Plasma cortisol and neuropeptide Y in female victims of intimate partner violence

Abstract

Background: The experience of intimate partner violence (physical and sexual violence) has been linked to psychiatric disorders such as posttraumatic stress disorder, yet data on the neuroendocrine profile in this population is sparse. This study sought to examine baseline plasma cortisol and neuropeptide Y (NPY) levels in female victims of intimate partner violence (IPV). Methods: Morning plasma samples were collected for cortisol and NPY determination in 22 women with histories of IPV (10 with current PTSD, 12 without current or lifetime PTSD) and 16 non-abused controls. Results: Mean cortisol levels were significantly lower in IPV subjects compared with controls, but did not distinguish IPV subjects with and without PTSD. There were no significant differences in mean NPY levels between the groups. Neither cortisol nor NPY levels were significantly correlated with PTSD symptoms. Conclusions: These preliminary findings suggest that victims of IPV, like women traumatized by childhood abuse, may be characterized by alterations in hypothalamic-pituitary-adrenal axis functioning, however, further study is needed to identify specific stress system disturbances in this group.

Introduction

There is compelling evidence that the hypothalamic-pituitary-adrenal (HPA) axis and autonomic sympathetic system are essential components of the human stress response. While the acute response is characterized by cortisol release from the adrenals and raised plasma cortisol concentrations (Selye, 1956, Munck et al., 1984, Chrousos and Gold, 1992, Morgan III et al., 2000a); cortisol findings in trauma victims (e.g. combat veterans, sexual abuse victims) with posttraumatic stress disorder (PTSD) have been mixed, with studies indicating high (Pitman and Orr, 1990, Liberzon et al., 1999), normal (Baker et al., 1999) and low levels (Mason et al., 1986, Yehuda et al., 1991, Yehuda et al., 1995a). For example, lower plasma cortisol levels have been reported in rape victims (n=37) with histories of prior assault compared with recently assaulted women (Resnick et al., 1995), while high urinary free cortisol levels have been documented in maltreated children (De Bellis et al., 1999) and premenopausal women with PTSD (Lemieux and Coe, 1995, Rasmusson et al., 2001). Neuroendocrine studies conducted in close proximity to trauma suggest that cortisol levels in the immediate aftermath of trauma may predict the later occurrence of PTSD. Delahanty et al. (2000) demonstrated that motor vehicle accident victims (n=99) diagnosed with PTSD had lower urinary cortisol levels in the first 15 hours post-trauma than did victims who did not go on to meet diagnostic criteria. Low urinary cortisol levels were significantly correlated with intrusive and avoidant symptoms at one month follow-up, suggesting that initial cortisol per se may contribute, in part, to subsequent PTSD (Anisman et al., 2001). In contrast, Resnick et al. (1997) found an association between higher mean cortisol levels and PTSD symptom distress in rape victims at three months’ follow-up, while Hawk and colleagues (2000) found elevated urinary cortisol levels in PTSD-symptomatic men, but not women, one month after involvement in serious motor vehicle accidents.

Several mechanisms have been postulated for abnormal cortisol levels in PTSD, including (i) increased sensitivity of the HPA axis to feedback inhibition by cortisol (as evidenced by cortisol hypersuppression in response to dexamethasone in combat veterans and women with childhood sexual abuse) or (ii) decreased adrenocortical responsiveness (Yehuda et al., 1995b, Stein et al., 1997, Yehuda, 1997, Heim et al., 1998, Heim et al., 2001, Kanter et al., 2001). In contrast to the pattern seen in major depression, patients with PTSD appear to have increased sensitivity of hippocampal glucocorticoid receptor signaling to circulating levels of cortisol, consonant with the hypothesis that increased sensitivity may be critical in mediating hippocampal toxicity in PTSD (Yehuda et al., 1995b, Sapolsky, 2000). However, recent findings of relatively low density glucocorticoid receptors in the primate hippocampus suggest that the stress-neurodegenerative effects of glucocorticoids may in fact be mediated by high density glucocorticoid receptors in neocortical and hypothalamic areas (Sanchez et al., 2000).

