Depression Recognition Based On Subgenual Anterior Cingulate Cortex Morphology And Brain Connectivity

Major depressive disorder（MDD）is a complex mental illness that poses serious harm to human health.Although previous studies have extensively explored the brain abnormalities of patients with major depressive disorder and proposed a typical pathological model based on the frontal-limbic circuit,the exact pathogenesis remains unclear.In the clinical treatment of MDD,the subgenual anterior cingulate cortex（sgACC:Brodmann area（BA）25）has always been an important brain area,which is often used as the target area for non-invasive brain stimulation therapy for MDD.Moreover,studies have found that the changes in the structure and function of sgACC are related to the clinical effect.Therefore,it is reasonable to identify sgACC as a potential biomarker in the pathophysiology of MDD.However,past researches have not fully characterized sgACC abnormalities in major depression,nor have they considered the potential impact of hemisphere differences.Therefore,in the present study,we aim to comprehensively investigate the morphology and connectivity abnormalities of sgACC,including hemisphere differences,in the context of major depression using magnetic resonance imaging（MRI）and（F-18）fluorodeoxyglucose（FDG）positron emission tomography（PET）.In this study,we used MRI and ¹⁸FDG PET brain imaging techniques to investigate the morphology and metabolic connectivity abnormalities of sgACC in MDD,as well as the possible hemisphere differences,based on three regions of interest:bilateral（left+right）sgACC（BA 25）,left sgACC（BA 25）,and right sgACC（BA 25）.Both MDD patients and healthy individuals were recruited as study subjects,and the study was divided into three parts.Experiment 1 examined the morphological abnormalities of the entire sgACC in major depression based on cortical thickness measurements,compensating for the limitations of previous studies that focused mainly on the gray matter volume indicators.Experiment 2focused on the hemisphere differences of the left and right sgACC morphological changes,based on the results of Experiment 1.Finally,in the Experiment 3,we used ¹⁸FDG PET imaging technology to further examine the metabolic connectivity patterns of the sgACC in major depressive disorder and any potential differences between the left and right hemispheres.Experiment 1 showed that the effect of group on the cortical thickness of sgACC was not significant,but the effect of gender was significant,and the interaction between group and gender was also significant.Post-hoc tests showed that the cortical thickness difference of sgACC between first-episode MDD patients and recurrent MDD patients was only present in male subjects.In addition,abnormal cortical thickness of sgACC in first-episode MDD patients compared with healthy controls was also found in male subjects.However,there were no significant differences between recurrent MDD patients and healthy controls in male and/or female subjects.Furthermore,we found significant gender differences of the sgACC thickness in the first-episode MDD patients.Experiment 2 showed that the results for the right sgACC were similar to those for the intact sgACC,significant gender and interaction effects were also observed.Specifically,cortical thickness changes in sgACC were only present in male subjects when comparing first-episode MDD patients with recurrent patients or healthy controls.In addition,gender differences of cortical thickness abnormalities still only existed in first-episode MDD patients.However,no significant results were observed for the left sgACC except for gender effect.Experiment 3 showed that compared with healthy controls,the metabolic connectivity patterns of sgACC in MDD patients were significantly enhanced,mainly involving some regions of the bilateral（para）hippocampi,the brainstem and bilateral frontal cortex.Additionally,our results also observed specific metabolic connectivity patterns of the left and right sgACC in MDD patients.The left sgACC had stronger metabolic connectivity with areas of the ventromedial frontal cortex,comprising medial parts of the frontopolar cortex and the pregenual ACC,while the right sgACC showed stronger metabolic connectivity with posterior parts of the hippocampus and bilateral cerebellum.In summary,our study indicates that the subgenual anterior cingulate cortex thickness is abnormally altered in the state of major depression,and this abnormality is mainly caused by the area in right hemisphere.In addition,metabolic connectivity patterns of sgACC are abnormally enhanced during episodes of major depression and differ between the left and right sgACC.These results confirm the role of the sgACC in MDD and highlight the potential influence of hemisphere differences and gender.This research provides valuable insights into the physiological mechanism of MDD and offers new avenues for clinical antidepressant treatment.The findings may help guide future research into the pathogenesis of MDD and the development of novel therapeutic strategies that target specific brain regions and connectivity patterns.