Effects of social exclusion on emotions and oxytocin and cortisol levels in patients with chronic depression
Introduction
Chronic depression (CD) is a severe mental disorder that develops in about 20%–30% of patients with major depressive disorder (MDD) (Angst et al., 2009, Kessler et al., 1994). CD can be characterized by interpersonal problems that may result from disturbed attachment and parenting as well as interpersonal trauma during childhood (Wiersma et al., 2009). This interpersonal dysfunction plays a major role in sustaining a depressive state and has been the focus of novel psychotherapeutic approaches, e.g. the cognitive behavioral system of psychotherapy (CBASP) (Keller et al., 2000). However, little is known about the neurobiological background of impaired interpersonal function in CD.
Theoretically, changes in interpersonal function, i.e. disturbed affiliative behaviors, impaired reading of social cues, impaired establishment of trust, reduced capacity for attachment, and inability to cope with social stressors, may be related to altered regulation of the oxytocin (OT) system (Eckstein and Hurlemann, 2013, Herpertz and Bertsch, 2014, Meyer-Lindenberg et al., 2011, Stanley and Siever, 2010, Striepens et al., 2011). OT, a hypothalamic neuropeptide, stimulates milk ejection and uterine contraction at parturition in mammals and has been linked to prosocial behavior and social approach in humans (Carter, 1998, Kosfeld et al., 2005). High peripheral levels of plasma OT are associated with trust and trustworthiness (Zak et al., 2005), and plasma OT levels can be increased by the warm touch of others (Holt-Lunstad et al., 2008). OT modulates the formation of social memories (Domes et al., 2012) and is involved in reading mental states of other individuals (mentalizing) (Domes et al., 2007). Moreover, it plays a major role in maternal care as well as parental and pair bonding, e.g. Ditzen and coworkers demonstrated an increase of positive communication behavior in relation to negative behavior together with a reduction of salivary cortisol levels after intranasal OT administration during a standard conflict discussion in heterosexual couples (Ditzen et al., 2009). Another study demonstrated a positive association between peripheral OT levels and positive communication in couples using a structured social support interaction task (Gouin et al., 2010).
OT has been shown to exhibit stress-attenuating functions in the Trier Social Stress Test (TSST) (Heinrichs et al., 2003), possibly mediated by a suppressive effect on the HPA axis, as has been shown in male rats (Neumann et al., 2000). Central OT release under stress has been observed in animals, accompanied by secretion of OT into the peripheral circulation (Nishioka et al., 1998, Wotjak et al., 1998). In humans, however, findings regarding the interaction of stress and OT release are inconsistent. Heinrichs and colleagues did not observe OT release in response to the TSST in breastfeeding women (Heinrichs et al., 2001), whereas Pierrehumbert and coworkers found a clear OT response during the TSST in people who had been exposed to traumatizing events such as abuse or potentially fatal illnesses during childhood or adolescence (Pierrehumbert et al., 2010). In addition, this response was related to the respective attachment representations (Pierrehumbert et al., 2012).
Dysregulation of the OT system has been suggested as a putative mechanism that contributes to interpersonal dysfunctions in conditions with social deficits, such as borderline personality disorder (BPD), autistic disorder, and schizophrenia (Goldman et al., 2008, Green et al., 2001, Stanley and Siever, 2010). Women with BPD had lower plasma OT levels than healthy controls, and their plasma OT levels were negatively correlated with a history of childhood trauma (Bertsch et al., 2012). Moreover, BPD patients showed an altered regulation of peripheral OT levels after social exclusion (Jobst et al., 2014), which may underlie the deficits in repairing broken cooperation (King-Casas et al., 2008). There is recent evidence of an altered OT regulation in MDD: Salivary OT levels were found to be reduced in mothers with CD and their children compared to non-depressed mothers (Apter-Levy et al., 2013). Similarly, plasma OT levels were lower in women with MDD than in healthy controls (Yuen et al., 2014). However, to date OT has not been investigated in CD, even though interpersonal deficits are particularly pronounced in this disorder.
