Scientific Approach

Human diseases are extremely complex. To address scientific challenges in this context, therefore, we leverage the power of cutting-edge tools from several scientific disciplines, including psychology, neuroscience, immunology, molecular biology, genetics, and genomics. We accomplish this employing a team science approach to the work we do. We have in-house expertise in several areas, but we also proudly partner with investigators from across UCLA and around the world to help solve our most important and pressing problems in the health sciences. In short, we believe we can accomplish much more by working together than by working alone.

Current Overarching Scientific Foci

  • Integrated, multi-level mechanisms linking social stress with depression across the lifespan
  • Behavioral and immunologic processes underlying the co-occurrence of mental and physical health problems
  • Social and biological risk factors for self-harming and suicidal behavior
  • Social and biological processes underlying ovarian cancer and breast cancer
  • Social, behavioral, and biological determinants of biological aging
  • Modifiable resilience factors for reducing stress reactivity and improving human health and well-being
  • Conceptualization and assessment of stress exposure across the life course
  • Development of biosensing devices for measuring health-relevant biomarkers

Specific Projects (Selected)

Neural, Inflammatory, and Genomic Mechanisms Underlying Risk for Depression in Adolescence

Although depression can be extremely debilitating for all, beginning in early adolescence, women are twice as likely to experience depression relative to men. Moreover, as they age, they are at disproportionately high risk for developing several very serious medical conditions that frequently co-occur with depression and presage early mortality, such as hypertension, heart disease, certain cancers, neurodegeneration, and stroke. One of the best markers of risk for depression in female adolescents involves having a mother with depression. As a result, we are currently conducting the first integrative, multi-level fMRI study of how adolescent girls with a maternal history of depression (high risk) and those with no maternal history of depression (low risk) respond to social stress at the psychological, neural, physiologic, molecular, and genomic level. This multi-method, multi-level study will permit us to characterize for the first time the full set of psychological and biological processes that are associated with increased risk for depression. We in turn hope to use this information to inform the development of novel strategies for reducing the enormous disease burden that is caused by this common and costly disorder.

An Online System for Assessing Lifetime Stress Exposure

One of the lab’s primary projects over the past eight years has involved developing the first online system for assessing a person’s lifetime exposure to stress. The system, called the Stress and Adversity Inventory (STRAIN), collects information about 55 different major life events and chronic difficulties that are known to impact health. One a stressor is endorsed, follow-up questions determine the precise timing, frequency, severity, and duration of the stress exposure. The measure takes approximately 20 minutes to complete, and can be self-administered or administered by an interviewer. Once completed, the system outputs 445 variables that can be combined to form more than 115 stress scores and life charts that summarize a person’s exposure to stress over the life course. The system is currently being used in several studies examining the effects of early adversity and cumulative stress exposure on a range of psychological, neural, biological, and physical health outcomes, including neural responsivity to threat, systemic inflammation, sleep quality, depression, cancer-related fatigue, and biological aging. All told, we currently have data from approximately 55 studies and more than 14,500 individuals. The system is also being used in several clinical settings to aid in psychosocial assessment and case conceptualization. One current focus involves integrating into the system a series of brief social-psychological interventions that can be used to modify a user’s disease-related risk factors based on his or her unique life stress profile.

Social Science for Social Change

We are currently examining different ways in which findings from the social sciences, particularly psychology, can be employed to induce positive social change. One such project involves using an online stress assessment tool that we have developed (i.e,. the STRAIN) to motivate people to adopt better health behaviors. Participants complete the stress assessment prior to their clinic or doctor’s visit and then receive different levels of feedback regarding their stress exposure and risk for disease. As described above, we are also using this system to deliver brief social-psychological interventions that aim to reduce stress-related disease risk. By combining the scientific goals of better stress assessment with the applied goals of improving healthcare, we hope to make important strides in how science can be used to promote social change and improve the human condition.

Mechanisms Linking Stress with Biological Aging

Although we all get biologically older as we increase in age, for some people, this biological aging occurs at a more rapid pace, leading to the development of several serious medical conditions and neurodegenerative disorders that presage early mortality. Stress has been identified as one factor that may contribute to biological aging, but it remains unclear how stress exerts these dramatic effects on the body. We are working to address these critical questions with Dr. Elissa Epel (UCSF) by characterizing the stress exposure histories and markers of biological aging in several longitudinal studies. We are specifically interested in whether exposure to stress over the lifespan accelerates a key marker of biological aging, telomere length, and what psychological and biological processes influence these effects. By studying these multi-level dynamics, we aim to address the fundamental question of how and why humans biologically age over time.

