A Comparative Study Of Brain White Matter Network In Bipolar Disorder And Major Depressive Disorder During Depressive Episode

Objective: Bipolar disorder(BD)and major depressive disorder(MDD)are two common emotional mental disorders.Both diseases have high recurrence rate and disability/fatality rate,and suicide mortality rate is much higher than that of normal people.Both diseases can cause serious emotional,cognitive and social impairment,bring great pain to patients,and also bring heavy burden to families and society.Although BD and MDD are two different diseases in diagnosis,their symptoms are almost the same in the stage of depressive episode.There is a high probability that BD with first onset in a depressive episode could be misdiagnosed as MDD.However,because the principles of BD and MDD in clinical drug treatment are completely different,such misdiagnosis often leads to ineffective pre-treatment of BD patients or rapid conversion to manic/hypomanic episodes,which complicates the condition,delays the best treatment time,and causes additional disease burden and poor prognosis.Therefore,early and accurate identification of BD in depressive episode(BDD)and MDD plays a vital role in clinical effective diagnosis and treatment and in reducing the burden of disease.The diagnosis of mental disorders relies mainly on symptomatology,and no biomarkers have been approved for the diagnosis of any mental disorders.Doctors obtain diagnostic evidence by inquiring medical history,clinical scale testing and behavioral observation,but BD and MDD are easily misdiagnosed by doctors and simple scales in the stage of depressive episode,which seriously affects the treatment and prognosis of patients.The research hotspot of mental disorders is to find biologic markers that can be objectively detected,and to provide reliable evidence-based basis for the diagnosis and classification of diseases.At present,some studies attempt to differentiate BDD and MDD from different perspectives.Neuroimaging study is one of them.Neuroimaging technology is a popular method for mental disease research in recent decades.Because of its advantages of minimally invasive or non-invasive,intuitive,large amount of information and post-processing,it has been applied by more and more researchers.Magnetic resonance imaging(MRI)has been widely used because of its advantages of non-invasive,non-radiation,high temporal and spatial resolution,and the ability to detect structural and functional changes in the brain.Diffusion tensor imaging(DTI)is reliable techniques for studying mental disorders from white matter aspect.The pathological basis of mental disorders is often not limited to a single brain area,and the brain function execution always depends on the extensive interaction between multiple brain areas.Previous studies have shown that brain damage in mental disorders involves a wide range of cortical areas,including frontal,temporal,parietal,occipital and some subcutaneous nuclei.The results of different studies are also inconsistent,which indicates that the study of single brain damage in mental disorders is not enough to reveal the pathogenesis of the disease.Therefore,it is necessary to study the changes of brain function and structure in mental disorders from the perspective of network.And under the current research technology,we have been able to study the brain at network level through the combination of MRI technology and computer.At present,there are many studies comparing brain function or structure differences between BD or MDD and health control(HC)using MRI technology,but there are few studies using MRI technology to directly identify BDD and MDD,but the clinical significance of such studies is obviously greater.This study will compare the imaging differences of BDD,MDD and HC in terms of white matter.DTI technology is used to construct white matter brain network,comparing the differences among the network topological coefficients.No similar study has been published yet.Through these brain network methods,we hope to find MRI imaging indicators that can differentiate BDD from MDD.Methods: The study eventually included 130 subjects,including 21 BDD,40 MDD and 69 HC.The demographic data of the subjects were collected,and the clinical evaluation was carried out with Hamilton Depression Scale-17 editions(HAMD-17),Hamilton Anxiety Scale(HAMA)and Young Mania Scale(YMRS).DTI and structure MRI scans were also performed.The patients were initially depressed and followed up by telephone every three months.The patients in BDD group were diagnosed as BD after follow-up and the patients in MDD group were individuals without manic or hypomanic after two years of follow-up.We used SPSS software to analyze the differences of clinical data in BDD,MDD and HC groups by variance analysis,posthoc-test,chi-square test and non-parametric test.On the software development platform of Matlab 2011 a,DTI data are preprocessed by PANDA software and white matter network is constructed.Topological coefficients are calculated by GRETNA software.Statistical analysis of DTI networks includes three parts:(1)Statistical analysis of network topological coefficients.The network topology coefficient was analyzed by variance analysis using SPSS software.The significant threshold was set to P < 0.05,and the posthoc-test was carried out(P < 0.05).The network topology coefficients we choose include network global efficiency,network local efficiency and small world coefficient.(2)Statistical analysis of node topological coefficients.SPSS software was used to analyze the variance of node topological coefficients.The significant threshold was set to P < 0.05,and between groups comparisons were made afterwards(P < 0.05).The node topological coefficients we choose include node degree centrality and node efficiency.(3)Correlation analysis.SPSS software was used to carry out the correlation anylysis between the topographic coefficients and clinical scales scores in BDD and MDD groups.Results:(1)Comparison of network topological coefficients.There was no significant difference in global efficiency,local efficiency and small-world property among the three groups,but the standard network shortest path of BDD group increased with statistical significance(P < 0.05).(2)Comparisons of node topological coefficients.BDD group and MDD group had significant changes in node degree centrality and node efficiency,but not widely,including cuneus,precuneus,insular cortex and temporal lobe related areas.BDD group showed more significant damage.(3)In correlation analysis,the right insular node efficiency in BDD group was significantly and strongly negatively correlated with the psychic anxiety sub-scores of HAMD-17.Conclusion: Our study demonstrates difference in the topological structure of white matter network between BDD and MDD.But the network structure of BDD may be more unstable.The structural or functional changes of the right superior temporal gyrus may be the common pathogenesis of BDD and MDD.The inferior parietal lobule may be the specific lesion area of MDD.The insula of BDD associated with anxiety,may be a specific symptom-related change of BDD.The inferior parietal lobule,cuneus,precuneus and insula may be the key areas to differentiate BDD from MDD.