Elsevier

Journal of Psychiatric Research

Volume 95, December 2017, Pages 68-75
Journal of Psychiatric Research

Frequency-specific alteration of functional connectivity density in antipsychotic-naive adolescents with early-onset schizophrenia

https://doi.org/10.1016/j.jpsychires.2017.07.014Get rights and content

Abstract

Early-onset schizophrenia (EOS) is a severe mental illness associated with dysconnectivity that widespread in the brain. However, the functional dysconnectivity in EOS are still mixed. Recently, studies have identified that functional connectivity (FC) arises from a band-limited slow rhythmic mechanism and suggested that the dysconnectivity at specific frequency bands may provide more robust biomarkers for schizophrenia. The frequency-specific changes of FC pattern in EOS remain unclear. To address this issue, resting-state functional magnetic resonance imaging data scans from 39 EOS patients (drug-naive) and 31 healthy controls (HCs) were used to assess the FC density (FCD) across slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz). Results revealed that a remarkable difference between the FCD of the two bands existed mainly in the default mode network (DMN) and subcortical areas. Compared with the HCs, EOS patients showed significantly altered FCD involved in audiovisual information processing, sensorimotor system, and social cognition. Importantly, a significant frequency-by-group interaction was observed in the left precuneus with significantly lower FCD in the slow-4 frequency band, but no significant effect in the slow-5 frequency band. In addition, decreased FC was found between the precuneus and other DMN regions in the slow-4 band. Furthermore, the change in FCD in precuneus was inversely proportional to the clinical symptom in slow-4 band, indicating the key role of precuneus in schizophrenia progress. Our findings demonstrated that the dysconnectivity pattern in EOS could be frequency-dependent.

Section snippets

Introductions

Schizophrenia is a devastating disease characterized in part by altered connectivity in brain function (Epstein et al., 2014, Kyriakopoulos et al., 2012). A large but variable body of studies found functional connectivity (FC) deficits in adult-onset schizophrenia (Garrity et al., 2007, Lynall et al., 2010). Adolescents with early-onset schizophrenia (EOS) provides a unique opportunity to explore the FC alterations as they are less affected by chronic antipsychotic medication and interaction

Participants

A total of 39 EOS patients were recruited from the Second Affiliated Hospital of Xinxiang Medical University. All patients were independently diagnosed by research psychiatrists and satisfied the following criteria: (1) DSM-IV-TR criteria for schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, American Psychiatric Association, 2000), (2) no co-morbid Axis I diagnosis, (3) duration of illness less than two years, and (4) antipsychotic naive.

Demographic characteristics and clinical symptoms

No significant differences were found in gender, age, and years of education between the patients and HCs. For the patient group, the mean duration of illness was 16.0 months (SD = 14.4) (Table 1).

Main effect of frequency band factor

Brain regions showed a significant main effect of bands in the right lingual gyrus (F(1,124)=34.94), left posterior cingulate gyrus (F(1,124)=75.18), medial prefrontal cortex, orbital part (F(1,124)=55.64), right angular gyrus (F(1,124)=87.10), left inferior temporal gyrus (F(1,124)=272.89), right

Discussion

In this study, we used the FCD method to investigate the changes in the FC pattern in EOS patients at two frequency bands (slow-4 and slow-5). Several brain regions exhibited significant differences in the FCD between the two bands and the two groups. Moreover, a significant frequency-by-group interaction effect was observed in the left precuneus. In addition, decreased FC between the left precuneus and other regions in the slow-4 band was found. Furthermore, in the slow-4 band, the FCD in the

Limitation

The limitations of the current study should be considered. The size of our sample was relatively small. However, it is comparable with other recent studies that examined drug-naive EOS patients. A larger sample size is necessary to confirm the results of the current study.

Conclusion

In this study, we investigated the changes in FC within the brains of EOS patients at specific frequency bands. Many brain areas showed significant differences in specific frequency bands. Furthermore, in EOS patients brain areas with abnormal FC were widespread and mainly associated with audiovisual information processing, sensorimotor system, and social cognition. Moreover, the FC in the precuneus was significantly band-limited, and the changes in the slow-4 band were associated with the

Contributors

Yan Zhang and Mi Yang designed the study and conceptualized the protocol for healthy subjects. Jingping Zhao and Huafu Chen adapted this protocol for schizophrenia patients and evaluated them. Junjie Zheng, Zhiliang Long and Shaoqiang Han managed the literature searches and analyses. Xiao Wang, Youxue Zhang, Yifeng Wang and Xunjun Duan undertook the statistical analyses, and Xiao Wang wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.

Conflict of interest

The authors have declared that there are no conflicts of interest in relation to the subject of this study.

Acknowledgements

This research was supported by the 863 project (2015AA020505), the Natural Science Foundation of China (61533006 and 61673089), the project of the Science and Technology Department in Sichuan province (2017JY0094), and the Fundamental Research Funds for Central Universities (ZYGX2016KYQD120 and ZYGX2015J141).

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