Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict

“…influence on individual stress resilience (Robles and Kiecolt-Glaser, 2003), health (Uchino, 2006; Thoits, 2011) and longevity (House et al., 1988; Holt-Lunstad et al., 2010), making couple relationships, as the most prominent social relationship for nearly all adults, an important predictor of…”

“…have a substantial influence on individual stress resilience (Robles and Kiecolt-Glaser, 2003), health (Uchino, 2006; Thoits, 2011) and longevity (House et al., 1988; Holt-Lunstad et al., 2010), making couple relationships, as the most prominent social relationship for nearly all adults, an…”

“They also correspond to ‘befriending’ mechanisms in women, as opposed to the fight-or-flight physiology in men, as suggested by Taylor et al. (2000), and to the anxiolytic effects which were found in previous research in humans (Meyer-Lindenberg et al., 2011).”

“OT is synthesized in the hypothalamus, from where it exerts its effects on widespread areas in the central nervous system (CNS) (Gimpl and Fahrenholz, 2001; de Bono, 2003; Landgraf and Neumann, 2004).”

“Consequently, research interest has turned to the neurobiological mechanisms underlying the effects of couple interaction on stress and individual health-relevant outcomes (Uchino et al., 1996; Robles and Kiecolt-Glaser, 2003; Karelina and DeVries, 2011).”

“…and affectionate social interactions have a substantial influence on individual stress resilience (Robles and Kiecolt-Glaser, 2003), health (Uchino, 2006; Thoits, 2011) and longevity (House et al., 1988; Holt-Lunstad et al., 2010), making couple relationships, as the most prominent social…”

“…this and in contrast to positive couple interaction (cf. Grewen et al., 2003; Coan et al., 2006; Ditzen et al., 2007; Holt-Lunstad et al., 2008), ongoing couple conflicts have been suggested to constantly increase stress and, thereby, to impair individual health (Kiecolt-Glaser and Newton, 2001).”

“Using this technique, an increasing number of human studies suggest effects of OT on the level of behavioral and neural systems, including social interaction, social memory and stress reactivity (Heinrichs et al., 2009; Bos et al., 2011; Meyer-Lindenberg et al., 2011).”

“Among other factors, this research points to the neuropeptide oxytocin (OT), which has been shown to improve social affiliation and attachment and to reduce anxiety and stress (Young et al., 2001; Donaldson and Young, 2008; Ross and Young, 2009; Insel, 2010).”

“On a central level, OT might modulate ANS responses via the amygdala-cingulate circuit processing of emotional and cognitive responses to stress (Kirsch et al., 2005; Domes et al., 2007).”

“As parallel data on OT effects in both men and women are still rare and, in part, conflicting (for an overview, see Bartz et al., 2011), it is particularly important to investigate both sexes within the same research design.”

“In order to reflect ANS activity and, more precisely, sympathetic activity (Ehlert et al., 2006; Nater et al., 2006; Nater and Rohleder, 2009), sAA was repeatedly assessed from saliva samples.”

“…and timing of the nasal spray administration were chosen based on published research on intranasal OT, behavior and emotions in humans (Meyer-Lindenberg et al., 2011) and on Born and colleagues’ results on cerebrospinal fluid levels after intranasal vasopressin administration (Born et al., 2002).”

“In line with this and in contrast to positive couple interaction (cf. Grewen et al., 2003; Coan et al., 2006; Ditzen et al., 2007; Holt-Lunstad et al., 2008), ongoing couple conflicts have been suggested to constantly increase stress and, thereby, to impair individual health (Kiecolt-Glaser and Newton, 2001).”

“Within the context of social interaction research, couple conflict is a valuable research paradigm, because for all subjects it involves a highly relevant social interaction partner during instructed and observable real-time behavior.”

“Research in couples shows that women tend to express demand behavior more frequently, while men tend to show withdraw behavior (Gottman and Krokoff, 1989; Christensen and Heavey, 1990; Bodenmann et al., 1998), the latter being a behavioral pattern that is consistently predictive of decreases Fig.”

