The effects of intranasal oxytocin on the efficacy of psychotherapy for major depressive disorder: a pilot randomized controlled trial.

BACKGROUND: Although both pharmacotherapy and psychological treatments are considered to be efficacious in the treatment of major depressive disorder (MDD), one third of patients do not respond to treatment and many experience residual symptoms post-treatment. In this double-blind placebo-controlled randomized control trial (RCT), we assessed whether intranasal oxytocin (OT) augments the therapeutic efficacy of psychotherapy for MDD and improves the therapeutic alliance. METHODS: Twenty-three volunteers (12 female) with MDD underwent 16 sessions of interpersonal therapy. Prior to each session, volunteers self-administered 24 International Units of intranasal OT (n = 12; Syntocinon) or placebo (n = 11). Depressive symptoms were assessed with the Inventory of Depressive Symptomatology at pre- and post-treatment, and at a six month follow-up. RESULTS: Multilevel modeling found a significant effect of OT on the negative slope of depressive symptoms over time (p < 0.05), with medium-large effect sizes at post-treatment (Cohen's d = 0.75) and follow-up (Cohen's d = 0.82). Drug intervention also predicted the intercept when examining the weekly ratings of the therapeutic alliance (p < 0.05), such that volunteers receiving OT, relative to placebo, reported improved therapeutic alliance at session 1. The agreement of goals between therapists and participants, a facet of the therapeutic alliance, mediated the relationship between drug intervention and clinical outcome. CONCLUSION: In this pilot study, the administration of intranasal OT, relative to placebo, improved the therapeutic alliance at the beginning of therapy and therapeutic efficacy of psychotherapy in persons with MDD. Future RCTs should attempt to replicate these findings in larger samples with different therapeutic modalities (ClinicalTrials.gov: NCT02405715).

Family dysfunction, stressful life events, and mental health problems across development in the offspring of parents with an affective disorder.

BACKGROUND: Offspring of parents with affective disorders (OAD) are at risk of developing a wide range of mental disorders. Deficits in the rearing environment and high levels of stress are well-known risk factors for negative outcomes in OAD. Building on prior research, we aim to examine the longitudinal relationships between family dysfunction, stressful life events, and mental health in OAD and control offspring of parents with no affective disorder. In the present study, we hypothesized that high levels of family dysfunction would be associated with more internalizing and externalizing problems across time in OAD than in controls, and that family dysfunction would mediate the relationship between stressful life events in adolescence and poor mental health in adulthood, particularly in OAD. METHODS: As part of the TRacking Adolescents' Lives Survey (TRAILS), 2230 participants (51% female, Mage = 11.1 years, SD = 0.6, at baseline) and their parents completed measures across six time points, spanning 15 years. Mental health, family dysfunction, and stressful life events were assessed with the Youth and Adult Self-Report, Family Assessment Device, and an in-house measure, respectively. RESULTS: Multi-group structured equation modeling revealed that family dysfunction was linked to internalizing and externalizing problems in OAD, but not controls, across time. Risk status did not moderate family dysfunction's mediation of the relationship between stressful life events and negative outcomes in adulthood. CONCLUSIONS: OAD show high sensitivity to dysfunction in the rearing environment across childhood and adolescence, which supports the use of family based interventions to prevent the development of mental disorders in high-risk youth.

Fear of depression recurrence among individuals with remitted depression: a qualitative interview study.

BACKGROUND: Major Depressive Disorder (MDD) is a prevalent psychiatric condition and the largest contributor to disability worldwide. MDD is highly recurrent, yet little is known about the mechanisms that occur following a Major Depressive Episode (MDE) and underlie recurrence. We explored the concept of fear of depression recurrence (FoDR) and its impact on daily functioning among individuals in remission from MDD. METHODS: 30 participants (83% female; 37% White; Mage = 27.7, SD = 8.96) underwent semi-structured qualitative interviews. The interviews explored participants' experiences of FoDR including the frequency, severity, content, triggers, and impact of fears and associated coping strategies. We used content analysis to analyze the transcriptions. RESULTS: Most participants (73%) reported having FoDR, with varying frequency, severity, and duration of fears. The triggers and content of participants' fears often mirrored the symptoms (e.g., low mood, anhedonia) and consequences (e.g., job loss, social withdrawal) endured during past MDEs. Some participants reported a minimal impact of FoDR on daily functioning, whereas others reported a positive (e.g., personal growth) or negative (e.g., increased anxiety) influence. LIMITATIONS: Our sample size did not allow for explorations of differences in FoDR across unique MDD subtypes or sociocultural factors. CONCLUSIONS: The concept of FoDR may present a window into understanding the unique cognitive and behavioural changes that occur following MDD remission and underlie depression recurrence. Future research should aim to identify underlying individual differences and characteristics of the disorder that may influence the presence and impact of FoDR. Finally, a FoDR measure should be developed so that associations between FoDR and recurrence risk, depressive symptoms, and other indices of functioning can be determined.

