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Chen K, Li Q, Zhu Z, Zhang J, Niu L, Dai H, Peng L, Wang X, Ma Q, Zhang R. Risk and Protective Factors for the Evolution of Subthreshold Depression During Early Adolescence. J Adolesc Health 2025; 76:385-395. [PMID: 39818657 DOI: 10.1016/j.jadohealth.2024.10.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 07/04/2024] [Accepted: 10/21/2024] [Indexed: 01/18/2025]
Abstract
PURPOSE Subthreshold depression refers to a condition involving clinically significant depressive symptoms that fall short of meeting the diagnostic criteria for major depressive disorder (MDD). Identifying risk and protective factors associated with the progression of subthreshold depression in early life is essential for timely prevention. However, there is limited research on this topic among early adolescents. METHODS This study analyzed data from the Adolescent Brain and Cognitive Development study to investigate the factors influencing the progression of subthreshold depression in individuals aged 9-13 years. Among 1,020 participants identified with subthreshold depression using the Child Behavior Checklist, 3 clinical outcomes were examined: developing MDD, persistent subthreshold depression, and remission from subthreshold depression. Using 31 diathesis-stress-related variables covering demographics, mental and physical health, and environmental factors, logistic regression was employed. RESULTS Compared to baseline healthy controls, adolescents with subthreshold depression had a 5.7-fold odds ratio for converting to MDD. Behavioral inhibition and traumatic experiences were identified as key risk factors in the transition from subthreshold depression to MDD. Individuals with subthreshold depression who exhibited traits of lack of perseverance, recent social deprivation, and school disengagement were likely to remain in subthreshold depression. Those who experienced remission from subthreshold depression had no family psychiatric history and experienced a good school environment. DISCUSSION Our study highlights the possible associations among maintaining regular sleep, using behavioral activation and resilience-based therapies, and fostering school belonging with enhanced prognosis for adolescents. Further research is needed to explore whether these interventions can reduce the risk of developing MDD.
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Affiliation(s)
- Keyin Chen
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Qian Li
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Ziqing Zhu
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jiayuan Zhang
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Lijing Niu
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Haowei Dai
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Lanxin Peng
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | - Xingqin Wang
- Department of Neurosurgery, Institute of Brain Diseases, Doctor of Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qing Ma
- Key Laboratory of Brain Functional Genomics (MOE&STCSM), Affiliated Mental Health Center (ECNU), School of Psychology and Cognitive Science, East China Normal University, Shanghai, China.
| | - Ruibin Zhang
- Laboratory of Cognitive Control and Brain Healthy, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China; Department of Psychiatry, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
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Panico F, Luciano SM, Salzillo A, Sagliano L, Trojano L. Investigating Cerebello-Frontal Circuits Associated with Emotional Prosody: A Double-Blind tDCS and fNIRS study. CEREBELLUM (LONDON, ENGLAND) 2024; 23:2397-2407. [PMID: 39276299 PMCID: PMC11585498 DOI: 10.1007/s12311-024-01741-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/04/2024] [Indexed: 09/16/2024]
Abstract
The emotional and cognitive cerebellum has been explored by several studies in the past years. Recent evidence suggested the possible contribution of the cerebellum in processing emotional prosody, namely the ability to comprehend the emotional content of a given vocal utterance, likely mediated by anatomical and functional cerebello-prefrontal connections. In the present study, the involvement of a functional cerebello-prefrontal network in recognising emotional prosody was assessed by combining non-invasive anodal transcranial direct current stimulation (tDCS) over the right or the left cerebellum and functional Near Infrared Spectroscopy of the prefrontal cortex, in a double-blind within-subject experimental design on healthy participants. The results showed that right and, to a less extent, left cerebellar tDCS (as compared to sham stimulation) reduced neural activation in the prefrontal cortex while accuracy and reaction times at the vocal recognition task remained unchanged. These findings highlight functional properties of the cerebello-frontal connections and the psychophysiological effects of cerebellar brain stimulation, with possible clinical applications in psychiatric and neurological conditions.
