Biology subjects

Scott, J. C.

Publications and source records attributed to Scott, J. C..

7 recordsLinked to original sources

bioRxiv2026

The PMADS Project: A Longitudinal Multimodal Cohort Study to Understand Risk for Perinatal Mood and Anxiety Disorders

BackgroundPerinatal mood and anxiety disorders (PMADs) are among the most common and consequential complications of pregnancy. The perinatal period is also characterized by profound hormonal fluctuations and large-scale brain plasticity. However, the mechanisms linking these neurobiological changes to psychiatric risk are poorly understood. Prospective, clinically informed studies are needed to identify quantitative biomarkers and clarify pathways linking perinatal neurobiology to PMADs risk. MethodsThis report describes the design of a prospective, longitudinal cohort study integrating multimodal neuroimaging, biofluid sampling, and deep clinical phenotyping to enable precision characterization of neurobiological trajectories of PMADs risk. Twenty-five individuals at elevated risk for PMADs will be recruited prior to conception and followed across six in-person timepoints spanning the menstrual cycle, pregnancy, and early postpartum, with additional remote follow-ups through the first postpartum year. Data collection includes high-resolution structural MRI, functional brain mapping using multi-echo resting-state fMRI, diffusion MRI, arterial spin labeling, ultra-high field MR-based techniques for measuring glutamate (GluCEST and 1HMRS), biofluid sampling, and comprehensive clinical, behavioral, and cognitive assessments. Structured clinical interviews assess categorical diagnoses while dimensional symptom measures capture heterogeneity and transdiagnostic features of perinatal psychopathology. Longitudinal analyses will model nonlinear trajectories of brain and symptom change across the perinatal period as well as evaluate whether preconception network features and menstrual cycle-related brain changes are associated with subsequent perinatal symptom emergence. DiscussionThis cohort study establishes a longitudinal, multimodal framework for investigating neurobiological changes across the transition to pregnancy in individuals at elevated risk for PMADs. By anchoring pregnancy-related brain changes to preconception and menstrual cycle-related variability within the same individuals, this study is designed to evaluate associations between preconception hormone sensitivity, pregnancy-induced neuroplasticity, and PMADs risk. The resulting dataset will provide a deeply phenotyped longitudinal resource for investigating brain-behavior relationships across the perinatal period. Findings are expected to inform future larger-scale studies aimed at advancing mechanistic understanding of PMADs, improving individualized risk stratification, and supporting development of personalized preventive and neuromodulatory interventions.

neuroscience↗

bioRxiv2025

An Open, Fully-processed, Longitudinal Data Resource to Study Brain Development and Transdiagnostic Executive Function

Executive function (EF) develops rapidly during adolescence. However, deficits in EF also emerge in adolescence, representing a transdiagnostic symptom associated with many forms of psychopathology. To promote transdiagnostic research on EF during development, we introduce a new data resource - the Penn Longitudinal Executive functioning in Adolescent Development study (Penn LEAD) - that combines longitudinal multimodal imaging data with rich clinical and cognitive phenotyping. These data include 225 imaging sessions from 132 individuals (8-16 years old at the time of enrollment) who are typically developing (27.3%), or meet criteria for attention-deficit hyperactivity disorder (20.5%) or the psychosis-spectrum (52.3%). In addition to phenotypic data from multiple cognitive tasks focused on EF, the study includes data from structural MRI, diffusion MRI, n-back task fMRI, resting-state fMRI, and arterial spin-labeled MRI. Notably, all raw data, fully-processed derived data, and detailed quality control recommendations are publicly shared on OpenNeuro. We anticipate that such analysis-ready data will accelerate research on EF development in psychiatry.

neuroscience↗

bioRxiv2025

Cannabis Use and Glutamate across the Psychosis Spectrum: In Vivo Evidence from 7T Proton Magnetic Resonance Spectroscopy

Cannabis use is linked to elevated psychosis risk, yet the neurobiological mechanisms that couple use to symptom expression remain unclear. Because glutamatergic dysregulation has been implicated in both cannabis effects and psychosis vulnerability, we examined whether brain glutamate relates to dimensional symptoms as a function of cannabis use across the psychosis spectrum. Seventy-nine participants--typically developing controls, clinical high-risk individuals, and patients with psychosis--completed dimensional clinical assessments, detailed cannabis surveys, urine toxicology, and ultra-high-field 7T 1HMRS quantification of anterior cingulate cortex (ACC) glutamate levels. Linear models assessed the main and interactive effects of ACC glutamate and cannabis use on positive and negative symptoms. Self-reported cannabis use showed strong concordance with urine toxicology. Cannabis use was associated with higher positive and negative symptoms. Independently, higher ACC glutamate predicted greater positive and negative symptoms. Notably, lower glutamate levels were associated with higher positive symptoms in cannabis users. Exploratory analyses suggested interactions for depressive and manic symptoms, indicating that glutamatergic abnormalities may amplify the overall severity of cannabis-related symptoms. Sensitivity analyses revealed lower ACC glutamate in psychosis patients--especially cannabis users--highlighting diagnostic group differences and reinforcing the link between cannabis exposure and glutamatergic dysfunction. These findings implicate ACC glutamatergic dysfunction as a transdiagnostic correlate of symptom burden, particularly in those with psychosis who are cannabis users. Glutamate-targeted interventions and longitudinal designs will be needed to examine causal pathways linking cannabis exposure to psychosis-relevant outcomes.

