RESEARCH

The Stress and Developmental Psychopathology Laboratory is committed to innovative multidisciplinary research and improving the lives of children and adults struggling with mental disorders. Research in the laboratory includes:

(1) EXOGENOUS CHALLENGE STUDIES OF THE OXYTOCINERGIC SYSTEM IN PATIENT AND HEALTHY POPULATIONS

(2) STUDIES OF THE OFFSPRING OF PARENTS WITH BIPOLAR DISORDER, WHO ARE AT HIGH RISK FOR DEVELOPING MENTAL DISORDERS

(3) STUDIES OF ATTENTION RETRAINING WITH EMOTIONAL PICTURES AND THEIR EFFECTS ON INTERPERSONAL FUNCTIONING AND STRESS REACTIVITY.

(4) FEAR OF RECURRENCE OF DEPRESSION, INCLUDING THE DEVELOPMENT OF A QUESTIONNAIRE.

OF LATE, WE HAVE MADE A CONCERTED EFFORT TO SHIFT THE RESEARCH TO KNOWLEDGE TRANSLATION INITIATIVES THAT INCLUDE THE STUDY OF PREVENTION AND INTERVENTION PROTOCOLS AIMED AT IMPROVING MENTAL HEALTH AND SOCIAL OUTCOMES. OUR NEW AND ONGOING AREAS OF RESEARCH ARE AS FOLLOWS:

INTRANASAL OXYTOCIN AS AN ADJUNCT TO PSYCHOTHERAPY

Major depressive disorder (MD) is recurrent, debilitating, and, to some extent, a chronic disorder, despite the many advances in treatment. Although both pharmacotherapy and psychological treatments are considered to be efficacious in the short-term treatment of MD, at least one third of patients do not respond to treatment and meta-analyses of published and non-published data have found substantially smaller effect sizes than previously reported. One strategy to improve treatment efficacy is to add an additional medication or psychological procedure (i.e. such as “mindfulness” meditation) to augment the therapeutic efficacy of a traditional treatment.
We are currently testing the hypothesis that the addition of intranasal oxytocin to psychotherapy, given prior to each session, will improve treatment efficacy. With funding from the Canadian Institutes of Health Research, we have completed a small randomized controlled trial (RCT) where participants with major depressive disorder were randomly assigned to either psychotherapy (interpersonal therapy, up to 16 sessions) with adjunct oxytocin administration or psychotherapy with adjunct placebo administration. Consistent with our hypothesis, we found that depressed participants administered oxytocin, relative to placebo, reported lower ratings of depression post-treatment, and that these effects were maintained at a six-month follow-up. We also observed that oxytocin improved participants' perception of the relationship with their therapist early on in therapy, suggesting a possible mechanism for the therapeutic effects of oxytocin. We are currently conducting a larger RCT trial to attempt to replicate and extend these finding to cognitive-behavioural therapy, an evidence-based psychological treatment for major depressive disorder. We will test specific hypotheses regarding how oxytocin may improve psychotherapy outcomes. Does oxytocin improve the therapeutic alliance between the therapist and participants, or does oxytocin improve social/emotional information processing so that psychotherapy is more effective. Also, we plan to explore whether adjunctive treatment with intranasal oxytocin will elicit peripheral DNA methylation changes in the oxytocin receptor and in the 5-HT transporter (SLC6A4) genes, as possible markers of clinical improvement. This research program is unique in Canada and at the forefront of international research on intranasal oxytocin, with the potential to improve the treatment of persons suffering from MD. Future research will likely examine if oxytocin can improve therapeutic outcomes in patients with treatment-resistant major depressive disorder (when a depressed person does not respond to a first-line treatment).

