Large-scale effective connectivity analysis reveals the existence of two mutual inhibitory systems in patients with major depression.

"appendix a supplementary data the following are the supplementary data to this article: supplementary data 1 data availability data will be made available on request. data availability data will be made available on request. acknowledgments this study was funded by the (61976248 81301199 81371478 61503411) the (2016yfc1307100 2017yfc0107400) (2017zdxm-sf-047)s wellcome principal research fellowship (ref: 088130"

"Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."

"This study was funded by the 10.13039/501100001809National Natural Science Foundation of China (61976248, 81301199, 81371478, 61503411), the 10.13039/501100012166National Key R&D Program of China (2016YFC1307100, 2017YFC0107400), 10.13039/501100017592Key Science and Technology Program of Shaanxi Province (2017ZDXM-SF-047)s Wellcome Principal Research Fellowship (Ref: 088130/Z/09/Z). Jia Wang: Data curation, Formal analysis, Visualization, Writing – original draft, Validation. Baojuan Li: Conceptualization, Formal analysis, Funding acquisition, Methodology, Writing – original draft, Writing – review & editing, Investigation. Jian Liu: Data curation, Formal analysis, Visualization, Writing – original draft, Validation. Jiaming Li: Formal analysis, Methodology, Visualization. Adeel Razi: Conceptualization, Methodology. Kaizhong Zheng: Data curation, Formal analysis, Methodology. Baoyu Yan: Formal analysis, Supervision, Visualization. Huaning Wang: Data curation, Project administration, Resources, Supervision. Hongbing Lu: Conceptualization, Methodology, Supervision, Writing – review & editing. Karl Friston: Conceptualization, Methodology, Writing – review & editing."

"A total of 65 patients were recruited from the Department of Psychiatry in Xijing hospital from 2014 to 2018. 75 healthy controls were also recruited via advertisement. The current study was approved by the Ethics Committee of Xijing Hospital of the Fourth Military Medical University and conducted in accordance with the Declaration of Helsinki. It has been registered with the ClinicalTrials.gov database (reference number: NCT01516931). All the participants provided written informed consent after a detailed description of the aims and procedure of the study. Sixty-five male and female subjects were diagnosed as MDD by trained psychiatrists according to the International Classification of Diseases, 10th revision (ICD-10), or Diagnostic and Statistical Manual for Mental Disorders IV. Severity of depression and anxiety symptoms were accessed by the 24-item Hamilton Rating Scale for Depression (HAMD-24) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. All MDD patients were enrolled for 8 weeks of antidepressant therapy. Patients were mainly treated with venlafaxine, a small number of patients received fluoxetine hydrochloride, paroxetine hydrochloride, escitalopram oxalate, sertraline hydrochloride in combination with the disease. At the same time, some patients also used a combination of anti-anxiety drugs. Following 8 weeks of antidepressant treatment, all patients were given the second assessment of severity of depression and anxiety symptoms. Clinically, it can be regarded as treatment effective (responder) when the ratio of score declines in behavioral scale more than 50 %, conversely, the patient was defined as non-responder."