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Affiliation(s)
- Francesco Panico
- University of Campania "Luigi Vanvitelli", Viale Ellittico 31, 81100, Caserta, Italy.
| | - Sharon Mara Luciano
- University of Campania "Luigi Vanvitelli", Viale Ellittico 31, 81100, Caserta, Italy
| | - Alessia Salzillo
- University of Campania "Luigi Vanvitelli", Viale Ellittico 31, 81100, Caserta, Italy
| | - Laura Sagliano
- University of Campania "Luigi Vanvitelli", Viale Ellittico 31, 81100, Caserta, Italy
| | - Luigi Trojano
- University of Campania "Luigi Vanvitelli", Viale Ellittico 31, 81100, Caserta, Italy
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Chen G, Guo Z, Chen P, Yang Z, Yan H, Sun S, Ma W, Zhang Y, Qi Z, Fang W, Jiang L, Tao Q, Wang Y. Bright light therapy-induced improvements of mood, cognitive functions and cerebellar functional connectivity in subthreshold depression: A randomized controlled trial. Int J Clin Health Psychol 2024; 24:100483. [PMID: 39101053 PMCID: PMC11296024 DOI: 10.1016/j.ijchp.2024.100483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 06/25/2024] [Indexed: 08/06/2024] Open
Abstract
Background The efficacy of bright light therapy (BLT) in ameliorating depression has been validated. The present study is to investigate the changes of depressive symptoms, cognitive function and cerebellar functional connectivity (FC) following BLT in individuals with subthreshold depression (StD). Method Participants were randomly assigned to BLT group (N = 47) or placebo (N = 41) in this randomized controlled trial between March 2020 and June 2022. Depression severity and cognitive function were assessed, as well as resting-state functional MRI scan was conducted before and after 8-weeks treatment. Seed-based whole-brain static FC (sFC) and dynamic FC (dFC) analyses of the bilateral cerebellar subfields were conducted. Besides, a multivariate regression model examined whether baseline brain FC was associated with changes of depression severity and cognitive function during BLT treatment. Results After 8-week BLT treatment, individuals with StD showed improved depressive symptoms and attention/vigilance cognitive function. BLT also increased sFC between the right cerebellar lobule IX and left temporal pole, and decreased sFC within the cerebellum, and dFC between the right cerebellar lobule IX and left medial prefrontal cortex. Moreover, the fusion of sFC and dFC at baseline could predict the improvement of attention/vigilance in response to BLT. Conclusions The current study identified that BLT improved depressive symptoms and attention/vigilance, as well as changed cerebellum-DMN connectivity, especially in the cerebellar-frontotemporal and cerebellar internal FC. In addition, the fusion features of sFC and dFC at pre-treatment could serve as an imaging biomarker for the improvement of attention/vigilance cognitive function after BLT in StD.
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Affiliation(s)
- Guanmao Chen
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
| | - Zixuan Guo
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
| | - Pan Chen
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
| | - Zibin Yang
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
| | - Hong Yan
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
| | - Shilin Sun
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
| | - Wenhao Ma
- Department of Public Health and Preventive Medicine, School of Basic Medicine, Jinan University, Guangzhou 510632, China
- Division of Medical Psychology and Behavior Science, School of Basic Medicine, Jinan University, Guangzhou 510632, China
| | - Yuan Zhang
- Department of Public Health and Preventive Medicine, School of Basic Medicine, Jinan University, Guangzhou 510632, China
- Division of Medical Psychology and Behavior Science, School of Basic Medicine, Jinan University, Guangzhou 510632, China
| | - Zhangzhang Qi
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
| | - Wenjie Fang
- Department of Public Health and Preventive Medicine, School of Basic Medicine, Jinan University, Guangzhou 510632, China
- Division of Medical Psychology and Behavior Science, School of Basic Medicine, Jinan University, Guangzhou 510632, China
| | - Lijun Jiang
- Department of Public Health and Preventive Medicine, School of Basic Medicine, Jinan University, Guangzhou 510632, China
- Division of Medical Psychology and Behavior Science, School of Basic Medicine, Jinan University, Guangzhou 510632, China
| | - Qian Tao
- Department of Public Health and Preventive Medicine, School of Basic Medicine, Jinan University, Guangzhou 510632, China
- Division of Medical Psychology and Behavior Science, School of Basic Medicine, Jinan University, Guangzhou 510632, China
| | - Ying Wang
- Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, 510630, China
