Brandon E. Gibb, Ph.D. - US grants

DESCRIPTION (provided by applicant): The primary goal of the current study is to better understand the development of depression by examining factors that may contribute to the development of a cognitive vulnerability to depression. Understanding the development of depression is important given that depression is the second most common psychological disorder, with lifetime prevalence estimates as high as 17.1 percent , and estimates that the economic burden of depression in the United States is $43.7 billion annually. Thus, understanding how vulnerability to depression develops is an important step in targeting interventions to buffer against the development of that vulnerability, thereby reducing the risk of depression onset. In the current study, therefore , the independent, unique, and combined influences of a number of factors hypothesized to contribute to the development of negative attributional styles in children will be examined over a 6-month longitudinal follow-up. These factors will include variables previously identified in longitudinal studies as contributing to the development of children?s and adolescents? attributional styles as well as factors demonstrating cross-sectional relationships with attributional styles but not yet examined longitudinally. In this way, the current study will seek to both integrate and extend previous findings.

Description (provided by applicant): Although the link between maternal and child depression is well established, little is known about the mechanism by which this risk is conferred. The proposed study is designed to address this gap by evaluating an etiological model linking maternal and child depression. In so doing, we will seek to integrate and extend findings from two separate lines of research - the expressed emotion and cognitive vulnerability to depression literatures. The proposed study involves the cross-sectional assessment of mothers and their children (ages 8-12 years). Two groups of mothers will be recruited for the study: (a) those with a history of major depressive disorder (MDD) during their child's life and (b) those with no lifetime history of any DSM-IV Axis I disorder. In testing our model, we hypothesize that mothers' levels of expressed emotion-criticism toward their children, as well as children's negative cognitive styles, will mediate the link between maternal diagnostic status (depressed versus nonclinical control) and children's symptoms and diagnoses of depression. A secondary goal of the proposed study is to examine the specificity of the links in the mediational model to children's depression versus other disorders (e.g., anxiety and disruptive behavior disorders).

Although the link between maternal and child depression is well established, little is known about the mechanisms by which this risk is conferred. The proposed study is designed to address this gap. In so doing, we seek to integrate and extend findings from two separate lines of research: cognitive-interpersonal models of depression and psychiatric genetics. The proposed study involves a longitudinal investigation of mothers and their children (ages 8-14 years) drawn from the community and assessed every six months for two years. Two groups of mothers will be recruited for the study: (a) those with a history of major depressive disorder (MDD) during their child's life and (b) those with no lifetime history of any depressive disorder and no current Axis I disorder. Our primary goal is to examine the development of children's cognitive vulnerability to depression (negative attributional style and attention and interpretation biases for facial displays of emotion). We hypothesize that maternal history of MDD will be associated with the presence of more negative cognitive styles in their children and that these cognitive styles will become more negative over the course of the follow-up as a function of mother's ongoing depressive symptom levels. We also hypothesize that negative events in the children's lives (maternal criticism as well as general negative events) will predict negative changes in children's cognitive styles. Integrating recent findings from psychiatric genetics, we predict that these effects on children's cognitive styles will be moderated by two specific genetic risk factors - a functional polymorphism in the serotonin transporter gene (5-HTTLPR) and a candidate polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Our secondary goal is to test a transactional cognitive-interpersonal mediation model linking maternal and child depression. In testing this model, we hypothesize that mothers with a history of MDD, compared to control mothers, will exhibit elevated levels of depressive symptoms across the follow-up. These depressive symptom elevations are hypothesized to contribute to the occurrence of negative events in children's lives, which will then contribute to the development of children's negative cognitive styles. These negative cognitive styles, then, are hypothesized to contribute to children's symptoms and diagnoses of depression. Building from the stress-generation literature, we will also test the hypothesis that children's levels of depression will reciprocally predict prospective changes in negative events and children's cognitive styles. We also predict that children's 5-HTTLPR and BDNF genotypes will moderate the impact of mother depression, negative events, and children's cognitions upon child depression, allowing increased precision in predicting which children are at greatest risk for the intergenerational transmission of depression. A tertiary goal is to examine the specificity of the links in the mediational model to children's depression versus other disorders (e.g., anxiety and disruptive behavior disorders).

DESCRIPTION (provided by applicant): As highlighted by the RDoC Negative Valence Systems Domain workshop, attentional biases to affective cues play a key role in the constructs of Responses to sustained threat and Loss. The neural circuitry underlying attentional biases relevant to both constructs is relatively well understood and is driven by a combination of bottom-up (amygdala) and top-down (regions of prefrontal cortex) processes. Despite their common neural influences, attentional biases relevant to threat versus loss are hypothesized to differ in their focus and time course. For example, responses to sustained threat are thought to be characterized by quicker initial allocation of attention toward threatening stimuli (e.g., angry faces). In contrast, responses to loss are thought to be characterized by deficits in the ability t disengage attention from sad faces. These attentional biases are hypothesized to develop during childhood, stabilize in adolescence, and contribute to the development and maintenance of psychopathology across the lifespan. Although there is growing support for these theories among adults and children, there are also a number of mixed findings in the literature, which we believe have resulted from the inadequate assessment of this key construct. To achieve the RDoC goal of developing new ways of classifying disorders based on dimensions of observable behaviors and brain functions, we need a more detailed understanding of which specific components of attention are disrupted in response to sustained threat and loss. This study will include 1,000 children aged 7-11 years and their mothers. Primary Aim 1 is to conduct a fine-grained examination of children's attentional biases using both behavioral (eyetracking) and physiological (event-related potential; ERP) indices to determine which specific components of children's attention are biased in relation to their broad symptoms of depression and anxiety, as well as the more specific symptom domains of low positive affect and physiological hyperarousal. Primary Aim 2 is to provide a better understanding of the genetic and epigenetic influences on these biases. We will utilize a circuit-level approach to examine aggregate levels of influence among genes known to be differentially expressed in amygdala versus PFC in this age group. Building from models of differential susceptibility to environmental influence, we will also examine how these genetic and epigenetic influences operate within the context of specific environmental influences. Finally, given that many maternal influences on children's attentional biases likely confound environmental and genetic factors, Primary Aim 3 is to examine attentional plasticity in the context of a laboratory-based conditioning task. We will examine genetic and epigenetic influences on changes in children's attentional biases as well as the generalizability of conditioning effects to a novel assessment of attentional allocation. Our goal is that this research will lead to a more detailed understanding of psychopathology in youth, emphasizing a new way of categorizing psychology based on the neural circuits disrupted, which is manifest as biased processing of emotional cues in ones environment.

