this bodily chemical are quite possibly the underlying cause of depression and aggressive actions (Reference Coccaro and Kavoussi29). In addition, early studies indicate that stress-induced elevation in 5-HT synthesis is a key counter-regulatory process allowing serotonergic homeostasis mediated by specific neuroendocrine mechanisms.

Serotonin secretion can be enhanced by increasing the recognition that happiness and well-being are important, both as factors protecting against mental and physical disorders and in their own right (Reference Delamothe30–Reference Adamsen, Stage, Laursen, Rørth and Quist32). Conversely, negative moods are associated with negative outcomes. For example, the negative mood hostility is a risk factor for many disorders. For the sake of brevity, hostility is discussed here mainly in relation to one of the biggest sources of mortality, coronary heart disease (CHD). Opposite of hostility, agreeableness, was a significant protective factor against mortality in a sample of older, frail participants (Reference Weiss and Costa33). Several studies found an association between measures related to serotonin and mood in the normal range. Lower platelet serotonin₂ receptor function was associated with lower mood in one study (Reference Peirson and Heuchert34), whereas better mood was associated with higher levels of blood serotonin in another study (Reference Williams, Stewart-Knox and Helander35). Two studies found that greater prolactin release in response to fenfluramine was associated with a more positive mood (Reference Zald and Depue36,Reference Flory, Manuck, Matthews and Muldoon37). The idea that these associations indicate a causal association between serotonin function and mood within the normal range is consistent with a study showing that, in healthy people with high trait irritability, tryptophan, relative to placebo, decreased quarrelsome behaviours, increased agreeable behaviours and improved mood (Reference aan het Rot, Moskowitz, Pinard and Young38). Serotonin may be associated with physical health as well as mood. In otherwise healthy individuals, a low prolactin response to the serotonin-releasing drug fenfluramine was associated with the metabolic syndrome, a risk factor for heart disease (Reference Muldoon, Mackey, Williams, Korytkowski, Flory and Manuck39), suggesting that low serotonin may predispose healthy individuals to suboptimal physical as well as mental functioning. Non-pharmacological methods of raising brain serotonin may not only improve mood and social functioning of healthy people – a worthwhile objective even without additional considerations – but would also make it possible to test the idea that increases in brain serotonin may help protect against the onset of various mental and physical disorders. The study by Perreau-Linck and colleagues (Reference Perreau-Linck, Beauregard and Gravel40) is the first to report that self-induced changes in mood can influence serotonin synthesis. This raises the possibility that the interaction between serotonin synthesis and mood may be two-way, with serotonin influencing mood and mood influencing serotonin. In one recent study, meditation was reported to increase release of DA (Reference Kjaer, Bertelsen, Piccini, Brooks, Alving and Lou41).

DA is a hormone and neurotransmitter which is found in a wide range of animals. Within the brain, it has a number of functions in behaviour, motor activity, motivation, sleep, stress, mood, learning, attention and milk production. In addition to this, DA is associated with the ‘pleasure system' of our brain (Reference Fisher, Aron and Brown42) which provides feeling of enjoyment, motivation and proactivity. Therefore, suppression of this chemical will make us feel demotivated, dissatisfied and generally unhappy. Although DA is a precursor of norepinephrine and epinephrine; by itself it also exerts widespread effects both on neuronal and non-neuronal tissues (Reference Hussain and Lokhandwala43).

DA at low concentrations acts through D₁-like receptors, relaxes blood vessels and decreases blood pressure (Reference Hussain and Lokhandwala43). It is reported that in the rat mesenteric artery, D₃ receptor agonist has no effect on vascular contractility. However, when the mesenteric rings are preconstricted with potassium chloride or norepinephrine, stimulation of D₁-like receptors or the D₃ receptor causes vasorelaxation (Reference Fan and Ellen44). When compared with vessels preconstricted with norepinephrine, the D₁-like receptor and D₃ receptor mediated vasorelaxation is greater in vessels preconstricted with norepinephrine than in vessels preconstricted with potassium chloride, indicating that norepinephrine could impair the vasodilatory effect of DA (Reference Fan and Ellen44). DA also has antiproliferative effects through D₁-like receptors in neuronal cells and VSMCs (Reference Yasunari, Kohno, Kano, Hanehira, Minami and Yoshikawa45). DA receptors have been reported to inhibit or stimulate cell proliferation that is subtype dependent (Reference Luo, Kokkonen, Wang, Neve and Roth46). There are increasing pieces of evidence for interactions among catecholamines and their receptors in neural and non-neural tissues. The D₂-like receptors such as D₂, D₃, and D₄, are located pre- and postsynaptically (Reference Fan and Ellen44). Prejunctional D₂ DA receptors in postganglionic sympathetic nerves innervating various organs including human gastric and uterine arteries can inhibit the release of catecholamine (Reference Morgadinho, Fontes Ribeiro and Macedo47). In contrast, the blockade of the presynaptic α ₂-adrenergic receptor enhances brain cortical DA output (Reference Hertel, Fagerquist and Svensson48). An activation of human peripheral blood mononuclear cells triggers endogenous production of catecholamines, an effect that is blocked by an activation of D₁-like receptor. The counter-regulatory actions of the α-adrenergic and DA receptors extend to the effects on vascular proliferation.

