Hippocampal subfields predict positive symptoms in schizophrenia: first evidence from brain morphometry.
Ontology highlight
ABSTRACT:
SUBMITTER: Kuhn S
PROVIDER: S-EPMC3384220 | biostudies-other | 2012
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Even with an overarching functional dysconnectivity model of adolescent-onset schizophrenia (AOS), there have been no functional connectome (FC) biomarkers identified for predicting patients' specific symptom domains. Adolescence is a period of dramatic brain maturation, with substantial interindividual variability in brain anatomy. However, existing group-level hypotheses of AOS lack precision in terms of neuroanatomical boundaries. This study aimed to identify individual-specific FC biomarkers associated with schizophrenic symptom manifestation during adolescent brain maturation. We used a reliable individual-level cortical parcellation approach to map functional brain regions in each subject, that were then used to identify FC biomarkers for predicting dimension-specific psychotic symptoms in 30 antipsychotic-naïve first-episode AOS patients (recruited sample of 39). Age-related changes in biomarker expression were compared between these patients and 31 healthy controls. Moreover, 29 antipsychotic-naïve first-episode AOS patients (analyzed sample of 25) were recruited from another center to test the generalizability of the prediction model. Individual-specific FC biomarkers could significantly and better predict AOS positive-dimension symptoms with a relatively stronger generalizability than at the group level. Specifically, positive symptom domains were estimated based on connections between the frontoparietal control network (FPN) and salience network and within FPN. Consistent with the neurodevelopmental hypothesis of schizophrenia, the FPN-SN connection exhibited aberrant age-associated alteration in AOS. The individual-level findings reveal reproducible FPN-based FC biomarkers associated with AOS positive symptom domains, and highlight the importance of accounting for individual variation in the study of adolescent-onset disorders.
| S-EPMC7927287 | biostudies-literature
Project description:The nature of hippocampal changes in schizophrenia before first treatment, and whether hippocampal subfields are affected by antipsychotic treatment are important questions for schizophrenia research. Forty-one first-episode antipsychotic-naïve acutely ill schizophrenia inpatients had MRI scans before and six weeks after antipsychotic treatment. Thirty-nine matched healthy controls were also scanned, twenty-two of which were scanned a second time six weeks later. Volumes of hippocampal subfields were measured via FreeSurfer v6.0 using a longitudinal analysis pipeline. Before treatment, schizophrenia patients had no significant changes in total hippocampal volume but exhibited significantly greater subfield volumes than controls in bilateral molecular layers of the hippocampus (ML), bilateral granular cell layers of the dentate gyrus (GC-DG), and bilateral cornu ammonis area 4 (CA4). After six weeks of antipsychotic treatment, patients showed volume reductions compared with pretreatment scans in total hippocampus bilaterally, with subfield volume reduction noted in previously enlarged subfields (i.e., bilateral ML, GC-DG and CA4) and in bilateral hippocampal tails, left CA1, CA3, and fimbria. Subfields with volume increases before treatment were reduced to the level of healthy controls (bilateral ML and GC-DG) or near to it (bilateral CA4) after treatment. These results indicate subfield-specific hippocampal hypertrophy prior to treatment, and that these abnormalities were reduced after acute antipsychotic therapy in a dose-related manner together with volume reductions in other areas that were not hypertrophic before treatment.
| S-EPMC6072650 | biostudies-literature
Project description:Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Data set 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Data set 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label seven hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Data set 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Data set 2. Consistent with this pattern, the longitudinal analysis of Data set 1 revealed progressive illness-related volume loss (~2-6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time.
