Elsevier

Psychoneuroendocrinology

Volume 38, Issue 12, December 2013, Pages 2831-2843
Psychoneuroendocrinology

Oxytocin and psychotherapy: A pilot study of its physiological, behavioral and subjective effects in males with depression

https://doi.org/10.1016/j.psyneuen.2013.05.014Get rights and content

Summary

Individual psychotherapy is an important treatment for a number of psychiatric conditions and involves a unique form of human attachment. This raises the question of whether oxytocin (OT), the paradigmatic “attachment hormone”, may have benefits in this context. In this randomized, double-blind, crossover trial, we gave male psychiatric outpatients with major depressive disorder 40 IU intranasal OT or placebo before a videotaped session with a therapist and measured a number of subjective, physiological, and behavioral parameters. We report three main findings. Surprisingly – in contrast to prior reports of OT's anxiolytic properties – we found OT caused an increase in anxiety over the course of the therapy session. Secondly, though it had no main effect on cortisol, eye contact, or overall behavior, we did find that OT caused a decrease in nonverbal behaviors that cut off social contact, after controlling for level of depressive symptoms. Lastly, we replicated prior findings that OT improves social cognition (performance on the reading the mind in the eyes test (RMET)), albeit in a depressed patient group. These results inform future studies of oxytocin and psychotherapy and suggest that in certain clinical populations and contexts, OT has heterogeneous subjective effects which may include acute anxiogenesis. Moreover, the similarity of some of these acute effects to those of single-dose serotonergic antidepressants raises interesting questions about the potential antidepressant benefits of chronic OT administration.

Introduction

Though a variety of other “delivery systems” for psychotherapy exist (i.e. computer-driven modules, group therapy), face-to-face, individual psychotherapy is an important treatment for a wide variety of psychiatric conditions (de Maat et al., 2009, Miklowitz, 2006, Trivedi et al., 2011). From the broadest perspective, certain aspects of a psychotherapeutic relationship exist over and above specific therapeutic techniques, and replicate other primary attachment relationships (i.e. parent–child) (Bowlby, 1977, Daniel, 2006, Holmes, 1993, Sable, 2004). In keeping with this broad, attachment-anchored perspective, adult attachment style has been shown to be an important factor in psychotherapy outcomes (Daniel, 2006, Fonagy et al., 1996, Levy et al., 2011), as has therapeutic alliance (Horvath et al., 2011), a proxy for a healthy adult attachment bond. As such, it has been proposed that oxytocin (OT), the paradigmatic attachment hormone, may have value as an “augmentation agent” in individual psychotherapy (Macdonald and Macdonald, 2010). From a psychobiological perspective, facilitation of the benefits of a psychotherapy relationship seems a natural extension of OT's salubrious role in other attachment relationships (Ditzen et al., 2009, Gordon et al., 2010, Heinrichs et al., 2003, Schneiderman et al., 2012, Seltzer et al., 2010).

In point of fact, several studies have directly examined the impact of OT in psychotherapeutic situations. In a placebo-controlled trial of OT as an adjunct to exposure therapy in patients with social anxiety disorder, Guastella et al. found that OT improved mental representations of self, but had otherwise modest benefits over and above the gold-standard exposure therapy (Guastella et al., 2009). In a second study related to psychotherapeutic alliance, OT augmented hypnotic responding, possibly through neural networks related to the connection between hypnotherapist and patient (Bryant et al., 2012). Other experiments relevant to OT's role in psychotherapy include those indicating that in certain patients it improves the ability to take in compassion (Rockliff et al., 2011), reflect on positive aspects of their own personality (Cardoso et al., 2012), share personal information (Mikolajczak et al., 2010), access secure attachment representations (Buchheim et al., 2009), recognize emotion (Van IJzendoorn and Bakermans-Kranenburg, 2012), process and remember social information (Striepens et al., 2011 for review), and trust others (especially in-group members) (Keri and Kiss, 2011, Van IJzendoorn and Bakermans-Kranenburg, 2012). Furthermore, in certain patients who have difficulty engaging in therapy due to anxiety, OT's stress-reducing profile, including its ability to decrease autonomic arousal and anxiety (de Oliveira et al., 2012a, de Oliveira et al., 2012b, Heinrichs et al., 2003, Keri and Kiss, 2011) and dampen the HPA axis reactivity (Cardoso et al., 2013, Ditzen et al., 2009, Quirin et al., 2011), may be beneficial (but see also Grillon et al., 2012).