“OT is synthesized in the hypothalamus, from where it exerts its effects on widespread areas in the central nervous system (CNS) (Gimpl and Fahrenholz, 2001; de Bono, 2003; Landgraf and Neumann, 2004).”

“Among other factors, this research points to the neuropeptide oxytocin (OT), which has been shown to improve social affiliation and attachment and to reduce anxiety and stress (Young et al., 2001; Donaldson and Young, 2008; Ross and Young, 2009; Insel, 2010).”

“In women, there were no associations of sAA with emotional arousal or with observed conflict behavior.”

“Among other factors, this research points to the neuropeptide oxytocin (OT), which has been shown to improve social affiliation and attachment and to reduce anxiety and stress (Young et al., 2001; Donaldson and Young, 2008; Ross and Young, 2009; Insel, 2010).”

“cortisol levels, during a couple conflict task (Ditzen et al., 2009).”

“Using this technique, an increasing number of human studies suggest effects of OT on the level of behavioral and neural systems, including social interaction, social memory and stress reactivity (Heinrichs et al., 2009; Bos et al., 2011; Meyer-Lindenberg et al., 2011).”

“On a central level, OT might modulate ANS responses via the amygdala-cingulate circuit processing of emotional and cognitive responses to stress (Kirsch et al., 2005; Domes et al., 2007).”

“Social integration and affectionate social interactions have a substantial influence on individual stress resilience (Robles and Kiecolt-Glaser, 2003), health (Uchino, 2006; Thoits, 2011) and longevity (House et al.”

“Research in couples shows that women tend to express demand behavior more frequently, while men tend to show withdraw behavior (Gottman and Krokoff, 1989; Christensen and Heavey, 1990; Bodenmann et al., 1998), the latter being a behavioral pattern that is consistently predictive of decreases Fig.”

“Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict Beate Ditzen,1 Urs M. Nater,2 Marcel Schaer,3 Roberto La Marca,1 Guy Bodenmann,4 Ulrike Ehlert,1 and Markus Heinrichs5 1Department of Psychology, Division of Clinical Psychology and Psychotherapy, Univers…”

“Among other factors, this research points to the neuropeptide oxytocin (OT), which has been shown to improve social affiliation and attachment and to reduce anxiety and stress (Young et al., 2001; Donaldson and Young, 2008; Ross and Young, 2009; Insel, 2010).”

“However, substantial sex differences might be expected here, as women show different amygdala activation in response to OT than men (Domes et al., 2010).”

“In line with this and in contrast to positive couple interaction (cf. Grewen et al., 2003; Coan et al., 2006; Ditzen et al., 2007; Holt-Lunstad et al., 2008), ongoing couple conflicts have been suggested to constantly increase stress and, thereby, to impair individual health (Kiecolt-Glaser and Newton, 2001).”

“Moreover, effects of a single neuropharmacological challenge might differ considerably from endogenous OT mechanisms, which are modulated by number and sensitivity of OT receptors in different areas of the CNS (Bale et al., 2001; Landgraf and Neumann, 2004).”

“Using this technique, an increasing number of human studies suggest effects of OT on the level of behavioral and neural systems, including social interaction, social memory and stress reactivity (Heinrichs et al., 2009; Bos et al., 2011; Meyer-Lindenberg et al., 2011).”

“Kiecolt-Glaser et al. (1993) and, more recently, Nealey-Moore et al. (2007) observed increased heart rate (HR) and blood pressure (BP) in response to couple conflict in both men and women, as did Flor et al. (1995) in chronic pain patients and healthy controls.”

“As no specific central nervous in-vivo markers are yet available, the interpretation of OT measures in humans is limited (Meyer-Lindenberg et al., 2011; Szeto et al., 2011).”

“Rilling et al. (2011) and Gamer and Buchel (2011) also failed to find such changes in HR.”