| S-EPMC4995163 | biostudies-literature
Project description:Incidence of schizophrenia (SZ) has two predominant peaks, in adolescent and young adult. Early-onset schizophrenia provides an opportunity to explore the neuropathology of SZ early in the disorder and without the confound of antipsychotic mediation. However, it remains unexplored what deficits are shared or differ between adolescent early-onset (EOS) and adult-onset schizophrenia (AOS) patients. Here, based on 529 participants recruited from three independent cohorts, we explored AOS and EOS common and unique co-varying patterns by jointly analyzing three MRI features: fractional amplitude of low-frequency fluctuations (fALFF), gray matter (GM), and functional network connectivity (FNC). Furthermore, a prediction model was built to evaluate whether the common deficits in drug-naive SZ could be replicated in chronic patients. Results demonstrated that (1) both EOS and AOS patients showed decreased fALFF and GM in default mode network, increased fALFF and GM in the sub-cortical network, and aberrant FNC primarily related to middle temporal gyrus; (2) the commonly identified regions in drug-naive SZ correlate with PANSS positive significantly, which can also predict PANSS positive in chronic SZ with longer duration of illness. Collectively, results suggest that multimodal imaging signatures shared by two types of drug-naive SZ are also associated with positive symptom severity in chronic SZ and may be vital for understanding the progressive schizophrenic brain structural and functional deficits.
| S-EPMC9248316 | biostudies-literature
Project description:Age-related memory impairments have been linked to differences in structural brain parameters, including cerebral white matter (WM) microstructure and hippocampal (HC) volume, but their combined influences are rarely investigated. In a population-based sample of 337 older participants aged 61-82 years (Mage = 69.66, SDage = 3.92 years), we modeled the independent and joint effects of limbic WM microstructure and HC subfield volumes on verbal learning. Participants completed a verbal learning task of recall over five repeated trials and underwent magnetic resonance imaging (MRI), including structural and diffusion scans. We segmented three HC subregions on high-resolution MRI data and sampled mean fractional anisotropy (FA) from bilateral limbic WM tracts identified via deterministic fiber tractography. Using structural equation modeling, we evaluated the associations between learning rate and latent factors representing FA sampled from limbic WM tracts, and HC subfield volumes, and their latent interaction. Results showed limbic WM and the interaction of HC and WM-but not HC volume alone-predicted verbal learning rates. Model decomposition revealed HC volume is only positively associated with learning rate in individuals with higher WM anisotropy. We conclude that the structural characteristics of limbic WM regions and HC volume jointly contribute to verbal learning in older adults.
| S-EPMC7174993 | biostudies-literature
Project description:Myelin and oligodendrocyte disruption may be a core feature of schizophrenia pathophysiology. The purpose of the present study was to localize the effects of previously identified risk variants in the myelin-associated glycoprotein (MAG) gene on brain morphometry in schizophrenia patients and healthy controls. Forty-five schizophrenia patients and 47 matched healthy controls underwent clinical, structural magnetic resonance imaging, and genetics procedures. Gray and white matter cortical lobe volumes along with hippocampal volumes were calculated from T1-weighted MRI scans. Each subject was also genotyped for the two disease-associated MAG single nucleotide polymorphisms (rs720308 and rs720309). Repeated measures general linear model (GLM) analysis found significant region by genotype and region by genotype by diagnosis interactions for the effects of MAG risk variants on lobar gray matter volumes. No significant associations were found with lobar white matter volumes or hippocampal volumes. Follow-up univariate GLMs found the AA genotype of rs720308 predisposed schizophrenia patients to left temporal and parietal gray matter volume deficits. These results suggest that the effects of the MAG gene on cortical gray matter volume in schizophrenia patients can be localized to temporal and parietal cortices. Our results support a role for MAG gene variation in brain morphometry in schizophrenia, align with other lines of evidence implicating MAG in schizophrenia, and provide genetically based insight into the heterogeneity of brain imaging findings in this disorder.
| S-EPMC3342517 | biostudies-literature
Project description:Purpose: In this study, we used LCM and RNA-Seq to characterize differences in the rat hippocampal expression profiles of CA1, CA2, CA3, and DG subfields Methods: Each subfield was bilaterally laser microdissected, collected from the rat's hippocampus (n=4), and submitted to Illuminas for massively parallel sequencing. Results: We found evident segregation of the transcriptomic profile from different regions of the hippocampus. Gene ontology enrichment analysis of CA1 subfield results in actin regulation genes and postsynaptic membrane AMPA receptors that are indispensable for long-term potentiation and learning and memory. CA2 and CA3 transcripts were found associated with the higher metabolic processes. DG expression was enriched for ribosome and spliceosome, both required for protein synthesis and maintenance of cell life. Conclusion: The present findings contribute to a deeper understanding of the differences in the molecular machinery expressed by the rat hippocampal neuronal populations, further exploring underlying mechanisms responsible for each subflied specific functions.
