Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Dec 19, 2021; 11(12): 1274-1287
Published online Dec 19, 2021. doi: 10.5498/wjp.v11.i12.1274
Differential aberrant connectivity of precuneus and anterior insula may underpin the diagnosis of schizophrenia and mood disorders
Katrin Aryutova, Rositsa Paunova, Sevdalina Kandilarova, Kristina Stoyanova, Michael HJ Maes, Drozdstoy Stoyanov
Katrin Aryutova, Sevdalina Kandilarova, Drozdstoy Stoyanov, Psychiatry and Medical Psychology, Medical University, Plovdiv 4002, Bulgaria
Rositsa Paunova, Kristina Stoyanova, Michael HJ Maes, Research Institute, Medical University, Plovdiv 4002, Bulgaria
Author contributions: Kandilarova S and Stoyanov D designed and coordinated the study; Kandilarova S, Aryutova K, Paunova R and Stoyanova K performed the experiments; Kandilarova S and Paunova R acquired and analyzed the data; Aryutova K and Paunova R interpreted the data; Aryutova K wrote the original draft; Aryutova K prepared the visualization; Maes MH, Kandilarova S and Stoyanov D reviewed and edited the original draft; all authors approved the final version of the article.
Institutional review board statement: The Ethics Committee at Medical University of Plovdiv has approved the protocol of the study on 29 May 2015 (ID: P-369/29.05.2015).
Informed consent statement: The informed consent statement was waived.
Conflict-of-interest statement: Authors declare no conflict of interest.
Data sharing statement: Data are available to share on demand.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed following the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Drozdstoy Stoyanov, DSc, PhD, Professor, Psychiatry and Medical Psychology, Medical University, Vassil Aprilov 15 a, Plovdiv 4002, Bulgaria.
Received: April 14, 2021
Peer-review started: April 14, 2021
First decision: June 5, 2021
Revised: June 15, 2021
Accepted: August 31, 2021
Article in press: August 31, 2021
Published online: December 19, 2021
Research background

The present resting-state functional magnetic resonance imaging (rs-fMRI) study was conducted in two groups of patients – schizophrenia (SCH) and individuals with mood disorders with the depressive syndrome (Ds) – to delineate the effective connectivity patterns at rest with the prior hypothesis that the salience network (SN) in SCH must have a fundamentally impaired connectivity, which prevents the switching between anticorrelated default mode network (DMN) and central executive network (CEN), thereby interfering with their basic functions and that this disruption may serve as neuroimaging biomarker to distinguish between the two groups of patients.

Research motivation

Our motivation to conduct such a comparative study comes from the lack of biological validity of available diagnostic tools, which ultimately leads to inaccurate diagnosis or high rates of comorbidity, and therefore an inadequate choice of treatment for psychotic and affective disorders.

Research objectives

By proving neurobiological markers to distinguish between SCH and mood disorders, we aimed to expand knowledge about their etiology and incorporate it into clinical practice, ultimately optimizing diagnosis and prognosis, and thus choosing the right treatment for these severe mental illnesses.

Research methods

The methods used include rs-fMRI and subsequent dynamic causal modeling (spDCM) to determine the direction and strength of connections to and from various nodes in the DMN, SN and CEN. The positive and negative syndrome scale was chosen for the assessment of the SCH group, and the severity of the Ds was assessed using the Montgomery–Åsberg Depression Rating Scale. The SPM 12 software running on MATLAB R2020b for Windows was used to perform data analysis. First level resting-state analysis was conducted using a general linear model. Regions of interest were predefined based on their involvement in the SN and the DNM. Furthermore, using the parametric empirical bayes method introduced in SPM12, the individual spDCM models were jointly estimated. Finally, the estimated spDCM models were used to extract connectivity strengths (A-matrix) for further statistical analysis in SPSS.

Research results

The coupling strengths of the connection from the precuneus (Pc) to the prefrontal cortex and from the anterior insula (aI) to the Pc, both inhibitory connections were present in the Ds group but absent in the SCH group. In the SCH patients, a significant excitatory connection from the dorsal part of the anterior cingulate cortex to the aI was present which was absent in the Ds study group.

Research conclusions

We managed to deliver evidence that despite the clinical overlaps, there are objective neuroimaging signatures of disease that can fundamentally distinguish SCH from mood disorders. The resting state of aberrant salience and proximal salience observed in the schizophrenic group has the potential to explain not only the psychotic symptoms, such as hallucinations and delusions, but also gives insight into the formation of the unique for SCH behavioral and thought disorganization.

Research perspectives

We suggest that our findings could help both in the biological understanding of the etiology of SCH and mood disorders in the development and improvement of the therapeutic approach. We visualize a future where translational neuroscience would ultimately integrate psychopathology, psychopharmacology, instrumental methods, and even neurosurgical techniques to restore brain imbalances by modulating the altered connectivity in the brains of people suffering from SCH and mood disorders.