scholarly journals Genes in immune pathways associated with abnormal white matter integrity in first-episode and treatment-naïve patients with schizophrenia

2019 ◽  
Vol 214 (5) ◽  
pp. 281-287
Author(s):  
Bo Xiang ◽  
Qiang Wang ◽  
Wei Lei ◽  
Mingli Li ◽  
Yinfei Li ◽  
...  
Keyword(s):  
White Matter ◽  
Anterior Cingulate Cortex ◽  
Genetic Variants ◽  
Rare Variants ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
White Matter Integrity ◽  
First Episode ◽  
Treatment Naïve ◽  
Left And Right

BackgroundPrevious studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.AimsTo detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.MethodThe analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.ResultsPatients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.ConclusionsThe pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.Declaration of interestsNone.

INTERACTION BETWEEN DARPP-32 AND DRD2 GENETIC VARIANTS ON ANTERIOR CINGULATE CORTEX ACTIVITY DURING ATTENTIONAL CONTROL IN HEALTHY SUBJECTS

2010 ◽  
Vol 117 (2-3) ◽  
pp. 472
Author(s):  
Paolo Taurisano ◽  
Giuseppe Blasi ◽  
Apostolos Papazacharias ◽  
Raffaella Romano ◽  
Gianluca Ursini ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Genetic Variants ◽  
Attentional Control ◽  
Healthy Subjects ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Anterior Cingulate Cortex Activity

Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study

2019 ◽  
Vol 54 (5) ◽  
pp. 509-518 ◽  
Author(s):  
Sanghoon Oh ◽  
Minah Kim ◽  
Taekwan Kim ◽  
Tae Young Lee ◽  
Jun Soo Kwon
Keyword(s):  
Functional Connectivity ◽  
Anterior Cingulate Cortex ◽  
Negative Symptoms ◽  
Primary Motor Cortex ◽  
Cingulate Cortex ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
First Episode ◽  
Healthy Controls ◽  
Episode Psychosis

Objective: The persistent disease burden of psychotic disorders often comes from negative symptoms; however, prognostic biomarkers for negative symptoms have not been fully understood. This study investigated whether the altered functional connectivity of the striatum predicts improvement in negative symptoms and functioning after 1 year of usual treatment in patients with first-episode psychosis. Methods: Resting-state functional magnetic imaging was obtained from 40 first-episode psychosis patients and 40 age- and sex-matched healthy control subjects. Whole-brain functional connectivity maps were generated with subdivisions of the striatum as seed regions and compared between first-episode psychosis patients and healthy controls. In 22 patients with first-episode psychosis, follow-up assessments of negative symptom severity and general functional status were conducted after 1 year of usual treatment. Multiple regression analyses were performed to examine factors predictive of symptomatic or functional improvements over the 1-year period. Results: First-episode psychosis patients showed greater functional connectivity between the left dorsal caudate and left primary motor cortex, as well as between the left ventral rostral putamen and right temporal occipital fusiform cortex, than healthy controls. Lower functional connectivity between the right dorsal rostral putamen and anterior cingulate cortex was observed in the first-episode psychosis patients than in healthy controls. In multiple regression analyses, lower functional connectivity of the left dorsal caudate–left primary motor cortex/right dorsal rostral putamen–anterior cingulate cortex predicted improvement in negative symptoms. In addition, lower right dorsal rostral putamen–anterior cingulate cortex functional connectivity predicted improvement in general functioning. Conclusion: These results suggest that altered striatal functional connectivity can be a potent neurobiological marker in the prognosis prediction of first-episode psychosis. Furthermore, altered striatal functional connectivity may provide a potential target in developing treatments for negative symptoms.

Altered proteins of the anterior cingulate cortex white matter proteome in schizophrenia

2007 ◽  
Vol 1 (2) ◽  
pp. 157-166 ◽  
Author(s):  
Danielle Clark ◽  
Irina Dedova ◽  
Stuart Cordwell ◽  
Izuru Matsumoto
Keyword(s):  
White Matter ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Altered Proteins

scholarly journals Fatty acid dysregulation in the anterior cingulate cortex of depressed suicides with a history of child abuse

2021 ◽  
Author(s):  
Kelly Perlman ◽  
Raphael Chouinard-Watkins ◽  
Arnaud Tanti ◽  
Giulia Cisbani ◽  
Massimiliano Orri ◽  
...  
Keyword(s):  
Child Abuse ◽  
White Matter ◽  
Anterior Cingulate Cortex ◽  
Methyl Esters ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Sequencing Data ◽  
Early Life Adversity ◽  
Age Related ◽  
History Of

Child abuse (CA) strongly increases the lifetime risk of suffering from major depression and predicts an unfavorable course for the illness. Severe CA has been associated with a specific dysregulation of oligodendrocyte function and thinner myelin sheaths in the human anterior cingulate cortex (ACC) white matter. Given that myelin is extremely lipid-rich, it is plausible that these findings may be accompanied by a disruption of the lipid profile that composes the myelin sheath. This is important to explore since the composition of fatty acids (FA) in myelin phospholipids can influence its stability, permeability, and compactness. Therefore, the objective of this study was to quantify and compare FA concentrations in postmortem ACC white matter in the choline glycerophospholipid pool (ChoGpl), a key myelin phospholipid pool, between adult depressed suicides with a history of CA (DS-CA) matched depressed suicides without CA (DS) and healthy non-psychiatric controls (CTRL). Total lipids were extracted according to the Folch method and separated into respective classes using thin-layer chromatography. FA methyl esters from the ChoGpl fraction were quantified using gas chromatography. Our analysis revealed a strong age-related decrease in most FAs, and specific effects of CA in FAs from the arachidonic acid synthesis pathway, which was further validated with RNA-sequencing data. Furthermore, the concentration of most FAs was found to decrease with age. By extending the previous molecular level findings linking CA with altered myelination in the ACC, these results provide further insights regarding white matter alterations associated with early-life adversity.

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