|
1
|
Miller AH. Advancing an Inflammatory Subtype of Major Depression. Am J Psychiatry 2025:appiajp20250289. [PMID: 40329642 DOI: 10.1176/appi.ajp.20250289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
Chronic inflammation plays a prominent role in multiple medical disorders, including psychiatric diseases such as major depression. Exposure to inflammatory stimuli leads to changes in neurotransmitter systems and neurocircuits in the brain that are associated with depressive symptoms. Blockade of inflammatory cytokines can reduce depressive symptoms in medically ill and medically healthy individuals with depression. Increased levels of biomarkers of inflammation are associated with an overrepresentation of neurovegetative symptoms, including anhedonia, fatigue, and psychomotor slowing, and can predict response to antidepressant treatments. Importantly, however, increased inflammatory biomarkers occur in only a subgroup of individuals with depression. Thus, there appears to be a subset of patients with depression with a unique symptom presentation and treatment response whose disease is primarily driven by inflammation. Further identifying and characterizing this inflammatory subtype of depression can foster the development of treatments targeting the immune system and its effects on the brain. Moreover, by using this mechanism-based approach to parsing the heterogeneity of depression, we can refine our diagnostic nosology and model a strategy for precision medicine and targeted therapeutics in psychiatry.
Collapse
Affiliation(s)
- Andrew H Miller
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta
| |
Collapse
|
|
2
|
Irwin MR. Insomnia and Inflammation Conspire to Heighten Depression Risk: Implications for Treatment and Prevention of Mood Disorders. Biol Psychiatry 2025:S0006-3223(25)01175-8. [PMID: 40328368 DOI: 10.1016/j.biopsych.2025.04.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 04/17/2025] [Accepted: 04/28/2025] [Indexed: 05/08/2025]
Abstract
Insomnia is ubiquitous, co-morbid with all major mental disorders, increases the risk of depression, and contributes to inflammatory morbidity and all-cause mortality. This review examines the relationships between insomnia and inflammation in the pathophysiology of depression. The unique role of insomnia on depression risk is examined with interrogation of what aspects of sleep disturbance contribute to depressed mood. Further, the influence of insomnia, as well as specific its specific aspects (i.e., short sleep duration, disturbance of sleep maintenance) on affective mechanisms are considered, with a focus on reward activation and emotion processing. Given that inflammation contributes to some types of depression, the bidirectional interactions between sleep and inflammation are examined with consideration of how sleep deprivation induces activation of systemic, cellular, and genomic inflammatory outcomes, and the causal role of inflammation in precipitating depressed mood and depressive symptoms. Key gaps in the literature linking insomnia and inflammation to depression risk are identified, and maps for future research are proposed. Specifically, this review considers how the components of insomnia and inflammation conspire together to exaggerate deficits in reward activation and recognition of emotion, which underlie depression risk and adverse depression outcomes. Finally, informed by this two-hit model of insomnia and inflammation on depression risk, this review examines the efficacy of behavioral interventions that target insomnia and reverse related inflammation, and discusses their potential to refine therapeutic approaches for depression treatment and prevention in persons with insomnia.
Collapse
Affiliation(s)
- Michael R Irwin
- Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, at University of California, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
| |
Collapse
|
|
3
|
Huang H, Zhang S, Weng Y, Li Z, Wang J, Huang R, Wu H. Characterizing childhood trauma in individuals based on patterns of intrinsic brain connectivity. J Affect Disord 2025; 375:103-117. [PMID: 39842674 DOI: 10.1016/j.jad.2025.01.094] [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: 05/12/2024] [Revised: 11/17/2024] [Accepted: 01/18/2025] [Indexed: 01/24/2025]
Abstract
Childhood maltreatment represents a strong psychological stressor that may lead to the development of later psychopathology as well as a heightened risk of health and social problems. Despite a surge of interest in examining behavioral, neurocognitive, and brain connectivity profiles sculpted by such early adversity over the past decades, little is known about the neurobiological substrates underpinning childhood maltreatment. Here, we aim to detect the effects of childhood maltreatment on whole-brain resting-state functional connectivity (RSFC) in a cohort of healthy adults and to explore whether such RSFC profiles can be used to predict the severity of childhood trauma in subjects based on a data-driven connectome-based predictive modeling (CPM). Resting-state functional MRI (rs-fMRI) data were acquired from 97 healthy adults, each of whom was assessed for childhood maltreatment levels using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). CPM was used to examine the association between whole-brain RSFC and childhood maltreatment levels. The results showed that CPM was able to decode individual childhood maltreatment levels from RSFC across multiple neural systems including RSFC between and within limbic and prefrontal systems as well as their connectivity with other networks. Key nodes contributing to the prediction model included the amygdala, prefrontal, and anterior cingulate regions that have been linked to childhood maltreatment. These results remained robust using different validation procedures. Our findings revealed that RSFC among multiple neural systems can be used to predict childhood maltreatment levels in individuals.
Collapse
Affiliation(s)
- Huiyuan Huang
- School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Center for the Study of Applied Psychology & MRI Center, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, School of Psychology, South China Normal University, Guangzhou 510631, China
| | - Shufei Zhang
- Center for the Study of Applied Psychology & MRI Center, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, School of Psychology, South China Normal University, Guangzhou 510631, China
| | - Yihe Weng
- Center for the Study of Applied Psychology & MRI Center, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, School of Psychology, South China Normal University, Guangzhou 510631, China
| | - Zezhi Li
- The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China
| | - Junjing Wang
- Department of Applied Psychology, Guangdong University of Foreign Studies, Guangzhou 510006, China
| | - Ruiwang Huang
- Center for the Study of Applied Psychology & MRI Center, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, School of Psychology, South China Normal University, Guangzhou 510631, China.
| | - Huawang Wu
- The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China.
| |
Collapse
|
|
4
|
Ferry RA, Adams EM, Nelson BD. Predictable and Unpredictable Threat Immune Enhancement. Stress Health 2025; 41:e70039. [PMID: 40243302 DOI: 10.1002/smi.70039] [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: 09/05/2024] [Revised: 03/28/2025] [Accepted: 04/08/2025] [Indexed: 04/18/2025]
Abstract
Acute social stress has been associated with increased immune system activation. However, less is known about whether non-social acute stressors also impact the immune response. In addition, most studies examine stressors that contain multiple characteristics (e.g., social, unpredictable) that could contribute to an increased immune response, but few studies have attempted to disentangle these factors. Finally, few studies have examined whether simultaneous changes in affect are associated with changes in the immune response. The present study used a between-subjects design to examine immune system activation, via changes in salivary cytokines interleukin-6 (IL-6), IL-8, IL-1β, and tumour necrosis factor-α, in response to predictable and unpredictable electric shock. A multimodal assessment of changes in defencive motivation (startle reflex), attention (event-related potential probe N100, P300), and self-reported affect were evaluated to confirm the effectiveness of the threat manipulation. As expected, results indicated that the threat manipulation enhanced defencive motivation, attention, and self-reported affect. Across all participants, both predictable and unpredictable threat increased IL-8 but decreased IL-6. Greater changes in self-reported negative affect were associated with greater increases in the overall immune response. The present study suggests that acute non-social stress enhances immune system activation, particularly in those who experience greater changes in negative affect.