Parenting practices in middle childhood mediate the relation between growing up with a parent having bipolar disorder and offspring psychopathology from childhood into early adulthood.

The offspring of parents with bipolar disorder (OBD) are at high risk for developing mental disorders. In addition to genetic factors, environmental risk is purported to be associated with these negative outcomes. However, few studies have examined this relation. Using concurrent and longitudinal data, we examined if support, structure, and control provided by parents in middle childhood mediated the relation between having a parent with or without bipolar disorder, and offspring mental health. The sample included 145 offspring (77 OBD, 68 controls) aged 4 to 14 years and their parents. Parent and teacher ratings of child behavior were collected, and diagnostic assessments were conducted in offspring 12 years later (n = 101). Bootstrapping analyses showed that low levels of structure mediated the relation between having a parent with bipolar disorder and elevated internalizing and externalizing difficulties during middle childhood. For the longitudinal outcomes, parental control emerged as the strongest mediator of the relation between parents' bipolar disorder and offspring psychopathology. Suboptimal childrearing may have different immediate and enduring consequences on mental health outcomes in the OBD. Parental structure has robust effects on emotional and behavioral problems in middle childhood, while levels of control promote psychological adjustment in the OBD as they mature.

A meta-analytic review of the correlation between peripheral oxytocin and cortisol concentrations.

The stress dampening effects of exogenous oxytocin in humans have been well documented. However, the relation between endogenous oxytocin and cortisol is poorly understood. We conducted a meta-analysis on the correlation between oxytocin and cortisol levels measured at baseline (k=24, N=739). The effect size for the baseline correlation statistic was small (Pearson r=0.163, p=0.008), with high heterogeneity (I2=67.88%). Moderation analysis revealed that studies where participants anticipated an experimental manipulation evidenced a greater positive correlation compared to those that did not (Pearson r=0.318, p=0.006). A supplementary analysis including additional studies indicated that oxytocin levels in unextracted samples were 60 times higher when using this questionable practice. The findings suggest that the interplay between oxytocin and cortisol is dynamic and sensitive to the anticipation of stress or novelty. Furthermore, extraction of oxytocin appears to be an essential methodological practice.

Reduced parenting stress following a prevention program decreases internalizing and externalizing symptoms in the offspring of parents with bipolar disorder.

BACKGROUND: Offspring of parents with bipolar disorder (OBD) are at risk for developing mental disorders, and the literature suggests that parenting stress may represent an important risk factor linking parental psychopathology to offspring psychopathology. We aimed to investigate whether improvements in parenting stress mediated the relationship between participation in a prevention program and offspring internalizing and externalizing symptoms at follow-up. METHODS: Families having a parent with BD (N = 25) underwent a 12-week prevention program. Assessments were conducted at pre-intervention, post-intervention, and at 3- and 6-month follow-ups. Families of parents with no affective disorders (i.e., control families) served as a comparison sample (N = 28). The Reducing Unwanted Stress in the Home (RUSH) program aimed to teach communication, problem-solving, and organization skills to improve the rearing environment. Measures included the Parenting Stress Index-4th Edition, the Behaviour Assessment Scales for Children-2nd Edition, and the UCLA Life Stress Interview. RESULTS: Families having a parent with BD reported more parenting stress at pre-intervention, and more change across time, than control families. Improvements in parenting stress mediated the relationship between participation in the intervention and reduced offspring internalizing and externalizing symptoms. While families having a parent with BD reported more chronic interpersonal stress at pre-intervention, no intervention effects were found. CONCLUSIONS: The findings demonstrate that a preventative intervention targeting parenting stress in families may serve to prevent the development of mental disorders in at-risk children.

Intranasal oxytocin and salivary cortisol concentrations during social rejection in university students.

