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Psychological Medicine: Experimentally Imposed Circadian Misalignment Alters the Neural Response to Monetary Rewards and Response Inhibition in Healthy Adolescents

During adolescence, circadian rhythm and natural sleep and wake times shift later, which can conflict with early school-start times. This incongruence commonly results in circadian misalignment (mismatch between the behavioral sleep-wake schedule and the timing of the circadian clock), which can in turn increase the risk for mood and substance use problems.

The link between circadian misalignment and mood and substance use problems may be in the altered function of neural circuitry underlying reward processing and impulse control in adolescents. To improve understanding of these potential associations, Pitt Psychiatry investigators including Brant Hasler, PhD; Adriane Soehner, PhD; Meredith Wallace, PhD; Erika Forbes, PhD; Daniel Buysse, MD; and Duncan Clark, MD, PhD, tested whether circadian misalignment alters the neural response to monetary reward and/or response inhibition. The study was recently published in Psychological Medicine. 

Twenty-five adolescents (ages 13-17) were placed randomly into one of two condition orders—aligned–misaligned, or misaligned–aligned—then completed two in-lab sleep schedules for a single night each. For the aligned condition, participants slept between midnight and 9:30 a.m., a schedule established at home before the lab visit.

For the misaligned condition, the schedule was advanced by four hours: 8:00 p.m. to 5:30 a.m. The misaligned schedule was intended to simulate the mismatch between adolescents' delayed circadian timing and early school-start times. Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward and response inhibition tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.

Results from the study indicated that bilateral ventral striatal activation during reward outcome was lower during the misaligned condition after accounting for the prior night's total sleep time. Bilateral ventral striatal activation during reward anticipation was lower during the misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.

“Although prior sleep deprivation studies in humans have demonstrated that an insufficient amount of sleep impacts reward-related brain function, to our knowledge, this is the first experimental study showing that improper timing of sleep also impacts reward-related brain function in ways that may increase teens’ risk for mood and substance use disorders,” said Dr. Hasler, the study’s corresponding author. “Although preliminary and in need of replication, the findings provide further causal evidence of the harmful effects of early school start times on vulnerable teen brains.” 

Experimentally imposed circadian misalignment alters the neural response to monetary rewards and response inhibition in healthy adolescents
Hasler BP, Soehner AM, Wallace ML, Logan RW, Ngari W, Forbes EE, Buysse DJ, Clark DB
Psychological Medicine, 1-9. doi:10.1017/S0033291721000787  

Human Brain Mapping: Opposing Relationships of Childhood Threat and Deprivation with Stria Terminalis White Matter

Childhood adversity—including threat (e.g., traumatic events, physical/sexual abuse, domestic/community violence) and deprivation (e.g., institutional rearing, neglect, poverty, and low socioeconomic status)—is a major predictor of mood and anxiety/trauma-related disorders in early adulthood. 

In a study recently published in Human Brain Mapping, University of Pittsburgh investigators including Layla Banihashemi, PhD; Meredith Wallace, PhD; Joseph Beeney, PhD; Howard Aizenstein, MD, PhD; and Anne Germain, PhD, examined the relationships between childhood adversity and specific stress-related white matter pathways—the stria terminalis and medial forebrain bundle—to determine whether these pathways act as a link between childhood adversity and affective symptoms and disorders.

The study was funded by Dr. Banihashemi’s National Institute of Mental Health-funded Mentored Research Scientist Career Development K01 Award.

One hundred young adults (ages 21-35) were assessed for a history of having experienced threat/deprivation, as well as for affective symptom severity. They then underwent diffusion spectrum imaging.

The research team found that childhood threat and socioeconomic deprivation have opposing relationships with stria terminalis generalized fractional anisotropy (a proxy of structural integrity), in which greater threat was associated with less stria terminalis generalized fractional anisotropy, while greater socioeconomic deprivation was associated with higher stria terminalis generalized fractional anisotropy. Further, threat (both abuse and early repeated trauma) also had a negative relationship with medial forebrain bundle generalized fractional anisotropy, while socioeconomic deprivation did not have an effect. Additionally, medial forebrain bundle generalized fractional anisotropy was negatively associated with post-traumatic stress symptoms.

“This study provides novel evidence that childhood threat and deprivation have opposing influences on stria terminalis white matter, and that different dimensions of childhood adversity may have differential influences on underlying microstructure, even within the same region. These findings may challenge the notion that early life stress creates neural changes that indicate maladaptive damage, but that neural differences in the context of childhood adversity may reflect neural adaptations to the relevant context.” said Dr. Banihashemi.

Opposing relationships of childhood threat and deprivation with stria terminalis white matter
Banihashemi L, Peng CW, Verstynen T, Wallace ML, Lamont DN, Alkhars HM, Yeh F, Beeney JE, Aizenstein HJ, Germain A.
Human Brain Mapping. 2021; 42: 2445– 2460. https://doi.org/10.1002/hbm.25378