Serum oxytocin levels are elevated in body dysmorphic disorder and related to severity of psychopathology

https://doi.org/10.1016/j.psyneuen.2019.104541Get rights and content

Highlights

  • We examined endogenous serum oxytocin levels in body dysmorphic disorder.

  • People with BDD displayed higher oxytocin levels.

  • Higher oxytocin levels significantly correlated with BDD symptom severity.

Abstract

The neurobiological mechanisms underlying the pathophysiology of body dysmorphic disorder (BDD) are not well-understood. Oxytocin is a central nervous system peptide which regulates socioemotional functioning and may mediate physiologic processes in a range of psychiatric disorders, particularly those characterized by interpersonal dysfunction. Examining the role of oxytocin in the development and maintenance of BDD may elucidate new targets for intervention. The present study examined endogenous serum oxytocin levels in BDD. Given the prominent deficits in social functioning in BDD, we expected that BDD would be characterized by low basal serum oxytocin concentrations, relative to healthy controls, and that low oxytocin levels would be associated with BDD symptom severity as well as poor performance on measures of social cognition. Twenty individuals with BDD and 28 healthy controls completed a fasting blood draw consisting of frequent sampling every five minutes for one hour to measure pooled levels of oxytocin. Contrary to our hypotheses, people with BDD displayed higher concentrations of oxytocin, compared to their healthy control counterparts, and their oxytocin levels were positively correlated with BDD symptom severity. There were no associations between oxytocin levels and measures of social cognition. These findings suggest increased production of endogenous oxytocin in BDD. Prospective research is needed to determine whether this contributes to or is a consequence of BDD symptomatology.

Introduction

Body dysmorphic disorder (BDD) is an obsessive-compulsive related disorder affecting approximately 1.7–2.4 % of the general population (Buhlmann et al., 2010; Koran et al., 2008; Rief et al., 2006). BDD often causes severe disability, such that many patients stop working, drop out of school, and even become housebound due to appearance-related concerns (Didie et al., 2008; Phillips et al., 2005b, c). Estimates suggest that between 24–28 % of patients with BDD attempt suicide in their lifetime (Phillips et al., 2005a; Phillips, 2007). Despite its prevalence and impairment, little is known about neuroendocrine contributions to BDD. This is a major unexamined gap in the literature, as it has important implications for advancing the discovery of markers of BDD illness and illness progression, as well as the identification of new targets for intervention.

Accumulating evidence suggests that the neurohormone oxytocin mediates physiologic processes in a range of psychiatric illnesses, particularly those characterized by social impairment (Bakermans-Kranenburg and van Ijzendoorn, 2013; Neumann and Slattery, 2016). Oxytocin is a nine amino acid peptide that is produced in specialized cells of the hypothalamus and has diverse effects throughout the brain via paracrine and synaptic release mechanisms, and throughout the body via release from the posterior pituitary gland into the peripheral circulation (Dölen, 2015). Central release and peripheral secretion may occur simultaneously or independently depending on the behavioral context and stimuli that trigger release (Neumann and Landgraf, 2012). As a neuromodulator, oxytocin plays a role in the regulation of socioemotional functioning (Leppanen et al., 2017) and has antidepressant and anxiolytic effects in animal models and human studies (Labuschagne et al., 2010; Neumann and Slattery, 2016; Scantamburlo et al., 2007). In people with BDD, experimental studies have demonstrated that intranasal administration of oxytocin may alter certain higher-order attributional biases (Fang et al., 2019) and resting state functional connectivity between brain regions involved in visual processing (Grace et al., 2019), which suggests that oxytocin may play a role in the pathophysiology of BDD. Oxytocin has also been implicated as a candidate biomarker of certain psychiatric disorders associated with BDD, such as psychosis, depression, anxiety disorders, and eating disorders, although the evidence has been mixed (Rutigliano et al., 2016). For example, in social anxiety disorder (which shares significant overlap with BDD in terms of social avoidance; Fang and Hofmann, 2010), plasma oxytocin levels were lower than controls when measured after the “Trust Game,” a neuroeconomic test examining trust behavior (Hoge et al., 2012), but were found to not differ from healthy controls when measured at rest (Hoge et al., 2008). Among individuals with obsessive-compulsive disorder (OCD), one study found elevated levels of oxytocin in cerebrospinal fluid (CSF) via lumbar puncture, relative to healthy controls (Leckman et al., 1994), but another study found no between-group differences (Altemus et al., 1999). As body image disorders, BDD and anorexia nervosa (AN) have similar clinical features, and studies in AN have shown lower basal levels of oxytocin in serum (Lawson et al., 2011) and plasma (Monteleone et al., 2016), but peripheral oxytocin secretion in AN may be increased after meals, compared to controls (Lawson et al., 2012). Some evidence also suggests that serum and CSF oxytocin levels in AN may depend on weight-recovered status (Lawson et al., 2012; Frank et al., 2000). In addition, low fasting oxytocin levels were associated with alexithymia when analyzed across women with acute and partially recovered AN and female healthy controls (Schmelkin et al., 2017), as well as greater eating disorder psychopathology and anxiety in partially-recovered patients with AN (Afinogenova et al., 2016). Overall, the role of oxytocin in the pathophysiology of BDD and related disorders remains to be fully understood.

