Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction

“The iterated Prisoner’s Dilemma game is a model for relationships based on reciprocal altruism (Trivers, 1971).”

“It has been shown to do so in other experimental contexts (Baumgartner et al., 2008; De Dreu, 2012a,b; Israel et al., 2012; Kosfeld et al., 2005).”

“05 corrected for multiple comparisons based on the volume of clusters of contiguous voxels, using a 3D extension (implemented in BrainVoyager) of a 2D Monte Carlo simulation procedure (Forman et al., 1995).”

“There is growing interest in the use of intranasal oxytocin (OT) as a potential treatment for a variety of psychiatric disorders (Heinrichs et al., 2009; Meyer-Lindenberg et al., 2011; Striepens et al., 2011), including autism spectrum disorders (ASD), a group of neurodevelopmental disorders with an estimated prevalen…”

“Within the same region of interest, defined independently of both samples using an ROI from Rilling et al (2002), we tested for drug and partner effects on the response to reciprocated cooperation among women.”

“Given the role of the ventral striatum in reward processing (Knutson et al., 2005; O’Doherty, 2004; Schultz et al., 2000), these results suggest that intranasal OT may augment the experienced (player 1) or anticipated (player 2) reward from mutual cooperation between men but not between women.”

“It has been shown to do so in other experimental contexts (Baumgartner et al., 2008; De Dreu, 2012a,b; Israel et al., 2012; Kosfeld et al., 2005).”

“In fact, across five such recently published studies, 71 of 78 participants were male (Anagnostou et al., 2012; Andari et al., 2010; Guastella et al., 2010; Hollander et al., 2003, 2007).”

“Given the role of the ventral striatum in reward processing (Knutson et al., 2005; O’Doherty, 2004; Schultz et al., 2000), these results suggest that intranasal OT may augment the experienced (player 1) or anticipated (player 2) reward from mutual cooperation between men but not between women.”

“Given the role of the ventral striatum in reward processing (Knutson et al., 2005; O’Doherty, 2004; Schultz et al., 2000), these results suggest that intranasal OT may augment the experienced (player 1) or anticipated (player 2) reward from mutual cooperation between men but not between women.”

“In fact, across five such recently published studies, 71 of 78 participants were male (Anagnostou et al., 2012; Andari et al., 2010; Guastella et al., 2010; Hollander et al., 2003, 2007).”

“There is growing interest in the use of intranasal oxytocin (OT) as a potential treatment for a variety of psychiatric disorders (Heinrichs et al., 2009; Meyer-Lindenberg et al., 2011; Striepens et al., 2011), including autism spectrum disorders (ASD), a group of neurodevelopmental disorders with an estimated prevalen…”

“Sabrina Stair collected and analyzed the data.”

“Studies with female subjects are complicated by the fact that estradiol, levels of which vary across the menstrual cycle, is known to induce OT receptors (Champagne et al., 2001; Pedersen et al., 1994) and presumably increase responsivity to OT.”

“…rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women.”

“On the other hand, intranasal OT increased the amygdala response to fearful faces in women, but had no effect on the amygdala response to angry or happy faces (Domes et al., 2007a,b; Domes et al., 2010).”

“The left amygdala ROI was defined as a 10 mm-side cube centered on the coordinates of the activation peak reported in Gamer et al. (Gamer et al., 2010), after converting from MNI to Talairach coordinates, and then manually adjusting the ROI location to more closely match the anatomical features of the MNI template.”

“Studies with female subjects are complicated by the fact that estradiol, levels of which vary across the menstrual cycle, is known to induce OT receptors (Champagne et al., 2001; Pedersen et al., 1994) and presumably increase responsivity to OT.”

“Given significant cross-reactivity between OT and AVP systems (Audigier & Barberis, 1985), coupled with evidence that OT and AVP can have similar effects on behavior (Bielsky & Young, 2004), it is important to determine whether intranasal OT and AVP activate similar or different brain regions.”

“For example, if central AVP levels are higher in men, additional exogenous AVP could saturate AVP receptors and cross-react with OT receptors (Manning et al., 2012; Young and Flanagan-Cato, 2012) and this, in turn, could drive increases in activity in regions involved in reward and bonding.”