Another way OT may benefit individuals in psychotherapy is through its prosocial effects on behavior: the observable manifestation of the “attachment behavioral system” posited by Bowlby to underlie mammalian bondedness (Bowlby, 1969/1982). Predating the recent upsurge in research on OT's role in human behavior, diverse disciplines have taken an ethological perspective on human dyads and studied human nonverbal behavior in relationships. These fields include developmental psychology (Brazelton et al., 1975, Main, 2000), social psychology (Ambady et al., 2001, Borkenau et al., 2004, Eckman and Friesen, 1969), personality psychology (Oltmanns et al., 2004), marital studies (Gottman, 1994), and psychiatry (Fossi et al., 1984, Schelde, 1998, Troisi, 1999). Supporting the importance of these nonverbal behaviors are a diverse collection of studies demonstrating that so-called “thin-slices” of nonverbal behavior correlate with affiliative emotions (Gonzaga et al., 2006), intelligence (Borkenau et al., 2004), deception (Albrechtsen et al., 2009), socioeconomic status (Kraus and Keltner, 2009), relationship outcomes (Carrere and Gottman, 1999), as well as treatment and remission in depression (Bouhuys and Van den Hoofdakker, 1993, Geerts et al., 2009, Hale et al., 1997). Specifically in regards to psychotherapy, awareness and microanalysis of nonverbal relational behavior figures prominently in the technical interventions in at least one evidence-based form of psychotherapy (short-term psychodynamic psychotherapy, STPP) (Abbass et al., 2006). Moreover, these typically nonconscious interpersonal behaviors often yield more verdical information than verbal reports (Gotlib and Robinson, 1982, Troisi et al., 2000). That said, although analysis of behavioral measures in humans has evolutionary significance, ecological coherence and translational applicability, this form of analysis is more labor-intensive than either biological markers or subjective ratings, inhibiting its widespread use (Geerts and Brune, 2009).

In spite of its shortcomings, an ethological and behavioral perspective is particularly salient in regards to OT, which has been shown to bias relational behavior in a prosocial direction in a diverse variety of mammalian species (Kendrick et al., 1987, Madden and Clutton-Brock, 2011, Neumann, 2008, Saito and Nakamura, 2011, Smith et al., 2010, Snowdon et al., 2010). Specifically in regards to humans, convergent evidence examining the endogenous OT system has validated the cross-species nature of attachment behavior by demonstrating that OT levels are related to expression of affiliative behavior in parent–infant samples (Feldman et al., 2011, Gordon et al., 2010, Strathearn et al., 2009), between mothers and daughters (Seltzer et al., 2010) and between couples (Gonzaga et al., 2006, Gouin et al., 2010, Schneiderman et al., 2012). Subtypes of the OT receptor are related to prosocial temperament (Tost et al., 2010), prosocial decision-making (Israel et al., 2009), thin-slices of prosocial behavior (Kogan et al., 2011), sensitive parenting behavior (Bakermans-Kranenburg and van Ijzendoorn, 2008) and pair-bonding behavior (Walum et al., 2012). Regarding exogenous OT, experiments specifically looking at behavioral measures have demonstrated that intranasal OT impacts a variety of attachment-related behaviors, increasing cooperation (Rilling et al., 2012), trusting behavior (Baumgartner et al., 2008, Kosfeld et al., 2005), eye contact (Guastella et al., 2008a), paternal (Naber et al., 2010), maternal (Bakermans-Kranenburg et al., 2012), and couple communication behavior (Ditzen et al., 2009), though we also note that a growing literature on OTs darker, “us vs. them” side (Bartz et al., 2011a, De Dreu et al., 2011, Grillon et al., 2012, Shamay-Tsoory et al., 2009) introduces the possibility for person- and context-dependent negative effects in certain interpersonal situations.

Based on this review of the role of attachment in psychotherapy, the role of the OT in diverse processes related to psychotherapy, and the relevance of an ethological approach to both of these topics, we designed a pilot study to examine the impact of OT on a suite of effects (subjective, physiological, endocrinological, behavioral) in a unique setting designed to model a first individual therapy session. Our hypothesis was that OT would decrease subjective anxiety and withdrawal-related behaviors, bias nonverbal behavior in a prosocial direction, and cause decreases in cortisol. Secondarily, we hypothesized that OT would improve social cognition.

Section snippets

Sample and procedure

To capture a naturalistic sample, we recruited 18 psychiatric outpatients who were in current treatment into this double-blind placebo-controlled crossover study. One subject with bipolar diagnosis was excluded and the remainder of the subjects were diagnosed with major depressive disorder. All diagnoses were confirmed via the MINI (Mini international neuropsychiatric interview) (Sheehan et al., 1998), along with the corroboration of the patient's treating clinicians. Main inclusion criteria

Demographics/clinical characteristics

In this trial, all subjects were in current outpatient psychiatric treatment and taking antidepressant medication. Table 2 lists other demographic information on participants. Seventeen male outpatients (mean age 43.6, SD 12.2, age range 20–64) who met criteria for MDD were included in this study. The average Beck Depression Inventory-FS score at entry to the study was 6.1 ± 3.5, consistent with mild current depressive symptoms; a majority of patients (88%) had a comorbid anxiety disorder.

STAI, PANAS

Discussion

The primary aim of the current study was to examine the hypothesis that OT would have beneficial subjective, physiological and behavioral effects in a “first contact” therapy session. Overall, our results were mixed, partly supporting and partly disconfirming our hypotheses. Specifically – in contrast to reports describing its ability to attenuate subjective anxiety (de Oliveira et al., 2012a, de Oliveira et al., 2012b, Heinrichs et al., 2003) – we found that OT actually increased it. Though

Role of the funding source

There is no funding source role for this research.

Conflict of interest

DF is a named inventor on a patent filed by UCSD relating to oxytocin and cognition.

All other authors reported no biomedical financial interests or potential conflicts of interest.

Acknowledgements

Thanks to our volunteer therapists: Allison Hadley, MD, Alana Iglewicz, MD, Pilar Placone, PhD, and to Mona Abdel-Hamid, dipl psych, (MA) and Yasmeen Iqbal, M.A., for help with video ratings.

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