A number of studies indicate that serotonin and DA systems interact closely at a basic neurophysiological level (Reference Daw, Kakade and Dayan49) and that impairment of the serotonin system function can lead to dysregulation of the DA system (Reference De Simoni, Dal Toso, Fodritto, Sokola and Algeri50). Approach and withdrawal related behaviours are thought to be determined by the balance between DA and serotonin activity (Reference Ikemoto and Panksepp51).

Endorphins

Endorphins are a group of 10 neurotransmitters that activate opiate receptors. Endorphins are composed of chains of amino acids that are between five and several dozen members long (Reference Höllt, Tulunay, Woo, Loh and Herz52). At least 20 types of endorphins have been found in humans. Endorphins can be found in the pituitary gland, other parts of the brain or distributed throughout the nervous system. The endogenous opioid system consists of µ-, δ-, and κ-opioid receptors (MOP, DOP and KOP) and the opioid peptides enkephalin, β-endorphin and dynorphin. These peptides are produced from specific precursors (enkephalin/preproenkephalin, β-endorphin/proopiomelanocortin and dynorphin/preprodynorphin) (Reference Kieffer and Gaveriaux-Ruff53). Enkephalins and β-endorphins are the endogenous ligands at MOP and DOP receptors. β-Endorphin binds MOP and DOP receptors with approximately equal affinity, whereas enkephalin has a more than 10-fold higher affinity for the DOP receptor. Dynorphins selectively activate KOP receptors and additionally several non-opioid receptors (Reference Clarke, Zimmer, Zimmer, Hill and Kitchen54). The endogenous opioid system has long been known as one of the principal modulators of the mesolimbic dopaminergic reward circuitry. It facilitates dopaminergic neurotransmission along the mesolimbic neurons by acting in the ventral tegmental area, or in the nucleus accumbens or elsewhere in the brain (Reference Kosterlitz and Hughes55). The mesolimbic DA system plays a well-established role in mediating the rewarding properties of addiction (Reference Peciña and Berridge56) and there is evidence that it interacts considerably with the endogenous opioid system (Reference Gonzales and Weiss57). This is evidenced by a suppressed DA response with opioid blockade by naltrexone (Reference Gonzales and Weiss57,Reference Gianoulakis58), as well as a rich supply of opioid receptors in reward centres of the brain, such as the ventral tegmental area and the nucleus accumbens (Reference Gianoulakis58).

Endorphins are released when the body is active, either through excitement or exercise, as well as during fear. These are a group of substances that are released from the pituitary gland. When a person is afraid, endorphins are released into the body, energising it, and making the muscles, ligaments and the mind ready for that flight-or-fight response (Reference Simmons and Self59,Reference Hawkes60). However, when they are released in this manner, there is so much in the system that it can be overloaded, and when they are expended, the body is tired. Serotonin is always present in the body, and it is basically a neurotransmitter that can affect a wide variety of body functions. People who suffer from depression have a much lower level of endorphin than others, and hence they have trouble sleeping, eating, are in bad moods, feel sad or have problems with sexual dysfunction. Antidepressants do elevate these levels, but they do it so much that the transmitters think that the body has enough, and stops making more.

