Biology subjects

Hegarty, C. E.

Publications and source records attributed to Hegarty, C. E..

3 recordsLinked to original sources

bioRxiv2024

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts

BackgroundEarly Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. MethodsA data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. ResultsIn both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. ConclusionsThis data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

neuroscience↗

bioRxiv2019

Symptom Severity in Youths with Attention Deficit Hyperactivity Disorder Associated with Normalizing Effects of Treatment on fMRI Response during a Stop Signal Task

Inhibitory control deficits represent one of many core cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD). Neuroimaging studies suggest that individuals with ADHD exhibit atypical engagement of neural systems during response inhibition, but the exact nature of this phenotype is obscured by mixed findings. We tested whether drug-free youths with ADHD (n=30, ages 7-14 years, 10 female) exhibited atypical neural correlates of response inhibition, as measured with a stop signal task and fMRI, compared to matched controls. We next investigated medication effects and whether there was a relationship between symptom severity and medication effects on the fMRI-evaluated signal. Finally, we tested for a significant difference between effects of monotherapy and combined pharmacological treatment. Patients showed significantly slower stop signal response time and lower percent inhibition, but no significant differences in the neural correlates of response inhibition relative to controls. However, patients showed significantly elevated signal in frontostriatal regions during responses. Prefrontal signal in patients was positively associated with reaction time variability in patients, and change (medicated - drug free) in the prefrontal signal was significantly associated with symptom scores, such that patients with elevated symptoms had greater BOLD signal reduction following treatment. Medication significantly improved go response time median and variability as well as stop signal reaction time, but there were no significant effects of medication or treatment type on BOLD signal. These findings challenge the notion of frontostriatal hypoactivation during response inhibition as a biomarker for ADHD and suggest that symptom severity may be associated with response to medication.

neuroscience↗

bioRxiv2018

Disruptions in White Matter Maturation and Mediation of Cognitive Development in Youth on the Psychosis Spectrum

BackgroundPsychosis onset typically occurs in adolescence, and subclinical psychotic experiences peak in adolescence as well. Adolescence is also a time of critical neural and cognitive maturation. Using cross-sectional data from the Philadelphia Neurodevelopmental Cohort, we examine whether regional white matter (WM) development is disrupted in psychosis spectrum (PS) youth whether WM maturation mediates the relationship between age and cognition in typically developing (TD) and PS youth. A third group with intermediate symptom severity (limited PS [LPS]) was included in follow-up analyses to determine whether age-related disruptions in WM scaled with symptom severity.\n\nMethodsWe examined WM microstructure, as assessed via diffusion tensor imaging, in 707 individuals (aged 10-22 years; 499 TD, 171 PS, 37 LPS) by using Tract-Based Spatial Statistics. Multiple regressions were used to evaluate age x group interactions on regional WM indices. Mediation analyses were conducted using a bootstrapping approach.\n\nResultsThere were age x group interactions on fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and retrolenticular internal capsule (RLIC). SLF FA mediated the relationship between age and Complex Cognition in TD, but not PS. Further, inclusion of LPS youth showed that the relationship between age and SLF FA decreased with increasing symptom severity\n\nConclusionsOur results show aberrant age-related changes in SLF and RLIC FA in PS youth. SLF development supports emergence of specific higher-order cognitive functions in TD youth, but not in PS. Future mechanistic explanations for these relationships could facilitate development of earlier and refined targets for therapeutic interventions.

neuroscience↗