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Qin K, Pan N, Lei D, Zhang F, Yu Y, Sweeney JA, DelBello MP, Gong Q. Common and distinct neural correlates of emotional processing in individuals at familial risk for major depressive disorder and bipolar disorder: A comparative meta-analysis. J Affect Disord 2024; 348:97-106. [PMID: 38113944 PMCID: PMC10846904 DOI: 10.1016/j.jad.2023.12.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 12/04/2023] [Accepted: 12/13/2023] [Indexed: 12/21/2023]
Abstract
Individuals at familial risk for mood disorders exhibit deficits in emotional processing and associated brain dysfunction prior to illness onset. However, such brain-behavior abnormalities related to familial predisposition remain poorly understood. To investigate robust abnormal functional activation patterns during emotional processing in unaffected at-risk relatives of patients with major depressive disorder (UAR-MDD) and bipolar disorder (UAR-BD), we performed a meta-analysis of task-based functional magnetic resonance imaging studies using Seed-based d Mapping (SDM) toolbox. Common and distinct patterns of abnormal functional activation between UAR-MDD and UAR-BD were detected via conjunction and differential analyses. A total of 17 studies comparing 481 UAR and 670 healthy controls (HC) were included. Compared with HC, UAR-MDD exhibited hyperactivation in the parahippocampal gyrus, amygdala and cerebellum, while UAR-BD exhibited parahippocampal hyperactivation and hypoactivation in the striatum and middle occipital gyrus (MOG). Conjunction analysis revealed shared hyperactivated PHG in both groups. Differential analysis indicated that the activation patterns of amygdala and MOG significantly differed between UAR-MDD and UAR-BD. These findings provide novel insights into common and distinct neural phenotypes for familial risk and associated risk mechanisms in MDD and BD, which may have implications in guiding precise prevention strategies tailored to the family context.
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Affiliation(s)
- Kun Qin
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China; Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, OH, United States of America
| | - Nanfang Pan
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China; Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China
| | - Du Lei
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, OH, United States of America; College of Medical Informatics, Chongqing Medical University, Chongqing 400016, China
| | - Feifei Zhang
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yifan Yu
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China
| | - John A Sweeney
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, OH, United States of America
| | - Melissa P DelBello
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, OH, United States of America
| | - Qiyong Gong
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China; Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen 361021, China.
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Wang X, Xia J, Wang W, Lu J, Liu Q, Fan J, Soondrum T, Yu Q, Tan C, Zhu X. Disrupted functional connectivity of the cerebellum with default mode and frontoparietal networks in young adults with major depressive disorder. Psychiatry Res 2023; 324:115192. [PMID: 37054552 DOI: 10.1016/j.psychres.2023.115192] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 03/15/2023] [Accepted: 04/04/2023] [Indexed: 04/15/2023]
Abstract
Cerebellar dysconnectivity has repeatedly been documented in major depressive disorder (MDD). The cerebellum is composed of multiple functionally distinct subunits, and whether those subunits show similar or distinct dysconnectivity patterns with the cerebrum in MDD, is still unclear and needs to be further clarified. In this study, 91 MDD patients (23 male and 68 female) and 59 demographically matched healthy controls (22 male and 37 female) were enrolled to explore the cerebellar-cerebral dysconnectivity pattern in MDD by using the cutting-edge cerebellar partition atlas. Results showed that MDD patients exhibit decreased cerebellar connectivity with cerebral regions of default mode (DMN), frontoparietal networks (FPN), and visual areas. The dysconnectivity pattern was statistically similar across cerebellar subunits, with no significant diagnosis-by-subunit interactions. Correlation analyzes showed that cerebellar-dorsal lateral prefrontal cortex (DLPFC) connectivity is significantly correlated with anhedonia in MDD patients. Such dysconnectivity pattern was not affected by sex, which, however, should be further replicated in larger samples. These findings suggest a generalized disrupted cerebellar-cerebral connectivity pattern in MDD across all cerebellar subunits, which partially accounts for depressive symptoms in MDD, thus highlighting the pivotal role of the disrupted connectivity of cerebellum with DMN and FPN in the neuropathology of depression.