There are many ways to obtain more of endorphins and serotonin naturally for treating depression. Sometimes, it is simply a change in diet that can help. Taking cod liver oil, cutting back on processed foods and taking dietary supplements can help. A heavy routine is not required to get the exercise that releases endorphins; just walking around the neighbourhood, taking a bike ride or other forms of mild activity can help. Doing the things that would normally give happiness will also help boost these chemicals in the system, without the use of antidepressants. Comfort foods have a tendency to help recover serotonin levels, if taken in moderation. Most comfort foods such as ice cream, chocolate and fried foods have a high fat content, which releases both of these into the system (Reference Bidlack, Khimich, Parkhill, Sumagin, Sun and Tipton61). This is however a double-edged sword, because these foods can also contribute to weight gain, so it is best not to overdo them. Eating them in combination with healthier foods can balance this out, as in whole grains, fresh fruits and vegetables.

Stress and pain are the two most common factors leading to the release of endorphins. Endorphins interact with the opiate receptors in the brain to reduce the perception of pain and act similarly to drugs such as morphine and codeine. In contrast to the opiate drugs, however, activation of the opiate receptors by the body's endorphins does not lead to addiction or dependence (Reference Rang and Urban62). Recently, scientists have hypothesised that the release of endorphins is the neurochemical cause for the feeling of pleasure. For example, a marathon runner's ‘high', which has been compared to the ‘rush' following opioid use, is the product of endorphin release (Reference Gianoulakis58). In addition to decreased feelings of pain, secretion of endorphins leads to feelings of euphoria, modulation of appetite, release of sex hormones and enhancement of the immune response (Reference Simmons and Self59). With high endorphin levels, there is less pain and fewer negative effects of stress. Endorphins have been suggested as modulators of the so-called runner's high that athletes achieve with prolonged exercise. While the role of endorphins and other compounds as potential triggers of this euphoric response has been debated extensively by doctors and scientists, it is at least known that the body does produce endorphins in response to prolonged, continuous exercise. Since the discovery of the endorphins in 1975, scientists have hypothesised that these neurotransmitters are released into synapses when the body encounters stress. After a physical injury, endorphins activate opiate receptors and produce an analgesic effect alleviating severe pain. During times of emotional stress, endorphins are released in the limbic system of the brain and produce an euphoria that lessens anxiety and melancholy (Reference Rang and Urban62).

Discussion

The constitution of the WHO states ‘Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity'(Reference Irvine, Elliott, Wallace and Crombie63). This may sound exaggerated but positive mood within the normal range is an important predictor of health and longevity. In a series of recent studies, negative emotions were associated with increased disability due to mental and physical disorders (Reference Danner, Snowdon and Friesen64), increased incidence of depression (Reference Koivumaa-Honkanen, Koskenvuo, Honkanen, Viinamäki, Heikkilä and Kaprio65), increased suicide (Reference Koivumaa-Honkanen, Kaprio, Honkanen, Viinamäki and Koskenvuo66) and increased mortality (Reference Koivumaa-Honkanen, Honkanen, Koskenvuo and Kaprio67), up to two decades later. Positive emotions were protected against these outcomes. A recent review including meta-analyses assessed cross-sectional, longitudinal and experimental studies and concluded that happiness is associated with and precedes numerous successful outcomes (Reference Koivumaa-Honkanen, Honkanen, Viinamäki, Heikkilä, Kaprio and Koskenvuo68). Mood may influence social behaviour, and social support is one of the most studied psychosocial factors in relation to health and disease (Reference Lyubomirsky, King and Diener69). Low social support is associated with higher levels of stress, depression, dysthymia and post-traumatic stress disorder (PTSD), and with increased morbidity and mortality from a host of medical illnesses (Reference Southwick, Vythilingam and Charney70).

