Bartholomew D. Brigidi

Ventral striatum reactivity to reward and recent life stress interact to predict positive affect.

BACKGROUND Stressful life events are among the most reliable precipitants of major depressive disorder; yet, not everyone exposed to stress develops depression. It has been hypothesized that robust neural reactivity to reward and associated stable levels of positive affect (PA) may protect against major depressive disorder in the context of environmental adversity. However, little empirical data exist to confirm this postulation. Here, we test the hypothesis that individuals with relatively low ventral striatum (VS) reactivity to reward will show low PA levels in the context of recent life stress, while those with relatively high VS reactivity will be protected against these potentially depressogenic effects. METHODS Differential VS reactivity to positive feedback was assessed using blood oxygen level-dependent functional magnetic resonance imaging in a sample of 200 nonpatient young adults. Recent life stress, current depressive symptoms, and PA were assessed via self-report. Linear regression models were used to investigate the moderating effects of VS reactivity on the relationship between recent stress and state PA across participants. RESULTS Recent life stress interacted with VS reactivity to predict self-reported state PA, such that higher levels of life stress were associated with lower PA for participants with relatively low, but not for those with high, VS reactivity. These effects were independent of age, gender, race/ethnicity, trait PA, and early childhood trauma. CONCLUSIONS The current results provide empirical evidence for the potentially protective role of robust reward-related neural responsiveness against reductions in PA that may occur in the wake of life stress and possibly vulnerability to depression precipitated by stressful life events.

Thinking and Feeling Individual Differences in Habitual Emotion Regulation and Stress-Related Mood Are Associated With Prefrontal Executive Control

Calculating math problems from memory may seem unrelated to everyday processing of emotions, but they have more in common than one might think. Prior research highlights the importance of the dorsolateral prefrontal cortex (dlPFC) in executive control, intentional emotion regulation, and experience of dysfunctional mood and anxiety. Although it has been hypothesized that emotion regulation may be related to “cold” (i.e., not emotion-related) executive control, this assertion has not been tested. We address this gap by providing evidence that greater dlPFC activity during cold executive control is associated with increased use of cognitive reappraisal to regulate emotions in everyday life. We then demonstrate that in the presence of increased life stress, increased dlPFC activity is associated with lower mood and anxiety symptoms and clinical diagnoses. Collectively, our results encourage ongoing efforts to understand prefrontal executive control as a possible intervention target for improving emotion regulation in mood and anxiety disorders.

Broad Spectrum Assessment of Psychopathology and Adaptive Functioning with the Older Adult Behavior Checklist: A Validation and Diagnostic Discrimination Study

Self‐administered by spouses and other collateral informants, the nationally normed Older Adult Behavior Checklist (OABCL) provides standardized data on diverse aspects of older adult psychopathology and adaptive functioning. We tested the validity of the Older Adult Behavior Checklist (OABCL) scale scores in terms of associations with diagnoses of dementia of the Alzheimers type (DAT) and mood disorders (MD) and with nine measures of psychopathology, cognitive performance, and adaptive functioning.

Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders

Accumulating mental-health research encourages a shift in focus toward transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology—sometimes called the ‘p factor’— that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the ‘p factor’ contributes to risk. Here we believe we first replicate the ‘p factor’ using cross-sectional data from a volunteer sample of 1246 university students, and then using high-resolution multimodal structural neuroimaging, we demonstrate that individuals with higher ‘p factor’ scores show reduced structural integrity of white matter pathways, as indexed by lower fractional anisotropy values, uniquely within the pons. Whole-brain analyses further revealed that higher ‘p factor’ scores are associated with reduced gray matter volume in the occipital lobe and left cerebellar lobule VIIb, which is functionally connected with prefrontal regions supporting cognitive control. Consistent with the preponderance of cerebellar afferents within the pons, we observed a significant positive correlation between the white matter integrity of the pons and cerebellar gray matter volume associated with higher ‘p factor’ scores. The results of our analyses provide initial evidence that structural alterations in corticocerebellar circuitry supporting core functions related to the basic integration, coordination and monitoring of information may contribute to a general liability for common mental disorders.

Heightened connectivity between the ventral striatum and medial prefrontal cortex as a biomarker for stress-related psychopathology: understanding interactive effects of early and more recent stress

BACKGROUND The experience of childhood maltreatment is a significant risk factor for the development of depression. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for this relation, little is known about biological correlates of these stress interactions. Identifying such correlates may provide biomarkers of risk for later depression. METHODS Here, we leverage behavioral, experiential, and neuroimaging data from the Duke Neurogenetics Study to identify potential biomarkers of stress exposure. Based on the past research, we were specifically interested in reward-related connectivity and the interaction of early and more recent stress. We examined psychophysiological interactions between the ventral striatum and other brain regions in relation to these stress variables, as well as measures of internalizing symptomatology (n = 926, participant age range = 18-22 years of age). RESULTS We found relatively increased reward-related functional connectivity between the left ventral striatum and the medial prefrontal cortex in individuals exposed to greater levels of childhood maltreatment who also experienced greater levels of recent life stress (β = 0.199, p < 0.005). This pattern of functional connectivity was further associated with elevated symptoms of depression (β = 0.089, p = 0.006). Furthermore, using a moderated mediation framework, we demonstrate that this functional connectivity provides a biological link between cumulative stress exposure and internalizing symptomatology. CONCLUSIONS These findings suggest a novel biomarker linking cumulative stress exposure with the later experience of depressive symptoms. Our results are discussed in the context of past research examining stress exposure in relation to depression.

