Progression from selective to general involvement of hippocampal subfields in schizophrenia

Ho, New Fei; Iglesias, Juan Eugenio; Sum, Min Yi; Kuswanto, Carissa Nadia; Sitoh, Yih Yian; Souza, Joshua de; Hong, Zhaoping; Fischl, Bruce; Roffman, Joshua L.; Zhou, Juan; Sim, Kang; Holt, Daphne J.

doi:10.1038/mp.2016.4

Cited by 135 publications

(156 citation statements)

References 84 publications

(110 reference statements)

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“…On the other side, it has been well documented that the largest magnitude of subcortical brain volume abnormalities in schizophrenia is in the hippocampus, which can be seen in both the early and chronic stages of this disorder 39,40. Hippocampus is hypothesized to underlie the neuropsychological deficits and symptoms observed in schizophrenia 41,42. Thereby, the role of CFH in schizophrenia could not be excluded, even though we did not detect any association of CFH with schizophrenia at molecular level.…”

Section: Discussionmentioning

confidence: 99%

Influence of <em>CFH</em> gene on symptom severity of schizophrenia

Zhang¹,

Lv²,

Fan³

et al. 2017

NDT

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ObjectiveRecent advances have provided compelling evidence for the role of excessive complement activity in the pathophysiology of schizophrenia. In this study, we aimed to detect the association of the gene encoding complement factor H (CFH), a regulator in complement activation, with schizophrenia.Materials and methodsA sample of 1783 individuals with or without schizophrenia was recruited for genetic analysis. Genomic DNA samples were extracted from peripheral blood cells using multiplex polymerase chain reaction and the SNaPshot assay. A Database for Schizophrenia Genetic Research (SZDB) was used to detect the association of brain CFH expression with schizophrenia. Next, we performed a genotype–phenotype analysis to identify the relationship between CFH Y402H polymorphism and clinical features of schizophrenia.ResultsThere was a significant association of hippocampal CFH expression with schizophrenia (P=0.017), whereas this significance did not survive after adjusting for false discovery rate (P=0.105). Comparing the genotype and allele frequencies of the genotyped single-nucleotide polymorphisms between case and control groups showed no significant difference. There were significant differences in the scores of negative symptoms and delayed memory between the patients with C allele and those without C allele (P<0.01 and P=0.04 after Bonferroni correction, respectively). Furthermore, we observed a marginally significant association between the Y402H polymorphism and CFH expression in the hippocampus (P=0.051); however, this significance was lost after multiple testing correction (P=0.51, after Bonferroni correction).ConclusionOur findings provide suggestive evidence for the role of CFH in the development of negative symptoms and cognitive dysfunction in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Influence of <em>CFH</em> gene on symptom severity of schizophrenia

Zhang¹,

Lv²,

Fan³

et al. 2017

NDT

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“…One control child was excluded due to a previously unknown structural brain abnormality, and 1 ELA child had to be excluded because of excessive head motion. To overcome the problem of estimating hippocampal volume in children [43] and the inconsistencies of hippocampal subfield delineation and previous automated procedures [44], the novel improved automated routine from FreeSurfer was used to calculate hippocampal volumes and subfield volumes in accordance with previous studies [45,46]. It is built on a computational atlas built from ex vivo and in vivo MRI data, and has been proven reliable in estimating hippocampal volume and its subfields according to histological and anatomical boundaries [46].…”

Section: Mri Acquisition and Volumetric Assessmentmentioning

confidence: 99%

“…The bilateral hippocampal volumes and the hippocampal subfield volumes of interest, the CA1, CA3, and the GCL-DG were used in the analyses. In line with previous studies, individual total intracranial volumes estimated from FreeSurfer's automated analysis pipeline were used to correct for differences in head size [45].…”

Section: Mri Acquisition and Volumetric Assessmentmentioning

confidence: 99%

Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions

Dahmen¹,

Puetz

Scharke

et al. 2017

Dev Neurosci

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Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life.

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“…The algorithm could also provide a better estimation of CA volumes. 34 In the current study, we included eight hippocampal subfields: CA1, CA2 and CA3 (noted as CA3 due to the indistinguishable MR contrast between CA2 and CA3), CA4, GCL, ML, presubiculum (Presub), subiculum (Sub) and the hippocampal tail (Tail; the posterior end of the hippocampus).…”

Section: Mri Data Acquisition and Preprocessingmentioning

confidence: 99%

“…32 The method used to segment the hippocampal subfields in the present study was developed based on ex vivo hippocampal tissues scanned with ultra-high field strength. 33 The resolution and accuracy of the segmentation were proved to be higher than the previous method using in vivo atlas, 33,34 which will help us to observe the localized changes within hippocampus related to mood disorders and their progression.…”

Section: Introductionmentioning

confidence: 97%