Dataset Information

Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function.

ABSTRACT: Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortex when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia.

SUBMITTER: Zhou L

PROVIDER: S-EPMC4756363 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function.

Zhou Li L Pu Weidan W Wang Jingjuan J Liu Haihong H Wu Guowei G Liu Chang C Mwansisya Tumbwene E TE Tao Haojuan H Chen Xudong X Huang Xiaojun X Lv Dongsheng D Xue Zhimin Z Shan Baoci B Liu Zhening Z

Scientific reports 20160217

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may pr ...[more]

PMID: 26882844

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Project description:The authors sought to examine the impact of multiple risk alleles for cognitive dysfunction and cardiovascular disease risk on cognitive function and to determine if these relationships varied by cognitive reserve (CR) or concomitant medication use in patients with schizophrenia. They conducted a cross-sectional study in ambulatory mental health centers. A total of 122 adults with a schizophrenia spectrum diagnosis who were maintained on a stable antipsychotic regimen for at least 6 months before study enrollment were included. Patients were divided into three CR groups based on years of formal education: no high school completion or equivalent (low-education group [18 patients]), completion of high school or equivalent (moderate-education group [36 patients], or any degree of post-high school education (high-education group [68 patients]). The following pharmacogenomic variants were genotyped for each patient: AGT M268T (rs699), ACE insertion/deletion (or ACE I/D, rs1799752), and APOE ε2, ε3, and ε4 (rs429358 and rs7412). Risk allele carrier status (identified per gene as AGT M268 T carriers, ACE D carriers, and APOE ε4 carriers) was not significantly different among CR groups. The Brief Assessment of Cognition in Schizophrenia (BACS) scale was used to assess cognitive function. The mean ± SD patient age was 43.9 ± 11.6 years. Cardiovascular risk factors such as hypertension and hyperlipidemia diagnoses, and use of antihypertensive and lipid-lowering agents, did not significantly differ among CR groups. Mixed modeling revealed that risk allele carrier status was significantly associated with lower verbal memory scores for ACE D and APOE ε4 carriers, but AGT T carrier status was significantly associated with higher verbal memory scores (p=0.0188, p=0.0055, and p=0.0058, respectively). These results were only significant in the low-education group. In addition, medication-gene interactions were not significant predictors of BACS scores. ACE D and APOE ε4 carrier status, independent of medication use, was associated with lower verbal memory scores in patients with schizophrenia who had relatively lower CR, as identified by formal education. These results suggest that increasing CR may be protective against cognitive impairment that may be worsened by select cardiovascular risk alleles in patients with schizophrenia.

Project description:BACKGROUND:Previous work designed a network-based protocol of cognitive training. This programme exploits a mechanism of induced task-oriented co-activation of multiple regions that are part of the default mode network (DMN), to induce functional rewiring and increased functional connectivity within this network. OBJECTIVE:In this study, the programme was administered to patients with a diagnosis of mild cognitive impairment to test its effects in a clinical sample. METHOD:Twenty-three patients with mild cognitive impairment (mean age: 73.74 years, standard deviation 5.13, female/male ratio 13/10) allocated to the experimental condition, underwent one month of computerised training, while fourteen patients (mean age: 73.14 years, standard deviation 6.16, female/ male ratio 7/7) assigned to the control condition underwent a regime of intense social engagement. Patients were in the prodromal stage of Alzheimer's disease (AD) as confirmed by clinical follow ups for at least two years. The DMN was computed at baseline and retest, together with other, control patterns of connectivity, grey matter maps and neuropsychological profiles. RESULTS:A condition-by-timepoint interaction indicating increased connectivity triggered by the programme was found in left parietal DMN regions. No decreases as well as no changes in the other networks or morphology were found. Although between-condition cognitive changes did not reach statistical significance, they correlated positively with changes in DMN connectivity in the left parietal region, supporting the hypothesis that parietal changes were beneficial. CONCLUSION:This programme of cognitive training up-regulates a pattern of connectivity which is pathologically down-regulated in AD. We argue that, when cognitive interventions are conceptualised as tools to induce co-activation repeatedly, they can lead to clinically relevant improvements in brain functioning, and can be of aid in support of pharmacological and other interventions in the earliest stages of AD.

Dataset Information

Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function.

Publications

Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function.

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