Collapse
Affiliation(s)
- Rachel A Ferry
- Department of Psychology, Stony Brook University, Stony Brook, New York, USA
| | - Elise M Adams
- Department of Psychology, Stony Brook University, Stony Brook, New York, USA
| | - Brady D Nelson
- Department of Psychology, Stony Brook University, Stony Brook, New York, USA
| |
Collapse
|
|
5
|
Iannuzzi V, Narboux-Nême N, Lehoczki A, Levi G, Giuliani C. Stay social, stay young: a bioanthropological outlook on the processes linking sociality and ageing. GeroScience 2025; 47:721-744. [PMID: 39527178 PMCID: PMC11872968 DOI: 10.1007/s11357-024-01416-5] [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: 07/31/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
In modern human societies, social interactions and pro-social behaviours are associated with better individual and collective health, reduced mortality, and increased longevity. Conversely, social isolation is a predictor of shorter lifespan. The biological processes through which sociality affects the ageing process, as well as healthspan and lifespan, are still poorly understood. Unveiling the physiological, neurological, genomic, epigenomic, and evolutionary mechanisms underlying the association between sociality and longevity may open new perspectives to understand how lifespan is determined in a broader socio/evolutionary outlook. Here we summarize evidence showing how social dynamics can shape the evolution of life history traits through physiological and genetic processes directly or indirectly related to ageing and lifespan. We start by reviewing theories of ageing that incorporate social interactions into their model. Then, we address the link between sociality and lifespan from two separate points of view: (i) considering evidences from comparative evolutionary biology and bioanthropology that demonstrates how sociality contributes to natural variation in lifespan over the course of human evolution and among different human groups in both pre-industrial and post-industrial society, and (ii) discussing the main physiological, neurological, genetic, and epigenetic molecular processes at the interface between sociality and ageing. We highlight that the exposure to chronic social stressors deregulates neurophysiological and immunological pathways and promotes accelerated ageing and thereby reducing lifespan. In conclusion, we describe how sociality and social dynamics are intimately embedded in human biology, influencing healthy ageing and lifespan, and we highlight the need to foster interdisciplinary approaches including social sciences, biological anthropology, human ecology, physiology, and genetics.
Collapse
Affiliation(s)
- Vincenzo Iannuzzi
- Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126, Bologna, Italy
| | - Nicolas Narboux-Nême
- Physiologie Moléculaire Et Adaptation, CNRS UMR7221, Département AVIV, Muséum National d'Histoire Naturelle, Paris, France
| | - Andrea Lehoczki
- Doctoral College, Health Sciences Program, Semmelweis University, Budapest, Hungary
- Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
| | - Giovanni Levi
- Physiologie Moléculaire Et Adaptation, CNRS UMR7221, Département AVIV, Muséum National d'Histoire Naturelle, Paris, France.
| | - Cristina Giuliani
- Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126, Bologna, Italy.
| |
Collapse
|
|
6
|
Terczynska M, Bargiel W, Grabarczyk M, Kozlowski T, Zakowicz P, Bojarski D, Wasicka-Przewozna K, Kapelski P, Rajewska-Rager A, Skibinska M. Circulating Growth Factors and Cytokines Correlate with Temperament and Character Dimensions in Adolescents with Mood Disorders. Brain Sci 2025; 15:121. [PMID: 40002454 PMCID: PMC11852978 DOI: 10.3390/brainsci15020121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/20/2025] [Accepted: 01/25/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: The incidence of mood disorders in adolescents is increasing. Bipolar disorder is often misdiagnosed in the early stages of the disease due to the prevalence of depressive symptoms, while manic episodes occur later. Identifying predictors of diagnosis conversion could facilitate timely and appropriate treatment. Our study aimed to find correlations of selected peripheral protein levels with temperament and character traits in adolescents diagnosed with major depressive disorder and bipolar disorder. Methods: A group of adolescents and young adults diagnosed with major depressive disorder (MDD, n = 50) or bipolar disorder (BD, n = 24) was enrolled in the study during the exacerbation of symptoms and followed up over two years. Diagnosis conversion from MDD to BD was monitored. The Temperament and Character Inventory was applied, and BDNF, proBDNF, EGF, MIF, SCF, S100B, TNF-alpha, and IL-8 serum levels were measured. Spearman's rank correlation analysis was conducted. Results: We found different patterns of correlations in MDD (TNF-alpha, IL-8, EGF, S100B with reward-dependence, self-directedness, and empathy) and BD (BDNF and EGF with persistence novelty-seeking and self-transcendence). Significant correlations were found in a group with diagnosis conversion. Conclusions: The findings of our study have the potential to significantly impact our understanding and treatment of mood disorders. Correlations obtained in the subgroup with diagnosis conversion may contribute to the development of prognostic markers in the future. Evaluating temperament and character traits alongside established biomarkers may offer a valuable method for predicting the conversion of mood disorders in adolescents, facilitating early and effective pharmacotherapy.
Collapse
Affiliation(s)
- Maria Terczynska
- The Student Scientific Society of Poznan University of Medical Sciences, Student’s Research Group “Biological Psychiatry”, Department of Psychiatric Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Weronika Bargiel
- The Student Scientific Society of Poznan University of Medical Sciences, Student’s Research Group “Biological Psychiatry”, Department of Psychiatric Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Maksymilian Grabarczyk
- The Student Scientific Society of Poznan University of Medical Sciences, Student’s Research Group “Biological Psychiatry”, Department of Psychiatric Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Tomasz Kozlowski
- The Student Scientific Society of Poznan University of Medical Sciences, Student’s Research Group “Biological Psychiatry”, Department of Psychiatric Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Przemyslaw Zakowicz
- Collegium Medicum, University of Zielona Gora, 65-417 Zielona Gora, Poland;
- Center for Children and Adolescent Treatment in Zabor, 66-003 Zabor, Poland
| | | | - Karolina Wasicka-Przewozna
- The Student Scientific Society of Poznan University of Medical Sciences, Student’s Research Group “Biological Psychiatry”, Department of Psychiatric Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland
- Department of Psychiatric Genetics, Poznan University of Medical Sciences, 61-701 Poznan, Poland (A.R.-R.)
| | - Pawel Kapelski
- Department of Psychiatric Genetics, Poznan University of Medical Sciences, 61-701 Poznan, Poland (A.R.-R.)
| | - Aleksandra Rajewska-Rager
- Department of Psychiatric Genetics, Poznan University of Medical Sciences, 61-701 Poznan, Poland (A.R.-R.)
| | - Maria Skibinska
- Department of Psychiatric Genetics, Poznan University of Medical Sciences, 61-701 Poznan, Poland (A.R.-R.)