UNDERSTANDING HOW OXYTOCIN FACILITATES SOCIAL BEHAVIOR

It is well known from animal studies that oxytocin is central in the formation social bonds, and there is now growing evidence of similar context-dependent effects in humans. Over the last few years, we have been conducting laboratory studies examining how intranasal oxytocin promotes affiliation and trust. Our working hypothesis is that oxytocin promotes prosocial behavior by facilitating the processing of social and emotional cues in the environment and by attenuating biological systems associated with the stress response and threat (see Ellenbogen, 2017). We have conducted a series of placebo-controlled double-blind studies of intranasal oxytocin which have include different stress paradigms (physical stress, interpersonal stress), various measures of social cognition (inhibition, attention, autobiographical memory, etc.), and different methodologies (reaction time tasks, memory recall, EEG, eye-tracking, etc.). Our current studies are exploring how individual differences and contextual factors can alter the behavioral effects of intranasal oxytocin, including research on possible negative effects of intranasal oxytocin administration.

OXYTOCIN AS A PROSPECTIVE MARKER OF SOCIAL VULNERABILITY AND RISK FOR DEPRESSION

Interpersonal functioning is integral to mental and physical health. Research on the biopsychosocial basis of affiliation offers important insight into the pathophysiology of mental disorders associated with social dysfunction, such as major depressive disorder (MD). The neuropeptide oxytocin is believed to have a central role in promoting affiliative behavior. We also know that MD is closely related to affiliative or interpersonal problems. Thus, we will test the hypothesis that the acute response to an oxytocin challenge on measures of social cognition (selective attention, inhibition, autobiographical memory) may signal an abnormality in the oxytocinergic system, and that this sensitivity to oxytocin may predict risk for interpersonal problems and MD prospectively. If this hypothesis is supported, then the administration of intranasal oxytocin could be used as a biological marker for poor interpersonal functioning and risk for MD. With funding from the Canadian Institutes of Health Research, we are testing this novel hypothesis with a prospective within-subject placebo-controlled study of remitted depressed and never-depressed participants followed for 18 months. Participants repeatedly underwent an eye-tracking protocol and an assessment of autobiographical memory, and were assessed for depressive symptoms and interpersonal functioning over this period. Data collection is complete and we are currently processing these data.

PREDICTING LONG-TERM OUTCOMES IN THE OFFSPRING OF PARENTS WITH BIPOLAR DISORDER

In a 10-year longitudinal study of families having a parent with BD and families where both parents are free of a mental disorder, we have tracked different behavioral (internalizing and externalizing problems, interpersonal functioning, risky behaviors, etc.) and neuroendocrine (salivary cortisol) outcomes in their offspring in late adolescence or early adulthood. Because comprehensive assessments of these children and their family environment were conducted in middle childhood, we are able to determine how early psychosocial risk factors in the family environment are related to different outcomes 10 years later, when the children entered late adolescence and early adulthood. Among areas of interest in the early environment, we have a comprehensive assessment of mental health in parents and their children, as well as measures of stress, coping, personality, parenting practices, social support, antisocial behavior, and intellectual functioning in parents. Although the longitudinal study has terminated, the archival database serves as a means to test new developmental hypotheses regarding the long term effects of growing up with a parent having bipolar disorder. Our work in this area has highlighted the role of parenting practices (Iacono et al, 2018) and parents’ personality (Nijjar et al, 2016) as key factors influencing the development of behavioral problems in middle childhood and later negative outcomes. In a recent publication (Serravalle et al, 2020), we show that the intimate partners of parents with bipolar disorder also exhibit high levels of mental illness, maladaptive personality traits and psychosocial difficulties, thus limiting their ability to provide support and stability in the these high risk families. A key focus of the project is to examine how family environmental factors, such as structure and organization in the home, can alter the development of stress-sensitive hormonal systems in children, via the measurement of the hormone cortisol from saliva (Ellenbogen et al, 2009)

