ORCID Profile
0000-0002-8946-6960
Current Organisations
UNSW Sydney
,
Understand Your Brain
,
Neuroscience Research Australia
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2021
DOI: 10.1007/S00406-021-01237-Z
Abstract: While the biological substrates of brain and behavioural changes in persons with schizophrenia remain unclear, increasing evidence implicates that inflammation is involved. In schizophrenia, including first-episode psychosis and anti-psychotic naïve patients, there are numerous reports of increased peripheral inflammation, cognitive deficits and neuropathologies such as cortical thinning. Research defining the relationship between inflammation and schizophrenia symptomatology and neuropathology is needed. Therefore, we analysed the level of C-reactive protein (CRP), a peripheral inflammation marker, and its relationship with cognitive functioning in a cohort of 644 controls and 499 schizophrenia patients. In a subset of in iduals who underwent MRI scanning (99 controls and 194 schizophrenia cases), we tested if serum CRP was associated with cortical thickness. CRP was significantly increased in schizophrenia patients compared to controls, co-varying for age, sex, overweight/obesity and diabetes (p < 0.006E-10). In schizophrenia, increased CRP was mildly associated with worse performance in attention, controlling for age, sex and education (R =- 0.15, p = 0.001). Further, increased CRP was associated with reduced cortical thickness in three regions related to attention: the caudal middle frontal, the pars opercularis and the posterior cingulate cortices, which remained significant after controlling for multiple comparisons (all p < 0.05). Together, these findings indicate that increased peripheral inflammation is associated with deficits in cognitive function and brain structure in schizophrenia, especially reduced attention and reduced cortical thickness in associated brain regions. Using CRP as a biomarker of peripheral inflammation in persons with schizophrenia may help to identify vulnerable patients and those that may benefit from adjunctive anti-inflammatory treatments.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2019
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.SCHRES.2022.08.025
Abstract: We previously identified a subgroup of schizophrenia cases (~40 %) with heightened inflammation in the neurogenic subependymal zone (SEZ) (North et al., 2021b). This schizophrenia subgroup had changes indicating reduced microglial activity, increased peripheral immune cells, increased stem cell dormancy/quiescence and reduced neuronal precursor cells. The present follow-up study aimed to replicate and extend those novel findings in an independent post-mortem cohort of schizophrenia cases and controls from Australia. RNA was extracted from SEZ tissue from 20 controls and 22 schizophrenia cases from the New South Wales Brain Tissue Resource Centre, and gene expression analysis was performed. Cluster analysis of inflammation markers (IL1B, IL1R1, SERPINA3 and CXCL8) revealed a high-inflammation schizophrenia subgroup comprising 52 % of cases, which was a significantly greater proportion than the 17 % of high-inflammation controls. Consistent with our previous report (North et al., 2021b), those with high-inflammation and schizophrenia had unchanged mRNA expression of markers for steady-state and activated microglia (IBA1, HEXB, CD68), decreased expression of phagocytic microglia markers (P2RY12, P2RY13), but increased expression of markers for macrophages (CD163), monocytes (CD14), natural killer cells (FCGR3A), and the adhesion molecule ICAM1. Similarly, the high-inflammation schizophrenia subgroup emulated increased quiescent stem cell marker (GFAPD) and decreased neuronal progenitor (DLX6-AS1) and immature neuron marker (DCX) mRNA expression but also revealed a novel increase in a marker of immature astrocytes (VIM). Replicating primary results in an independent cohort demonstrates that inflammatory subgroups in the SEZ in schizophrenia are reliable, robust and enhance understanding of neuropathological heterogeneity when studying schizophrenia.
