When provided individually, both the serotonin (5-HT 1A )-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and environmental enrichment (EE) enhance behavioral outcome and reduce histopathology after experimental traumatic brain injury (TBI). The aim of this study was to determine whether combining these therapies would yield greater benefit than either used alone. Anesthetized adult male rats received a cortical impact or sham injury and then were randomly assigned to enriched or standard (STD) housing, where either 8-OH-DPAT (0.1 mg/kg) or vehicle (1.0 mL/kg) was administered intraperitoneally once daily for 3 weeks. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. CA1/ CA3 neurons and choline acetyltransferase-positive (ChAT þ ) medial septal cells were quantified at 3 weeks. 8-OH-DPAT and EE attenuated CA3 and ChAT þ cell loss. Both therapies also enhanced motor recovery, acquisition of spatial learning, and memory retention, as verified by reduced times to traverse the beam and to locate an escape platform in the water maze, and a greater percentage of time spent searching in the target quadrant during a probe trial in the TBI þ STD þ 8-OH-DPAT, TBI þ EE þ 8-OH-DPAT, and TBI þ EE þ vehicle groups versus the TBI þ STD þ vehicle group ( p 0.0016). No statistical distinctions were revealed between the TBI þ EE þ 8-OH-DPAT and TBI þ EE þ vehicle groups in functional outcome or CA1/CA3 cell survival, but there were significantly more ChAT þ cells in the former ( p ¼ 0.003). These data suggest that a combined therapeutic regimen of 8-OH-DPAT and EE reduces TBI-induced ChAT þ cell loss, but does not enhance hippocampal cell survival or neurobehavioral performance beyond that of either treatment alone. The findings underscore the complexity of combinational therapies and of elucidating potential targets for TBI.

Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence.

Background Environmental enrichment (EE) is a complex living milieu that has been shown to enhance functional recovery vs. standard (STD) housing after experimental traumatic brain injury (TBI) and therefore may be considered a rodent correlate of rehabilitation. However, the typical EE paradigm consists of continuous exposure to enrichment after TBI, which is inconsistent with the limited time frame in clinical rehabilitation. Objective To determine whether abbreviated EE (i.e., rehabilitation-relevant dose response) confers benefits similar to typical EE after TBI. Methods Adult male rats received either a controlled cortical impact (2.8 mm depth at 4 m/sec) or sham injury and were then randomly assigned to TBI + EE, TBI + EE (2hr), TBI + EE (4hr), TBI + EE (6hr), TBI + STD, and respective sham controls. Motor (beam-balance/beam-walk; BB/BW) and cognitive (Morris water maze; MWM) performance was assessed on post-operative days 1-5 and 14-19, respectively. Results The TBI + EE (2hr) and TBI + EE (4hr) groups were not statistically different from the TBI + STD group in any behavioral assessment. In contrast, the TBI + EE (6hr) group exhibited significant enhancement of motor and cognitive performance vs. the TBI + STD group, as well as the TBI + EE (2hr) and TBI + EE (4hr) groups (p < 0.003), and did not differ from the TBI + EE (typical) group. Conclusions These data demonstrate that abbreviated EE (6hr) produces motor and cognitive benefits similar to continuous EE after TBI and thus may be considered a dose-relevant rehabilitation paradigm.

Background Children who experience socioeconomic disadvantage are at heightened risk for developing depression; however, little is known about neurobiological mechanisms underlying this association. Low socioeconomic status (SES) during childhood may confer risk for depression through its stress-related effects on the neural circuitry associated with processing monetary rewards. Methods In a prospective study, we examined the relationships among the number of years of household receipt of public assistance from age 5–16 years, neural activation during monetary reward anticipation and receipt at age 16, and depression symptoms at age 16 in 123 girls. Results Number of years of household receipt of public assistance was positively associated with heightened response in the medial prefrontal cortex during reward anticipation, and this heightened neural response mediated the relationship between socioeconomic disadvantage and current depression symptoms, controlling for past depression. Conclusions Chronic exposure to socioeconomic disadvantage in childhood may alter neural circuitry involved in reward anticipation in adolescence, which in turn may confer risk for depression.

Importance African American women living in urban, low-income environments are at high risk for poor nutrition during pregnancy and birth complications. Objective To test the effectiveness of prenatal docosahexaenoic acid (DHA) supplementation on birth outcomes and infant development in a sample of African American women with Medicaid insurance and living in the city of Pittsburgh. Design The Nutrition and Pregnancy Study (NAPS) is a double-blind, randomized controlled trial of prenatal DHA supplementation conducted between 2012 and 2014. Setting Participants were recruited from obstetric clinics at the University of Pittsburgh Medical Center. Participants Sixty-four pregnant, African American women were enrolled at 16–21 weeks of gestation and randomized to either 450 mg/day of DHA (22:6n-3)(n=43) or a soybean placebo (n=21). Four women (6.3%) withdrew from the study: two participants from each study arm; complete data were obtained for 49 infants (76.5%) at the 3-month assessment. Interventions Supplementation with DHA or placebo continued from the beginning of enrollment through delivery. Main Outcome and Measures Data on birth outcomes were collected from medical records. At approximately 3 months post-partum, mothers brought their infants to the laboratory where the Bayley Scales of Infant Development (BSID-III) were administered and cortisol response to the Face-to-Face Still-Face (FFSF) paradigm was assessed. Results Infants of mothers who received DHA supplementation had higher birth weight (3,174 grams versus 2,890 grams) than infants of mothers receiving placebo (F [2,40] = 6.09, p = .018, eta = .36), and were more likely to have a 1-minute Apgar score greater than 8 (OR = 5.99 [95% CI = 1.25–28.75], p = .025). Infants of mothers who received DHA compared with infants of mothers receiving placebo had lower levels of cortisol in response to the FFSF paradigm (F [1,32] = 5.36, p = .018, eta = .36). None of the scores on the BSID-III differed as a function of active supplement versus placebo. Conclusions Infants of women living in urban, low-income environments who received DHA supplementation had more optimal birth outcomes and more modulated cortisol response to a stressor. DHA supplementation may be effective in attenuating the negative effects of prenatal stress on offspring development.