“In a most recent review paper, McCall and Singer (2012) presented the hypothesis that OT might modulate the motivational states approach and quiescence, and that Table 1 HLM with increases in sAA as dependent variable Fixed effects Coefficient; B SE T-ratio d.f. P-value Intercept 26.28 13.07 2.01…”

“However, neuropeptides have been shown to gain access to the brain following intranasal administration (Born et al., 2002; Chang et al., 2012).”

“Interestingly, however, in women, these changes were related to affective content and quality of the interaction, whereas in men, these (overall smaller) changes were related to speech rate (Ewart et al., 1991).”

“In female prairie voles, peripheral OT administration reduced HR responses to social isolation (Grippo et al., 2009) and to social stress (resident intruder test) (Grippo et al., 2012).”

“Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict Beate Ditzen,1 Urs M. Nater,2 Marcel Schaer,3 Roberto La Marca,1 Guy Bodenmann,4 Ulrike Ehlert,1 and Markus Heinrichs5 1Department of Psychology, Division of Clinical Psychology and Psychotherapy, Univers…”

“In women, there were no associations of sAA with emotional arousal or with observed conflict behavior.”

“Moreover, intranasal OT increased both sympathetic activity (assessed by PEP) and parasympathetic activity (assessed by high-frequency HR variability) (Norman et al., 2011).”

“(NE) in blood were found to raise during conflict tasks in the laboratory (Malarkey et al., 1994), although again with sex differences, as revealed by significantly higher responses in EPI levels in women than in men.”

“In order to reflect ANS activity and, more precisely, sympathetic activity (Ehlert et al., 2006; Nater et al., 2006; Nater and Rohleder, 2009), sAA was repeatedly assessed from saliva samples.”

“The authors concluded that ‘gender differences in OT may be evident in different categories of social behaviors’ (Fischer-Shofty et al., 2012).”

“In a recent study, ANS responses were triggered by positive couple interactions (as compared to neutral interactions; Nealey-Moore et al., 2007), an effect which was attributed to the emotional nature of the task.”

“Consequently, research interest has turned to the neurobiological mechanisms underlying the effects of couple interaction on stress and individual health-relevant outcomes (Uchino et al., 1996; Robles and Kiecolt-Glaser, 2003; Karelina and DeVries, 2011).”

“Kiecolt-Glaser et al. (1993) and, more recently, Nealey-Moore et al. (2007) observed increased heart rate (HR) and blood pressure (BP) in response to couple conflict in both men and women, as did Flor et al. (1995) in chronic pain patients and healthy controls.”

“However, the opposite is the case in men, in whom results strikingly resemble the data recently reported by Gamer and Buchel (2011).”

“In female prairie voles, peripheral OT administration reduced HR responses to social isolation (Grippo et al., 2009) and to social stress (resident intruder test) (Grippo et al., 2012).”

“Research in couples shows that women tend to express demand behavior more frequently, while men tend to show withdraw behavior (Gottman and Krokoff, 1989; Christensen and Heavey, 1990; Bodenmann et al., 1998), the latter being a behavioral pattern that is consistently predictive of decreases Fig.”

“In humans, an association of OT receptor gene polymorphism rs53576 with cardiac pre-ejection period (PEP) was recently found in males, with A allele carriers displaying higher levels of sympathetic cardiac control, as revealed by lower resting PEP levels (Norman et al., 2012).”

“However, the underlying mechanisms may be different, because OT decreased sympathetic activity measures during couple conflict in women, but increased sympathetic activity measures in men (Ditzen et al., 2013).”

“But it is likely that effects are not only sex-specific, but task specific (some suggest OT does not change the salience of social-emotional cues) and task-specific between sexes (Ditzen et al., 2012).”

“Initial studies in healthy humans show that oxytocin, a nine– amino acid neuropeptide, reduces anxiety and endocrine responses to social stress (18,19), modulates social memory (20–22), promotes trust in social interactions (23), improves the ability to infer the emotional or mental states of others from subtle facial…”