Dataset Information

Associations between polygenic risk, negative symptoms, and functional connectome topology during a working memory task in early-onset schizophrenia.

ABSTRACT: Working memory (WM) deficit in schizophrenia is thought to arise from a widespread neural inefficiency. However, we do not know if this deficit results from the illness-related genetic risk and influence the symptom burden in various domains, especially in patients who have an early onset illness. We used graph theory to examine the topology of the functional connectome in 99 subjects (27 early-onset schizophrenia (EOS), 24 asymptomatic siblings, and 48 healthy subjects) during an n-back task, and calculated their polygenic risk score (PRS) for susceptibility to schizophrenia. Linear regression analysis was used to test associations of the PRS, clinical symptoms, altered connectomic properties, and WM accuracy in EOS. Indices of small-worldness and segregation were elevated in EOS during the WM task compared with the other two groups; these connectomic aberrations correlated with increased PRS and negative symptoms. In patients with higher polygenic risk, WM performance was lower only when both the connectomic aberrations and the burden of negative symptoms were higher. Negative symptoms had a stronger moderating role in this relationship. Our findings suggest that the aberrant connectomic topology is a feature of WM task performance in schizophrenia; this relates to higher polygenic risk score as well as higher burden of negative symptoms. The deleterious effects of polygenic risk on cognition are played out via its effects on the functional connectome, as well as negative symptoms.

SUBMITTER: Deng M

PROVIDER: S-EPMC9261080 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveWorking memory (WM) deficits are consistently reported in schizophrenia and are related to poor functional outcomes. Functional magnetic resonance imaging studies of adult-onset schizophrenia have reported decreased functional activations and connectivity in the WM network, but no prior functional magnetic resonance imaging study has examined WM in childhood-onset schizophrenia (COS). The aim of this study was to examine the neural correlates of WM in COS.MethodAdult patients with COS (n = 32, 21.3 ± 1.1 years), nonpsychotic siblings of patients with COS (n = 30, 19.4 ± 0.8 years), and healthy controls (n = 39, 20.0 ± 0.7 years) completed 1- and 2-back WM tasks during 3-T functional magnetic resonance imaging. Functional activation and connectivity analyses were conducted. A separate group of 23 younger patients with COS (17.9 ± 7.4 years) could not perform the tasks after twice completing a standard training and are not included in this report.ResultsPatients with COS who were included scored significantly lower than controls on all tasks (p < .001). Patients with COS showed significantly lower activations in the dorsolateral prefrontal cortices, posterior parietal cortices, cerebellum, and caudate and decreased frontoparietal and corticostriatal functional connectivity compared with controls (p < .05, corrected). Siblings had functional activations and connectivity intermediate between those of patients and controls in a similar set of regions (p < .05, corrected). In patients, functional connectivity strength in the left frontoparietal network correlated positively with accuracy scores during the 1-back task (p = .0023, corrected).ConclusionDecreased functional activation and connectivity in the WM network in COS supports pathophysiologic continuity with adult-onset schizophrenia. The low participation rate and accuracy of the patients highlights the disease severity of COS. Hypo-activations and hypo-connectivity were shared by siblings of patients with COS, suggesting COS as a potential endophenotype.Clinical trial registration informationEvaluating Genetic Risk Factors for Childhood-Onset Schizophrenia; http://ClinicalTrials.gov;NCT00001198.

Dataset Information

Associations between polygenic risk, negative symptoms, and functional connectome topology during a working memory task in early-onset schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets