Hippocampal subfield alterations in schizophrenia: A selective review of structural MRI studies

Hu, Na; Chen, Luo; Zhang, Wenjing; Yang, Xiaobo; Xiao, Yuan; Sweeney, John A.; Lui, Su; Gong, Qiyong

doi:10.1016/j.bionps.2020.100026

Cited by 15 publications

(32 citation statements)

References 76 publications

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“…While SCZ cis-eGenes were enriched in lower layer neurons, SCZ trans-eGenes were enriched in upper-layer neurons, suggesting that cis-and trans-regulatory mechanisms may influence distinct cortical circuitry. Moreover, SCZ trans-eGenes were enriched in parvalbumin-expressing interneurons, whose genetic and transcriptional association with SCZ were reported previously [26,40,41].…”

Section: Discussionsupporting

confidence: 74%

Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex

Liu

Won

Clarke

et al. 2021

Preprint

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Psychiatric disorders exact immense human and economic tolls in societies globally. Underlying many of these disorders is a complex repertoire of genomic variants that influence the expression of genes involved in pathways and processes in the brain. Identifying such variants and their associated brain functions is thus essential for understanding the molecular underpinnings of psychiatric disorders. Genome-wide association studies (GWASes) have provided many variants associated with these disorders; however, our knowledge of the precise biological mechanisms by which these contribute to disease remains limited. In connection with this, expression quantitative trait loci (eQTLs) have provided useful information linking variants to genes and functions. However, most eQTL studies on human brain have focused exclusively on cis-eQTLs. A complete understanding of disease etiology should also include trans-regulatory mechanisms. Thus, we conduct one of the first genome-wide surveys of trans-eQTLs in the dorsolateral prefrontal cortex (DLPFC) by leveraging the large datasets from the PsychENCODE consortium. We identified ~80,000 trans-eQTLs. We found that a significant number of these overlap with cis-eQTLs, thereby implicating cis-mediators as key players in trans-acting regulation. We show, furthermore, that trans-regulatory mechanisms provide novel insights into psychiatric disease. Particularly, colocalization analysis between trans-eQTLs and schizophrenia (SCZ) GWAS loci identified 90 novel SCZ risk genes and 23 GWAS loci previously uncharacterized by cis-eQTLs. Moreover, these 90 genes tend to be more central in transcriptome-wide co-expression networks and more susceptible to rare variants than SCZ-risk genes associated by cis-variation.

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Section: Discussionsupporting

confidence: 74%

Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex

Liu

Won

Clarke

et al. 2021

Preprint

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“…10 Overlaps in structural brain alterations have also been found in schizophrenia and MDD, 11 including reductions in hippocampal volume. 12,13 Because the hippocampus consists of several subfields that relate to cognitive and affective disturbances, abnormalities in its subregions are worthy of investigation. Subfield-level comparisons of volumetric alterations in schizophrenia and MDD would help us to better understand the pathophysiology of both disorders.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal subfield alterations in schizophrenia and major depressive disorder: a systematic review and network meta-analysis of anatomic MRI studies

Sun

Wang

et al. 2023

jpn

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Background: Hippocampal disturbances are important in the pathophysiology of both schizophrenia and major depressive disorder (MDD). Imaging studies have shown selective volume deficits across hippocampal subfields in both disorders. We aimed to investigate whether these volumetric alterations in hippocampal subfields are shared or divergent across disorders. Methods: We searched PubMed and Embase from database inception to May 8, 2021. We identified MRI studies in patients with schizophrenia, MDD or both, in which hippocampal subfield volumes were measured. We excluded nonoriginal, animal or postmortem studies, and studies that used other imaging modalities or overlapping data. We conducted a network meta-analysis to estimate and contrast alterations in subfield volumes in the 2 disorders. Results: We identified 45 studies that met the initial criteria for systematic review, of which 15 were eligible for network metaanalysis. Compared to healthy controls, patients with schizophrenia had reduced volumes in the bilateral cornu ammonis (CA) 1, granule cell layer of the dentate gyrus, subiculum, parasubiculum, molecular layer, hippocampal tail and hippocampus-amygdala transition area (HATA); in the left CA4 and presubiculum; and in the right fimbria. Patients with MDD had decreased volumes in the left CA3 and CA4 and increased volumes in the right HATA compared to healthy controls. The bilateral parasubiculum and right HATA were smaller in patients with schizophrenia than in patients with MDD. Limitations: We did not investigate medication effects because of limited information. Study heterogeneity was noteworthy in direct comparisons between patients with MDD and healthy controls. Conclusion: The volumes of multiple hippocampal subfields are selectively altered in patients with schizophrenia and MDD, with overlap and differentiation in subfield alterations across disorders. Rigorous head-to-head studies are needed to validate our findings.

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“…These discrepancies among previous studies may be partly explained by the possibility that hippocampal reduction exists only in specific subfields ( 16 , 21 ). However, limited studies of hippocampal subfields reported mixed results [reviewed by Haukvik et al ( 31 ) and Hu et al ( 32 )], with schizophrenia patients having prominent volume reduction in the CA1 ( 33 ) or more widespread reductions in the CA2/3, CA4/DG, presubiculum, subiculum, and CA1 ( 34 , 35 ). Similar findings were reported in a few studies examining hippocampal subfield volumes in ARMS individuals ( 23 , 36 ).…”

Section: Introductionmentioning

confidence: 99%

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis

et al. 2021

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Magnetic resonance imaging (MRI) studies in schizophrenia demonstrated volume reduction in hippocampal subfields divided on the basis of specific cytoarchitecture and function. However, it remains unclear whether this abnormality exists prior to the onset of psychosis and differs across illness stages. MRI (3 T) scans were obtained from 77 patients with schizophrenia, including 24 recent-onset and 40 chronic patients, 51 individuals with an at-risk mental state (ARMS) (of whom 5 subsequently developed psychosis within the follow-up period), and 87 healthy controls. Using FreeSurfer software, hippocampal subfield volumes were measured and compared across the groups. Both schizophrenia and ARMS groups exhibited significantly smaller volumes for the bilateral Cornu Ammonis 1 area, left hippocampal tail, and right molecular layer of the hippocampus than the healthy control group. Within the schizophrenia group, chronic patients exhibited a significantly smaller volume for the left hippocampal tail than recent-onset patients. The left hippocampal tail volume was positively correlated with onset age, and negatively correlated with duration of psychosis and duration of medication in the schizophrenia group. Reduced hippocampal subfield volumes observed in both schizophrenia and ARMS groups may represent a common biotype associated with psychosis vulnerability. Volumetric changes of the left hippocampal tail may also suggest ongoing atrophy after the onset of schizophrenia.

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Hippocampal subfield alterations in schizophrenia: A selective review of structural MRI studies

Cited by 15 publications

References 76 publications

Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex

Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex

Hippocampal subfield alterations in schizophrenia and major depressive disorder: a systematic review and network meta-analysis of anatomic MRI studies

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis

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