Oxytocin facilitates pro-social behaviour and is proposed as a regulatory factor controlling stress reactivity. Previous research on oxytocin and stress has focused on achievement-related stressors among male participants. The aims of the study were to (1) examine the influence of oxytocin on the affective and cortisol response to the Yale Interpersonal Stressor (YIPS), a live social rejection paradigm, and (2) to replicate the finding that women exhibit a greater cortisol response to interpersonal stress than men (Stroud et al. 2002). Sex differences in stress responses: Social rejection versus achievement stress. Biol Psychiat 53:318-327. Ninety-six undergraduate students underwent the YIPS, where participants were excluded from two separate conversations by two same-sex confederates. Salivary cortisol concentrations and mood were repeatedly measured throughout the study. Participants were administered, in a double-blind design, a single dose of intranasal oxytocin (24 IU) or placebo prior to beginning the YIPS. The YIPS elicited a significant negative mood response that was more pronounced in females than in males. However, no significant cortisol response to the stressor and no sex difference in cortisol reactivity were observed. A significant effect of drug condition on cortisol levels was observed. Participants who were administered oxytocin exhibited a decrease in cortisol levels, relative to placebo, during the YIPS, F (4, 184)=4.50, p<0.05. The study failed to replicate the sex difference in the cortisol response to interpersonal stress reported by Stroud et al. (2002). Intranasal oxytocin, however, appeared to reduce cortisol concentrations during an interpersonal challenge.

Personality of parents with bipolar disorder and interpersonal functioning among their offspring: a prospective 10-year study.

A comparison of offspring of parents with bipolar disorder (OBD) and offspring of parents with no mental disorder (ONMD) showed that parents' neuroticism was associated with internalizing and externalizing problems among their children. The present study examined whether parents' neuroticism predicted poor interpersonal functioning among offspring 10 years later and whether the problems observed in middle childhood mediated the association between parents' neuroticism and offspring functioning. When offspring were in middle childhood, parents completed the revised NEO Personality Inventory and rated the child's behavior on the Child Behavior Checklist. Ten years later, 65 OBD and 59 ONMD completed interviews assessing mental disorders and interpersonal and noninterpersonal functioning. High neuroticism and low agreeableness in parents predicted poor interpersonal functioning in their offspring in late adolescence-early adulthood. The offspring's externalizing and internalizing problems in middle childhood partially mediated the association between parents' personality and offspring interpersonal functioning. Moreover, the association between parents' neuroticism and offspring internalizing problems was stronger among the OBD than the ONMD. Overall, the results suggested an intergenerational transmission of risk whereby high neuroticism and low agreeableness in parents were associated with behavioral problems among offspring in middle childhood that, in turn, predicted poor interpersonal functioning 10 years later.

Improved Parent-Child Interactions Predict Reduced Internalizing Symptoms Among the Offspring of Parents with Bipolar Disorder Undergoing a Prevention Program: A Proof-of-Concept Study.

The offspring of parents with bipolar disorder (OBD) exhibit elevated rates of psychopathology. However, preventative interventions are lacking. Using a quasi-experimental design with an assessment-only control group, we examined if a 12-week program (entitled Reducing Unwanted Stress in the Home, RUSH) decreases internalizing and externalizing symptoms in the OBD (aged 6-11 years) via intervention-related gains in parent-child interaction quality. Participants consisted of 55 offspring (26 OBD; 29 controls) and their parents. Assessments were conducted at four time points up to six months following the end of the RUSH program, during which parent and teacher ratings of child symptoms, and parent-child interaction quality (parental positivity and negativity, and dyadic mutuality) were measured. Multilevel modelling showed improved parental positivity and negativity, and dyadic mutuality among target dyads immediately and six months post-intervention. For the bootstrapping mediation analyses, intervention-related change in parental negativity fully mediated the relations between having participated in the RUSH program and lower parent-reported internalizing problems among the OBD six months later. These data provide evidence of the efficacy of the RUSH program for OBD who exhibited improved interactions with their parents post-intervention. Further investigation via a randomized controlled trial is warranted.

Depressive symptoms and social context modulate oxytocin's effect on negative memory recall.

