Biology subjects

Narr, K. L.

Publications and source records attributed to Narr, K. L..

3 recordsLinked to original sources

bioRxiv2026

HARMONY: A large-scale harmonized neuroimaging dataset for research on anxious misery disorders

Patterns of brain circuit dysfunction underlying depression and anxiety have been increasingly characterized, including dimensional and subtype variation. A key challenge is determining how such patterns generalize across populations and measurement frameworks. Here, we introduce HARMONY, a harmonized multimodal neuroimaging dataset supporting large-scale investigation of brain-behavior associations across symptom-defined dimensions. HARMONY integrates four Human Connectome Project-style Connectomes Related to Human Disease cohorts spanning adolescence to later adulthood and capturing anxious misery symptoms. The resource combines standardized HCP-style preprocessing, quality control, imaging-derived phenotypes, and harmonized symptom measures into a clinically enriched public dataset. Proof-of-concept analyses using HARMONY showed that pooling heterogeneous cohorts increased statistical power for detecting associations between imaging-derived phenotypes and anhedonia and depression severity. Effect sizes remained modest, consistent with symptom-based measures across heterogeneous samples. Functional imaging-derived phenotypes showed the strongest multivariate predictive performance. In summary, HARMONY provides a large multi-cohort resource for reproducible mental health neuroimaging research.

neuroscience↗

bioRxiv2025

Maternal and child immune profiles are associated with neurometabolite measures of early-life neuroinflammation in children who are HIV-exposed and uninfected: a South African birth cohort

Children who are HIV-exposed and uninfected (HEU) are at risk of neurodevelopmental delays, which may be partially due to maternal immune dysregulation during pregnancy. This study investigates associations between maternal and child immune profiles and early neurometabolite profiles in HEU and HIV-unexposed (HU) children from a South African birth cohort. A subgroup of 156 children (66 HEU, 90 HU) from the Drakenstein Child Health Study underwent magnetic resonance spectroscopy at age 2-3 years, and maternal and child serum markers were measured at multiple timepoints via immunoassays. In HEU children, serum concentrations of maternal pro-inflammatory cytokines IL-5 ({beta}=0.79, p=0.005) and IL-8 ({beta}=0.64, p=0.02) were associated with myo-inositol ratios in parietal grey and white matter regions, respectively, while child serum MMP-9 at two years was associated with myo-inositol ratios in the midline parietal grey matter ({beta}=1.30, p=0.03). The association of maternal anti-inflammatory cytokine IL-13 with glutamate ratios in the midline parietal grey matter was negative in HEU ({beta}=-0.41, p=0.038) and positive in HU children ({beta}=0.42, p<0.0001). These findings suggest maternal immune activation may affect neurometabolite profiles in HEU children.

neuroscience↗

bioRxiv2021

Neural excitation/inhibition imbalance and the treatment of severe depression

An influential hypothesis holds that depression is related to a neural excitation/inhibition imbalance, but its role in the treatment of depression remains unclear. Here, we show that unmedicated patients with severe depression demonstrated reduced inhibition of brain-wide resting-state networks relative to healthy controls. Patients using antidepressants showed inhibition that was higher than unmedicated patients and comparable to controls, but they still suffered from severe depression. Subsequent treatment with electroconvulsive therapy (ECT) reduced depressive symptoms, but its effectiveness did not depend on changes in network inhibition. Concomitant pharmacotherapy increased the effectiveness of ECT, but only when the strength of neural inhibition before ECT was within the normal range and not when inhibition was excessive. These findings suggest that reversing the excitation/inhibition imbalance may not be sufficient nor necessary for the effective treatment of severe depression, and that brain-state informed pharmacotherapy management may enhance the effectiveness of ECT.

neuroscience↗