Within the domain of socioemotional processing, previous research examining the role of oxytocin suggests more consistent evidence in favor of oxytocin enhancing the recognition of basic emotions and expression of positive emotions in healthy humans rather than in clinical populations (Leppanen et al., 2017). However, one study in a BDD-related population (patients with eating disorders) found that exogenous administration of oxytocin led to an enhancement of emotion recognition in patients with bulimia nervosa, but not AN (Kim et al., 2015). Inconsistent findings in clinical samples may possibly be due to high between-disorder and within-disorder heterogeneity (Leppanen et al., 2017). Given that BDD is characterized by pervasive social avoidance and deficits in socioemotional processing, such as selective attentional biases to imagined flaws in one’s own and corresponding areas in unfamiliar others’ faces (Greenberg et al., 2014; Grocholewski et al., 2012), emotion recognition biases for contempt and anger (Buhlmann et al., 2006), and biases in perspective taking (Buhlmann et al., 2015), oxytocin may be a plausible biomarker of social cognitive deficits in individuals with BDD.

To date, no studies have assessed oxytocin levels in BDD. Our primary goal was to assess basal endogenous concentrations of oxytocin in individuals with BDD compared to healthy controls and determine their associations with markers of BDD pathology (e.g., BDD symptom severity) and impairments in various domains of social cognition. Based on previous reports of lower oxytocin levels associated with increased pathology and impaired social cognition in a related disorder, namely current or past AN (Afinogenova et al., 2016; Schmelkin et al., 2017), we hypothesized that BDD would be characterized by low basal serum oxytocin concentrations, relative to healthy controls, and that low oxytocin levels would be associated with increased BDD pathology and poor performance on measures of social cognition. To determine whether the association between oxytocin and BDD pathology occurs independent of related symptoms, we assessed subjective mood, anxiety, and attachment symptoms. Given the role of oxytocin in stress regulation (Neumann and Slattery, 2016), we also measured cortisol levels to explore whether oxytocin levels would be associated with a heightened stress response in BDD. We expected that low oxytocin levels would correlate with higher cortisol levels as well as greater subjective stress and anxiety levels.

Section snippets

Participants

We studied 50 male and female participants between ages 18–51. Individuals with BDD (n = 20, 11 females) were recruited from a specialty outpatient program and age-matched healthy controls (n = 30, 14 females) were recruited from the community. Participants in the BDD group met criteria for a principal diagnosis of BDD according to DSM-IV-TR1

Participant characteristics

See Table 1 for a full description of participant characteristics. The final sample consisted of 48 participants (mean age = 28.60 years, SD =  8.41). Participants were balanced by sex (n = 25 females, 52.08 %) and were mostly non-Hispanic (n = 38, 79.17 %). Individuals with BDD reported an average of 3 body areas of concern, which included concerns about hair (n = 12), skin (n = 11), nose (n = 4), stomach/midsection (n = 4), legs (n = 3), overall face (n = 3), arms (n = 3), eyes (n = 3),

Discussion

This is the first study to assess endogenous oxytocin levels in BDD. A strength of our approach was the use of an integrated measure of oxytocin secretion based on frequent sampling over the course of one hour. We found that fasting oxytocin levels were elevated in BDD compared to controls, and oxytocin levels correlated positively with BDD symptom severity.

Although in the opposite direction of our hypothesis, our finding that pooled oxytocin levels were higher in BDD is consistent with

Conclusions

We have demonstrated higher oxytocin levels among people with BDD, compared to healthy controls, and a positive association between oxytocin levels and BDD symptom severity. Future prospective studies in both sexes are needed to evaluate whether high basal peripheral oxytocin levels contribute to and/or result from clinical features of BDD.

Declaration of Competing Interest

A.F. has received salary support from Telefonica Alpha, Inc.

C.B. and F.P. have no financial disclosures to report.

R.J.J. has received salary support from Telefonica Alpha, Inc. She is paid as a faculty member of the Massachusetts General Hospital Psychiatry Academy for filming role plays for course content and for moderating the course discussion boards. She also receives book royalties from Hogrefe Publishing.

L.G. is on the Scientific Advisory Board for Sage Bionetworks, a nonprofit technology

Acknowledgments

This work was supported by a Harvard University Mind Brain Behavior Interfaculty Initiative Award and National Institute of Mental Health Career Development Awards (K23 MH109593-04 and K24 MH120568). This work was also supported by the protocol nurses and administrative staff at the MGH Translational Clinical Research Center (TCRC) under Grant Number 1UL1TR001102. The authors would like to thank the following individuals for their assistance in preparing and conducting the study protocol: Dylan

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