| |
Collapse
|
|
7
|
Lynch JM, Stange KC, Dowrick C, Getz L, Meredith PJ, Van Driel ML, Harris MG, Tillack K, Tapp C. The sense of safety theoretical framework: a trauma-informed and healing-oriented approach for whole person care. Front Psychol 2025; 15:1441493. [PMID: 39877223 PMCID: PMC11772489 DOI: 10.3389/fpsyg.2024.1441493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 12/09/2024] [Indexed: 01/31/2025] Open
Abstract
Objectives This research describes four aspects of the development of the Sense of Safety Theoretical Framework for whole person care: exploring the meaning of the phrase "sense of safety"-the whole person language; the range of human experience that impacts sense of safety-whole person scope; the dynamics that build sense of safety-the healing goals; and the personal and cross-disciplinary trauma-informed practitioner skills and attitudes that facilitate sense of safety. Methods This qualitative participatory study was conducted in two phases. Researchers iteratively explored the concept of sense of safety using focus groups and semi-structured interviews. Overarching research questions were: "Does the transdisciplinary concept of Sense of Safety make sense as an approach to the whole person in distress?"; "How do participants describe the meaning of the phrase "sense of safety"?"; "What does a person experience when they feel safe?" and "What can practitioners do to facilitate a sense of safety?" Phase One involved rural and urban family doctors, mental health clinicians across multiple disciplines, people with lived experience of mental distress, and Indigenous Australian academics. Phase Two widened the scope of disciplines involved to iteratively reflect on their clinical and personal experience with "sense of safety" and included international family doctors, physiotherapists, occupational therapists, social workers, teachers, multidisciplinary rural clinicians and multidisciplinary clinicians with a lived experience of physical trauma, grief, and severe mental illness. Results The everyday language "sense of safety" was found to describe a whole person experience that integrates awareness of self, others, and context. The scope of human experience that impacts sensed safety was found to include seven domains: Environment, Social Climate, Relationships, Body, Inner Experience, Sense of Self and Spirit/Meaning (Whole Person Domains). Five dynamic healing goals were identified that build sense of safety: Broad Awareness; Calm Sense-Making; Respectful Connection; Capable Engagement; and Owning Yourself (Sense of Safety Dynamics). Five practitioner skills and attitudes that facilitate sense of safety were named: Valuing the Whole Picture; Holding Story Safely; Being with You; Learning Together; and Validating Dignity (Sense of Safety Practitioner Skills). Conclusion The Sense of Safety Theoretical Framework developed in this study focusses on an experience that is a fundamental prerequisite of health. Sense of safety is affected by, and influences, life story, relationships, meaning, sense of self, and - physical health: the whole person. The language "sense of safety" communicates an integrative experience that can help clinicians to see the whole person and describe a cross-disciplinary goal of care. The Whole Person Domains clarify the scope of care required, while the Sense of Safety Dynamics offer practical processes of care. The Sense of Safety Practitioner Skills describe trauma-informed skills and attitudes that facilitate a sense of safety. Each of these parts of the Sense of Safety Theoretical Framework translate practitioner, lived experience, and First Nations wisdom and a wide existing transdisciplinary literature into a framework and language ready for practice. Assessing and building sense of safety prioritizes a healing-oriented and trauma-informed approach. The Sense of Safety Theoretical Framework facilitates a paradigm shift that towards integrating sensation, subjective experience, physiology, and social determinants into everyday quality care in health, education and public policy.
Collapse
Affiliation(s)
- Johanna M. Lynch
- General Practice Clinical Unit, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Kurt C. Stange
- Center for Community Health Integration and Departments of Family Medicine and Community Health, Population and Quantitative Health Sciences, and Sociology, Case Western Reserve University, Cleveland, OH, United States
| | - Christopher Dowrick
- Primary Medical Care, The Institute of Population Health, University of Liverpool, Liverpool, United Kingdom
| | - Linn Getz
- General Practice Research Unit, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Pamela J. Meredith
- Occupational Therapy, School of Health, University of the Sunshine Coast, Sunshine Coast, QLD, Australia
| | - Mieke L. Van Driel
- General Practice Clinical Unit, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Meredith G. Harris
- School of Population Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Brisbane, QLD, Australia
| | - Kate Tillack
- General Practice Clinical Unit, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Caley Tapp
- School of Population Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Brisbane, QLD, Australia
| |
Collapse
|
|
8
|
Shaw ZA, Handley ED, Warmingham JM, Starr LR. Patterns of life stress and the development of ruminative brooding in adolescence: A person-centered approach. Dev Psychopathol 2024; 36:1685-1697. [PMID: 37589100 PMCID: PMC10873479 DOI: 10.1017/s0954579423000974] [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] [Indexed: 08/18/2023]
Abstract
Research links life stressors, including acute, chronic, and early life stress, to the development of ruminative brooding. However, singular forms of life stress rarely occur in isolation, as adolescents typically encounter stressors that vary on important dimensions (e.g., types, timings, quantities) across development. The current study employs latent profile analysis (LPA) to identify natural clusters of life stress that, over time, may be differently associated with ruminative brooding. Evaluations of episodic, chronic, and early life stress were conducted with community-recruited mid-adolescents (N = 241, Mage = 15.90 years, 53% female) and their parents using the UCLA Life Stress Interview and lifetime adversity portions of the Youth Life Stress Interview. Analyses identified four distinct patterns: low stress, high peer stress, moderate home / family stress, and multifaceted / high school stress. Adolescents in the high peer stress and moderate home / family stress profiles were at highest risk for developing a brooding style over time. Despite high overall levels of stress, teens in the multifaceted / high school stress profile were at not at elevated risk for developing a brooding style. Findings demonstrate the utility of person-centered approaches to identify patterns of stress exposure that heighten risk for brooding over time.
Collapse
Affiliation(s)
- Zoey A Shaw
- Department of Psychiatry, Boston Children's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | | | - Jennifer M Warmingham
- Department of Pediatrics, Columbia University, Irving Medical Center, New York, NY, USA
| | - Lisa R Starr
- Department of Psychology, University of Rochester, Rochester, NY, USA
| |
Collapse
|
|
9
|
Arasappan D, Spears A, Shah S, Mayfield RD, Akula N, McMahon FJ, Jabbi M. Brain transcriptomic signatures for mood disorders and suicide phenotypes: an anterior insula and subgenual ACC network postmortem study. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.14.606080. [PMID: 39185191 PMCID: PMC11343154 DOI: 10.1101/2024.08.14.606080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Abstract
Mood disorders affect over ten percent of humans, but studies dissecting the brain anatomical and molecular neurobiological mechanisms underlying mood (dys)functions have not consistently identified the patterns of pathological changes in relevant brain regions. Recent studies have identified pathological changes in the anterior insula (Ant-Ins) and subgenual anterior cingulate (sgACC) brain network in mood disorders, in line with this network's role in regulating mood/affective feeling states. Here, we applied whole-tissue RNA-sequencing measures of differentially expressed genes (DEGs) in mood disorders versus (vs.) psychiatrically unaffected controls (controls) to identify postmortem molecular pathological markers for mood disorder phenotypes. Using data-driven factor analysis of the postmortem phenotypic variables to determine relevant sources of population variances, we identified DEGs associated with mood disorder-related diagnostic phenotypes by combining gene co-expression, differential gene expression, and pathway-enrichment analyses. We found downregulation/under expression of inflammatory, and protein synthesis-related genes associated with psychiatric morbidity (i.e., all co-occurring mental disorders and suicide outcomes/death by suicide) in Ant-Ins, in contrasts to upregulation of synaptic membrane and ion channel-related genes with increased psychiatric morbidity in sgACC. Our results identified a preponderance of downregulated metabolic, protein synthesis, inflammatory, and synaptic membrane DEGs associated with suicide outcomes in relation to a factor representing longevity in the Ant-Ins and sgACC (AIAC) network. Our study revealed a critical brain network molecular repertoire for mood disorder phenotypes, including suicide outcomes and longevity, and provides a framework for defining dosage-sensitive (i.e., downregulated vs. upregulated) molecular signatures for mood disorder phenotypic complexity and pathological outcomes.
