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New research from Pitt Psychiatry investigators provides insight into the development of anxiety, depression, and/or bipolar in adolescence. A Biological Psychiatry study examines the association between trauma exposure, reward neural circuitry function, and affective and anxiety disorders. In the Journal of Affective Disorders, investigators study whether child maltreatment and cognitive function influence the clinical course of bipolar symptoms.

Biological Psychiatry: Trauma affects prospective relationships between reward-related ventral striatal and amygdala activation and 1-year future hypo/mania trajectories

Trauma exposure during childhood and adolescence is associated greater odds of developing symptoms of depression and anxiety, as well as risk for bipolar disorder. In addition, trauma exposure has been shown to impact markers of reward neural circuitry function and, independently, predict the future course of affective symptoms.
To improve understanding of how trauma exposure influences reward neural circuitry function and the possible future development of anxiety or depression, scientists including postdoctoral scholar Kristen Eckstrand, MD, PhD; Erika Forbes, PhD; Michele Bertocci, PhD; Henry Chase, PhD; and Mary Phillips, MD, MD (Cantab) focused on investigating reward prediction error (the difference between expected and received rewards) in relation to trauma and development of anxiety or affective disorders over one year. 

“Markers of neural reward circuitry function can predict changes in affective and anxiety symptoms. Given the treatment implications of biomarkers, we wanted to explore whether number of lifetime traumatic events would impact the relationship between neural reward circuitry function and one-year affective and anxiety symptom trajectories,” said Dr. Eckstrand, lead author of the study, which was recently published in Biological Psychiatry. 

The investigators followed a sample of 59 young adults (ages 18-25 years) for more than one year. At baseline, they assessed lifetime trauma exposure, and neural reward circuitry function as measured by activation of the ventral striatum, amygdala, and anterior cingulate cortex during a reward functional magnetic resonance imaging task. During baseline, six-month, and one-year follow up visits, they monitored affective and anxiety symptoms to determine one-year affective and anxiety symptom trajectories.

Findings revealed that trauma exposure interacts with ventral striatum and amygdala reward prediction error activation to predict the development of affective and anxiety symptoms. In particular, they found that the interaction between greater trauma and greater left ventral striatum reward prediction error activation was associated with a shallower increase in hypo/mania severity, whereas the interaction between greater trauma and greater right amygdala reward prediction error activation was associated with increasing hypo/mania severity. Greater right amygdala reward prediction error activation in individuals with more trauma exposure predicted increasing depression severity over six months and increasing hypo/mania severity over one year.

Dr. Phillips, the study’s senior author, commented on the implications of these findings. “This study provides important findings indicating how trauma may differentially impact functioning in two key brain areas important for reward processing and future mania and depression. These findings can aid the future development of novel treatments targeting these brain areas to help prevent worsening mood in vulnerable individuals.”

Trauma affects prospective relationships between reward-related ventral striatal and amygdala activation and 1-year future hypo/mania trajectories
Eckstrand KL, Forbes EK, Bertocci MA, Chase HW, Greenberg T, Lockovich J, Stiffler R, Aslam HA, Graur S, Bebko G, Phillips ML.
Biological Psychiatry, 2020, Available online 25 November 2020, ISSN 0006-3223, https://doi.org/10.1016/j.biopsych.2020.11.017

Journal of Affective Disorders: Longitudinal course of depressive symptom severity among youths with bipolar disorders: Moderating influences of sustained attention and history of child maltreatment

Pediatric bipolar disorders are often characterized by disruptions in cognitive functioning. In addition, for children with bipolar disorder, exposure to maltreatment, such as physical and sexual abuse, is associated with a significantly poorer course of illness. Although research has shown that such maltreatment can be strongly associated with poorer cognitive functioning (e.g., attention), as well as  a more severe course of illness with longer duration, it is unclear whether maltreatment and cognitive function jointly influence the clinical course of bipolar symptoms.

To explore how child maltreatment history and cognitive disruptions influence bipolar depressive symptoms over time, investigators—including Rachel Vaughn-Coaxum, PhD; Boris Birmaher, MD; Danella Hafeman, MD, PhD; Jessica Levenson, PhD; Neal Ryan, MD; Rasim Diler, MD; and Tina Goldstein, PhD—from Pitt Psychiatry analyzed data from 198 youths, ages 7-17, involved in the longitudinal Course and Outcome of Bipolar Youth (COBY) study. 

“There is compelling evidence that child maltreatment and disruptions in cognitive functioning during development are interconnected risk pathways for youth psychopathology that do not operate independently from one another,” said Dr. Vaughn-Coaxum, the study’s lead author. “Less is known about the effects these factors may jointly exert on the ongoing clinical course of mood symptoms in youth. Based on prior cognitive research in the COBY study, we wanted to assess associations of maltreatment exposure with depression symptom severity over time, specifically in the context of poorer average performance on attention and affective information processing tasks. Identifying factors that exacerbate mood symptoms in youth with bipolar disorders is important for understanding the long-term influence of environmental and biobehavioral factors on the course of mood disorders.” 

Youth participants and their parents were administered clinical assessments that included participants’ history of experiencing physical or sexual abuse prior to age 18 at each timepoint. Follow-up assessments included evaluation of new onset comorbid psychiatric disorders, the occurrence of negative life events, and any subsequent exposure to abuse. Cognitive function was assessed using Cambridge Neuropsychological Testing Automated Battery (CANTAB).

Results suggested that specific aspects of lower sustained attention and a history of childhood abuse may moderate depressive symptom severity over time. Among youths exposed to maltreatment, lower average sustained attention was correlated with higher average symptom severity during childhood and early adolescence (but not late adolescence). There was no association between maltreatment and symptom severity in the context of higher sustained attention, and no association between attention and depression symptom severity for non-maltreated youths.

“These findings further contribute to our understanding of mechanisms by which childhood adversity may lead to or maintain subsequent psychiatric disturbance. Critically, Dr. Vaughn-Coaxum’s innovative work is building on these findings to meaningfully inform assessment and treatment optimization for youth with mood disorders,” said Dr. Goldstein, the study’s senior author. 

Longitudinal course of depressive symptom severity among youths with bipolar disorders: Moderating influences of sustained attention and history of child maltreatment
Vaughn-Coaxum RA, Merranko J, Birmaher B, Dickstein DP, Hafeman D, Levenson JC, Liao F, Gill MK, Hower H, Goldstein BI, Strober M, Ryan ND, Diler R, Keller MB, Yen S, Weinstock LM, Axelson D, Goldstein TR.
Journal of Affective Disorders Volume 282, 1 March 2021, Pages 261-271