scholarly journals Monocytic Subsets and Their Signature Genes Differentially Impact Cortex and Cognition in First-Episode Schizophrenia

Author(s):  
Song Chen ◽  
Keerthana Chithanathan ◽  
Fengmei Fan ◽  
Meihong Xiu ◽  
Hongzhen Fan ◽  
...  

Accumulating evidence supports involvement of innate immunity in the pathophysiology of schizophrenia. Monocytes are a highly heterogeneous population, subcategorized into classical (CD14++CD16-), intermediate (CD14++CD16+) and nonclassical subsets (CD14+CD16++). How monocytic subsets may shape brain structures and functions remains unclear. The primary goal of this cross-sectional study was to investigate the inter-relationships among monocytic subsets and their specific transcriptomic profiles, cerebral cortical thickness, and cognitive functions in first-episode schizophrenia (FES) patients. We performed whole-blood RNA sequencing (RNAseq) in 128 FES patients and 111 healthy controls (HCs) along with MATRICS Consensus Cognitive Battery (MCCB) measurement, as well as neuroimaging and flow cytometry among partial participants. RNAseq revealed significantly changed expressions of 54 monocytic signature genes in FES patients compared to HCs, especially for intermediate and nonclassical monocytic subsets, with the most outstanding alterations being downregulated S100 Calcium Binding Protein A (S100A) and upregulated Interferon Induced Transmembrane Protein (IFITM) family members, respectively. The percentage of nonclassical monocytes was decreased in FES patients. Cortical thicknesses and MCCB performance were expectantly reduced in FES patients too. Interestingly, negative inter-relationships of monocytic signature genes with both cortical thicknesses and cognition were found in HCs, which were weakened or even reversed in FES patients. Furthermore, the lateral occipital cortex fully mediated the negative effect of a classical monocytic gene Ribonuclease A Family Member 2 (RNASE2) on visual learning in patient group. This study suggests that monocytic dysfunctions play an essential role in cognitive deficit of schizophrenia, and their subtypes should be considered in future research.

2019 ◽  
Vol 45 (6) ◽  
pp. 1291-1299 ◽  
Author(s):  
Long-Biao Cui ◽  
Yongbin Wei ◽  
Yi-Bin Xi ◽  
Alessandra Griffa ◽  
Siemon C De Lange ◽  
...  

Abstract Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P = .012, uncorrected), with rich club connection strength (P = .032, uncorrected) and SC-FC coupling (P < .001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder.


2008 ◽  
Vol 192 (6) ◽  
pp. 429-434 ◽  
Author(s):  
Mark Walterfang ◽  
Amanda G. Wood ◽  
David C. Reutens ◽  
Stephen J. Wood ◽  
Jian Chen ◽  
...  

BackgroundThe shape of the corpus callosum may differ in schizophrenia, although no study has compared first-episode with established illness.AimsTo investigate the size and shape of the corpus callosum in a large sample of people with first-episode and established schizophrenia.MethodCallosal size and shape were determined using highresolution magnetic resonance imaging on 76 patients with first-episode schizophrenia-spectrum disorders, 86 patients with established schizophrenia and 55 healthy participants.ResultsThere were no significant differences in total area across groups. Reductions in callosal width were seen in the region of the anterior genu in first-episode disorder (P<0.005). Similar reductions were seen in the chronic schizophrenia group in the anterior genu, but also in the posterior genu and isthmus (P = 0.0005).ConclusionsReductions in anterior callosal regions connecting frontal cortex are present at the onset of schizophrenia, and in established illness are accompanied by changes in other regions of the callosum connecting cingulate, temporal and parietal cortices.


2006 ◽  
Vol 23 (1) ◽  
pp. 6-9 ◽  
Author(s):  
Blanaid Gavin ◽  
Walter Cullen ◽  
Brian O'Donoghue ◽  
Juan Carlos Ascencio-Lane ◽  
Gerard Bury ◽  
...  

