Biology subjects

Hegarty, C.

Publications and source records attributed to Hegarty, C..

3 recordsLinked to original sources

bioRxiv2018

Association between Apolipoprotein E genotype and the gut microbiome composition in humans and mice

Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimers disease. Numerous studies have provided insights into the pathological mechanisms. However, a comprehensive understanding of the impact of APOE genotype on microflora speciation and metabolism is completely lacking. The aim of this study was to investigate the association between APOE genotype and the gut microbiome composition in human and APOE-targeted replacement (TR, APOE3 and APOE4) transgenic mice. Faecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity (alpha or beta diversity) in group-aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gut microbiota of APOE-TR mice. Furthermore, metabolomic analysis of faecal water from murine samples detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, the findings indicate that APOE genotype associated with specific gut microbiome profiles in both humans and in APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential therapeutic target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention and treatment of AD.

genomics↗

bioRxiv2018

Structural brain alterations in youth with psychosis and bipolar spectrum symptoms

ObjectiveAdults with established diagnoses of serious mental illness (bipolar disorder and schizophrenia) exhibit structural brain abnormalities, yet less is known about how such abnormalities manifest earlier in development.\n\nMethodsWe analyzed the data publicly available from the Philadelphia Neurodevelopmental Cohort (PNC). Structural magnetic resonance neuroimaging data (sMRI) were collected on a subset of the PNC (N=989, ages 9-22 years old). We calculated measures of cortical thickness (CT) and surface area (SA), along with subcortical volumes. Study participants were assessed for psychiatric symptomatology via structured interview and the following groups were created: typically developing (TD, N=376), psychosis spectrum (PS, N=113), bipolar spectrum (BP, N=117), and BP + PS (N=109). We examined group and developmental differences in sMRI measures. We also examined to what extent any structural aberration was related to neurocognition, global functioning, and clinical symptomatology.\n\nResultsIn comparison to all other groups, PS youth exhibited significantly reduced SA in orbitofrontal, cingulate, precentral, and postcentral regions. PS youth also exhibited reduced thalamic volume in comparison to all other groups. Strongest effects for precentral and posterior cingulate SA reductions were seen during early adolescence (ages 13-15) in PS youth. Strongest effects for reductions in thalamic volume and orbitofrontal and postcentral SA were observed in mid-adolescence (16-18 years) in PS youth. Across groups, better overall functioning was associated with increased lateral orbitofrontal SA. Increased postcentral SA was associated with better executive cognition and less severe negative symptoms in the entire sample.\n\nConclusionIn a community-based sample, we found that reduced cortical SA and thalamic volume are present early in adolescent development in youth with psychosis spectrum symptoms, but not in youth with bipolar spectrum symptoms, or with both bipolar and psychosis spectrum symptoms. These findings point to potential biological distinctions between psychosis and bipolar spectrum conditions, which may suggest additional biomarkers relevant to early identification.

neuroscience↗

bioRxiv2018

Transient patterns of functional dysconnectivity in youth with psychosis spectrum symptoms

Psychosis spectrum disorders are conceptualized as neurodevelopmental disorders accompanied by disruption of large-scale functional brain networks. Both static and dynamic dysconnectivity have been described in patients with schizophrenia and, more recently, in help-seeking individuals at clinical high-risk for psychosis. Less is known, however, about developmental aspects of dynamic functional network connectivity (FNC) associated with psychotic symptoms (PS) in the general population. Here, we investigate resting state fMRI data using established dynamic FNC methods in the Philadelphia Neurodevelopmental Cohort (ages 8-22), including 129 participants experiencing PS and 452 participants without PS (non-PS).\n\nApplying a sliding window approach and k-means clustering, 5 dynamic states with distinct whole-brain connectivity patterns were identified. PS-associated dysconnectivity was most prominent in states characterized by synchronization or antagonism of the default mode network (DMN) and cognitive control (CC) domains. Hyperconnectivity between DMN, salience, and CC domains in PS youth only occurred in a state characterized by synchronization of the DMN and CC domains, a state that also becomes less frequent with age. However, dysconnectivity of the sensorimotor and visual systems in PS youth was revealed in other transient states completing the picture of whole-brain dysconnectivity patterns associated with PS.\n\nOverall, state-dependent dysconnectivity was observed in PS youth, providing the first evidence that disruptions of dynamic functional connectivity are present across a broader psychosis continuum.

neuroscience↗