neuroscience↗

bioRxiv2024

Phenotypically wild barley shows evidence of introgression from cultivated barley

Plant conservation hinges on preserving biodiversity, which is crucial for long-term adaptation. Multiple studies have reported genetic evidence of crop-to-wild introgression in phenotypically wild accessions of wild barley (Hordeum vulgare ssp. spontaneum). We examined 318 Wild Barley Diversity Collection (WBDC) accessions for evidence of introgression from cultivated barley. Using SNP genotype and exome capture data, we performed local ancestry inference between the 318 WBDC accessions and cultivated barley to identify genomic regions with evidence of introgression. Using the genomic intervals for well-characterized genes involved in domestication and improvement, we examined the evidence for introgression at genomic regions potentially important for maintaining a wild phenotype. Our analysis revealed that nearly 16% (48 of 318) of WBDC accessions showed evidence of introgression from cultivated barley, and up to 16.6% of the genome has been introgressed. All accessions identified as introgressed based on domestication-related phenotypes show clear genetic evidence of introgression. The size of runs of identity by state and local ancestry inference suggests that most introgression did not occur recently. This study suggests a long history of genetic exchange between wild and cultivated barley, highlighting the potential for introgression to influence the genetic makeup and future adaptation of wild populations, with implications for plant conservation strategies.

evolutionary biology↗

bioRxiv2021

Association between Neighborhood Socioeconomic Status and Executive System Activation in Youth

Low socioeconomic status has been shown to have detrimental effects on cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may have a particularly strong impact on cognitive outcomes. Here, we sought to examine how neighborhood socioeconomic status (SES) impacts task-related activation of the executive system during adolescence, and to determine whether this effect mediates the relationship between neighborhood SES and WM performance. To address these questions, we studied 1,158 youths (age 8-22) that completed a fractal n-back WM task during fMRI at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that higher neighborhood SES was associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. These associations remained significant when controlling for related factors like parental education and exposure to traumatic events. Furthermore, high dimensional multivariate mediation analysis identified two distinct patterns of brain activity within the executive system that significantly mediated the relationship between neighborhood SES and task performance. Together, these findings underscore the importance of the neighborhood environment in shaping executive system function and WM in youth.

neuroscience↗

bioRxiv2019

Convergent neural representations of acute nociceptive pain in healthy volunteers: A large-scale fMRI meta-analysis

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute pain.\n\nHIGHLIGHTSO_LIPain stimulation recruits a core set of pain-related brain regions.\nC_LIO_LIThis core set includes thalamus, SII, insula and mid-cingulate cortex.\nC_LIO_LIThese regions were recruited regardless of stimulus modality and stimulus location.\nC_LI

neuroscience↗

bioRxiv2018

Cannabis Use in Youth is Associated with Limited Alterations in Brain Structure

Frequent cannabis use during adolescence has been associated with alterations in brain structure. However, studies have featured relatively inconsistent results, predominantly from small samples, and few studies have examined less frequent users to shed light on potential brain structure differences across levels of cannabis use. In this study, high-resolution T1-weighted MRIs were obtained from 781 youth aged 14-21 years who were studied as part of the Philadelphia Neurodevelopmental Cohort. This sample included 147 cannabis users (109 Occasional [[≤]1-2 times per week] and 38 Frequent [[≥] 3 times per week] Users) and 634 cannabis Non-Users. Several structural neuroimaging measures were examined in whole brain analyses, including gray and white matter volumes, cortical thickness, and gray matter density. Established procedures for stringent quality control were conducted, and two automated neuroimaging software processing packages were used to ensure robustness of results. There were no significant differences by cannabis group in global or regional brain volumes, cortical thickness, or gray matter density, and no significant group by age interactions were found. Follow-up analyses indicated that values of structural neuroimaging measures by cannabis group were similar across regions, and any differences among groups were likely of a small magnitude. In sum, structural brain metrics were similar among adolescent and young adult cannabis users and non-users. Our data converge with prior large-scale studies suggesting small or limited associations between cannabis use and structural brain measures in youth. Detailed studies of vulnerability to structural brain alterations and longitudinal studies examining long-term risk are indicated.

neuroscience↗