Collapse
Affiliation(s)
- Dhivya Arasappan
- Center for Biomedical Research Support, The University of Texas at Austin, Dell Medical School, Austin, Texas, USA
| | - Abigail Spears
- Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin, Dell Medical School, Austin, Texas, USA
| | - Simran Shah
- Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin, Dell Medical School, Austin, Texas, USA
| | - Roy D Mayfield
- Department of Neuroscience and Waggoner Center for Addiction Research, The University of Texas at Austin
| | - Nirmala Akula
- Genetic Basis of Mood & Anxiety Section, Intramural Research Program, NIMH, NIH, Bethesda, MD USA
| | - Francis J McMahon
- Genetic Basis of Mood & Anxiety Section, Intramural Research Program, NIMH, NIH, Bethesda, MD USA
| | - Mbemba Jabbi
- Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin, Dell Medical School, Austin, Texas, USA
- Center for Learning and Memory, The University of Texas at Austin, Dell Medical School, Austin, Texas, USA
- Mulva clinics for the Neurosciences, Dell Medical School, Austin, Texas, USA
| |
Collapse
|
|
10
|
Lei Y, Li M, Lin C, Zhang C, Yu Z. The effect of ostracism on social withdrawal behavior: the mediating role of self-esteem and the moderating role of rejection sensitivity. Front Psychol 2024; 15:1411697. [PMID: 39171229 PMCID: PMC11337101 DOI: 10.3389/fpsyg.2024.1411697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 07/08/2024] [Indexed: 08/23/2024] Open
Abstract
Extant studies have empirically tested the main two behavior responses following ostracism: prosocial or antisocial. Few studies have investigated the relationship between ostracism and social withdrawal. According to the temporal need-threat model and the self-verification theory, the present study aimed to examine the influence mechanism of ostracism on social withdrawal, especially the mediating role of self-esteem and the moderating role of rejection sensitivity. A total of 1,315 Chinese high school students (52.6% female) completed a written questionnaire. Results showed that ostracism was positively correlated with social withdrawal. Ostracism not only directly predicted social withdrawal, but also indirectly affected social withdrawal by threatening adolescents' self-esteem. High rejection sensitivity may help aggravate adolescents' self-esteem threaten perceive from ostracism. Adolescents with high rejection sensitivity felt a greater threat to self-esteem when ostracized. Findings suggest a new direction for understanding individuals' responses to ostracism.
Collapse
Affiliation(s)
- Yuju Lei
- School of Education, Hubei University of Arts and Science, Xiangyang, China
| | | | | | | | | |
Collapse
|
|
11
|
Gabbay V, Ely BA, Vileisis JN, Petrovic Z, Cicvaric A, Asnis GM, Kim-Schulze S, Radulovic J. Immune and neural response to acute social stress in adolescent humans and rodents. Transl Psychiatry 2024; 14:306. [PMID: 39054336 PMCID: PMC11272929 DOI: 10.1038/s41398-024-03008-5] [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: 01/08/2024] [Revised: 06/13/2024] [Accepted: 07/03/2024] [Indexed: 07/27/2024] Open
Abstract
Studies in adults have linked stress-related activation of the immune system to the manifestation of psychiatric conditions. Using a translational design, this study aimed to examine the impact of social stress on immune activity in adolescents and on neuronal activity in a preclinical mouse model. Participants were 31 adolescents (ages 12-19), including 25 with mood and anxiety symptoms. Whole-blood samples were collected before and after the Trier Social Stress Test (TSST), a stress-inducing public speaking task, then cultured for 6 hours in the presence and absence of the inflammatory endotoxin lipopolysaccharide (LPS). Effects of TSST and LPS on 41 immune biomarkers were examined using repeated-measures analysis of variance. Separately, juvenile (8-week-old) male mice were non-stressed or exposed to reminder social defeat then intraperitoneally injected with saline or LPS (n = 6/group). Brains were perfused and collected for immunohistochemistry and confocal microscopy at 0, 1, 6, and 24 hours post-injection. The activity was determined by the density of cFos-positive neurons in the paraventricular hypothalamus, paraventricular thalamus, and basolateral amygdala, regions known to show sustained activation to immunological challenge. Analyses in the adolescent study indicated a strong effect of LPS but no effects of TSST or TSST×LPS interaction on immune biomarkers. Similarly, reminder social defeat did not induce sustained neuronal activity changes comparable to LPS immunological challenge in juvenile mice. Our convergent findings across species suggest that the acute immune response to stress documented in adults is not present in youth. Thus, aging and chronicity effects may play an important role in the inflammatory response to acute psychosocial stress.
Collapse
Affiliation(s)
- Vilma Gabbay
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
- Department of Clinical Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
| | - Benjamin A Ely
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Julia N Vileisis
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Zorica Petrovic
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
- Department of Neuroscience, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Ana Cicvaric
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
- Department of Neuroscience, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Gregory M Asnis
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Seunghee Kim-Schulze
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jelena Radulovic
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
- Department of Neuroscience, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA
| |
Collapse
|
|
12
|
Claro AE, Palanza C, Mazza M, Rizzi A, Corsello A, Tartaglione L, Marano G, Muti Schuenemann GEU, Rigoni M, Pontecorvi A, Janiri L, Muti P, Pitocco D. Reconsidering the role of depression and common psychiatric disorders as partners in the type 2 diabetes epidemic. World J Diabetes 2024; 15:1374-1380. [PMID: 38983820 PMCID: PMC11229977 DOI: 10.4239/wjd.v15.i6.1374] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 02/27/2024] [Accepted: 04/18/2024] [Indexed: 06/11/2024] Open
Abstract
Common psychiatric disorders (CPDs) and depression contribute significantly to the global epidemic of type 2 diabetes (T2D). We postulated a possible pathophysiological mechanism that through Bridge-Symptoms present in depression and CPDs, promotes the establishment of emotional eating, activation of the reward system, onset of overweight and obesity and, ultimately the increased risk of developing T2D. The plausibility of the proposed pathophysiological mechanism is supported by the mechanism of action of drugs such as naltrexone-bupropion currently approved for the treatment of both obesity/overweight with T2D and as separate active pharmaceutical ingredients in drug addiction, but also from initial evidence that is emerging regarding glucagon-like peptide 1 receptor agonists that appear to be effective in the treatment of drug addiction. We hope that our hypothesis may be useful in interpreting the higher prevalence of CPDs and depression in patients with T2D compared with the general population and may help refine the integrated psychiatric-diabetic therapy approach to improve the treatment and or remission of T2D.
Collapse
Affiliation(s)
- Angelo Emilio Claro
- Diabetes Care Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
| | - Clelia Palanza
- Istituto Italiano di Antropologia, ISItA, Rome 00100, Italy
| | - Marianna Mazza
- Unit of Psychiatry, Department of Neurosciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Alessandro Rizzi
- Diabetes Care Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Andrea Corsello
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Linda Tartaglione
- Diabetes Care Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Giuseppe Marano
- Unit of Psychiatry, Department of Neurosciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | - Marta Rigoni
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
| | - Alfredo Pontecorvi
- Department of Endocrine-Metabolic and Dermo-Rheumatology, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luigi Janiri
- Unit of Psychiatry, Department of Neurosciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Paola Muti
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy
| | - Dario Pitocco
- Diabetes Care Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| |
Collapse
|
|
13
|
Antici EE, Kuhlman KR, Treanor M, Craske MG. Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder. Brain Behav Immun 2024; 118:300-309. [PMID: 38467380 DOI: 10.1016/j.bbi.2024.03.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 02/17/2024] [Accepted: 03/02/2024] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.