There is evidence from a broad set of research findings that the biological processes set in motion by exposure to severe, chronic or repeated stressors exert a toll on key physiological systems and play a role in the development of a wide range of mental and physical disorders. Dysregulation within the core emotional systems of the brain is implicated in the aetiology of many mental disorders, particularly the mood and anxiety disorders. Consistent with dynamic systems' notions of multifinality discussed earlier, there are many potential outcomes of dysregulation in the system. Examples include depression (Reference Arborelius, Owens, Plotsky and Nemeroff71), anxiety (Reference Rosen, Schulkin and Schulkin72) and PTSD (Reference Rauch, Whalen, Shin, McInerney, Macklin and Lasko73). Investigation of structural and functional differences in the hippocampus and amygdala has been of particular interest in neuroimaging studies of these disorders. For example, smaller hippocampal volume has been correlated with the length of depression (Reference Sheline, Wang, Gado, Csernansky and Vannier74) and with chronic PTSD in adults (Reference Drevets, Videen, Price, Preskorn, Carmichael and Raichle75). Depression has also been linked to alterations in the amygdala structure and function (Reference Drevets, Videen, Price, Preskorn, Carmichael and Raichle75). Anxiety has been associated with hyperactivation of the amygdala (Reference Thomas, Drevets and Dahl76), suggesting that hyperexcitability of the amygdala may be part of the mechanism through which the normal fear process gets translated into anxiety disorder in some individuals (Reference Rosen, Schulkin and Schulkin72). This may also be an underlying factor in the observation that PTSD is associated with dysregulation in a neural circuit that includes both the amygdala and medial prefrontal cortex. In sum, there is accumulating evidence that disruption in the core emotional systems of the brain plays a causal role in an array of mental disorders.

Similarly, the effect of stressor exposure on current physical health is mediated by peripheral accommodation to that stressor (as influenced by central allostatic accommodation and by peripheral load). For example, chronic or repeated stress is associated with suppressed immunity (Reference Glaser, Kiecolt-Glaser, Malarkey and Sheridan77). This has direct implications for health, as immunity and inflammation play a key role in many disorders, including arthritis, cardiovascular disease, viral infections, tumour invasion and metastatic spread (Reference McEwen, Biron and Brunson12). There are also important feedback effects of glucocorticoids on central allostatic accommodation; cortisol feeds back on the brain to assist in memory formation regarding threat-relevant stimuli and interferes with other cognitive skills (Reference Lupien and McEwen78). Chronic stress is also thought to contribute to hypertension through a variety of physiological processes that result in sustained blood pressure (Reference Sterling and Schulkin79). In short, changes in CRH and in the autonomic nervous system together lead to vasoconstriction, requiring greater blood flow to maintain the same blood pressure even after the threat is removed. There are also important feedback effects on the brain, in that the effects of chronic stress on vasopressin lead to an increased appetite for sodium, resulting in behavioural changes that further support the organisms' response to stress but add more challenges to the cardiovascular system. Our immune system plays a very important role in maintaining good health and keeping away infections, allergies and cancers. It has been proved by psychoneuroimmunologists that all negative emotions such as anxiety, depression or anger weaken the immune system of the body, thereby reducing its fighting capacity against infections. Similarly, release of cortisol increases blood pressure and blood sugar levels in response to stress (Reference Fraser, Ingram, Anderson, Morrison, Davies and Connell10). Chronically elevated levels of cortisol have been associated with negative health outcomes such as reduced bone density, lean mass, atrophy of hippocampal cells (Reference Epel, Burke, Wolkowitz, Aldwin, Park and Spiro11), abdominal obesity, type 2 diabetes, hypertension and autoimmune conditions (Reference McEwen, Biron and Brunson12). Prolonged neuroendocrine response to stress has also been associated with depressed mood (Reference Gold, Zakowski, Valdimarsdottir and Bovbjerg13), whereas lower levels of salivary cortisol have been associated with measures of well-being (Reference Lindfors and Lundberg14).

Yet, the relatively narrow focus on the risk of negative emotional health may have diverted attention away from the exploration of the potential health benefits of positive emotions. Findings from a growing body of research suggest that positive emotions may be a key factor to sustaining health, including cardiovascular health, as one ages. For example, vitality is a positive and restorative emotional state that is associated with a sense of enthusiasm and energy. Men and women with high versus low emotional vitality had only 68% of the risk of CHD at a follow-up of over 20 years (Reference Kubzansky and Thurston80). The effect of vitality remained significant even after controlling for health behaviours and other potential confounders, including depression and conventional CHD risk factors. Positive emotions may have direct, beneficial effects on physiological processes, including those involving the neuroendocrine, inflammatory, immunological and cardiovascular systems. Recent work has shown that individuals with higher positive emotion have lower cortisol output over the course of a day than those with low positive emotion, independent of levels of distress (Reference Steptoe, Wardle and Marmot81). Moreover, positive emotionality is related to lower ambulatory heart rate in men (Reference Steptoe, Wardle and Marmot81) and to lower levels of inflammatory markers in women. In addition, compared to those with lower levels of positive emotion, individuals with a positive emotional style are less likely to develop an upper respiratory illness when exposed to the common cold or influenza virus(Reference Cohen, Alper, Doyle, Treanor and Turner82). Positive emotion may also provide health benefits by dampening physiological responses to acute stressors. Individuals who are high in positive emotion show smaller stress-related increases in fibrinogen, an inflammatory marker associated with cardiovascular risk (Reference Steptoe, Wardle and Marmot81), and more rapid blood pressure recovery following stress than those who are low in positive emotion (Reference Steptoe, Gibson, Hamer and Wardle3). Positive psychosocial factors such as positive beliefs (optimism, finding meaning and spirituality), positive affect, positive behaviours (expressing/processing emotions, proactive coping, adherence etc.), active ways of interacting (openness and extraversion) and fostering social support can help a person with AIDS to cope and to remain engaged in living. We found substantial and consistent evidence that chronic depression, stressful events and trauma negatively affect AIDS disease progression in terms of decreases in CD4 T-lymphocytes, increases in viral load and greater risk for clinical decline and mortality (Reference Ironson and Hayward83).

