Investigating Associations Between Early Life Stress, Neural Response to Reward, and Depression

The link between exposure to early life stress (ELS), such as child maltreatment, and the development of depression has been well-replicated. However, the mechanisms that underlie this connection remain poorly understood. One potential mechanism may be neural alterations in reward-related brain regions, such as the ventral striatum and sub-regions of the prefrontal cortex. Recent research indicates that exposure to child maltreatment is associated with aberrant reward-related brain activity. A separate body of work implicates similar reward-related neural alterations in the etiology and maintenance of depression. The current study investigated whether altered neural response to reward plays a mechanistic role in explaining the association between ELS and depression. Here, we examined associations between history of child maltreatment, depressive symptoms, and neural response to reward during a reward processing fMRI task in a sample of adult men (N = 165; 30.5% White, 60.6% Black) who were a part of the Pittsburgh Youth Study (PYS), a longitudinal study examining the development of negative mental health outcomes. History of child maltreatment was assessed via referrals prior to age 18 from the Allegheny County’s Office of Children, Youth, and Families. Neuroimaging data and self-reported depressive symptoms were collected in adulthood (M age = 32.64, SD age = 3.62). Child maltreatment significantly predicted greater depressive symptoms. Child maltreatment and depressive symptoms were, however, not significantly associated with altered neural response to reward. Findings from the current study suggest directions for future work probing characteristics of adversity (e.g., chronicity, timing), as well as specific factors likely to moderate neural responses to reward (e.g., reward phase, magnitude of gains)

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Modeling relations between early life interpersonal stress, neural response to social reward, and depressive symptoms in adolescent girls

Experiencing stressful events early in life is very common and widespread across the globe. Despite strong links between experiencing such stress and developing depression, the factors that drive this association remain unclear. Recent evidence suggests that interpersonal stressors (e.g., maltreatment), compared to impersonal stressors (e.g., poverty), uniquely relate to depression. Therefore, a focus on early life interpersonal stress (ELIS) may be critical for our understanding of the factors that contribute to stress-related depression. Prior work demonstrates that youth who experience ELIS exhibit altered neural response to social reward (e.g., positive social stimuli/ feedback) in reward-related brain regions (e.g., striatum, anterior cingulate cortex). Similar disruptions in neural response to social reward are also noted in studies of youth with depression. However, limited work has examined relations between ELIS, neural response to social reward, and depression all in one study. The present dissertation aimed to synthesize these separate, yet related, bodies of literature by investigating whether 1) ELIS related to altered neural response to social reward, 2) disruptions in neural response to social reward related to depression, and 3) altered neural response to social reward moderated links between ELIS and depression. An exploratory aim further tested whether developmentally relevant interpersonal stress vs. impersonal stress differentially associated with neural response to social reward. Notably, these aims were examined in a sample of adolescent girls (N = 31, M/SD age = 15.94/1.44), which is particularly important given the increases in interpersonal stressors, sensitivity to reward, and risk for depression that occur during this time, especially for girls compared to boys. The participants completed self-report measures of ELIS and depressive symptoms, a clinical interview measuring interpersonal stress vs. impersonal stress, and the fMRI Chatroom Interact Task. Neural response to the peer acceptance > control feedback contrast was examined in regions implicated in reward processing. Unfortunately, multiple regression and moderation analyses did not find significant associations between ELIS, neural response to social reward, and depression. Nevertheless, the present dissertation still provides novel contributions that positions future work to better understand the potential central role of social reward processing in the link between ELIS and depression

Poverty and self-regulation: Connecting psychosocial processes, neurobiology, and the risk for psychopathology

In the United States, over 40% of youth under the age of 18 live at or near the federal poverty line. Several decades of research have established clear links between exposure to child poverty and the development of psychopathology, yet the mechanisms that convey this risk remain unclear. We review research in developmental science and other allied disciplines that identify self-regulation as a critical factor that may influence the development of psychopathology after exposure to poverty. We then connect this work with neurobiological research in an effort to further inform these associations. We propose a starting framework focused on the neural correlates of self-regulation, and discuss recent work relating poverty to alterations in brain regions related to self-regulation. We close this review by highlighting important considerations for future research on poverty/socioeconomic status, neurobiology, self-regulation, and the risks related to the development of negative mental health outcomes

Lower neural value signaling in the prefrontal cortex is related to childhood family income and depressive symptomatology during adolescence

Lower family income during childhood is related to increased rates of adolescent depression, though the underlying mechanisms are poorly understood. Evidence suggests that individuals with depression demonstrate hypoactivation in brain regions involved in reward learning and decision-making processes (e.g., portions of the prefrontal cortex). Separately, lower family income has been associated with neural alterations in similar regions. Motivated by this research, we examined associations between family income, depression, and brain activity during a reward learning and decision-making fMRI task in a sample of adolescents (full n = 94; usable n = 78; mean age = 15.2 years). We focused on brain activity for: 1) expected value (EV), the learned subjective value of an object, and 2) prediction error, the difference between EV and the actual outcome received. Regions of interest related to reward learning were examined in connection to childhood family income and parent-reported adolescent depressive symptoms. As hypothesized, lower activity in the subgenual anterior cingulate (sACC) for EV in response to approach stimuli was associated with lower childhood family income, as well as greater symptoms of depression measured one-year after the neuroimaging session. These results are consistent with the hypothesis that lower early family income leads to disruptions in reward and decision-making brain circuitry, contributing to adolescent depression