Collapse
Affiliation(s)
- Elizabeth E Antici
- Department of Psychological Science, School of Social Ecology, University of California, Irvine, Irvine, CA, USA.
| | - Kate R Kuhlman
- Department of Psychological Science, School of Social Ecology, University of California, Irvine, Irvine, CA, USA; Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA
| | - Michael Treanor
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Michelle G Craske
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
| |
Collapse
|
|
14
|
Trachtenberg E. The beneficial effects of social support and prosocial behavior on immunity and health: A psychoneuroimmunology perspective. Brain Behav Immun Health 2024; 37:100758. [PMID: 38524896 PMCID: PMC10960128 DOI: 10.1016/j.bbih.2024.100758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 02/16/2024] [Accepted: 03/17/2024] [Indexed: 03/26/2024] Open
Abstract
The COVID-19 pandemic emphasized the pivotal role of the social environment, prompting a surge in research on its impact on well-being and health. This article aims to examine the link between the social environment, the immune system, and health outcomes, with a particular focus on positive aspects like social support and prosocial behaviors that are under-explored. Different aspects of the social environment are examined: the negative effects of loneliness and adverse social conditions, contrasted with the benefits of social support and prosocial behaviors. While the mechanisms behind negative effects are partially studied, those driving the positive effects remain elusive. Understanding the mechanisms of lack of social connection and their effects will allow us to explore the benefits of social connections and whether they can reverse the adverse outcomes. Potential psychoneuroimmunology mechanisms are proposed, highlighting the promotion of a 'safe' state by the vagus nerve, oxytocin circuits, and the additional contribution of the reward pathways. This article reviews the need to bridge knowledge gaps, urging further research to study the causal effects of positive social interactions on immune response and health outcomes to raise clinical awareness and interventions. Such interventions may include integrating lonely individuals with prosocial activities, thereby improving their physical and mental health. There is growing potential to harness the power of social connections for the betterment of individual health and society as a whole.
Collapse
Affiliation(s)
- Estherina Trachtenberg
- Sagol School of Neuroscience, Tel Aviv University, Israel
- School of Psychological Sciences, Faculty of Social Sciences, Tel Aviv University, Israel
| |
Collapse
|
|
15
|
Chen Q, Zhu X, Hu Y, Chen Y, Dai R, Li J, Zhuang J, Lin Y, Zeng Y, You L, Zeng Y, Huang Q. A study on the impact of marital status on the survival status of prostate cancer patients based on propensity score matching. Sci Rep 2024; 14:6162. [PMID: 38485743 PMCID: PMC10940582 DOI: 10.1038/s41598-024-56145-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 03/01/2024] [Indexed: 03/18/2024] Open
Abstract
Marital status is an independent prognostic factor for survival in many types of cancers, but its prognostic impact on patients with prostate cancer (PCa) has not been established. The aim of this study was to explore the independent prognostic factors of PCa and to investigate the effect of marital status on survival outcomes in patients with different stratified by PCa. Using the surveillance, epidemiology, and end results (SEER) database, we collected data on 584,655 PCa patients diagnosed between 1975 and 2019. Marital status was classified as married, divorced, widowed, and single. We used the Kaplan-Meier analysis and single multivariate Cox proportional hazards regression analysis to determine the effect of marital status on overall survival (OS) and cancer-specific survival (CSS). In addition, we performed subgroup analyses for different ages, Gleason score and PSA values, and performed a 1:1 propensity score matching (PSM) to reduce the impact of confounding factors to obtain more accurate matching results. According to our findings, marital status was an independent prognostic factor for the survival of PCa patients and a better prognosis of married patients. Moreover, we also found that factors such as age, TNM stage, Gleason score, and PSA concentration were also considered as important predictors for the prognosis of PCa. The above findings can facilitate early detection and treatment of high-risk PCa patients, prolong their life and reduce family burden.
Collapse
Affiliation(s)
- Qingquan Chen
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China
- The School of Public Health, Fujian Medical University, Fuzhou, 350108, Fujian, China
| | - Xi Zhu
- The School of Public Health, Fujian Medical University, Fuzhou, 350108, Fujian, China
| | - Yiming Hu
- The School of Public Health, Fujian Medical University, Fuzhou, 350108, Fujian, China
- National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 100050, China
| | - Yao Chen
- The School of Public Health, Fujian Medical University, Fuzhou, 350108, Fujian, China
| | - Rongrong Dai
- The School of Public Health, Fujian Medical University, Fuzhou, 350108, Fujian, China
| | - Jiaxin Li
- Anyang University, Anyang, 455000, Henan, China
| | - Jiajing Zhuang
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, 350108, Fujian, China
| | - Yifei Lin
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, 350108, Fujian, China
| | - Yifu Zeng
- Cyberspace Institute of Advanced Technology, Guangzhou University, Guangzhou, China
| | - Liuxia You
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China
| | - Yanyu Zeng
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China.
| | - Qian Huang
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China.
| |
Collapse
|
|
16
|
Ito M, Ito H, Miyoshi K, Kanai-Azuma M. Chronic non-discriminatory social defeat stress during the perinatal period induces depressive-like outcomes in female mice. Brain Res 2024; 1825:148734. [PMID: 38110072 DOI: 10.1016/j.brainres.2023.148734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 11/13/2023] [Accepted: 12/15/2023] [Indexed: 12/20/2023]
Abstract
Depression is more prevalent in women than in men. Perinatal stress is one of the main risk factors for depression in women. However, there is no suitable female model for perinatal depression that uses the social defeat stress (SDS) paradigm. The standard chronic SDS protocol, which is the most useful method for developing a depression-like model, is effective only in male mice. Thus, this study aimed to characterize a novel SDS method for producing a perinatal depression-like model mouse. We induced chronic SDS in perinatal female mice, wherein chronic non-discriminatory SDS (ND-SDS) was used to induce substantial stress in female mice. The female mice were placed in aggressive ICR mouse cages with sentinel male mice under ND-SDS conditions. Stressed female mice subjected to ND-SDS during the perinatal period efficiently exhibited stress-susceptible phenotypes, such as a social avoidance phenotype and anhedonic behavior, whereas stressed female mice subjected to SDS did not show depressive-like behaviors. These results indicate that chronic ND-SDS in perinatal females could be used to develop a female perinatal depression-like model that can be used to study women's health.
Collapse
Affiliation(s)
- Masumi Ito
- Department of Basic Life Science, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793 Japan; Research Facility Center for Science and Technology, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793 Japan
| | - Hikaru Ito
- Department of Basic Life Science, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793 Japan; Research Facility Center for Science and Technology, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793 Japan; Department of Experimental Animal Model for Human Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 Japan; Center for Experimental Animals, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 Japan.
| | - Kaori Miyoshi
- Department of Experimental Animal Model for Human Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 Japan; Center for Experimental Animals, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 Japan
| | - Masami Kanai-Azuma
- Department of Experimental Animal Model for Human Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 Japan; Center for Experimental Animals, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 Japan
| |
Collapse
|
|
17
|
Gabbay V, Ely B, Vileisis J, Petrovic Z, Cicvaric A, Asnis G, Kim-Schulze S, Radulovic J. Immune and Neural Response to Acute Social Stress in Adolescent Humans and Rodents. RESEARCH SQUARE 2024:rs.3.rs-3845793. [PMID: 38405791 PMCID: PMC10889054 DOI: 10.21203/rs.3.rs-3845793/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
Studies in adults have linked stress-related activation of the immune system to the manifestation of psychiatric conditions. Using a translational design, this study aimed to examine the impact of social stress on immune activity in adolescents and on neuronal activity in a preclinical mouse model. Participants were 31 adolescents (ages 12-19), including 25 with mood and anxiety symptoms. Whole-blood samples were collected before and after the Trier Social Stress Test (TSST), a stress-inducing public speaking task, then cultured for 6 hours in the presence and absence of the inflammatory endotoxin lipopolysaccharide (LPS). Effects of TSST and LPS on 41 immune biomarkers were examined using repeated-measures analysis of variance. Separately, juvenile (8-week-old) male mice were non-stressed or exposed to reminder social defeat then intraperitoneally injected with saline or LPS (n = 6/group). Brains were perfused and collected for immunohistochemistry and confocal microscopy at 0, 1, 6, and 24 hours post-injection. Activity was determined by the density of cFos-positive neurons in the paraventricular hypothalamus, paraventricular thalamus, and basolateral amygdala, regions known to show sustained activation to immunological challenge. Analyses in the adolescent study indicated a strong effect of LPS but no effects of TSST or TSST×LPS interaction on immune biomarkers. Similarly, reminder social defeat did not induce sustained neuronal activity changes comparable to LPS immunological challenge in juvenile mice. Our convergent findings across species suggest that the acute immune response to stress documented in adults is not present in youth. Thus, aging and chronicity effects may play an important role in the inflammatory response to acute psychosocial stress.
