Biology subjects

Forbes, E. E.

Publications and source records attributed to Forbes, E. E..

5 recordsLinked to original sources

bioRxiv2025

Basal Ganglia Dopamine Availability and Immune Activation Interact and Relate to Anhedonia Severity among Youth with Depression

Anhedonia emerges in adolescence, has putative substrates in neural reward and dopamine systems, and is a hallmark of poor course in depression. Psychoneuroimmunology models suggest altered immune and reward systems may jointly underlie its development. When dopamine availability (rather than function) is considered, immune activation may be understood as a moderator amplifying how lower dopamine levels translate into motivational deficits. This cross-sectional study analyzed data from 55 youth with current depression (Mage=21.4 years; Female=75%). Plasma was assayed for relative quantification of 92 immune proteins, followed by dimensionality reduction via principal component (PC) analysis, forming five PC scores. Dopamine availability was indexed by basal ganglia tissue iron, quantified by MRI R2, a measure detectable in youth. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS), thought to capture overall anhedonia, and Positive Valence Systems Scale (PVSS), which provides overall, anticipatory, and consummatory anhedonia scores. PC1 scores--whose loadings indicated broadly distributed immune protein elevations consistent with general immune activation--moderated the relationship between basal ganglia dopamine availability and anhedonia: At higher PC1 levels, lower dopamine availability was linked to greater overall anhedonia (as measured by SHAPS) and anticipatory anhedonia, but not to consummatory anhedonia. Lower PC2 scores were associated with greater PVSS overall and consummatory anhedonia. Analyses examining individual basal ganglia regions suggest potential differences in dopaminergic-immune interactions across these regions, with effects most consistently observed in the putamen. Findings highlight nuanced neuroimmune pathways underlying anhedonia components in youth and support inflammation-based models of depression emphasizing dopaminergic-immune interplay.

neuroscience↗

bioRxiv2023

The association between cortical gyrification and sleep in adolescents and young adults.

Study objectivesHealthy sleep is important for adolescent neurodevelopment, and relationships between brain structure and sleep can vary in strength over this maturational window. Although cortical gyrification is increasingly considered a useful index for understanding cognitive and emotional outcomes in adolescence, and sleep is also a strong predictor of such outcomes, we know relatively little about associations between cortical gyrification and sleep. MethodsUsing Local gyrification index (lGI) of 34 bilateral brain regions and regularized regression for feature selection, we examined gyrification-sleep relationships in the Neuroimaging and Pediatric Sleep databank (252 participants; 9-26 years; 58.3% female) and identified developmentally invariant (stable across age) or developmentally specific (observed only during discrete age intervals) brain-sleep associations. Naturalistic sleep characteristics (duration, timing, continuity, and regularity) were estimated from wrist actigraphy. ResultsFor most brain regions, greater lGI was associated with longer sleep duration, earlier sleep timing, lower variability in sleep regularity, and shorter time awake after sleep onset. lGI in frontoparietal network regions showed associations with sleep patterns that were stable across age. However, in default mode network regions, lGI was only associated with sleep patterns from late childhood through early-to-mid adolescence, a period of vulnerability for mental health disorders. ConclusionsWe detected both developmentally invariant and developmentally specific ties between local gyrification and naturalistic sleep patterns. Default mode network regions may be particularly susceptible to interventions promoting more optimal sleep during childhood and adolescence.

neuroscience↗

bioRxiv2021

Associations between brain structure and sleep patterns across adolescent development

ImportanceStructural brain maturation and sleep are complex processes that exhibit significant changes over adolescence and are linked to healthy physical and mental development. The precise timing and magnitude of these changes influence function throughout the lifespan. However, the relationships between gray matter structure and sleep patterns during adolescence are not fully understood. A detailed characterization of brain-sleep associations during this sensitive period is crucial for understanding factors contributing to optimal neurodevelopmental trajectories in adolescence. ObjectiveTo investigate whether sleep-gray matter relationships are developmentally-invariant (i.e., stable across age) or developmentally-specific (i.e., only present during discrete time windows) from late childhood through young adulthood. SettingThe Neuroimaging and Pediatric Sleep Databank was constructed from 8 research studies conducted at the University of Pittsburgh between 2009 and 2020. ParticipantsThe final sample consisted of 240 participants without current psychiatric diagnoses (9-25 years), and with good quality sleep tracking and structural MRI (sMRI) data. DesignParticipants completed a sMRI scan and 5-7 days of wrist actigraphy to assess naturalistic sleep. We examined cross-sectional associations between sMRI measures and sleep patterns, as well as the effects of age, sex, and their interaction with sMRI measures on sleep. Main Outcome(s) and Measure(s)Using Freesurfer software, we extracted cortical thickness and subcortical volumes from T1-weighted MRI. Sleep patterns (duration, timing, continuity, regularity) were estimated from wrist actigraphy. ResultsShorter sleep duration, later sleep timing, and poorer sleep continuity were associated with a stable pattern of thinner cortex and altered subcortical volumes in diverse brain regions across adolescence. In a discrete subset of regions (e.g., posterior cingulate), thinner cortex was associated with these sleep patterns from late childhood through early-to-mid adolescence, but not in late adolescence and young adulthood. Conclusions and RelevanceIn childhood and adolescence, developmentally-invariant and developmentally-specific associations exist between sleep patterns and gray matter structure, in a wide array of brain regions linked to many sensory, cognitive, and emotional processes. Sleep intervention during specific developmental periods could potentially promote healthier neurodevelopmental outcomes. KEY POINTSO_ST_ABSQuestionC_ST_ABSDoes age modulate associations between gray matter structure and actigraphic sleep patterns across adolescent development? FindingsThis cross-sectional study reports stable associations between regional gray matter structure and shorter duration, later timing, and poorer continuity of sleep from ages 9 to 25 years-old, as well as developmentally-specific associations that are present only from late childhood to early-to-mid adolescence. MeaningStronger coupling of gray matter and sleep patterns from late childhood to early-to-mid adolescence potentially implicates this discrete developmental window as a period of vulnerability to adverse sleep-brain interactions. Sleep intervention during this developmental stage may support healthier neurodevelopmental trajectories.

neuroscience↗

bioRxiv2020

The longitudinal stability of fMRI activation during reward processing in adolescents and young adults

BackgroundThe use of functional neuroimaging has been an extremely fruitful avenue for investigating the neural basis of human reward function. This approach has included identification of potential neurobiological mechanisms of psychiatric disease and examination of environmental, experiential, and biological factors that may contribute to disease risk via effects on the reward system. However, a central and largely unexamined assumption of much of this research is that neural reward function is an individual difference characteristic that is relatively stable over time. MethodsIn two independent samples of adolescents and young adults studied longitudinally (Ns = 145 & 153, 100% female & 100% male, ages 15-21 & 20-22, 2-4 scans & 2 scans respectively), we tested within-person stability of reward-task BOLD activation, with a median of 1 and 2 years between scans. We examined multiple commonly used contrasts of active states and baseline in both the anticipation and feedback phases of a card-guessing reward task. We examined the effects of cortical parcellation resolution, contrast, network (reward regions and resting-state networks), region-size, and activation strength and variability on the stability of reward-related activation. ResultsOverall, stability (ICC; intra-class correlation) across 1-2 years was modest. In both samples, contrasts of an active state relative to a baseline were more stable (e.g., Win>Baseline; mean ICC = 0.13 - 0.33) than contrasts of two active states (e.g., Win>Loss; mean ICC = 0.048 - 0.05). Additionally, activation in reward regions was less stable than in many non-task networks (e.g., dorsal attention), and activation in regions with greater between-subject variability showed higher stability in both samples. ConclusionsThese results show that functional neuroimaging activation to reward has modest stability over 1-2 years. Notably, results suggest that contrasts intended to map cognitive function and show robust group-level effects (i.e. Win > Loss) may be less effective in studies of individual differences and disease risk. The robustness of group-level activation should be weighed against other factors when selecting regions of interest in individual difference fMRI studies.

neuroscience↗

bioRxiv2019

Cannabis, Connectivity, and Coming of Age: Associations between Cannabis Use and Anterior Cingulate Cortex Connectivity during the Transition to Adulthood

BackgroundCannabis use is common among adolescents and emerging adults and is associated with significant adverse consequences for a subset of users. Rates of use peak between the ages of 18-25, yet the neurobiological consequences for neural systems that are actively developing during this time remain poorly understood. In particular, cannabis exposure may interfere with adaptive development of white matter pathways underlying connectivity of the anterior cingulate cortex, including the cingulum and anterior thalamic radiations (ATR).\n\nMethodsThe current study examined the association between cannabis use during adolescence and emerging adulthood and white matter microstructure of the cingulum and ATR among 158 male subjects enrolled in the Pitt Mother & Child Project, a prospective, longitudinal study of risk and resilience among men of low socioeconomic status. Participants were recruited in infancy, completed follow-up assessments throughout childhood and adolescence, and underwent diffusion imaging at age 20 and 22.\n\nResultsAt age 20, moderate cannabis use across adolescence (age 12-19) was associated with higher fractional anisotropy of the cingulum and ATR, relative to both minimal and heavy adolescent use. Longitudinally, moderate and heavy extended cannabis use (age 12-21) was associated with reduced positive change in FA in both pathways from age 20 to 22, relative to minimal use.\n\nConclusionsThese results suggest that precocious white matter development may be linked to increased risk for use, whereas cannabis exposure may delay white matter maturation during the transition to adulthood and potentially impact individuals functioning later in development.

neuroscience↗