Sympathetic nervous system activation associated with trauma exposure also results in norepinephrine and epinephrine release (Tanaka et al., 2000). Neuropeptide Y (NPY), a neurohormone- and neurotransmitter-polypeptide, closely involved in the regulation of both central and peripheral noradrenergic system functioning, is densely concentrated in brain regions known to be activated by stress, e.g., amygdala and hypothalamus (Renshaw and Hinson, 2001). Several lines of evidence in animal models of anxiety indicate that the stress-buffering effects of NPY following central administration are mediated by Y₁ and Y₂ receptors (Sajdyk et al., 1999, Sajdyk et al., 2002), both of which are abundant in the amygdala. NPY appears to inhibit the release of norepinephrine and the firing of locus ceruleus neurons involved in hyperarousal states (Illes and Regenold, 1990). These findings have provided a rationale for studying the role of NPY in PTSD (Heilig et al., 1989, Heilig and Widerlov, 1990, Griebel, 1999). Significantly increased levels of plasma NPY, cortisol, and norepinephrine have been observed in active-duty soldiers exposed to acute, uncontrollable stress during military survival training (Morgan III et al., 2000b, Morgan III et al., 2001). Furthermore, plasma NPY levels obtained after interrogation stress have been negatively correlated with dissociative symptoms in healthy active-duty military personnel participating in an intense training exercise (Morgan III et al., 2001). In combat veterans with PTSD compared with healthy controls, low baseline and blunted yohimbine-stimulated increases in plasma NPY and negative correlations between baseline NPY, degree of combat exposure, PTSD, and panic attacks, have been reported (Rasmusson et al., 1998, Rasmusson et al., 2000). In military settings, combat-related decreases in NPY may in fact be advantageous in lowering the threshold for fight/flight responses, whereas in individuals with chronic PTSD persistent decreases in NPY may contribute to exaggerated startle reactions and increased vigilance. While it is still unclear if NPY levels measured in plasma parallel levels measured in brain and whether different settings (e.g. military survival training vs chronic PTSD) alter the effects of peripheral and central release, preliminary work suggests that stress-induced alterations may contribute, in part, to PTSD and anxiety. The occurrence of low cerebrospinal fluid (CSF) NPY levels in suicide victims (Widdowson et al., 1992), patient with major depression (Widerlöv et al., 1988) and patients with previous suicide attempts, raises the question of whether or not chronic or repeated stress may, in fact, induce lowering of NPY levels (Westrin et al., 1999).

In animal models of anxiety, interactions between NPY, glucocorticoids and CRF (corticotropin-releasing factor) have been demonstrated. Stress (emotional or autonomic) activates the secretion of CRF/cortisol which in turn activates the release of NPY/norepinephrine from neuron populations located in the central nucleus of the amygdala (an area critical to fear conditioning and stress-responding (Gray and Bingaman, 1996, Koob, 1999). CRF and NPY produce reciprocal effects on anxiety in the amygdala and glucocorticoids, like cortisol, can increase the expression of NPY (Heilig et al., 1997, Sheriff et al., 2001). In the aggregate, while studies consistently document long-term dysregulation of both hypothalamic-pituitary-adrenal (HPA) and noradrenergic systems in PTSD (Bremner and Vermetten, 2001, Geriacoti et al., 2001), the pattern of activation in traumatic stress does not appear to be consensual. The trauma associated with intimate partner violence (IPV) encompasses physical and sexual abuse, both of which frequently occur in the context of emotional abuse. Abused women are significantly more likely than non-victims to suffer from psychiatric morbidities, in particular major depression and PTSD (Koss, 1990, Mullen et al., 1988, Bell et al., 1996, Stein and Kennedy, 2001). Based on previous findings in female sexual abuse victims, the objective of this investigation was to examine basal plasma cortisol and NPY in women exposed to intimate partner violence (IPV). We hypothesized that there would be evidence of both low cortisol and NPY in women with IPV in comparison with non-abused controls.