Collapse
|
|
18
|
Shields GS, Vinograd M, Bui T, Sichko S, Irwin MR, Slavich GM. Heightened neural activity and functional connectivity responses to social rejection in female adolescents at risk for depression: Testing the Social Signal Transduction Theory of Depression. J Affect Disord 2024; 345:467-476. [PMID: 37852590 PMCID: PMC11121539 DOI: 10.1016/j.jad.2023.10.113] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 10/13/2023] [Accepted: 10/15/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND Although social rejection is among the strongest proximal precipitants of major depressive disorder (MDD), little is known about the underlying neurobiological mechanisms and whether neural sensitivity to social rejection may help explain differences in MDD risk. To address this issue, we tested whether neural responses to social threat differed in female adolescents at high vs. low maternal risk for MDD. METHOD Female adolescents with (high-risk; n = 22, Mage = 14.68) and without (low-risk; n = 30, Mage = 15.07) a maternal history of depression were experimentally exposed to negative and neutral social evaluation while undergoing an fMRI scan. Neural responses were assessed by event-related activity and functional connectivity, as well as multivoxel pattern analysis. Activity and functional connectivity analyses focused on a priori-selected regions of interest implicated in self-referential processing and emotion regulation. RESULTS Compared to low-risk female adolescents, high-risk female adolescents exhibited greater increases in self-reported depression and social disconnection following social evaluation. Moreover, compared to low-risk female adolescents, high-risk female adolescents exhibited greater amygdala responses to negative social evaluation and a differential pattern of functional connectivity in brain regions related to emotion regulation, self-referential processing, and negative affect. Additionally, these markers of neural threat reactivity were related to depressive symptoms. LIMITATIONS A cross-sectional study design and relatively small, Western sample. CONCLUSIONS These results suggest that exaggerated neural reactivity to social threat-and an atypical pattern of related functional connectivity-is evident in individuals with a preclinical risk factor for depression. Targeting such responding may thus be a fruitful strategy for preventing depression in at-risk youth.
Collapse
Affiliation(s)
- Grant S Shields
- Department of Psychological Science, University of Arkansas, Fayetteville, AR, USA
| | - Meghan Vinograd
- Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, Department of Psychiatry, University of California, San Diego, CA, USA
| | - Theresa Bui
- Tulane University School of Medicine, New Orleans, LA, USA
| | - Stassja Sichko
- Department of Psychology, University of California, Los Angeles, CA, USA
| | - Michael R Irwin
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | - George M Slavich
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
| |
Collapse
|
|
19
|
Mengelkoch S, Gassen J, Slavich GM, Hill SE. Hormonal contraceptive use is associated with differences in women's inflammatory and psychological reactivity to an acute social stressor. Brain Behav Immun 2024; 115:747-757. [PMID: 37914104 PMCID: PMC11216059 DOI: 10.1016/j.bbi.2023.10.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 10/06/2023] [Accepted: 10/29/2023] [Indexed: 11/03/2023] Open
Abstract
Women using hormonal contraceptives (HCs) exhibit numerous signs of chronic inflammation, including elevated C-reactive protein levels and greater risk of developing mood and autoimmune disorders. However, users and non-users of HCs often have similar circulating proinflammatory cytokine levels, making the mechanism of association unclear. One possible explanation for this paradox is that HC users exhibit differences in their inflammatory responses to psychosocial stress that, over time, could contribute to chronic inflammation and its pathologies. Here, we tested this possibility by examining women's glucocorticoid, inflammatory, and psychological responses to the Trier Social Stress Test (TSST) in 67 naturally cycling (NC) and 60 oral HC-using women (Mage = 19.31, SDage = 1.95). As hypothesized, HC users and NC women exhibited different glucocorticoid and proinflammatory cytokine responses to the TSST. For NC women, TSST-induced increases in glucocorticoids were uncommon, and increases in glucocorticoids were accompanied by elevations in IL-6. In contrast, for women using HCs, increases in glucocorticoids in response to the TSST were common, and increases in glucocorticoids were accompanied by increases in TNF-α. HC users and NC women also differed in their psychological responses to the TSST, with HC users reporting elevated stress levels compared to NC women. Together, these results suggest that HC use impacts women's glucocorticoid, inflammatory, and psychological responses to psychosocial stress, potentially contributing to observed differences in these women's mental and physical health.
Collapse
Affiliation(s)
- Summer Mengelkoch
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, United States; Department of Psychology, Texas Christian University, 2955 South University Drive, Fort Worth TX 76129, United States.
| | - Jeffrey Gassen
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, United States
| | - George M Slavich
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, United States
| | - Sarah E Hill
- Department of Psychology, Texas Christian University, 2955 South University Drive, Fort Worth TX 76129, United States
| |
Collapse
|
|
20
|
Gilgoff R, Mengelkoch S, Elbers J, Kotz K, Radin A, Pasumarthi I, Murthy R, Sindher S, Harris NB, Slavich GM. The Stress Phenotyping Framework: A multidisciplinary biobehavioral approach for assessing and therapeutically targeting maladaptive stress physiology. Stress 2024; 27:2327333. [PMID: 38711299 PMCID: PMC11219250 DOI: 10.1080/10253890.2024.2327333] [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: 10/23/2023] [Accepted: 03/02/2024] [Indexed: 05/08/2024] Open
Abstract
Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers of toxic stress physiology; no biological, behavioral, or cognitive treatments specifically focused on normalizing toxic stress processes; and no agreed-upon guidelines for treating stress in the clinic or evaluating the efficacy of interventions that seek to reduce toxic stress and improve human functioning. We address these critical issues by (a) systematically describing key systems and mechanisms that are dysregulated by stress; (b) summarizing indicators, biomarkers, and instruments for assessing stress response systems; and (c) highlighting therapeutic approaches that can be used to normalize stress-related biopsychosocial functioning. We also present a novel multidisciplinary Stress Phenotyping Framework that can bring stress researchers and clinicians one step closer to realizing the goal of using precision medicine-based approaches to prevent and treat stress-associated health problems.