Oxytocin promotes social affiliation across various species, in part by altering social cognition to facilitate approach behaviour. However, the effects of intranasal oxytocin on human social cognition are mixed, perhaps because its effects are context dependent and subject to inter-individual differences. Few studies have included explicit manipulations of social context to test this supposition. We examined oxytocin's effects on autobiographical memory recall in two contexts, with and without social contact, and evaluated whether these effects were moderated by depressive symptoms. Two non-clinical samples (Study 1, n = 48; Study 2, n = 63) completed randomised, placebo-controlled, within-subject experiments. We assessed autobiographical memory recall across two sessions (intranasal oxytocin or placebo) and two contexts (memories elicited by an experimenter or by computer). Overall, intranasal oxytocin increased ratings of the vividness of recalled memories during the social context only. Individuals with elevated depressive symptoms also recalled memories that were more negative following oxytocin relative to placebo only in the non-social context across the two studies. Findings highlight the negative consequences of increasing oxytocin bioavailability in vulnerable persons in the absence of social contact. Contextual factors such as social isolation among depressed populations may complicate the clinical use of oxytocin.

Intranasal oxytocin increases state anhedonia following imagery training of positive social outcomes in individuals lower in extraversion, trust-altruism, and openness to experience.

Psychological disorders such as major depressive disorder are characterised by interpersonal difficulties and anhedonia. A cognitive mechanism proposed to contribute to the maintenance of these problems is a diminished ability to generate positive mental imagery, especially regarding social interactions. The current study examined whether the effects of social imagery training on social activity and anhedonia could be enhanced with the addition of intranasal oxytocin, and whether these effects might be augmented in persons with a high propensity to engage socially (i.e., high extraversion). University students (N = 111) were randomised to self-administer intranasal oxytocin or placebo, followed by a single session of positive social or non-social imagery training that required participants to imagine 64 positive scenarios occurring in either a social or non-social context, respectively. There were no main effects of imagery type and drug, and no interaction effect on anhedonia and social activity, measured respectively via self-report and a behavioural task. Individuals low in extraversion, trust-altruism, and openness to experience reported significantly more anhedonia after receiving oxytocin relative to placebo, but only following imagery training of positive social outcomes. Results highlight the negative consequences of increasing oxytocin bioavailability after priming social contact in more withdrawn individuals.

Automatic emotional information processing and the cortisol response to acute psychosocial stress.

Attentional shifting may represent a means of regulating the stress response. Previously, automatic processing of emotional information was predictive of subsequent cortisol levels during a repeated loss stressor (Ellenbogen, Schwartzman, Stewart, & Walker, 2006). The stress induction did not, however, elicit a substantive cortisol increase. Thus, we sought to replicate this finding using the Trier Social Stress Test (TSST), a validated psychosocial stress induction. Seventy-nine students performed a modified spatial cuing task with supraliminal and masked pictorial stimuli during the TSST (n = 36) and a control condition (n = 43). The TSST elicited a greater cortisol response than did the control condition [F(1,76) = 4.6, p < .05]. Attentional shifting during trials with masked angry faces predicted cortisol change during the TSST (beta = .76; t = 2.1, p < .05), but not during the control condition. These data suggest that early automatic emotional information processing is important in the regulation of the cortisol stress response, although the direction of effect is not known.

High cortisol levels in the offspring of parents with bipolar disorder during two weeks of daily sampling.

OBJECTIVES: The hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression, bipolar disorder (BD), and in the offspring of parents with major depression. Less is known about the offspring of parents with BD (FH+). The present project provides follow-up to a previous study showing that the adolescent (mean age 16.7 years) FH+ offspring had higher salivary cortisol levels than the offspring of parents with no mental disorder (FH-) throughout the day in their natural environment, and that girls had higher cortisol levels than boys (Ellenbogen MA, Hodgins S, Walker C-D, Adam S, Couture S. Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder. Psychoneuroendocrinology 2006; 31: 1164-1180). The goal of the present study was to determine whether FH+ offspring, approximately two years later, continued to exhibit elevated cortisol levels relative to FH- offspring during two weeks of daily sampling. METHODS: The present study examined salivary cortisol levels in 24 (18.3 +/- 2.6 years) FH+ and 22 (18.0 +/- 2.3 years) FH- offspring who are part of the same longitudinal cohort as the previous study. Saliva was collected at 1300 h and 1500 h in the natural environment of the offspring during 14 consecutive days. RESULTS: Multilevel modelling analyses indicated that FH+ offspring had higher afternoon levels of cortisol in their natural environment than FH- offspring, but group differences in slope and gender differences were not found. CONCLUSIONS: The FH+ offspring exhibited increased daytime secretion of cortisol that, at the level of the group, persisted into late adolescence and young adulthood. Perhaps this change in HPA functioning is associated with an increased vulnerability for the development of an affective disorder.