Biobehavioral Influences in Ovarian Cancer

Together with Dr. Susan Lutgendorf (University of Iowa), we are investigating the biobehavioral factors that impact tumor growth, and morbidity and mortality in ovarian cancer. We are particularly interested in how early adversity, recent life stress, social support, and depression influence quality of life and survival, and how these outcomes are influenced by stress-related inflammatory processes that get triggered in the ovarian tumor microenvironment. The tumor microenvironment is rich with pro-inflammatory cytokines, which mediate the inflammatory response and can promote tumor growth. However, very little is known about how biobehavioral factors, such as stress, social support, and depression, regulate inflammatory biology in the context of ovarian cancer. To address this issue, we are comprehensively characterizing a large sample of women recently diagnosed with ovarian cancer. The LEDS is being administered to assess their exposure to early adversity and recent life stress, and blood draws are being conducted to assess a large number of biomarkers that are relevant for inflammation. Participants’ social support and depression status is also being comprehensively assessed.

Biobehavioral Predictors of Fatigue in Breast Cancer Patients

Together with Dr. Julie Bower (UCLA), we are investigating the roles that early adversity, cumulative life stress, and major depression play in promoting symptoms of fatigue in breast cancer. Participants are a sample of otherwise-healthy breast cancer survivors who had been originally diagnosed with early-stage (i.e., Stage 0, I, or II) breast cancer. They were well-characterized with respect to their clinical and psychiatric status. In addition, all participants have completed the STRAIN to comprehensively assess their exposure to cumulative life stress. We also have extensive genetic and genomic data on these participants, in addition to information on their HPA-axis and inflammatory-related functioning.

Psychoneuroimmunological Correlates of Life Stress in Major Depression

In collaboration with Dr. Heather Burke (UCSF), we are investigating the effects of early adversity and recent life stress on psychological and biological functioning in depression. A sample of healthy adult women with major depression and an age-, ethnicity-, and BMI-matched group of non-depressed women were administered the LEDS to assess for exposure to early adversity and recent life stress. These women subsequently completed a laboratory-based stress task (the Trier Social Stress Test, or TSST) while psychological, emotional, and biological parameters were monitored. We are analyzing these data to examine how early adversity and recent life stress affect baseline and TSST-induced levels of cortisol and inflammatory cytokine production (e.g., IL-1, IL6, IL-10, TNF-α, etc.). We are also examining how stress influences diurnal salivary cortisol, DHEA, Alpha Amylase, Estradiol, Progesterone, and ACTH.

Neuroimaging Study of Reward Processing & Life Stress in Major Depression

In collaboration with Dr. Diego Pizzagalli (Harvard University), we are investigating how early adversity, recent life stress, and experimentally-induced acute social stress (social evaluation) relate to responsiveness to reward and anhedonic symptomatology in major depression. Participants are healthy adults diagnosed with major depressive disorder and a comparison group of non-depressed individuals. They completed the LEDS (Life Events and Difficulties Schedule) to comprehensively assess their exposure to early adversity and recent life stress. They also completed a series of computer-based tasks that assess for differences in responsiveness to reward while anatomical and functional brain scans were obtained using fMRI. With these data, we will be able to examine how life stress relates to anhedonic symptoms of depression and whether ability to modulate stress-related reward responding mediates the anhedonic symptom profile. We will also be able to elucidate the neurobiological pathways that underlie these effects.

Effects of Stress, Nutrition, & Exercise on Health and Fat Distribution

Together with Drs. Elissa Epel, Patty Moran, and Frederick Hecht (UCSF), we are examining the effects of cumulative (lifetime) stress exposure on exercise behavior, dietary behavior, cardiovascular health, autonomic nervous system activity, body fat distribution (using abdominal MRI), cytokine response to an influenza vaccine, and psychobiological responses to a laboratory-based social stress task (i.e., the TSST). Participants are a community sample of adults who were followed prospectively for 20 months, during which time they were randomly assigned to one of two different six-month weight loss regiments.

Life Stress, Cognitive, & Clinical Aspects of Major Depression

In collaboration with Dr. Scott Monroe (University of Notre Dame) and Ian Gotlib (Stanford University), we are investigating how early adversity and recent life stress impact cognitive and clinical aspects of major depression. These data, which we collected over the past ten years, are from a community sample of healthy adults diagnosed with depression. The LEDS was used to characterize participants’ exposure to early adversity, and recent acute and chronic life stress. Differing subsets of participants also completed computer-based tasks assessing cognitive vulnerability for depression, a mood induction/psychophysiological session, and an fMRI session. We also have genetic data for a subset of participants. Recent papers on these data have examined how early adversity and recent life stress relate to the onset and clinical course of depression, as well as symptomatic profiles in depression and cognitive/information processing biases in depression. We are particularly interested in whether all types of stress are “created equal” with respect to their impact on these depressive features, or, alternatively, whether certain types of stress, such as social rejection, are particularly impactful.

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