Research on Child and Adolescent Psychopathology - Interview with the Authors: Dr. Autumn Kujawa and Lindsay Dickey

RCAP interview with Dr. Autumn Kujawa, Assistant Professor of Psychology and Human Development and Director of Mood, Emotion, and Development Lab at Vanderbilt University and Lindsay Dickey, a doctoral student in clinical science at Vanderbilt University about their recently published article titled - Neural predictors of improvement with cognitive behavioral therapy for adolescents with depression: An examination of reward responsiveness and emotion regulation (this opens in a new tab)

1. Your group is doing lots of innovative work in the area of adolescent and emerging adult depression. It seems like the prevalence and severity of depression and suicidality has gotten worse over the past 10 years or so. What factors are leading to increased internalizing problems in youth and how does your program of research seek to address these trends?

Yes, there is evidence that the prevalence of adolescent depression and suicidal ideation has been increasing over the past 10 years or so. We know that the causes of depression are complex and involve interactions between environmental, biological, cognitive, and behavioral risk processes, so it's not entirely clear what specific factors are driving the increasing rates. But there are a number of possibilities. Some research points to changes in technology, and use of smartphones and social media as possible contributing factors. We also know that stress plays a key role in depression risk. So things like economic factors, more college and career pressures and financial strains could contribute to increasing rates, as well as socio-cultural stressors, including racial injustices, and the widespread impacts of the COVID 19 pandemic. It's also possible that some of the increases could be due in part to greater awareness about mental health and recognition of depression and depressive symptoms. We're really glad that this issue is getting attention because it is a major public health concern and an area where more research and access to effective treatments is needed.

In our lab, we aim to identify more objective, early emerging risk markers for depression and suicidality that we can use to determine which youth are at increased risk, and to develop more targeted and personalized early intervention efforts. Our idea is really that rather than treating the big, the broader symptoms or disorders, we can get more to the core of what's driving those symptoms and develop interventions for healthy emotional functioning with regard to both positive and negative emotions. Then we can apply those in ways that best meet the needs of individual youth, potentially even before symptoms or disorders develop.

2. Your study is unique in that unlike loss of published research, it was the objective neural variables that predicted CBT outcomes rather than self-report ratings. Can you help us better understand these variables and how they might present in patients? What would a patient with reduced responsiveness to reward look like clinically speaking, and how would that manifest? Similarly, what does a large frontal LPP residual mean? How might that play out in everyday interactions, for example?

We know that self-report measures are somewhat subjective and influenced by recall biases. These biases tend to be even more pronounced among individuals with depression and other mental health challenges. An alternative is to look at neural markers as more objective measures of different types of processes. In the RCAP study, we looked at reward responsiveness and emotion regulation and we measured these processes in an immediate context, instead of asking participants to retrospectively estimate how much they engage in these processes.

It's also possible that a mismatch between an individual's perception of their ability or a tendency to engage in a process, and the actual effectiveness or impact of that effort on their neural functioning may contribute to feelings of depression. For example, individuals with depression often report attempting to engage in emotion regulation strategies like cognitive reappraisal, where they try to reframe or change the way they think about an experience to decrease their negative emotions. Despite their repeated efforts, maybe they have impairments in the ability to actually down regulate or reduce their neural reactivity to negative emotions, so that mismatch may maintain feelings of dysphoria and even potentially contribute to feelings of hopelessness. The LPP, or late positive potential, is an event related potential that measures reactivity to emotional stimuli. A larger LPP indicates greater reactivity to emotion and the LPP has been shown to be modifiable by explicit emotion regulation efforts. The more that an individual is able to reduce their LPP, while intentionally using emotion regulation strategies like reappraisal, it's indicative of better overall emotion regulation ability.

In our study, the LPP was compared when viewing naturally sad or dysphoric images and participants were instructed to respond however they would naturally respond to those images. Then participants were also asked to try to intentionally reduce their emotional responses by changing the way they think about them. A larger LPP during the emotion regulation condition would reflect less control or less of an ability to regulate responses to that negative information, which is what we saw. For reward responsiveness, individuals with depression often express a desire to feel positive emotions again, to feel happy again. Yet despite this goal of wanting to feel better and wanting to feel more positive emotions, there are often these neurobiological impairments that can inhibit their ability to enjoy typically rewarding experiences. In other words, even if an individual with depression was to attempt to engage in a positive rewarding activities, such as spending time with close family members, hanging out with friends, or doing an extracurricular activity that they enjoy, this neurobiological blunting and reward related brain function can inhibit that individual's ability to feel positive emotions following those experiences.