“This activation also encompassed basal forebrain regions rich in OT receptors (Loup et al., 1991), including the preoptic area, basal nucleus of Meynert, diagonal band of Broca, and lateral septum (supplementary Table 1, Fig.”

“In fact, across five such recently published studies, 71 of 78 participants were male (Anagnostou et al., 2012; Andari et al., 2010; Guastella et al., 2010; Hollander et al., 2003, 2007).”

“Among rodents, the social bonds supporting both maternal care and female adult partner preference are heavily dependent on interactions between OT and DA in the ventral striatum (Skuse and Gallagher, 2009; Young et al., 2005).”

“However, in women, AVP enhanced affiliative facial motor patterns in response to unfamiliar female faces and increased perception of friendliness in those faces (Thompson et al., 2006).”

“For example, although AVP injections in the anterior hypothalamus of male hamsters stimulate aggression in the resident-intruder test, the same injections decrease aggression in females (Albers, 2012).”

“There is growing interest in the use of intranasal oxytocin (OT) as a potential treatment for a variety of psychiatric disorders (Heinrichs et al., 2009; Meyer-Lindenberg et al., 2011; Striepens et al., 2011), including autism spectrum disorders (ASD), a group of neurodevelopmental disorders with an estimated prevalen…”

“In addition to ASD, studies have begun to investigate the effectiveness of intranasal OT as a treatment for schizophrenia, social anxiety disorder and depression (Striepens, et al., 2011).”

“…to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of various psychiatric disorders involving social behavioral deficits (Goodson & Thompson, 2010; MeyerLindenberg, Domes, Kirsch, & Heinrichs, 2011; Yamasue, Kuwabara, Kawakubo, & Kasai, 2009).”

“In addition to ASD, studies have begun to investigate the effectiveness of intranasal OT as a treatment for schizophrenia, social anxiety disorder and depression (Striepens, et al., 2011).”

“Our results also show that AVP can contribute to cooperation among men, and call for greater investigation of its role as a potential treatment for males with ASD, although potential pleitropic effects on stress and anxiety should be carefully investigated (Goodson, 2013; Shalev, et al., 2011).”

“, 2006), along with evidence that AVP is more influential in males compared with females (Young et al., 2005), we did not expect AVP to augment activation in BNST, lateral septum and stria terminalis in women as it did in men.”

“Given significant cross-reactivity between OT and AVP systems (Audigier & Barberis, 1985), coupled with evidence that OT and AVP can have similar effects on behavior (Bielsky & Young, 2004), it is important to determine whether intranasal OT and AVP activate similar or different brain regions.”

“Such effects may be attributable to developmental influences on OTreceptor expression (Bales and Perkeybile, 2012), which in turn should affect responsiveness to intranasal OT.”

“If it does the same for males with ASD, it could potentially help to normalize their social behavior by increasing their motivation to participate in and therefore learn from social interactions (Stavropoulos and Carver, 2013).”

“For example, if central AVP levels are higher in men, additional exogenous AVP could saturate AVP receptors and cross-react with OT receptors (Manning et al., 2012; Young and Flanagan-Cato, 2012) and this, in turn, could drive increases in activity in regions involved in reward and bonding.”

“Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of various psychiatric disorders involving social behavioral deficits (Goodson and Thompson, 2010; Meyer-Lindenberg et al., 2011; Yamasue et al., 2009).”

“Women have higher CSF oxytocin levels than men do (Altemus et al., 1999).”

“Our results also show that AVP can contribute to cooperation among men, and call for greater investigation of its role as a potential treatment for males with ASD, although potential pleitropic effects on stress and anxiety should be carefully investigated (Goodson, 2013; Shalev et al., 2011).”

“Importantly, both OT and AVP increased activity in males during cooperation, while in females, OT and AVP either decreased activity or had no effect in these and other regions (Rilling et al., 2014).”

“indistinguishable from the baseline activation patterns in women following placebo (77).”

“Intranasal VP increased activity in areas such as the striatum, basal forebrain, insula, amygdala, and hippocampus in men, but decreased or had no effect in women (Rilling et al., 2012; 2014).”