Publisher: Springer Science and Business Media LLC
Date: 31-05-2021
DOI: 10.1038/S41380-021-01149-3
Abstract: Neural stem cells in the human subependymal zone (SEZ) generate neuronal progenitor cells that can differentiate and integrate as inhibitory interneurons into cortical and subcortical brain regions yet the extent of adult neurogenesis remains unexplored in schizophrenia and bipolar disorder. We verified the existence of neurogenesis across the lifespan by chartering transcriptional alterations (2 days-103 years, n = 70) and identifying cells indicative of different stages of neurogenesis in the human SEZ. Expression of most neural stem and neuronal progenitor cell markers decreased during the first postnatal years and remained stable from childhood into ageing. We next discovered reduced neural stem and neuronal progenitor cell marker expression in the adult SEZ in schizophrenia and bipolar disorder compared to controls (n = 29-32 per group). RNA sequencing identified increased expression of the macrophage marker CD163 as the most significant molecular change in schizophrenia. CD163
Publisher: Springer Science and Business Media LLC
Date: 07-01-2022
DOI: 10.1038/S41598-021-03976-4
Abstract: The generation of new neurons within the mammalian forebrain continues throughout life within two main neurogenic niches, the subgranular zone (SGZ) of the hippoc al dentate gyrus, and the subependymal zone (SEZ) lining the lateral ventricles. Though the SEZ is the largest neurogenic niche in the adult human forebrain, our understanding of the mechanisms regulating neurogenesis from development through aging within this region remains limited. This is especially pertinent given that neurogenesis declines dramatically over the postnatal lifespan. Here, we performed transcriptomic profiling on the SEZ from human post-mortem tissue from eight different life-stages ranging from neonates (average age ~ 2 months old) to aged adults (average age ~ 86 years old). We identified transcripts with concomitant profiles across these decades of life and focused on three of the most distinct profiles, namely (1) genes whose expression declined sharply after birth, (2) genes whose expression increased steadily with age, and (3) genes whose expression increased sharply in old age in the SEZ. Critically, these profiles identified neuroinflammation as becoming more prevalent with advancing age within the SEZ and occurring with time courses, one gradual (starting in mid-life) and one sharper (starting in old age).
Publisher: Springer Science and Business Media LLC
Date: 15-12-2021
DOI: 10.1038/S41398-021-01742-8
Abstract: Inflammation regulates neurogenesis, and the brains of patients with schizophrenia and bipolar disorder have reduced expression of neurogenesis markers in the subependymal zone (SEZ), the birthplace of inhibitory interneurons. Inflammation is associated with cortical interneuron deficits, but the relationship between inflammation and reduced neurogenesis in schizophrenia and bipolar disorder remains unexplored. Therefore, we investigated inflammation in the SEZ by defining those with low and high levels of inflammation using cluster analysis of IL6 , IL6R , IL1R1 and SERPINA3 gene expression in 32 controls, 32 schizophrenia and 29 bipolar disorder cases. We then determined whether mRNAs for markers of glia, immune cells and neurogenesis varied with inflammation. A significantly greater proportion of schizophrenia (37%) and bipolar disorder cases (32%) were in high inflammation subgroups compared to controls (10%, p 0.05). Across the high inflammation subgroups of psychiatric disorders, mRNAs of markers for phagocytic microglia were reduced ( P2RY12 , P2RY13 ), while mRNAs of markers for perivascular macrophages ( CD163 ), pro-inflammatory macrophages ( CD64 ), monocytes ( CD14 ), natural killer cells ( FCGR3A ) and adhesion molecules ( ICAM1) were increased. Specific to high inflammation schizophrenia, quiescent stem cell marker mRNA ( GFAPD ) was reduced, whereas neuronal progenitor ( ASCL1 ) and immature neuron marker mRNAs ( DCX ) were decreased compared to low inflammation control and schizophrenia subgroups. Thus, a heightened state of inflammation may d en microglial response and recruit peripheral immune cells in psychiatric disorders. The findings elucidate differential neurogenic responses to inflammation within psychiatric disorders and highlight that inflammation may impair neuronal differentiation in the SEZ in schizophrenia.
No related grants have been discovered for Hayley North.