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Affiliation(s)
- Xiang Wang
- Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China
| | - Jie Xia
- Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China
| | - Weiyan Wang
- National Clinical Research Center for Mental Disorders, Changsha, Hunan, China; Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Jingjie Lu
- Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China
| | - Qian Liu
- Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China
| | - Jie Fan
- Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China
| | - Tamini Soondrum
- Association Alzheimer of Mauritius, Old Moka Road, Belle Rose, Quatre Bornes, Mauritius
| | - Quanhao Yu
- Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China
| | - Changlian Tan
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiongzhao Zhu
- Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; National Clinical Research Center for Mental Disorders, Changsha, Hunan, China.
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Dennison JB, Tepfer LJ, Smith DV. Tensorial independent component analysis reveals social and reward networks associated with major depressive disorder. Hum Brain Mapp 2023; 44:2905-2920. [PMID: 36880638 PMCID: PMC10089091 DOI: 10.1002/hbm.26254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 03/08/2023] Open
Abstract
Major depressive disorder (MDD) has been associated with changes in functional brain connectivity. Yet, typical analyses of functional connectivity, such as spatial independent components analysis (ICA) for resting-state data, often ignore sources of between-subject variability, which may be crucial for identifying functional connectivity patterns associated with MDD. Typically, methods like spatial ICA will identify a single component to represent a network like the default mode network (DMN), even if groups within the data show differential DMN coactivation. To address this gap, this project applies a tensorial extension of ICA (tensorial ICA)-which explicitly incorporates between-subject variability-to identify functionally connected networks using functional MRI data from the Human Connectome Project (HCP). Data from the HCP included individuals with a diagnosis of MDD, a family history of MDD, and healthy controls performing a gambling and social cognition task. Based on evidence associating MDD with blunted neural activation to rewards and social stimuli, we predicted that tensorial ICA would identify networks associated with reduced spatiotemporal coherence and blunted social and reward-based network activity in MDD. Across both tasks, tensorial ICA identified three networks showing decreased coherence in MDD. All three networks included ventromedial prefrontal cortex, striatum, and cerebellum and showed different activation across the conditions of their respective tasks. However, MDD was only associated with differences in task-based activation in one network from the social task. Additionally, these results suggest that tensorial ICA could be a valuable tool for understanding clinical differences in relation to network activation and connectivity.
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Affiliation(s)
- Jeff B. Dennison
- Department of Psychology & NeuroscienceTemple UniversityPhiladelphiaPennsylvaniaUSA
| | - Lindsey J. Tepfer
- Department of Psychological and Brain ScienceDartmouth UniversityHanoverNew HampshireUSA
| | - David V. Smith
- Department of Psychology & NeuroscienceTemple UniversityPhiladelphiaPennsylvaniaUSA
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Wang K, Hu Y, He Q, Xu F, Wu YJ, Yang Y, Zhang W. Network analysis links adolescent depression with childhood, peer, and family risk environment factors. J Affect Disord 2023; 330:165-172. [PMID: 36828149 DOI: 10.1016/j.jad.2023.02.103] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 02/19/2023] [Accepted: 02/20/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND Adolescent mental health is influenced by various adverse environmental conditions. However, it remains unclear how these factors jointly affect adolescent depression. This study aimed to use network analysis to assess the associations between different environmental factors and depressive symptoms in adolescents and to identify key pathways between them. METHODS This study included 610 adolescents with depression from inpatient and outpatient units recruited between March 2020 and November 2021. The mean age was 14.86 ± 1.96, with no significant difference between males (n = 155, 15.10 ± 2.19) and females (n = 455, 14.78 ± 1.88). Depressive symptoms were measured using the Children's Depression Inventory, and individual risk environment factors included childhood trauma, social peer and family risk factors. Network features, including network centrality, stability, and bridge centrality, were investigated. RESULTS Anhedonia and self-esteem were found to be more central in depressive symptoms. Insult experiences from the social peer and emotional abuse experience from childhood were more central environmental factors. Childhood trauma experiences were more related to adolescent depressive symptoms compared to family and peer factors. Bridge analyses identified emotional abuse, emotional neglect and physical neglect as the main bridges linking environment risk to depressive symptoms. LIMITATIONS This was a cross-sectionally designed study, which limited its ability to examine longitudinal dynamic interactions between environmental factors and adolescent depressive symptoms. CONCLUSIONS Our findings suggested that childhood trauma experiences might have greater psychological impacts on adolescent depression than family and social peer environments, and should be considered as crucial targets for preventing severe depressive moods.