DESCRIPTION (provided by applicant): As highlighted by the RDoC Negative Valence Systems Domain workshop, attentional biases to affective cues play a key role in the constructs of Responses to sustained threat and Loss. The neural circuitry underlying attentional biases relevant to both constructs is relatively well understood and is driven by a combination of bottom-up (amygdala) and top-down (regions of prefrontal cortex) processes. Despite their common neural influences, attentional biases relevant to threat versus loss are hypothesized to differ in their focus and time course. For example, responses to sustained threat are thought to be characterized by quicker initial allocation of attention toward threatening stimuli (e.g., angry faces). In contrast, responses to loss are thought to be characterized by deficits in the ability t disengage attention from sad faces. These attentional biases are hypothesized to develop during childhood, stabilize in adolescence, and contribute to the development and maintenance of psychopathology across the lifespan. Although there is growing support for these theories among adults and children, there are also a number of mixed findings in the literature, which we believe have resulted from the inadequate assessment of this key construct. To achieve the RDoC goal of developing new ways of classifying disorders based on dimensions of observable behaviors and brain functions, we need a more detailed understanding of which specific components of attention are disrupted in response to sustained threat and loss. This study will include 1,000 children aged 7-11 years and their mothers. Primary Aim 1 is to conduct a fine-grained examination of children's attentional biases using both behavioral (eyetracking) and physiological (event-related potential; ERP) indices to determine which specific components of children's attention are biased in relation to their broad symptoms of depression and anxiety, as well as the more specific symptom domains of low positive affect and physiological hyperarousal. Primary Aim 2 is to provide a better understanding of the genetic and epigenetic influences on these biases. We will utilize a circuit-level approach to examine aggregate levels of influence among genes known to be differentially expressed in amygdala versus PFC in this age group. Building from models of differential susceptibility to environmental influence, we will also examine how these genetic and epigenetic influences operate within the context of specific environmental influences. Finally, given that many maternal influences on children's attentional biases likely confound environmental and genetic factors, Primary Aim 3 is to examine attentional plasticity in the context of a laboratory-based conditioning task. We will examine genetic and epigenetic influences on changes in children's attentional biases as well as the generalizability of conditioning effects to a novel assessment of attentional allocation. Our goal is that this research will lead to a more detailed understanding of psychopathology in youth, emphasizing a new way of categorizing psychology based on the neural circuits disrupted, which is manifest as biased processing of emotional cues in ones environment.

PROJECT SUMMARY/ABSTRACT Although the link between depression in mothers and their children is well established, little is known about the specific mechanisms by which this risk is conferred. There is growing evidence that children?s biased attention to facial displays of emotion ? specifically, attentional avoidance of sad faces ? may represent a key mechanism of risk that develops early in life. There is growing evidence that these biases develop as early as infancy, with evidence that infants of depressed mothers look less at their mothers? faces, as well as sad facial expressions more generally, than infants of never depressed mothers. This attentional avoidance has been proposed as an emotion regulation strategy in which looking at a depressed mother is upsetting to the infant and shifting their gaze away from their mother then reduces their arousal and negative affect. This negatively reinforces the attentional avoidance which, although potentially adaptive in the short term, is likely to increase risk for depression in the future. To date, however, no study has tested this key hypothesis that the attentional avoidance of sad faces observed in infants of depressed mothers serves to regulate infants? arousal. The goal of this project is to provide a fine-grained test of this hypothesis while also addressing other key gaps in the literature. For example, although the majority of research focuses on the impact of maternal depression on infant outcomes, there are likely bidirectional influences between mothers and their infants. The proposed study will examine these bidirectional influences at multiple units of analysis including affect, behavior, attention, and physiology. The study will include 150 women and their 6-12-month-old infants. Half of the mothers will meet criteria for current major depressive disorder and the other half will be lifetime free of any depressive disorder. Specific Aim 1 is to conduct a multi-method assessment of attention biases in infants of depressed mothers using a combination of mother-infant interaction and computer-based tasks. Specific Aim 2 is to examine infants? arousal as a mechanism underlying their attentional avoidance of sad faces. To do this, we will measure dynamic changes in infants? physiological activity during the interaction tasks. Specific Aim 3 is to examine potential bidirectional influences in affect, behavior, attention, and physiology between mothers and their infants. Our goal is for this research to lead to a more detailed understanding of the mechanisms by which maternal depression may impact children?s attention to facial displays of emotion, which is implicated not only in future depression risk but is also important for infants? broader social and emotional functioning throughout life.