The correlation between perceived social support, cortisol and brain derived neurotrophic factor levels in healthy women
Introduction
The hypothalamic–pituitary–adrenal (HPA) axis regulates several neuroendocrinological functions through feedback interactions between corticotrophin-releasing hormone (CRH) and the downstream glucocorticoids from the adrenal gland. Studies have shown that elevated cortisol levels are correlated to stress responses (Ozbay et al., 2007), and that these levels may be dysregulated in mental disorders (Dinan, 2005, McEwen et al., 2015). The dexamethasone suppression test (DST) is used to detect stress responses and measures feedback sensitivity during HPA axis hyperactivity (Grossman et al., 2003). Various studies have demonstrated that HPA hyperactivity presents as suppressed plasma adenocorticotropic hormone (ACTH) and cortisol levels (Tsai et al., 2012), and individuals without suppression of these hormones during the DST examination may be more vulnerable to stress (Ceulemans et al., 1985).
Another stress-related substrate is brain derived neurotrophic factor (BDNF); a protein involved in the survival of neuronal cells and regulation of synaptic plasticity in the adult brain (Cowansage et al., 2010). The role of BDNF in affective disorders and posttraumatic stress disorder has been studied (Agid et al., 1999, Karege et al., 2002, Pivac et al., 2012) and it was found that BDNF expression in the brain is influenced by stress. However, the effects are different in different brain areas (Smith et al., 1995, Lakshminarasimhan and Chattarji, 2012, Yang et al., 2015). Recent evidence demonstrated that the neural plasticity supported by BDNF is vital for establishing and maintaining resilience to stress (Krishnan et al., 2007). Therapeutic pharmacological, behavioral, or environmental interventions focusing on BDNF may therefore prevent or reverse stress-related mental illness by enhancing resilience (Holmes, 2014). Furthermore, BDNF can cross the blood–brain barrier, and its levels in serum and plasma are highly correlated with its levels in cerebrospinal fluid (CSF). Therefore, BDNF can be regarded as a biomarker for mood disorders and also treatment response (Fernandes et al., 2014, Polyakova et al., 2015).
The most common form of stress stems from the social environment and is perceived as more intense than other types of stressors (Wood and Bhatnagar, 2015). Good social support may modulate genetic and environmental vulnerabilities and strengthen the stress resilience, but poor social support may contribute to illness, both in physical and mental disorders (Wade and Kendler, 2000, Tomfohr et al., 2015). Perceived social support is defined as the subjects’ perceptions of the general availability of support, when the support is provided, and how satisfied they are with the support (Gottlieb and Bergen, 2010). Perceived social support may moderate vulnerabilities and confer resilience to stress through its effects on the HPA system and related neural circuits (Ozbay et al., 2007; Ozbay et al., 2008; Chen et al., 2011; Ho et al., 2013; Stanton and Campbell, 2014). The perception of a high level of social support may ameliorate stress responses via the suppression of cortisol levels (Heinrichs et al., 2003). Lack of perceived social support may lead to mental health problems (Drogendijk et al., 2011) and poor life quality (Bucholz et al., 2014). Despite the robust relationship between the perception of social support and the stress response, the mechanisms underlying this relationship remain largely unexplored. Interestingly, the level of subjective social support is associated with BDNF gene polymorphism in humans (Taylor et al., 2008). And social deprivation significantly enhanced corticosterone levels and reduced BDNF levels in animal studies (Berry et al., 2012). The above results indicate that BDNF and HPA axis regulation is associated with the perception of social support, but this has not been definitively shown in human studies. With a focus on healthy subjects, here we explored whether plasma BDNF levels are correlated with DST status and subjectively perceived social support.
Section snippets
Subjects
Seventy-two healthy controls were recruited from the community using advertisements for various studies (Yang et al., 2007, Tsai et al., 2009, Yeh et al., 2009a, Wu et al., 2010, Yeh et al., 2012). The participants’ health was checked by a physician, and an experienced psychiatrist used the Chinese version of the Mini International Neuropsychiatric Interview (MINI) (Sheehan et al., 1998) to exclude individuals with any psychiatric conditions. The inclusion criteria for the healthy group were:
Results
The demographic data are shown in Table 1. There was a significant correlation between DST suppression rate and BDNF levels (r=0.37, p=0.001). Further gender analysis showed that the significant correlation existed only in the female group (r=0.44, p=0.003), but not in the males (r=0.14, p=0.49). After controlling for age, the significant positive correlation between DST suppression rate and BDNF level remained (Table 2).
We also found a significant positive correlation between the perceived
Discussion
Our results indicate that plasma BDNF levels are associated with stress resilience in a sex-specific manner. The significant correlation between DST suppression rate and plasma BDNF levels existed only in healthy female subjects. This result is consistent with previous findings, and we further showed a sex specific relationship between BDNF and stress response, measured via the DST status.
HPA axis activation has been shown to be influenced by CRF neurons in female rats facing stress (Babb et
Acknowledgements
This study was supported in part by grants from the National Science Council of Taiwan (NSC 93-2314−B-006-107, NSC 97-2314−B-006-006-MY3, NSC 100-2314−B-006-041-MY3, NSC 101-2314−B-006-064-MY3, and NSC 101-2314−B-006-065), the Atomic Energy Council of Taiwan (NSC 93-NU-7-006-004 and NSC 99-NU-E-006-003), the Ministry of Science and Technology, R.O.C (MOST 104-2321−B-006-031), and National Cheng Kung University Hospital (NCKUH-9903019). This research also received funding (D102-35001 and
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