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Affiliation(s)
- Kangcheng Wang
- School of Psychology, Shandong Normal University, Jinan 250358, China; Shandong Mental Health Center, Shandong University, Jinan 250014, China
| | - Yufei Hu
- School of Psychology, Shandong Normal University, Jinan 250358, China
| | - Qiang He
- Shandong Mental Health Center, Shandong University, Jinan 250014, China
| | - Feiyu Xu
- Shandong Mental Health Center, Shandong University, Jinan 250014, China; School of Mental Health, Jining Medical University, Jining 272067, China
| | - Yan Jing Wu
- Faculty of Foreign Languages, Ningbo University, Ningbo, Zhejiang, China
| | - Ying Yang
- Shandong Mental Health Center, Shandong University, Jinan 250014, China; Department of Psychiatry, School of Clinical Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
| | - Wenxin Zhang
- School of Psychology, Shandong Normal University, Jinan 250358, China.
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Structural and Functional Brain Alterations in Populations with Familial Risk for Depression: A Narrative Review. Harv Rev Psychiatry 2022; 30:327-349. [PMID: 36534836 DOI: 10.1097/hrp.0000000000000350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
LEARNING OBJECTIVES After completing this activity, practitioners will be better able to:• Discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk• Define how structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD. AIM Familial history is associated with an increased risk for major depressive disorder (MDD). Despite the increased risk, some members of the familial high-risk population remain healthy, that is, resilient. Defining the structural and functional brain alterations associated with vulnerability or resilience could lead to a better understanding of the pathophysiology of MDD. This study aimed to review the current literature and discuss the association between brain alterations and vulnerability or resilience to MDD in people with familial risk. METHODS A literature search on MRI studies investigating structural and functional alterations in populations at familial risk for MDD was performed using the PubMed and SCOPUS databases. The search was conducted through June 13, 2022. RESULTS We reviewed and summarized the data of 72 articles (25 structural MRI, 35 functional MRI, 10 resting-state fMRI, one structural/functional MRI combined, and one structural/functional/resting-state fMRI combined). These findings suggested that resilience in high-risk individuals is related to the amygdala structure, frontal lobe activity, and functional connectivity between the amygdala and multiple frontal regions. CONCLUSION Resilient and vulnerable individuals exhibit structural and functional differences in multiple frontal and limbic regions. However, further systematic longitudinal research incorporating environmental factors is required to validate the current findings.
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Li XK, Qiu HT, Hu J, Luo QH. Changes in the amplitude of low-frequency fluctuations in specific frequency bands in major depressive disorder after electroconvulsive therapy. World J Psychiatry 2022; 12:708-721. [PMID: 35663299 PMCID: PMC9150034 DOI: 10.5498/wjp.v12.i5.708] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/26/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Major depressive disorder (MDD) tends to have a high incidence and high suicide risk. Electroconvulsive therapy (ECT) is currently a relatively effective treatment for MDD. However, the mechanism of efficacy of ECT is still unclear.
AIM To investigate the changes in the amplitude of low-frequency fluctuations in specific frequency bands in patients with MDD after ECT.
METHODS Twenty-two MDD patients and fifteen healthy controls (HCs) were recruited to this study. MDD patients received 8 ECT sessions with bitemporal placement. Resting-state functional magnetic resonance imaging was adopted to examine regional cerebellar blood flow in both the MDD patients and HCs. The MDD patients were scanned twice (before the first ECT session and after the eighth ECT session) to acquire data. Then, the amplitude of low-frequency fluctuations (ALFF) was computed to characterize the intrinsic neural oscillations in different bands (typical frequency, slow-5, and slow-4 bands).