Microstructural integrity of white matter moderates an association between childhood adversity and adult trait anger

Amongst a number of negative life sequelae associated with childhood adversity is the later expression of a higher dispositional tendency to experience anger and frustration to a wide range of situations (i.e., trait anger). We recently reported that an association between childhood adversity and trait anger is moderated by individual differences in both threat-related amygdala activity and executive control-related dorsolateral prefrontal cortex (dlPFC) activity, wherein individuals with relatively low amygdala and high dlPFC activity do not express higher trait anger even when having experienced childhood adversity. Here, we examine possible structural correlates of this functional dynamic using diffusion magnetic resonance imaging data from 647 young adult men and women volunteers. Specifically, we tested whether the degree of white matter microstructural integrity as indexed by fractional anisotropy modulated the association between childhood adversity and trait anger. Our analyses revealed that higher microstructural integrity of multiple pathways was associated with an attenuated link between childhood adversity and adult trait anger. Amongst these pathways was the uncinate fasciculus, which not only provides a major anatomical link between the amygdala and prefrontal cortex but also is associated with individual differences in regulating negative emotion through top-down cognitive reappraisal. These findings suggest that higher microstructural integrity of distributed white matter pathways including but not limited to the uncinate fasciculus may represent an anatomical foundation serving to buffer against the expression of childhood adversity as later trait anger, which is itself associated with multiple negative health outcomes.

Microstructural integrity of a pathway connecting the prefrontal cortex and amygdala moderates the association between cognitive reappraisal and negative emotions.

Cognitive reappraisal is a commonly used form of emotion regulation that utilizes frontal-executive control to reframe an approaching emotional event to moderate its potential psychological impact. Use of cognitive reappraisal has been associated with diminished experience of anxiety and depressive symptoms, as well as greater overall well-being. Using data from a study of 647 healthy young adults, we provide initial evidence that an association between typical use of cognitive reappraisal in daily life and the experience of anxiety and depressive symptoms is moderated by the microstructural integrity of the uncinate fasciculus, which provides a major anatomical link between the amygdala and prefrontal cortex. Our findings are consistent with the nature of top-down regulation of bottom-up negative emotions and suggest the uncinate fasciculus may be a useful target in the search for biomarkers predicting not only disorder risk but also response to psychotherapy utilizing cognitive reappraisal.

A Link between Childhood Adversity and Trait Anger Reflects Relative Activity of the Amygdala and Dorsolateral Prefrontal Cortex

BACKGROUND Trait anger, or the dispositional tendency to experience a wide range of situations as annoying or frustrating, is associated with negative mental and physical health outcomes. The experience of adversity during childhood is one risk factor for the later emergence of high trait anger. This association has been hypothesized to reflect alterations in neural circuits supporting bottom-up threat processing and top-down executive control. METHODS Here, using functional magnetic resonance imaging and self-report questionnaire data from 220 volunteers, we examined how individual differences in top-down prefrontal executive control and bottom-up amygdala threat activity modulate the association between childhood adversity and trait anger during young adulthood. RESULTS We report that the association between childhood adversity and trait anger is attenuated specifically in young adults who have both relatively low threat-related amygdala activity and high executive control-related dorsolateral prefrontal cortex activity. CONCLUSIONS These brain activity patterns suggest that simultaneous consideration of their underlying cognitive processes-namely, threat processing and executive control-may be useful in strategies designed to mitigate the negative mental health consequences of childhood adversity.

Reward-Related Ventral Striatum Activity Buffers against the Experience of Depressive Symptoms Associated with Sleep Disturbances

Sleep disturbances represent one risk factor for depression. Reward-related brain function, particularly the activity of the ventral striatum (VS), has been identified as a potential buffer against stress-related depression. We were therefore interested in testing whether reward-related VS activity would moderate the effect of sleep disturbances on depression in a large cohort of young adults. Data were available from 1129 university students (mean age 19.71 ± 1.25 years; 637 women) who completed a reward-related functional MRI task to assay VS activity and provided self-reports of sleep using the Pittsburgh Sleep Quality Index and symptoms of depression using a summation of the General Distress/Depression and Anhedonic Depression subscales of the Mood and Anxiety Symptoms Questionnaire-short form. Analyses revealed that as VS activity increased the association between sleep disturbances and depressive symptoms decreased. The interaction between sleep disturbances and VS activity was robust to the inclusion of sex, age, race/ethnicity, past or present clinical disorder, early and recent life stress, and anxiety symptoms, as well as the interactions between VS activity and early or recent life stress as covariates. We provide initial evidence that high reward-related VS activity may buffer against depressive symptoms associated with poor sleep. Our analyses help advance an emerging literature supporting the importance of individual differences in reward-related brain function as a potential biomarker of relative risk for depression. SIGNIFICANCE STATEMENT Sleep disturbances are a common risk factor for depression. An emerging literature suggests that reward-related activity of the ventral striatum (VS), a brain region critical for motivation and goal-directed behavior, may buffer against the effect of negative experiences on the development of depression. Using data from a large sample of 1129 university students we demonstrate that as reward-related VS activity increases, the link between sleep disturbances and depression decreases. This finding contributes to accumulating research demonstrating that reward-related brain function may be a useful biomarker of relative risk for depression in the context of negative experiences.