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

Abstract

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.

Is Oxytocin “Nature’s Medicine”?

“…For example, studies of the effects of oxytocin on neural responses measured by functional magnetic resonance imaging have revealed marked sex differences in the effects of even a single intranasal treatment (Domes et al, 2010). Connectivity in the orbital frontal cortex, which is important in emotion processing, was correlated with oxytocin in women and vasopressin in men (Rubin et al, 2018). The developmental effects of these peptides are of special concern and are different in males and females (Carter, 2003;Bales et al, 2007) and in the face of adversity and stressful experiences.…”

“…A recurring issue in attempts to use oxytocin as a medicine is the need to understand its role in behavioral and physiologic adaptations and resilience in the face of stressors and trauma. Nervous system activity, neural connectivity, and responses to social stimuli have been related to peripheral peptide concentrations in both neurotypical individuals ( Lancaster et al, 2018a ) and those diagnosed with various mental illnesses, such as schizophrenia or bipolar disorder ( Rubin et al, 2018 ). Peripheral levels of oxytocin and vasopressin or variations in their receptors have been associated with function in Williams syndrome ( Dai et al, 2012 ), autism spectrum disorders ( Oztan et al, 2018b ), schizophrenia ( Rubin et al, 2014 , 2018 ), depression ( Cyranowski et al, 2008 ; Goekoop et al, 2011 ), postpartum depression ( Zelkowitz et al, 2014 ; Bell et al, 2015 ), borderline personality disorders ( Brune, 2016 ), eating disorders ( Aulinas et al, 2019 ), and substance abuse ( Buisman-Pijlman et al, 2014 ).…”

Oxytocin and Sensory Network Plasticity

“…Finally, though much attention has been paid to the link between oxytocin signaling and ASDs, a number of other neuropsychiatric illnesses also show provocative links to oxytocin signaling (Kawamura et al, 2010;Rubin et al, 2014Rubin et al, , 2018Kirsch, 2015). Thus, discovering the neural and circuitrelevant mechanisms of oxytocin signaling will yield important information regarding the etiology of these diseases.…”

Acoustic prepulse inhibition in male and female prairie voles: Implications for models of neuropsychiatric illness

“…Despite this strong rationale for use as a model studying social behaviors, voles have been underutilized to model social deficits in neuropsychiatric illnesses, likely due to their high behavioral and genetic heterogeneity compared to other laboratory rodents [2]. However, as recent treatments for schizophrenia and autism spectrum disorder (ASD) have targeted oxytocin as a potential therapeutic target [4][5][6][7], the prairie vole may offer valuable insight into the neurochemistry of such mental illnesses [6,[8][9][10].…”