Sex differences in associations of arginine vasopressin and oxytocin with resting‐state functional brain connectivity

Rubin, Leah H.; Yao, Li; Keedy, Sarah K.; Reilly, James L.; Bishop, Jeffrey R.; Carter, C. Sue; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L.; Tamminga, Carol A.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Clementz, Brett A.; Hill, S. Kristian; Liao, Wei; Ji, Gong‐Jun; Lui, Su; Sweeney, John A.

doi:10.1002/jnr.23820

Cited by 29 publications

(24 citation statements)

References 80 publications

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“…This difference of plasma Oxt levels between sex is also reported in rats and prairie voles 37 . However, no significant difference in plasma Oxt levels between males and females is reported in humans 34 , 38 , 39 . Further studies are required to clarify whether there is a difference in Oxt levels between sex, as seen in this study, is specific to only rodents.…”

Section: Discussionmentioning

confidence: 91%

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Impact of sex, fat distribution and initial body weight on oxytocin’s body weight regulation

Maejima

Aoyama

Sakamoto

et al. 2017

Sci Rep

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Obesity is considered as a worldwide problem in both males and females. Although many studies have demonstrated the efficiency of oxytocin (Oxt) as an anti-obesity peptide, there is no comparative study of its effect in males and females. This study aims to determine factors (sex, initial body weight, and fat distribution) that may affect the ability of Oxt to regulate body weight (BW). With regard to sex, Oxt reduced BW similarly in males and females under both high fat diet (HFD) and standard chow-fed condition. The BW reduction induced by Oxt correlated with initial BW in male and female mice under HFD conditions. Oxt showed an equal efficacy in fat degradation in both the visceral and subcutaneous fat mass in both males and females fed with HFD. The effect of Oxt on BW reduction was attenuated in standard chow-fed male and female mice. Therefore, our results suggest that administration of Oxt is more effective in reducing BW in subjects with a high initial BW with increased fat accumulation. The present data contains important information for the possible clinical application of Oxt for the treatment of obesity.

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Section: Discussionmentioning

confidence: 91%

“…The plasma samples were extracted by C18 Sep-Pak column (Waters MA) 46 . Plasma Oxt concentration was measured by Oxt EIA kit (Enzo Life Sciences/ Assay Designs NY) 39 . Intra-assay and inter-assay variation was 12.6–13.3% and 11.8–20.9%, respectively.…”

Section: Methodsmentioning

confidence: 99%

Impact of sex, fat distribution and initial body weight on oxytocin’s body weight regulation

Maejima

Aoyama

Sakamoto

et al. 2017

Sci Rep

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“…Due to the sex differences observed in our previous study [ 13 ] and in other studies relating genotypes to empathy [ 41 – 44 ], we conducted an exploratory analysis into males and females separately, to test for a possible sexually dimorphic impact of the C393T genotype on empathy. Of note, none of the IRI scores was near to being significantly associated with C393T genotypes for men (see Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…As we did not find a significant association of the GNAS C393T polymorphism with empathy scores in the complete sample, post hoc testing for sex-specific effects, though guided by our assumptions based on previous research [ 13 , 41 – 44 ], had to take into account the problem of multiple comparisons.…”

Section: Adjustment For Multiple Comparisonsmentioning

confidence: 99%

Sex-specific association of a common GNAS polymorphism with self-reported cognitive empathy in healthy volunteers

2018

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BackgroundIn a recent study, we found associations of a common oxytocin receptor (OXTR) polymorphism with inter-individual differences in empathy, especially with emotional empathy in women. Many other studies found specific associations of oxytocin, arginine-vasopressin, serotonin and dopamine receptor gene polymorphisms with various aspects of trait empathy. As all these receptors belong to the guanine-binding protein (G protein) coupled receptor family, it is a reasonable assumption, that alterations in genes encoding G protein subunits also influence the signal transduction in empathy related circuits. However, to the best of our knowledge, these genomic variations have not yet been studied in genetic research on empathy.MethodsHere, we analysed associations of a common polymorphism of the GNAS gene (C393T) in a previously characterized sample of 421 healthy blood donors (231 M, 190 F; age 18–74). The GNAS gene encodes the G protein adenylyl cyclase stimulator (Gαs) G protein subunit, which activates cyclic adenosine monophosphate (cAMP)-dependent pathways by stimulating the adenylyl cyclase. Cognitive and emotional aspects of dispositional empathy were tested using Davis’ Interpersonal Reactivity Index (IRI).ResultsIn the complete sample, associations of C393T genotype with IRI empathy scores, including cognitive empathy (p = 0.055) and perspective taking (p = 0.057) scores did not reach a level of significance. None of the IRI scores was near to being significantly associated with C393T genotype for men alone. In females, however, genotype was significantly associated with cognitive empathy (r = -.204, p = 0.005) and perspective taking (r = -.209, p = 0.004), accounting for 4.2% and 4.4% of variability. The association of genotype with perspective taking remained significant after adjustment for multiple comparisons (p = 0.045). The 393C-allele, which had been identified as a risk factor in several medical conditions such as hypertension, obesity and diabetes, was associated with higher cognitive empathy compared to the T allele in our sample.ConclusionsThe results suggest a significant association of GNAS C393T genotypes with the cognitive empathic capacity of perspective taking. This association could only be found in female participants.

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“…First, there are alterations in OT and AVP systems in schizophrenia (Rubin et al, 2014). Second, these hormones are known to be differentially important contributors to resting brain function in healthy individuals, and these effects are seen in networks important for emotion and cognition (Rubin et al, 2017) and which are impacted in schizophrenia (Lui et al, 2015). For example, in healthy individuals higher AVP levels in men and higher OT levels in women have been associated with reductions in functional network connectivity of the orbital frontal cortex, which is important in emotion regulation (Rubin et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Peripheral oxytocin and vasopressin modulates regional brain activity differently in men and women with schizophrenia

Rubin

Li²,

Yao³

et al. 2018

Schizophrenia Research

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Background Oxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients. Methods OT and AVP serum concentrations were assayed in 35 individuals with schizophrenia (23 men) and 60 controls (24 men) from the Chicago BSNIP study site. Regional cerebral function was assessed with resting state fMRI by measuring the amplitude of low-frequency fluctuations (ALFF) which are believed to reflect intrinsic spontaneous neuronal activity. Results In female patients, lower OT levels were associated with lower ALFF in frontal and cerebellar cortices (p’s<0.05) and in female controls AVP levels were inversely associated with ALFF in the frontal cortex (p=0.01). In male patients, lower OT levels were associated with lower ALFF in the posterior cingulate and lower AVP levels were associated with lower ALFF in frontal cortex (p’s<0.05). In male controls, lower OT levels were associated with lower ALFF in frontal cortex and higher ALFF in the thalamus (p’s<0.05). There were some inverse ALFF-behavior associations in patients. Conclusions Alterations in peripheral hormone levels are associated with resting brain physiology in a sex-dependent manner in schizophrenia. These effects may contribute to sex differences in psychiatric symptom severity and course of illness in schizophrenia.

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Sex differences in associations of arginine vasopressin and oxytocin with resting‐state functional brain connectivity

Cited by 29 publications

References 80 publications

Impact of sex, fat distribution and initial body weight on oxytocin’s body weight regulation

Impact of sex, fat distribution and initial body weight on oxytocin’s body weight regulation

Sex-specific association of a common GNAS polymorphism with self-reported cognitive empathy in healthy volunteers

Peripheral oxytocin and vasopressin modulates regional brain activity differently in men and women with schizophrenia

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