RESULTS Compared to before ECT (pre-ECT), we found that MDD patients after the eighth ECT (post-ECT) session had a higher ALFF in the typical band in the right middle frontal gyrus, posterior cingulate, right supramarginal gyrus, left superior frontal gyrus, and left angular gyrus. There was a lower ALFF in the right superior temporal gyrus. Compared to pre-ECT values, the ALFF in the slow-5 band was significantly increased in the right limbic lobe, cerebellum posterior lobe, right middle orbitofrontal gyrus, and frontal lobe in post-ECT patients, whereas the ALFF in the slow-5 band in the left sublobar region, right angular gyrus, and right frontal lobe was lower. In contrast, significantly higher ALFF in the slow-4 band was observed in the frontal lobe, superior frontal gyrus, parietal lobe, right inferior parietal lobule, and left angular gyrus.
CONCLUSION Our results suggest that the abnormal ALFF in pre- and post-ECT MDD patients may be associated with specific frequency bands.
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Affiliation(s)
- Xin-Ke Li
- College of Medical Informatics, Chongqing Medical University, Chongqing 400016, China
| | - Hai-Tang Qiu
- Mental Health Center, the First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing 400016, China
| | - Jia Hu
- Institute for Advanced Studies in Humanities and Social Science, Chongqing University, Chongqing 400044, China
| | - Qing-Hua Luo
- Mental Health Center, the First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing 400016, China
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Nguyen KP, Chin Fatt C, Treacher A, Mellema C, Cooper C, Jha MK, Kurian B, Fava M, McGrath PJ, Weissman M, Phillips ML, Trivedi MH, Montillo AA. Patterns of Pretreatment Reward Task Brain Activation Predict Individual Antidepressant Response: Key Results From the EMBARC Randomized Clinical Trial. Biol Psychiatry 2022; 91:550-560. [PMID: 34916068 PMCID: PMC8857018 DOI: 10.1016/j.biopsych.2021.09.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 08/31/2021] [Accepted: 09/14/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND The lack of biomarkers to inform antidepressant selection is a key challenge in personalized depression treatment. This work identifies candidate biomarkers by building deep learning predictors of individual treatment outcomes using reward processing measures from functional magnetic resonance imaging, clinical assessments, and demographics. METHODS Participants in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study (n = 222) underwent reward processing task-based functional magnetic resonance imaging at baseline and were randomized to 8 weeks of sertraline (n = 106) or placebo (n = 116). Subsequently, sertraline nonresponders (n = 37) switched to 8 weeks of bupropion. The change in Hamilton Depression Rating Scale was measured after treatment. Reward processing, clinical measurements, and demographics were used to train treatment-specific deep learning models. RESULTS The predictive model for sertraline achieved R2 of 48% (95% CI, 33%-61%; p < 10-3) in predicting the change in Hamilton Depression Rating Scale and number-needed-to-treat (NNT) of 4.86 participants in predicting response. The placebo model achieved R2 of 28% (95% CI, 15%-42%; p < 10-3) and NNT of 2.95 in predicting response. The bupropion model achieved R2 of 34% (95% CI, 10%-59%, p < 10-3) and NNT of 1.68 in predicting response. Brain regions where reward processing activity was predictive included the prefrontal cortex and cerebellar crus 1 for sertraline and the cingulate cortex, caudate, orbitofrontal cortex, and crus 1 for bupropion. CONCLUSIONS These findings demonstrate the utility of reward processing measurements and deep learning to predict antidepressant outcomes and to form multimodal treatment biomarkers.
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Affiliation(s)
- Kevin P Nguyen
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Cherise Chin Fatt
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Alex Treacher
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Cooper Mellema
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Crystal Cooper
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas; Jane and John Justin Neuroscience Center, Cook Children's Health Care System, Fort Worth, Texas
| | - Manish K Jha
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Benji Kurian
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Maurizio Fava
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Patrick J McGrath
- New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York
| | - Myrna Weissman
- New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York
| | - Mary L Phillips
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Madhukar H Trivedi
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas.
| | - Albert A Montillo
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas.
