Associations Of Local Functional Connectivity And Plasma Leptin Levels With Common Depressive Symptoms In Major Psychiatric Disorders

Background: Schizophrenia(SCZ),bipolar disorder(BPD)and major depressive disorder(MDD)are three most common severe and persistent chronic psychiatric disorders.Based on the Diagnostic and Statistical Manual of Mental Disorders(DSM)and(International Classification of Diseases,ICD),SCZ,BPD,and MDD are three distinct diagnostic categories in current psychiatric nosology.However,there is increasing evidence for shared clinical symptoms,neuroimaging features,endocrine and metabolic disturbance,and genetic susceptibility.Recent studies have urged rethinking of SCZ,BPD,and MDD as lying along a continuum of major endogenous psychoses rather than dichotomous disorders.The Research Domain Criteria(RDoC)proposed by the National Institute of Mental Health(NIMH)has broken through traditional diagnostic categories to conduct a transdiagnostic scientific study of psychiatric disorders from multiple levels of psychological phenomena,neural circuits,molecules,and genomics.Accumulating evidences implicated that depressive symptom is one of the critical transdiagnostic symptoms across SCZ,BPD,and MDD.This study employed resting state functional magnetic resonance imaging(fMRI)and multiplex liquid-chip assay based on the Luminex platform(Bioplex technology)to explore the association of depressive symptoms in psychiatry patients,the neural circuitry(local functional connectivity)and the molecular level(endocrine and metabolism feature-leptin)respectively.The novel combination study in clinical symptoms,the neural circuitry and the molecular level would greatly advance the psychiatric nosology and the medical precision of psychiatric disorders.Methods: We recruited 282 healthy controls(HC)and 403 patients with major psychiatry disorders that fulfil the diagnostic criteria for the DSM-Ⅳ(DSM-IV)that are aged 17-55 years from the First Hospital of China Medical University and the outpatient clinic of Shenyang Mental Health Centre.We evaluated clinical symptoms,underwent magnetic resonance imaging,and collected demographic information and blood samples for all participants.The depressive symptom was assessed using the Hamilton Depression Rating Scale(HAMD).GE Signa 3.0T superconducting magnetic resonance image scanner was used for resting state fMRI imaging.MRI data analysis was carried out using voxel-based local functional connectivity(FC).The multiplex liquid-chip assay based on the Luminex Platform(Bioplex technology)was used to quantitate plasma leptin levels.Statistical analysis methods were two-sample t-tests,Chi-squared tests,exploratory factor analyses(EPA)and partial correlation analyses.Results: 1.Compared with HCs,major psychiatry disorders patients showed that [P<0.05,Gaussian Random Field(GRF)correction] increased local FC values were mainly in classical emotional processing brain regions(left dorsolateral prefrontal cortex,bilateral orbitofrontal cortices,bilateral insulae and left putamen)and right inferior temporal gyrus,while decreased local FC values were in the primary cortex(left superior temporal gyrus,left lingual gyrus,and right postcentral gyrus)as well as right supplementary motor area.Among these regions,alterations in local FC values in the left superior temporal gyrus and the right postcentral gyrus showed a positive correlation with HAMD total score,factor 1(depressed mood,guilt,suicide,work and interests,psychic anxiety and hypochondria)and factor 2(early insomnia,middle insomnia,late insomnia,somatic anxiety,gastrointestinal symptoms,general somatic symptoms,genital symptoms and weight loss)respectively in patients(SCZ,BPD,and MDD).2.Compared with HCs,the plasma leptin levels in patients were significantly increased.In patients group,increased local FC values in the left putamen and the left dorsolateral prefrontal cortex were positively correlated with plasma leptin levels.Decreased local FC values in the right lingual gyrus and right postcentral gyrus were negatively correlated with plasma leptin levels.Alterations in plasma leptin levels were found to be negatively correlated with HAMD total score,factor 1(depressed mood,guilt,suicide,work and interests,psychic anxiety and hypochondria)and factor 2(early insomnia,middle insomnia,late insomnia,somatic anxiety,gastrointestinal symptoms,general somatic symptoms,genital symptoms and weight loss)respectively in patients.Conclusion: 1.Patients(SCZ,BPD,and MDD)showed increased local FC values in classical emotional processing brain regions and the right inferior temporal gyrus,as well as decreased local FC values in the primary cortex and supplementary motor area.Among these regions,local FC alterations in the left superior temporal gyrus and the right postcentral gyrus are associated with depressive symptoms in patients.The left superior temporal gyrus and the right postcentral gyrus may play a critical role in the pathophysiology of major psychiatry disorders.2.The endocrine and metabolic feature-plasma leptin levels were increased in patients.Plasma leptin levels are associated with local FC alterations in the left putamen,left dorsolateral prefrontal cortex,right lingual gyrus,and right postcentral gyrus,plasma leptin levels are also associated with depressive symptoms inpatients(SCZ,BPD,and MDD).Leptin may play a key role in the pathophysiology of depressive symptoms in patients focus on the neural circuitry of emotional processing 3.Our findings of the association between depressive symptoms and local FC alterations in the right postcentral gyrus and plasma leptin levels,support new hypotheses.Major psychiatric disorders are manifest alterations at multi-level from clinical depression symptoms,to the neural circuitry and molecules.Additionally,the transdiagnostic research,which integrating of data and findings from clinical symptoms,neural circuitry,to molecular across multi-level could yield new route for explaining the pathophysiology of major psychiatry disorders.