3. Your study discusses how both positive and negative emotional processing are important for clinicians and researchers seeking to understand depression. Can you provide some examples of positive and negative emotional processing, and how they may differ in adolescents with depression?

When we think about the criteria for diagnosing depression, the two main symptoms are either a sustained dysphoric or sad mood, which is a negative emotion, or anhedonia, which is the limited capacity to experience pleasure or positive emotions. While everyone experiences fluctuations in emotions with both good days and bad days, what tends to differentiate adolescents with depression is the duration of those changes. That's often happening very frequently, most of the time for two weeks or longer, or for persistent depressive disorder more days than not for at least a year or longer. Individuals with depression often have difficulties downregulating experiences of negative emotions and difficulties upregulating experiences of positive emotion. Adolescents with depression have been shown to have these reduced neural responses to positive or rewarding stimuli. And that could include receiving a monetary reward, performing well on a task, or receiving positive feedback from peers in a task compared to healthy adolescents. They also have been shown to have reduced activation in regions involved in the regulation of negative emotions, such as the dorsolateral prefrontal cortex. This differs from the typical developmental patterns we see for emotion processing where, with age, across childhood adolescence into adulthood, you see reduced neural responses to emotion overall with age and an improved ability to regulate emotions with age.

It’s worth noting that there is substantial variability within depression. Some individuals may experience impairments specifically in the processing of negative emotions and others may be specific to impairments and positive emotions, or there may be individuals who struggle with both. Adolescence is a vulnerable developmental period. There's this increased activation in the subcortical regions contributing to emotional reactivity. But that also coincides with this kind of delayed or protracted development of the regions implicated in cognitive control and emotion regulation. This kind of mismatch in these two developmental timeframes contributes to increased risk for mental health challenges during these periods. That also coincides with increased social pressures, peer relationships become a lot more important, as adolescents tend to orient themselves away from family relationships and place a lot of emphasis and value on peer relationships. Interpersonal stress specifically, is established as a robust predictor of depression. The combination of both these neural alterations and these environmental and social risk factors likely contribute to the increased risk for depression during this time.

4. I wanted to end by asking you, what would you say to other early career researchers who want to help adolescents with depression and their families? And are there particular areas of study that you think are promising and that have potential to have a major impact on how we practice clinically.

There is so much work to be done in this area. In terms of research, we've talked a lot about how much variability there is within the disorder of depression, and also the developmental pathways that lead to depression. We think these have really important implications when we think about treatment and prevention. We need better methods to understand this complexity and this variability. We need more research with large samples, integrating multiple measures of these risk processes and leveraging more advanced quantitative approaches to understand heterogeneity within the disorder. We're really encouraged by the findings from this study, because they suggest that there could be clinical utility in other types of measures, including EEG, for helping to inform what interventions are most likely to be effective for whom, and extending beyond what information we typically get from self-report in clinical interviews.

There's also a lot of challenges in this work and a lot of questions remain, like being able to define what typical reward responsiveness and emotion regulation look like at the neural level, how do we know when there's a problem, and how can we integrate multiple types of information to inform clinical decision making. There's a lot of future directions there. In terms of clinically, we first we need more providers offering evidence-based interventions for youth depression, because there's so many challenges with even accessing services. We're really excited about this idea of interventions that can enhance reward responsiveness and how we kind of upregulate those positive emotions with interventions. CBT for depression tends to be mostly focused on negative emotions. The neuroscience literature is really pointing us in this direction of needing to understand more of what is happening with positive emotions, motivation, and reward.  Michelle Kraske and colleagues have developed a positive affect treatment for adults with internal internalizing disorders that's showing great promise. In our lab, we've been developing a similar intervention for children of mothers with depression, that aims to upregulate reward responsiveness and looking at whether we can change these neural markers before depression develops. We're very excited about this idea of more targeted and personalized interventions and thinking about how to develop and apply them and how they can be integrated with prevention. We think that's a really promising direction for future work also.