Early Adversity and Genetic Neuroplasticity Factors Shape Amygdala-Prefrontal Circuitry Function and Internalizing Behavior

• In Event: 1-096 - Sensitive Periods in Development Shaping Risk for Psychopathology Across the Life Course

Integrative Statement

Introduction: Understanding how the environment shapes emotion regulation circuitry during developmental sensitive periods of heightened neuroplasticity is critical for understanding psychopathology risk. Parental deprivation in the early postnatal period can accelerate sensitive period timing for an amygdala-prefrontal cortex (PFC) circuit central to emotion regulation. Here, we sought to identify how early deprivation timing and duration, indexed by previous institutionalization (PI), interacts with individuals’ genetically-regulated neuroplasticity to influence amygdala-PFC circuitry sensitive period dynamics and internalizing behavior.

Hypotheses: We hypothesized that youths with both prior deprivation and higher genetically-driven neuroplasticity levels (indexed by BDNF Val66met polymorphism) would show an accelerated amygdala-prefrontal cortex (PFC) sensitive period and worse internalizing behavior. We anticipated that later deprivation timing and shorter duration in PI youth would spare amydala-PFC connectivity and lead to lower internalizing scores.

Study population: The present study leveraged data from a sample of 44 PI youth and 49 age-matched comparison youth without prior deprivation between ages 6 an 18 years. Each youth contributed usable resting-state fMRI, BDNF genotype (via saliva), and Child Behavior Checklist (CBCL) questionnaire data, and a subsample of 26 PI and 32 comparison youth additionally contributed CBCL data 2 years later.

Methods: Amygdala-seeded resting-state connectivity with the whole-brain was generated (FWE alpha < 0.05). Connectivity weights were extracted for a BDNF genotype x deprivation interaction effect, and submitted to offline simple effect T-tests. Regressions were run to examine effects of deprivation timing (age deprivation began) and duration on connectivity weights, and the relation between connectivity weights and CBCL internalizing scores.

Results: We found that deprivation experience and BDNF genotype interactively affected amygdala-ventral PFC connectivity. Connectivity for youth with the lower BDNF-regulated neuroplasticity levels was significantly more negative in the PI relative to the comparison youth (T(38) = -2.82, p = 0.008). In contrast, amygdala-PFC connectivity for youth with the higher BDNF-regulated neuroplasticity levels was significantly more positive in PI relative to comparison youth (T(51) = 4.64, p > 0.0001). These findings suggest that increased BDNF-regulated neuroplasticity was associated with an accelerated amygdala-PFC sensitive period following parental deprivation, but a prolonged sensitive period through adolescence in the absence of deprivation. In the PI youth, over and above the BDNF effects, delayed deprivation timing predicted more positive connectivity, while longer deprivation durations predicted more negative connectivity (timing: B = 0.41, T(34) = 3.68, p = 0.001; duration: B = -0.50, T(34) = -2.97, p = 0.006). These dose and timing effects accounted for between one-third and one-half of the variance in subsequent amygdala-PFC connectivity profiles. Notably, positive connectivity was associated with lower concurrent and future internalizing scores (B = -7.09, T(30) = -2.84, p = 0.008; two years later: B = -5.21, T(45) = -2.50, p = 0.016). Thus, later, shorter deprivation, and the accelerated sensitive period timing in the PI youth with high BDNF-regulated neuroplasticity have adaptive short-term behavioral consequences. Together, these findings show that an individual’s genetically-determined neuroplasticity coupled with the developmental timing and duration of deprivation experience differentially influence amygdala-PFC sensitive period timing and subsequent psychopathology-related behavior.

Author

• Laurel Gabard-Durnam, Boston Children's Hospital
  Presenting Author