Predicting Interpersonal Outcomes From Information Processing Tasks Using Personally Relevant and Generic Stimuli: A Methodology Study.

Despite evidence of differential processing of personally relevant stimuli (PR), most studies investigating attentional biases in processing emotional content use generic stimuli. We sought to examine differences in the processing of PR, relative to generic, stimuli across information processing tasks and to validate their use in predicting concurrent interpersonal functioning. Fifty participants (25 female) viewed generic and PR (i.e., their intimate partner's face) emotional stimuli during tasks assessing selective attention (using a modified version of the Spatial Cueing Task) and inhibition (using the Negative Affective Priming task) of emotional content. Ratings of relationship quality were also collected. Evidence of increased selective attention during controlled and greater avoidance during automatic stages of processing emerged when viewing PR, relative to generic, emotional faces. We also found greater inhibition of PR sad faces. Finally, male, but not female, participants who displayed greater difficulty disengaging from the sad face of their partner reported more conflict in their relationships. Taken together, findings from information processing studies using generic emotional stimuli may not be representative of how we process PR stimuli in naturalistic settings.

Poor inhibition of personally-relevant facial expressions of sadness and anger predicts an elevated cortisol response following awakening six months later.

Failure to inhibit interference from distracting emotional stimuli may obstruct an individual's ability to regulate their behavioural and emotional responses to environmental stressors. Few studies have examined the longitudinal association between cognitive inhibition and regulation of the hypothalamic-pituitary-adrenal axis (HPA) in the natural environment. Seventy-nine healthy adults underwent two assessments 6 months apart. Participants' ability to suppress interference from distracting emotional stimuli was assessed using a negative affective priming task that included both generic and personally-relevant (i.e., participants' intimate partners) facial expressions of emotion. Poorer inhibition of personally-relevant sad and angry faces, but not generic stimuli, significantly predicted an increased cortisol awakening response (CAR) six months later. Moreover, poor inhibition of personally-relevant sad faces mediated the relation between chronic stress and an elevated CAR. Difficulties inhibiting personally-relevant emotional information may represent a key mechanism in understanding how environmental stress influences HPA functioning.

A comprehensive assessment of personality traits and psychosocial functioning in parents with bipolar disorder and their intimate partners.

BACKGROUND: Individuals with bipolar disorder (BD) often possess maladaptive traits and present with various difficulties in psychosocial functioning. However, little is known about the intimate partners of adults with bipolar disorder (BD) and how mental illnesses other than BD within couples may further complicate the picture. Such knowledge is needed to inform both couple and family interventions. METHODS: Participants were parents whose children were enrolled in a prospective study: 55 with BD and their partners, and 47 healthy control couples. All completed diagnostic interviews, and questionnaires describing personality traits, negative life events, coping skills, social support, marital adjustment and inter-partner verbal aggression. Parents with BD and healthy control parents were compared, as were the intimate partners. A series of exploratory analyses focused on the average measures within couples, with and without BD, and took account of comorbid personality disorders among those with BD and major depressive disorder among their partners. RESULTS: Intimate partners of adults with BD, relative to healthy control partners, presented with more mental disorders, higher neuroticism, lower extraversion, more emotion-focused coping, smaller social networks, less satisfaction with their social networks, and little, satisfying social contact. Additionally, they reported less consensus and satisfaction in their marital relationships, and engaged in more verbal aggression towards their partners. Participants with BD showed similar, more extreme, characteristics. Marital distress and verbal aggression were greatest among couples with an adult having BD and a comorbid personality disorder or a partner with major depressive disorder. CONCLUSION: This study contributes to the literature by demonstrating that both parents with BD and their intimate partners exhibit high levels of mental illness, maladaptive personality traits and psychosocial difficulties, thus limiting their partners' ability to provide support and stability in the these high risk families. Moreover, mental illnesses other than BD may contribute to marital problems within couples. Some statistical analyses, particularly those involving comorbid conditions, were under-powered in this study. As clinical implications, the current study suggests that both individuals with BD and their partners could benefit from interventions aimed at lowering emotionality and verbal aggression, and increasing social support and effective coping skills.

Oxytocin and Facial Emotion Recognition.