2021-06-30 | GSE179101 | GEO
Project description:The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ).After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions.Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p < .0001; right: p < .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ.The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia.
| S-EPMC4575843 | biostudies-literature
Project description:While age-related volumetric changes in human hippocampal subfields have been reported, little is known about patterns of subfield functional connectivity (FC) in the context of healthy ageing. Here we investigated age-related changes in patterns of FC down the anterior-posterior axis of each subfield. Using high resolution structural MRI we delineated the dentate gyrus (DG), CA fields (including separating DG from CA3), the subiculum, pre/parasubiculum, and the uncus in healthy young and older adults. We then used high resolution resting state functional MRI to measure FC in each group and to directly compare them. We first examined the FC of each subfield in its entirety, in terms of FC with other subfields and with neighboring cortical regions, namely, entorhinal, perirhinal, posterior parahippocampal, and retrosplenial cortices. Next, we analyzed subfield to subfield FC within different portions along the hippocampal anterior-posterior axis, and FC of each subfield portion with the neighboring cortical regions of interest. In general, the FC of the older adults was similar to that observed in the younger adults. We found that, as in the young group, the older group displayed intrinsic FC between the subfields that aligned with the tri-synaptic circuit but also extended beyond it, and that FC between the subfields and neighboring cortical areas differed markedly along the anterior-posterior axis of each subfield. We observed only one significant difference between the young and older groups. Compared to the young group, the older participants had significantly reduced FC between the anterior CA1-subiculum transition region and the transentorhinal cortex, two brain regions known to be disproportionately affected during the early stages of age-related tau accumulation. Overall, these results contribute to ongoing efforts to characterize human hippocampal subfield connectivity, with implications for understanding hippocampal function and its modulation in the ageing brain.
| S-EPMC6849752 | biostudies-literature
Project description:BACKGROUND:Over the past 30 years, evidence has been accumulating for an immunological component to schizophrenia etiology, including genetic links to the major histocompatibility complex, microglia activation, and dysregulated cytokine profiles. However, the degree of similarity in cytokine profiles for schizophrenia and bipolar disorder, as well as the relationship between cytokine levels and brain structure, is less well understood. METHODS:To address this, we recruited 69 first-episode schizophrenia-spectrum patients, 16 first-episode bipolar patients with psychotic features, and 53 healthy controls, from the UC Davis EDAPT clinic. Blood plasma was collected and analyzed for all participants with a subset of participants that also underwent structural MRI on a 1.5T GE scanner. RESULTS:Plasma levels of interleukin (IL)-1?, IL-2, IL-6, and interferon (IFN)-? were elevated in schizophrenia patients compared to those in controls. Patients with bipolar disorder had elevated plasma IL-10 levels compared to controls, and the two patient groups did not differ significantly on any immunological measure. Percent whole-brain gray matter was inversely correlated with IFN-? and IL-12 levels in patients with schizophrenia, with a trend relationship between IFN-? and IL-12 and prefrontal cortical thickness. Furthermore, psychotic symptoms were positively related to IL-1? levels in individuals with schizophrenia. CONCLUSIONS:These data suggest a partially overlapping pattern of elevated blood cytokine levels in patients with first-episode schizophrenia and bipolar disorder with psychotic features. Furthermore, our findings suggest that elevated pro-inflammatory cytokines may be particularly involved in schizophrenia etiology, given evidence of cytokine-related decreases in total gray matter.
| S-EPMC5970482 | biostudies-literature