**2.3 Salivary CgA**

250 Biomarker

some sort of long-term or chronic mental stress state while it is not necessary to consider in

Although the transient increase of IgA by laboratory stressors has been consistently observed in the past PNEI studies, the decline of basal IgA over longer period of time according to chronic stress has not been always observed. A review paper on IgA studies pointed out that studies targeting on chronic stress had methodological defects such as less control of subjects' physical conditions e.g. sleep and diet, variety of saliva sampling methods, and introducing non-standardized psychological questionnaires (Bosh, 2002). Moreover the transient increase of IgA would easily mask the change in the basal IgA level over long period of time: if a subject got nervous at the moment of saliva sampling, the

There are also IgA studies focusing on the effects of various relaxing factors. These studies also reported a transient increase of IgA as the same as studies focusing on laboratory stressors. However few attempts have been made to investigate the effects of such relaxing factors with/under stressful situation (Valdimarsdottir, 1997), so it is not clear whether such a transient increase of IgA induced by relaxing factor would be derived from the same

Other IgA studies have revealed that the higher cognitive process could mediate the IgA secretion. Psycho-social support alleviated the IgA secretion under long-term (Jemmott III, 1988) and short-term (Ohira, 2004) stressors. Subjects categorized in Type A trait, who are typically represented as short tempered and strong hostile, showed higher baseline of IgA and lower reactivity of IgA against an acute stressor (Ohira, 1999). Controllability of a given stressor unconsciously determined the salivary IgA (Ohira, 2001). These studies suggest that the higher cognitive process could mediate the IgA secretion. However the number of

Altogether IgA can be a useful stress biomarker, especially for laboratory stressors, representing SAM system activation, while the change in the basal IgA level over long

Cortisol is the most potent glucocorticoid produced and secreted from adrenal cortex playing a quite important role for maintain our body, e.g., keeping blood glucose level adequately. Cortisol levels can be measured in serum, urine, and saliva. Cortisol is considered to be released into blood stream via activation of HPA system. In addition significant positive correlation has been obtained between salivary and blood cortisol. Therefore salivary cortisol is assumed as a possible stress biomarker representing HPA

In the past cortisol studies, a transient increase of salivary cortisol was observed by shortterm laboratory stressors, such as mental arithmetic task, stroop task, and oral presentation (Dickerson, 2004; Kirschbaum, 1994). With regard to a long-term or chronic stress, higher level of cortisol secretion has been revealed to associate with chronic stress state, such as job stress (Steptoe, 2000), job loss (Ockenfels, 1995), and divorce (Powell, 2002). By contrast positive affect was found to associate with lower total cortisol secretion during daytime

observed IgA level would no longer a "basal" level of the IgA of the sampling day.

physiological mechanism as the response against laboratory stressors.

studies targeting on these potential mediators remains small.

period of time is still be a matter in discussion.

**2.2 Salivary cortisol** 

system activity.

relation to HPA system modulation.

Chromogranin A (CgA), a major member of the granin family of acidic secretory glycoproteins, is known to be released from the adrenal medulla into the blood with catecholamine(Kim, 2005). Therefore it is considered to be a possible biomarker of SAM system (Nakane, 1999; Winkler, 1992). CgA has been reported to transiently increase in response to short-term laboratory stressors such as a calculation test (Nakane, 1999), white noise (Miyakawa, 2006), and a cognitive task (Kanamaru, 2006). On the other hand there are studies failed to observe increase or rather decrease against a laboratory stressors (e.g., Yamakoshi, 2009) and observed a transient increase in subjects who declared the positive affection after watching a comic video (Toda, 2007).

CgA is expected as a possible stress marker representing SAM system activity as just described. However, the number of studies on salivary CgA is still small comparing with that on Cortisol and IgA. Moreover commercial available assay protocol for CgA is limited as just one product (Human Chromogranin A EIA Kit,Yanaihara Institute Inc.). So is necessary to accumulate more studies for further discussion.