Collapse
Affiliation(s)
- Rachel Gilgoff
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA
| | - Summer Mengelkoch
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | - Jorina Elbers
- Trauma recovery Program, HeartMath Institute, Boulder Creek, CA, USA
| | | | | | - Isha Pasumarthi
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA
| | - Reanna Murthy
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA
| | - Sayantani Sindher
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA
| | | | - George M. Slavich
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| |
Collapse
|
|
21
|
Filho AMC, Gomes NS, Lós DB, Leite IB, Tremblay MÈ, Macêdo DS. Microglia and Microbiome-Gut-Brain Axis. ADVANCES IN NEUROBIOLOGY 2024; 37:303-331. [PMID: 39207699 DOI: 10.1007/978-3-031-55529-9_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
The mammalian gut contains a community of microorganisms called gut microbiome. The gut microbiome is integrated into mammalian physiology, contributing to metabolism, production of metabolites, and promoting immunomodulatory actions. Microglia, the brain's resident innate immune cells, play an essential role in homeostatic neurogenesis, synaptic remodeling, and glial maturation. Microglial dysfunction has been implicated in the pathogenesis of several neuropsychiatric disorders. Recent findings indicate that microglia are influenced by the gut microbiome and their derived metabolites throughout life. The pathways by which microbiota regulate microglia have only started to be understood, but this discovery has the potential to provide valuable insights into the pathogenesis of brain disorders associated with an altered microbiome. Here, we discuss the recent literature on the role of the gut microbiome in modulating microglia during development and adulthood and summarize the key findings on this bidirectional crosstalk in selected examples of neuropsychiatric and neurodegenerative disorders. We also highlight some current caveats and perspectives for the field.
Collapse
Affiliation(s)
- Adriano Maia Chaves Filho
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
- Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Nayana Soares Gomes
- Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Deniele Bezerra Lós
- Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Isabel Bessa Leite
- Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil
| | - Marie-Ève Tremblay
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
- Department of Molecular Medicine, Université de Laval, Québec City, Canada.
- Department of Neurology and Neurosurgery, McGill University, Montréal, Canada.
- Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
- Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria, Victoria, BC, Canada.
| | - Danielle S Macêdo
- Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
- National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil.
| |
Collapse
|
|
22
|
Defayette AB, Esposito-Smythers C, Cero I, Kleiman EM, López R, Harris KM, Whitmyre ED. Examination of proinflammatory activity as a moderator of the relation between momentary interpersonal stress and suicidal ideation. Suicide Life Threat Behav 2023; 53:922-939. [PMID: 37578098 PMCID: PMC10840613 DOI: 10.1111/sltb.12993] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 07/27/2023] [Accepted: 07/31/2023] [Indexed: 08/15/2023]
Abstract
INTRODUCTION Peer-related interpersonal stress can increase risk for suicidal thoughts among adolescents and young adults. However, not all individuals who undergo peer-related interpersonal stressors experience suicidal thoughts. Heightened proinflammatory activity is one factor that may amplify the relation between interpersonal stress and suicidal thinking. METHODS This pilot study examined the relation between interpersonal stress and suicidal ideation in real time, as well as whether proinflammatory cytokine (IL-6 and TNF-α) activity across a laboratory social stressor moderated this association in a sample of 42 emerging adults with recent suicidal ideation. Participants completed 28 days of 6×/daily ecological momentary assessment that assessed for suicidal ideation (presence vs. absence, ideation intensity), occurrence of negative peer events, and feelings of exclusion. RESULTS There was a trend for within-person increases in feelings of exclusion to be associated with increases in concurrent suicidal ideation intensity. Additionally, within-person increases in negative peer events were associated with increased odds of subsequent suicidal ideation among individuals with very low IL-6 activity. However, this finding is considered preliminary. CONCLUSION Interventions targeting perceptions of exclusion and increasing social support may be of benefit. However, findings require replication in larger samples, and thus must be interpreted with caution.
Collapse
Affiliation(s)
- Annamarie B. Defayette
- Department of Psychology, George Mason University, 4400 University Drive, 3F5, Fairfax, VA 22030, USA
- Department of Psychiatry, University of Rochester Medical Center, 300 Crittenden Blvd., Rochester, NY 14642, USA
| | | | - Ian Cero
- Department of Psychiatry, University of Rochester Medical Center, 300 Crittenden Blvd., Rochester, NY 14642, USA
| | - Evan M. Kleiman
- Department of Psychology, Rutgers, The State University of New Jersey, 53 Avenue E., Room 627, Piscataway, NJ 08854, USA
| | - Roberto López
- Department of Psychology, George Mason University, 4400 University Drive, 3F5, Fairfax, VA 22030, USA
| | - Katherine M. Harris
- Department of Psychology, George Mason University, 4400 University Drive, 3F5, Fairfax, VA 22030, USA
| | - Emma D. Whitmyre
- Department of Psychology, George Mason University, 4400 University Drive, 3F5, Fairfax, VA 22030, USA
| |
Collapse
|
|
23
|
Schulz MA, Hetzer S, Eitel F, Asseyer S, Meyer-Arndt L, Schmitz-Hübsch T, Bellmann-Strobl J, Cole JH, Gold SM, Paul F, Ritter K, Weygandt M. Similar neural pathways link psychological stress and brain-age in health and multiple sclerosis. iScience 2023; 26:107679. [PMID: 37680475 PMCID: PMC10480681 DOI: 10.1016/j.isci.2023.107679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 07/30/2023] [Accepted: 08/14/2023] [Indexed: 09/09/2023] Open
Abstract
Clinical and neuroscientific studies suggest a link between psychological stress and reduced brain health in health and neurological disease but it is unclear whether mediating pathways are similar. Consequently, we applied an arterial-spin-labeling MRI stress task in 42 healthy persons and 56 with multiple sclerosis, and investigated regional neural stress responses, associations between functional connectivity of stress-responsive regions and the brain-age prediction error, a highly sensitive machine learning brain health biomarker, and regional brain-age constituents in both groups. Stress responsivity did not differ between groups. Although elevated brain-age prediction errors indicated worse brain health in patients, anterior insula-occipital cortex (healthy persons: occipital pole; patients: fusiform gyrus) functional connectivity correlated with brain-age prediction errors in both groups. Finally, also gray matter contributed similarly to regional brain-age across groups. These findings might suggest a common stress-brain health pathway whose impact is amplified in multiple sclerosis by disease-specific vulnerability factors.
Collapse
Affiliation(s)
- Marc-Andre Schulz
- Charité – Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health), Department of Psychiatry and Psychotherapy, Berlin, Germany
- Bernstein Center for Computational Neuroscience, Berlin, Germany
- Department of Psychiatry, Psychotherapy, and Psychosomatics, Rheinisch-Westfälische Technische Hochschule (RWTH), Aachen University, Aachen, Germany
| | - Stefan Hetzer
- Bernstein Center for Computational Neuroscience, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin Center for Advanced Neuroimaging, Berlin, Germany
| | - Fabian Eitel
- Charité – Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health), Department of Psychiatry and Psychotherapy, Berlin, Germany
- Bernstein Center for Computational Neuroscience, Berlin, Germany
| | - Susanna Asseyer
- Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Lil Meyer-Arndt
- NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Berlin, Germany
| | - Tanja Schmitz-Hübsch
- Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Judith Bellmann-Strobl
- Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - James H. Cole
- Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK
- Dementia Research Centre, Institute of Neurology, University College London, London, UK
| | - Stefan M. Gold
- Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department, Section Psychosomatic Medicine, Berlin, Germany
| | - Friedemann Paul
- Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Kerstin Ritter
- Charité – Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health), Department of Psychiatry and Psychotherapy, Berlin, Germany
- Bernstein Center for Computational Neuroscience, Berlin, Germany
| | - Martin Weygandt
- Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| |
Collapse
|
|
24
|
Boyle CC, Bower JE, Eisenberger NI, Irwin MR. Stress to inflammation and anhedonia: Mechanistic insights from preclinical and clinical models. Neurosci Biobehav Rev 2023; 152:105307. [PMID: 37419230 DOI: 10.1016/j.neubiorev.2023.105307] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 06/30/2023] [Accepted: 07/04/2023] [Indexed: 07/09/2023]
Abstract
Anhedonia, as evidenced by impaired pleasurable response to reward, reduced reward motivation, and/or deficits in reward-related learning, is a common feature of depression. Such deficits in reward processing are also an important clinical target as a risk factor for depression onset. Unfortunately, reward-related deficits remain difficult to treat. To address this gap and inform the development of effective prevention and treatment strategies, it is critical to understand the mechanisms that drive impairments in reward function. Stress-induced inflammation is a plausible mechanism of reward deficits. The purpose of this paper is to review evidence for two components of this psychobiological pathway: 1) the effects of stress on reward function; and 2) the effects of inflammation on reward function. Within these two areas, we draw upon preclinical and clinical models, distinguish between acute and chronic effects of stress and inflammation, and address specific domains of reward dysregulation. By addressing these contextual factors, the review reveals a nuanced literature which might be targeted for additional scientific inquiry to inform the development of precise interventions.