AbstractObjective: We sought to establish the views of general practitioners about detecting and managing patients with a first episode of schizophrenia in Ireland.Method: Twenty per cent of GPs were invited to participate in a cross-sectional postal survey.Results: Sixty-two per cent (n = 261) participated. Almost all (99.2%) see at least one case of suspected first episode schizophrenia annually. The most commonly (80.7%) encountered symptom is ‘bizarre behaviour’. Many (47.7%) rarely or never prescribe antipsychotics to patients whom they suspect have a first episode of schizophrenia. However, 80.6% of GPs reported that they ‘always’ refer this group of patients to psychiatric services. Over half (57.8%) advised patients with schizophrenia to continue medication for less than a year. A large number of respondents reported that it is difficult to obtain a rapid psychiatric assessment.Conclusions: GPs want more information about identifying early psychosis, a closer liaison with psychiatric services and a rapid intervention service.


2015 ◽  
Vol 165 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Catherine Bois ◽  
Liat Levita ◽  
Isabelle Ripp ◽  
David C.G. Owens ◽  
Eve C. Johnstone ◽  
...  

2013 ◽  
Vol 151 (1-3) ◽  
pp. 259-264 ◽  
Author(s):  
Emma Sprooten ◽  
Martina Papmeyer ◽  
Annya M. Smyth ◽  
Daniel Vincenz ◽  
Sibylle Honold ◽  
...  

2012 ◽  
Vol 136 ◽  
pp. S109
Author(s):  
Meina Puan ◽  
Marek Kubicki ◽  
Ryan Eckbo ◽  
Zora Kikinis ◽  
Robert W. McCarley ◽  
...  

2013 ◽  
Vol 28 (6) ◽  
pp. 332-339 ◽  
Author(s):  
R. Andersen ◽  
B. Fagerlund ◽  
H. Rasmussen ◽  
B.H. Ebdrup ◽  
B. Aggernaes ◽  
...  

AbstractBackground:Impaired cognition is a prominent feature of schizophrenia. To what extent the heterogeneous cognitive impairments can be accounted for by considering only a single underlying impairment or a small number of core impairments remains elusive. This study examined whether cognitive impairments in antipsychotic-naïve, first-episode schizophrenia patients may be determined by a relative slower speed of information processing.Method:Forty-eight antipsychotic-naïve patients with first-episode schizophrenia and 48 matched healthy controls were administered a comprehensive battery of neuropsychological tests to assess domains of cognitive impairments in schizophrenia. Composite scores were calculated, grouping tests into cognitive domains.Results:There were significant differences between patients and healthy controls on global cognition and all cognitive domains, including verbal intelligence, processing speed, sustained attention, working memory, reasoning and problem solving, verbal learning and memory, visual learning and memory, and reaction time. All these significant differences, except for verbal intelligence and global cognition, disappeared when processing speed was included as a covariate.Conclusion:At the first stage of illness, antipsychotic-naïve patients with schizophrenia display moderate/severe impairments in all the cognitive domains assessed. The results support the contention of a global cognitive dysfunction in schizophrenia that to some extent may be determined by impaired processing speed.


Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Forough Riahi ◽  
Maryam Izadi-mazidi ◽  
Ali Ghaffari ◽  
Elham Yousefi ◽  
Shahram Khademvatan

Background.The present study aimed to compare plasma levels of cortisol, testosterone, dehydroepiandrosterone (DHEA), and prolactin in patients with schizophrenia and healthy individuals.Method.A total of 100 patients with schizophrenia disorder (69 men and 31 women) and 190 healthy individuals (94 men and 96 women) participated in this cross-sectional study. They were tested for hormone levels and completed demographic questionnaires. Data were analyzed using multivariate analysis of variance (MANOVA) and one-way analysis of variance.Results.Serum testosterone level was significantly higher in men with schizophrenia than in healthy men. Women with schizophrenia had a significantly higher level of testosterone and lower level of prolactin compared to healthy women. There were no significant differences in hormone levels across various subtypes of schizophrenia. No significant differences also were observed in hormones levels in patients with first-episode schizophrenia disorder compared to those in patients with recurrent episodes.Conclusion.This study indicated that abnormal testosterone and prolactin levels might be associated with pathophysiology of schizophrenia disorder.


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