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11
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O'Shea IM, Popal HS, Olson IR, Murty VP, Smith DV. Distinct alterations in cerebellar connectivity with substantia nigra and ventral tegmental area in Parkinson's disease. Sci Rep 2022; 12:3289. [PMID: 35228561 PMCID: PMC8885704 DOI: 10.1038/s41598-022-07020-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 02/04/2022] [Indexed: 12/26/2022] Open
Abstract
In Parkinson's disease (PD), neurodegeneration of dopaminergic neurons occurs in the midbrain, specifically targeting the substantia nigra (SN), while leaving the ventral tegmental area (VTA) relatively spared in early phases of the disease. Although the SN and VTA are known to be functionally dissociable in healthy adults, it remains unclear how this dissociation is altered in PD. To examine this issue, we performed a whole-brain analysis to compare functional connectivity in PD to healthy adults using resting-state functional magnetic resonance imaging (rs-fMRI) data compiled from three independent datasets. Our analysis showed that across the sample, the SN had greater connectivity with the precuneus, anterior cingulate gyrus, and areas of the occipital cortex, partially replicating our previous work in healthy young adults. Notably, we also found that, in PD, VTA-right cerebellum connectivity was higher than SN-right cerebellum connectivity, whereas the opposite trend occurred in healthy controls. This double dissociation may reflect a compensatory role of the cerebellum in PD and could provide a potential target for future study and treatment.
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Affiliation(s)
- Ian M O'Shea
- Department of Psychology and Neuroscience, Temple University, Weiss Hall, 1701 N. 13th St, Philadelphia, PA, 19112, USA
| | - Haroon S Popal
- Department of Psychology and Neuroscience, Temple University, Weiss Hall, 1701 N. 13th St, Philadelphia, PA, 19112, USA
| | - Ingrid R Olson
- Department of Psychology and Neuroscience, Temple University, Weiss Hall, 1701 N. 13th St, Philadelphia, PA, 19112, USA
| | - Vishnu P Murty
- Department of Psychology and Neuroscience, Temple University, Weiss Hall, 1701 N. 13th St, Philadelphia, PA, 19112, USA.
| | - David V Smith
- Department of Psychology and Neuroscience, Temple University, Weiss Hall, 1701 N. 13th St, Philadelphia, PA, 19112, USA.
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12
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Liu F, Dong YY, Lei G, Zhou Y, Liu P, Dang YH. HINT1 Is Involved in the Chronic Mild Stress Elicited Oxidative Stress and Apoptosis Through the PKC ε/ALDH-2/4HNE Pathway in Prefrontal Cortex of Rats. Front Behav Neurosci 2021; 15:690344. [PMID: 34177485 PMCID: PMC8219906 DOI: 10.3389/fnbeh.2021.690344] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 05/14/2021] [Indexed: 01/02/2023] Open
Abstract
Major depressive disorder (MDD) is a severe, highly heterogeneous, and life-threatening psychiatric disease which affects up to 21% of the population worldwide. A new hypothesis suggests that the mitochondrial dysfunction causing oxidative stress (OS) and dysregulation of apoptosis in brain might be one of the key pathophysiological factors in MDD. Histidine triad nucleotide binding protein 1 (HINT1), which was first supposed to be protein kinase C (PKC) inhibitor, has been gradually demonstrated to be involved in diverse neuropsychiatric diseases. It still remains elusive that how HINT1 involves in depression. The present study utilized a rat model exposed to chronic mild stress (CMS) to explore the involvement of HINT1 in depression. Face validity, construct validity and predictive validity of CMS model were comprehensive evaluated in this study. Behavioral tests including sucrose preference test, open field test, and elevated plus maze and forced swimming test revealed that stressed rats displayed elevated level of anxiety and depression compared with the controls. CMS rats showed a significant decrease of superoxide dismutase, and a marked increase malondialdehyde levels in prefrontal cortex (PFC). We also found the CMS rats had elevated expression of HINT1, decreased levels of phosphorylated-PKC ε and aldehyde dehydrogenase-two (ALDH-2), and accumulated 4-hydroxynonenal (4HNE) in PFC. Moreover, CMS increased the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 in PFC. The alterations in behavior and molecule were prevented by antidepressant venlafaxine. These results demonstrated that HINT1 was involved in the CMS elicited OS and apoptosis in PFC, probably through the PKC ε/ALDH-2/4HNE pathway. The results suggest that the suppression of HINT1 might have potential as a novel therapeutic strategy for depression.
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Affiliation(s)
- Fei Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.,College of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Ying-Ying Dong
- Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Gang Lei
- College of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Yuan Zhou
- Department of Disaster Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Peng Liu
- College of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Yong-Hui Dang
- College of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, China
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