Anterior cingulate cortex metabolites and white matter microstructure: a multimodal study of emergent alcohol use disorder

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.

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Differences in White Matter Microstructure and Connectivity in Nontreatment-Seeking Individuals with Alcohol Use Disorder

Alcoholism Clinical and Experimental Research ◽

10.1111/acer.13629 ◽

2018 ◽

Vol 42 (5) ◽

pp. 889-896 ◽

Cited By ~ 3

Author(s):

Evgeny J. Chumin ◽

Joaquín Goñi ◽

Meredith E. Halcomb ◽

Timothy C. Durazzo ◽

Mario Dzemidzic ◽

...

Keyword(s):

White Matter ◽

Alcohol Use ◽

Alcohol Use Disorder ◽

White Matter Microstructure

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Random Forest Classification of Alcohol Use Disorder Using fMRI Functional Connectivity, Neuropsychological Functioning, and Impulsivity Measures

Brain Sciences ◽

10.3390/brainsci10020115 ◽

2020 ◽

Vol 10 (2) ◽

pp. 115 ◽

Cited By ~ 3

Author(s):

Chella Kamarajan ◽

Babak A. Ardekani ◽

Ashwini K. Pandey ◽

Sivan Kinreich ◽

Gayathri Pandey ◽

...

Keyword(s):

Functional Connectivity ◽

Random Forest ◽

Alcohol Use ◽

Long Range ◽

Alcohol Use Disorder ◽

Neuropsychological Functioning ◽

Brain Networks ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Neuropsychological Performance

Individuals with alcohol use disorder (AUD) are known to manifest a variety of neurocognitive impairments that can be attributed to alterations in specific brain networks. The current study aims to identify specific features of brain connectivity, neuropsychological performance, and impulsivity traits that can classify adult males with AUD (n = 30) from healthy controls (CTL, n = 30) using the Random Forest (RF) classification method. The predictor variables were: (i) fMRI-based within-network functional connectivity (FC) of the Default Mode Network (DMN), (ii) neuropsychological scores from the Tower of London Test (TOLT), and the Visual Span Test (VST), and (iii) impulsivity factors from the Barratt Impulsiveness Scale (BIS). The RF model, with a classification accuracy of 76.67%, identified fourteen DMN connections, two neuropsychological variables (memory span and total correct scores of the forward condition of the VST), and all impulsivity factors as significantly important for classifying participants into either the AUD or CTL group. Specifically, the AUD group manifested hyperconnectivity across the bilateral anterior cingulate cortex and the prefrontal cortex as well as between the bilateral posterior cingulate cortex and the left inferior parietal lobule, while showing hypoconnectivity in long-range anterior–posterior and interhemispheric long-range connections. Individuals with AUD also showed poorer memory performance and increased impulsivity compared to CTL individuals. Furthermore, there were significant associations among FC, impulsivity, neuropsychological performance, and AUD status. These results confirm the previous findings that alterations in specific brain networks coupled with poor neuropsychological functioning and heightened impulsivity may characterize individuals with AUD, who can be efficiently identified using classification algorithms such as Random Forest.

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White matter integrity correlates with choline level in dorsal anterior cingulate cortex of obsessive compulsive disorder patients: A combined DTI-MRS study

2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) ◽

10.1109/embc.2017.8037616 ◽

2017 ◽

Cited By ~ 2

Author(s):

R. Wang ◽

Q. Fan ◽

Z. Zhang ◽

Y. Chen ◽

S. Tong ◽

...

Keyword(s):

White Matter ◽

Anterior Cingulate Cortex ◽

Obsessive Compulsive Disorder ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

White Matter Integrity ◽

Obsessive Compulsive ◽

Dorsal Anterior Cingulate Cortex ◽

Compulsive Disorder

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

PROTEOMICS - CLINICAL APPLICATIONS ◽

10.1002/prca.200600541 ◽

2007 ◽

Vol 1 (2) ◽

pp. 157-166 ◽

Cited By ~ 28

Author(s):

Danielle Clark ◽

Irina Dedova ◽

Stuart Cordwell ◽

Izuru Matsumoto

Keyword(s):

White Matter ◽

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Altered Proteins

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

10.1101/2021.06.21.449337 ◽

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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