Positive affect was assessed by aggregating momentary experience samples of happiness over a working day and was inversely related to cortisol output over the day, independent of age, gender, socioeconomic position, body mass and smoking. Similar patterns were observed on a leisure day. Happiness was also inversely related to heart rate assessed by using ambulatory monitoring methods over the day. The relationship between reduced cortisol and positive affect is potentially relevant to health. Cortisol is a key stress hormone related to a range of pathologies including abdominal obesity, type 2 diabetes, hypertension and autoimmune conditions (Reference Björntorp84). The average difference in cortisol of 32.1% between the lowest and highest happiness quintiles is substantial and might contribute to health risk if it persists over months or years. Because high cortisol is characteristic of some depressed individuals (Reference Brown, Varghese and McEwen85), it is important to note that the link with happiness was independent of negative affect. Lundberg and Lindfors (Reference Lundberg and Lindfors86) reported a small study involving 23 individuals in whom salivary cortisol sampled every 2 h over the working day was inversely related to scores on eudaimonic psychological well-being scales. It suggested that the rise in salivary cortisol upon awakening is significantly lower for individuals who more frequently experience positive affect. A larger cortisol increase upon awakening has been associated with chronic stress (Reference Schulz, Kirschbaum, Prüssner and Hellhammer87) and depression (Reference Pruessner, Hellhammer, Pruessner and Lupien88). More broadly, increased cortisol levels are known to be important for the development of numerous health problems (Reference Luecken, Dausch, Gulla, Hong and Compas89) including cardiovascular disease (Reference Girod and Brotman90). Positive affect is inversely associated with cortisol, ambulatory blood pressure, heart rate and with reduced fibrinogen stress responsiveness independent of other factors known to influence these biological variables. Other studies evaluating mechanisms that may account for associations between positive emotion and health have examined measures of neuroendocrine function (Reference Steptoe, Gibson, Hamer and Wardle3). Current studies suggest that the tendency to experience positive affect is associated with lower levels of norepinephrine. Throughout the three measurement periods for plasma catecholamines during the reactivity protocol, norepinephrine was lower among individuals who experience higher levels of positive affect, as compared with those who experience lower levels of positive emotion. Flory et al. (Reference Flory, Manuck, Matthews and Muldoon37) found that maximal prolactin response to fenfluramine was positively associated with ratings of positive mood, suggesting that individuals who experience higher levels of positive emotions have greater CNS serotonergic tone. Thus, although highly speculative, it is possible that an association between positive affect and norepinephrine is accounted for by higher levels of CNS serotonin.