PREVENTING NEGATIVE OUTCOMES IN CHILDREN HAVING A PARENT WITH AN AFFECTIVE DISORDER

Based on 15 years of research on the offspring of parents with bipolar disorder, we have developed a new prevention program aimed at improving the lives of children growing up in families having a parent with an affective disorder. The twelve week program for parents and their children, entitled Reducing Unwanted Stress in the Home (RUSH), aims to reduce stress in the home and improve family functioning. Funded by the Brain and Behaviour Research Foundation in the USA, we completed a “proof-of-concept” pilot project in families where one parent had bipolar disorder, comparing their improvement with children of families having two healthy parents.
The RUSH program consists of 12 sessions designed to teach stress management techniques, problem solving, effective communication and emotion regulation skills in parents and their offspring, and a parenting intervention aimed at improving the consistency, organization, and emotional climate of the home environment. Parents and children participate in separate groups that are run in parallel. The goal of the program is to reduce the development of depressive and anxious symptoms, as well as disruptive behavioral problems, in children aged 6 to 11 years who are at high risk for developing a mental disorder. The program was also designed to prevent maladaptive changes in neuroendocrine function (the stress hormone cortisol), which we know from our past research is altered in these at-risk children. The RUSH program has been shown to decrease behavioral problems in children, to improve parent-child interactions (Serravalle et al., 2020), and to reduce parenting stress (Resendes et al., 2022). We have observed that improvements in child behaviour are greatest in families experiencing robust changes in structure and organization in the home. We are not currently conducting research on the RUSH program, but have submitted a grant to the Canadian Institutes of Health Research to launch a new phase of research in this area.

ATTENTION RETRAINING, STRESS, AND INTERPERSONAL FUNCTIONING

Do biases in selective attention influence our relationships and how we navigate complex social environments? Recent advances in cognitive and social psychology have shown that information processing biases (i.e. the propensity to allocate attention to negative stimuli) can be modified through repetitive training protocols (i.e. having people shift attention away from negative cues), and that attention retraining protocols reduce anxiety and sensitivity to negative feedback, and increase self-esteem. With funding from the Social Sciences and Humanities Research Council (SSHRC), we are examining whether modifying social information processing via attention retraining has a causal effect on interpersonal functioning in the natural environment and its associated hormone levels, via the assessment of cortisol in saliva. The program of research includes laboratory studies examining whether attention retraining modifies the cortisol response to psychosocial stress and a new longitudinal study. We are launching a new SSHRC-funded study assessing the use of trait-matched attention re-training as a means of promoting improved interpersonal functioning in persons who are at risk for interpersonal difficulties due to their attachment style. In this study, adult participants will be randomly allocated to two weeks (10 sessions) of a control training or an attention re-training protocol that matches their attachment style. For those with an anxious attachment style (characterized by fears of rejection and abandonment, vigilant for signs of negative emotion), the re-training protocol will be to shift away from emotional sad and angry faces. For those with an avoidant attachment style (characterized by discomfort with closeness and interdependence, avoids signs of negative emotion), the re-training protocol will be to shift attention towards emotional sad and angry faces. The facial expressions of participants' intimate partners, for the first time, will be used as the stimuli in the re-training protocols, in an attempt to improve the saliency of these procedures, as we have reported previously (Serravalle et al, 2020; Wong et al, 2020). The long term goal of these studies is to develop cognitive training protocols, which can be implemented in the home or online, to target problems of interpersonal sensitivity, chronic loneliness, and social isolation, or as an adjunct to the treatment of major depressive disorder.

FEAR OF RECURRENCE OF DEPRESSION

Recurrence of a depressive episode following successful treatment is common among persons struggling with major depressive disorder. At least 50% of individuals who have had at least one depressive episode go on to experience a second episode, with this percentage growing for individuals with multiple past depressive episodes. Individuals may behave differently following a depressive episode out of fear they will relapse and become depressed again. These changes may include being more fearful of taking occupational and social risks and displaying hypervigilance to somatic and psychological symptom changes. However, after an examination of the published literature, the concept of fear of recurrence of depression and its influence on the course of the disorder remains essentially unexamined. Given this, there is a need for the development of a psychometrically sound measure of fear of depression recurrence. Our research team recently completed the first part of this research project which included conducting qualitative interviews with individuals with remitted major depressive disorder. The data collected from the qualitative interview provided the empirical basis to create our Fear of Depression Recurrence (FODR) questionnaire. We are currently conducting a cross-sectional study designed to validate and assess the psychometric properties of the FODR questionnaire in persons with remitted depression. We also plan to conduct research assessing how fears of depressive recurrence might alter daily functioning, emotions, and health behaviours, to demonstrate the validity of the questionnaire. Once validated, the questionnaire will help guide research on predictors of depression recurrence and serve as a useful tool for clinicians.

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