The expression of emotion in faces serves numerous meaningful functions, such as conveying messages of danger or approach, facilitating communication, and promoting the formation of social bonds and relationships. The study of facial expressions of emotion has become integral to research in social psychology and social neuroscience, particularly with respect to the neuropeptide oxytocin. This chapter examines how oxytocin influences the processing of emotion in faces by reviewing intranasal administration studies of automatic processing, selective attention, and emotion recognition. Two important trends in the literature have been identified: exogenous oxytocin attenuates early attentional biases towards negative stimuli and increases selective attention and recognition of emotional cues in faces, particularly around the eyes. Both of these effects can be traced to well-delineated neural circuits involving amygdala, early visual processing areas, and reward circuits, and both purportedly facilitate approach-related behavior when affiliative opportunities are available. These data are integrated into a conceptual model incorporating contextual factors and moderating influences, as oxytocinergic effects on cognition and social behavior appear to vary in persons along indices of social competence, interpersonal sensitivity, and early adversity. Limitations of this literature and future directions for research are briefly discussed.

Automatic and effortful emotional information processing regulates different aspects of the stress response.

There is increasing evidence that stress and self-regulation are important factors in the development and treatment of psychopathology. A key issue is to determine how cognitive-emotional systems modulate the stress response. We sought to determine whether effortful and automatic processing were differentially associated with subsequent mood and cortisol levels during a stressful challenge. We examined this question by having clinically anxious, depressed, and control participants perform a modified spatial cueing task with supraliminal and masked pictorial stimuli during a stressful challenge and control condition. The stressful challenge, relative to the control condition, lowered mood, but did not influence cortisol levels. In the full sample, disengagement from supraliminal dysphoric pictures was associated with subsequent mood ratings, whereas disengagement from masked pictures depicting threat was associated with subsequent cortisol levels. Effortful and automatic processing appears to regulate different aspects of the stress response.

Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder.

The hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression and bipolar disorder (BD). It is not known however whether HPA abnormalities predate the onset of these disorders. Preliminary data indicated that the adolescent offspring of parents with BD (high-risk), as compared to adolescents of parents with no mental disorder (low-risk), had higher levels of daytime salivary cortisol. The present study re-examined the cortisol increase after awakening and basal cortisol levels in a larger sample, and tested the hypothesis that high-risk offspring are more reactive to psychosocial stress than low-risk offspring. Saliva samples were collected from 58 adolescents, 29 high-risk (14 male/15 female, 16.8 years) and 29 (14 male/15 female, 16.6 years) low-risk, in their natural environment during at least two days. Twenty-five high-risk (13 male/12 female) and 25 low-risk (13 male/12 female) youth completed a child adaptation (15 years) or the standard version of the "Trier Social Stress Test". Consistent with our previous finding, high-risk offspring had higher daytime levels of cortisol in their natural environment than low-risk offspring, and the difference was unrelated to clinical symptoms or other known confounds. Irrespective of risk status, female participants had higher daytime levels of cortisol than male participants. In contrast, there were no group differences in the cortisol response to the laboratory psychosocial stressor. The offspring of parents with BD show evidence of increased daytime basal HPA functioning with normal reactivity to psychosocial stress.

Oxytocin and social context moderate social support seeking in women during negative memory recall.

BACKGROUND: Oxytocin is theorized to promote social support seeking under stress- an alternate biobehavioural response to challenge known as the tend-and-befriend response. These effects may be context dependent, however, and no study has evaluated this effect in the presence and absence of social support. The aim of this study was to evaluate the effects of oxytocin on the experience of recalling emotional autobiographical memories in two contexts-with and without social contact with an experimenter. METHOD: Sixty-three individuals (32 female) participated in this randomized, double-blind, placebo-controlled, and within-subject study. RESULTS: During recall of negative memories in the absence of social contact, oxytocin decreased perceived emotional support relative to placebo F(1,62)=10.75, p=0.002. In this same context, women who were motivated to affiliate with the experimenter following oxytocin administration showed this effect in greater magnitude t(57)=-2.04, p=0.047, but showed the reverse effect (i.e. increased perceived support in response to oxytocin) when social contact with the experimenter was available t(57)=2.78, p=0.007. Male participants did not evidence this pattern. CONCLUSION: These findings support the role of oxytocin in social support seeking in distressed women, and highlight the negative consequences of increasing oxytocin bioavailability in the absence of social support. Supportive relationships may be necessary to elicit the prosocial effects oxytocin.