Rejection and feeling isolated from others can be experimentally mimicked with social exclusion (ostracism) paradigms, e.g. the Cyberball paradigm. In the Cyberball paradigm, participants are excluded from a computer-based virtual ball-tossing game (Williams and Jarvis, 2006). Using this paradigm, Renneberg and colleagues observed higher scores of negative emotions (anger) after exclusion in BPD patients than in healthy controls. BPD patients felt excluded even when they were not, and the exclusion resulted in dysfunctional behavioral intentions (Renneberg et al., 2012, Staebler et al., 2011).
To our knowledge, so far no studies have addressed the effects of social exclusion on the regulation of emotions, OT and CT levels in patients with CD. Consequently, this pilot study used the Cyberball social exclusion paradigm to investigate the effects of social exclusion on these variables in a group of CD patients and healthy controls.
Section snippets
Participants
Twenty-one inpatients (15 men, 6 women, mean age 45.79 ± 15.55, range: 20–72 yrs) with a diagnosis of CD and 21 healthy controls (15 men, 6 women, mean age 46.43 ± 14.37), matched for gender, age and education, were included in the study. The patients were recruited at the Department of Psychiatry and Psychotherapy, Ludwig Maximilian University of Munich. CD diagnoses and comorbid axis I and II diagnoses were assessed with the German version of the Structural Clinical Interview for DSM-IV (
Sample characteristics
CD patients and HC did not differ significantly with regard to age and education. As expected, depression scores were significantly higher in patients than in HC (Table 1). The CD group had higher CTQ scores for emotional abuse and emotional neglect (moderate trauma as defined by Bernstein and Fink (Bernstein & Fink, 1998) than the HC, indicating early emotional childhood trauma, but not for physical abuse, physical neglect, or sexual abuse. The control group scored below cut-off values on all
Discussion
The main finding of this study was a differential regulation of emotions and OT plasma levels in CD patients and HC after social exclusion (ostracism). Immediately after playing Cyberball, plasma OT levels were lower in patients than at baseline, but higher in healthy controls; the difference in the direction of the change was significant (p = .035*). CT levels did not differ between the groups at any timepoint. Patients' emotional needs were more threatened by the exclusion paradigm (NTQ), and
Conclusions
In summary, our results suggest a higher sensitivity of CD patients to ambiguous threat of social exclusion as we observed an increase of negative emotions and subjective threat to emotional needs and a reduction in OT plasma levels after a social exclusion paradigm (Cyberball) compared to HC. These findings resemble our previous observations in BPD (Jobst et al., 2014). The reduced OT reactivity to a negative bonding stimulus might indicate a disrupted attachment system in patients with
Financial disclosures
F.P. reports having received grants and research support from Brainsway Inc., Jerusalem, Israel, and neuroConn GmbH, Ilmenau, Germany. Until 2010, P.F. received grants and research support from Astra Zeneca; speaker honoraria from Astra Zeneca, BMS, Essex, GSK, Janssen-Cilag, and Lundbeck; and was a speaker or member of the advisory boards of Janssen-Cilag, Astra Zeneca, Lilly, and Lundbeck. The remaining authors reported no biomedical financial interests or potential conflicts of interest.
Role of the funding source
The study was supported by the FöFoLe Program of the Faculty of Medicine of the Ludwig Maximilian University, Munich (grant to A. Jobst, grant number 732).
Author contribution
Andrea Jobst and Frank Padberg have done (1) substantial contributions to conception and design of the work and the acquisition, analysis, and interpretation of data for the work; and (2) drafting of the work or revising it critically for important intellectual content; and (3) final approval of the version to be published' and (4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately
Acknowledgments
This study was part of A. Palagyi's MD thesis at the Faculty of Medicine of the Ludwig Maximilian University, Munich (in preparation).
We thank the following clinicians, psychologists, and students who provided support for the study: Anna Albert, Amalie Boldischar, Tanja Daltrozzo, Jonathan Hall, Eva Holzamer, Constance Jacob, Ariane Klughardt, Aischa Letters, Annika Plöger, Richard Musil, Anja Palagyi, Uli Palm, Elias Seidl, Christina Selberdinger, and Charlotte Wink. We thank also Jacquie
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