Another study found that mirthful laughter reduced the levels of three detrimental stress hormones: cortisol, epinephrine and dopac (the major catabolite of DA) were reduced 39, 70 and 38%, respectively (Reference Levi91). Patients in a laughter group had lower epinephrine and norepinephrine levels by the second month, suggesting lower stress levels. They had increased HDL (good) cholesterol (Reference Berk, Tan and Nehlsen-Cannarella25). The laughter group also had lower levels of TNF-α, IFN-γ, IL-6 and hs-CRP indicating lower levels of inflammation. Laughter helps to increase the count of natural killer cells and also raises the antibody levels (Reference Berk, Tan, Napier and Evy24). Researchers have found that after laughter therapy there is an increase in antibodies (immunoglobulin A) in the mucous of the nose and respiratory passages which is believed to have protective capacity against some viruses, bacteria and other micro-organisms. Many members of Laughter Clubs say they have noticed that the frequency of common colds, sore throats and chest infections has decreased after joining the clubs (Reference Berk, Tan and Nehlsen-Cannarella25). The effect of laughter on our immune system is considered to be very significant in regard to fatal diseases such as AIDS and cancer. Laughter is one of the finest, most economical and easy to practice anti-stress measures (Reference Fry92). It is also one of the best muscle relaxants. Laughter expands blood vessels and sends more blood rising to the extremities and other muscles all over the body. A good bout of laughter also reduces the levels of stress hormones, epineprine and cortisol (Reference Aapm93). It can be said to be a form of dynamic meditation or relaxation. Laughter increases the levels of endorphins in our bodies, which are natural pain killers. Endorphins released as a result of laughter may help in reducing the intensity of pain in those suffering from arthritis, spondylitis and muscular spasms of the body (Reference Aapm93). Many women have reported a reduced frequency of migraine and tension headaches. Laughter helps to control blood pressure by reducing the release of stress-related hormones and bringing relaxation (Reference Aapm93). It also reduces the stress-related chemicals in the body and boosts the level of endorphins. Studies have shown that not only humour but faith, hope, love, cheerfulness and other positive emotions are also beneficial in regard to health and healing.

Laughing is also a full body workout. Some researchers estimate that laughing 100 times is as much of a workout as 15 min on an exercise bike (Reference Angst and Clark94). Laughing exercises the cardiovascular system by lowering blood pressure and increasing heart rate, which any aerobic exercise will also do (Reference Angst and Clark94). It improves coordination of brain functions, which increases alertness and memory, and helps clear the respiratory tract from coughing. Laughter increases blood oxygen, and strengthens internal muscles by tightening and releasing them (Reference Paskind95). Studies show that 20 s of laughing works the heart as much as 3 min of hard rowing (Reference Angst and Clark94). Exercising is also an effective way of triggering endorphin production. Endorphins induced during exercise are good for the body because they essentially promote the body's insulin process by lessening or weakening its resistance to insulin (Reference Overeem, Taal, Ocal Gezici, Lammers and Van Dijk96). Therefore, people with diabetes will greatly benefit from exercise-induced endorphins. This kind of endorphins can also help people with metabolic syndrome that causes hypertension, obesity and cardiovascular diseases and women with polycystic ovary syndrome (Reference Steinberg and Sykes97). Eating chocolate, body massage and meditation are other ways of encouraging endorphin release in the body. Thus, to enjoy a healthy life free of stress, infections, diseases and even a minor ailment like common cold, endorphins are the best option (Reference Steinberg and Sykes97). When the body is in a relaxed state as in meditation it triggers the outflow of endorphins. It is easy to do and free-of-charge. One just has to close the eyes and concentrate solely on breathing in and out in a slow and rhythmic process. Meditation also increases blood flow, slows the heart rate and decreases muscle tension (Reference Aapm93). Although it may be difficult for younger children to try this, older children and teenagers can benefit from meditation. High concentrations of endorphins in the brain produce a sense of euphoria, enhance pleasure and suppress pain, both emotionally and physically (Reference Vale, Spiess, Rivier and Rivier98). Low levels of endorphins cause anxiety and people are also more aware of pain. They crave for fat and fatty foods such as fries, cheese, creamy sauces, margarine, butter, fried chicken, potato chips and chocolate to name a few popular examples. Eating fatty foods creates a noticeable change in mood and feeling of pleasure. This feeling is related to a higher concentration of endorphin. Exercise which releases fat from within the body raises endorphins and causes the same mood changes.

Conclusion

Negative emotions and stress result in increased release of cortisol and epinephrine and disturb the normal balance of dopaminergic and serotoninergic coordination through the functional relation between these systems. Disturbance of the normal balance of the neurohormonal system through negative emotions leads to development of depression and fatal diseases. On the other hand, positive affective states provide health benefits by maintaining and improving the normal neuronal and hormonal functional balance. Also, it enhances chemicals such as endorphins in the brain and provides a state of euphoria. In conclusion, positive affective states are related to favourable profiles of functioning in several biological systems and may therefore be relevant to improving one's functional status and diminishing the risk of physical illness.