Collapse
Affiliation(s)
- Chloe C Boyle
- Norman Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, UCLA, USA.
| | - Julienne E Bower
- Norman Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, UCLA, USA; Department of Psychology, UCLA, Los Angeles, CA, USA
| | | | - Michael R Irwin
- Norman Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, UCLA, USA
| |
Collapse
|
|
25
|
Ojha A, Teresi GI, Slavich GM, Gotlib IH, Ho TC. Social threat, fronto-cingulate-limbic morphometry, and symptom course in depressed adolescents: a longitudinal investigation. Psychol Med 2023; 53:5203-5217. [PMID: 36117278 PMCID: PMC10024647 DOI: 10.1017/s0033291722002239] [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: 11/12/2021] [Revised: 05/05/2022] [Accepted: 06/28/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Psychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression. METHODS We assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months. RESULTS General stressor severity was related to greater depression severity at baseline and over 9 months. Moreover, greater severity of social threat (but not non-social threat) stressors was associated with smaller bilateral amygdala and NAcc GMVs, and smaller bilateral surface areas of caudal and rostral ACC (all pFDR ⩽ 0.048). However, neither social threat nor non-social threat stressor severity was related to hippocampal GMVs (all pFDR ⩾ 0.318). All fronto-cingulate-limbic structures that were associated with the severity of social threat were negatively associated with greater depression severity over 9 months (all pFDR ⩽ 0.014). Post-hoc analyses suggested that gray matter morphometry of bilateral amygdala, NAcc, and rostral and caudal ACC mediated the association between social threat and depression severity in adolescents over 9 months (all pFDR < 0.048). CONCLUSIONS Social threat specifically affects fronto-cingulate-limbic pathways that contribute to the maintenance of depression in adolescents.
Collapse
Affiliation(s)
- Amar Ojha
- Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA
| | - Giana I. Teresi
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - George M. Slavich
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | - Ian H. Gotlib
- Department of Psychology, Stanford University, Stanford, CA, USA
| | - Tiffany C. Ho
- Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA
| |
Collapse
|
|
26
|
Chen K, Wüstenberg T, Stiglbauer V, El-Ahmad L, Rosenthal A, Pelz P, Gold SM, Heinz A, Sebold M. Distinct dynamic behavioural response to social exclusion in male patients with a history of alcohol dependence. Addict Biol 2023; 28:e13287. [PMID: 37369124 DOI: 10.1111/adb.13287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 03/15/2023] [Accepted: 04/27/2023] [Indexed: 06/29/2023]
Abstract
Social exclusion contributes to alcohol consumption, whereas the development of alcohol dependence (AD) can in turn lead to the social exclusion of people with AD. Previous research observed altered neural responses to experimentally induced social exclusion (i.e., Cyberball game) in patients with AD. In addition, inflammation has been associated with both social behaviours and AD. Our study aimed to investigate the dynamic behavioural response and the inflammatory effects of social exclusion in male patients with a history of AD. To this end, we analysed dynamic changes in ball tossing during a partial exclusion Cyberball game and the cytokine interleukin (IL)-1b in saliva in 31 male patients who had a history of AD and 29 gender-matched healthy controls without AD. Participants were included in the first 2 min of the Cyberball game and then excluded by one of the two co-players in the proceeding 5 min. Saliva was collected three times: one before and two after the Cyberball game. Across groups, participants passed the ball more often to the excluder during the partial exclusion period. Analysis using piece-wise linear mixed models showed that patients rapidly increased ball tosses to the excluder upon exclusion, which lasted to the late response phase, whereas the early behavioural response to exclusion took longer for controls. There was no significant change of salivary IL-1b level to exclusion in either patients or controls. The results indicate a distinct dynamic behavioural response to social exclusion in male patients with a history of AD.
Collapse
Affiliation(s)
- Ke Chen
- Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
| | - Torsten Wüstenberg
- Core Facility for Neuroscience of Self-Regulation (CNSR), Research Council Field of Focus IV, Heidelberg University, Heidelberg, Germany
- Psychological Institute, Heidelberg University, Heidelberg, Germany
| | - Victoria Stiglbauer
- Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Linda El-Ahmad
- Medical Department, Section Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Annika Rosenthal
- Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
- Department of Social and Preventive Medicine, University of Potsdam, Potsdam, Germany
| | - Patricia Pelz
- Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
| | - Stefan M Gold
- Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
- Medical Department, Section Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
- Institute of Neuroimmunology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas Heinz
- Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
| | - Miriam Sebold
- Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
- Faculty of Business and Law, Aschaffenburg University of Applied Sciences, Aschaffenburg, Germany
| |
Collapse
|
|
27
|
Kim H, Kwak S, Baek EC, Oh N, Baldina E, Youm Y, Chey J. Brain connectivity during social exclusion differs depending on the closeness within a triad among older adults living in a village. Soc Cogn Affect Neurosci 2023; 18:7135903. [PMID: 37084399 PMCID: PMC10121205 DOI: 10.1093/scan/nsad015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 12/06/2022] [Accepted: 03/19/2023] [Indexed: 04/23/2023] Open
Abstract
Social exclusion occurs in various types of social relationships, from anonymous others to close friends. However, the role that social relationships play in social exclusion is less well known because most paradigms investigating social exclusion have been done in laboratory contexts, without considering the features of individuals' real-world social relationships. Here, we addressed this gap by examining how pre-existing social relationships with rejecters may influence the brain response of individuals experiencing social exclusion. Eighty-eight older adults living in a rural village visited the laboratory with two other participants living in the same village and played Cyberball in an Magnetic Resonance Imaging scanner. Utilizing whole-brain connectome-based predictive modeling, we analyzed functional connectivity (FC) data obtained during the social exclusion task. First, we found that the level of self-reported distress during social exclusion was significantly related to sparsity, i.e. lack of closeness, within a triad. Furthermore, the sparsity was significantly predicted by the FC model, demonstrating that a sparse triadic relationship was associated with stronger connectivity patterns in brain regions previously implicated in social pain and mentalizing during Cyberball. These findings extend our understanding of how real-world social intimacy and relationships with excluders affect neural and emotional responses to social exclusion.
Collapse
Affiliation(s)
- Hairin Kim
- Department of Psychology, Seoul National University, Seoul 08826, South Korea
| | - Seyul Kwak
- Department of Psychology, Pusan National University, Busan 46241, South Korea
| | - Elisa C Baek
- Department of Psychology, University of California, Los Angeles, CA 90095, USA
| | - Naeun Oh
- Department of Psychology, Seoul National University, Seoul 08826, South Korea
| | - Ekaterina Baldina
- Department of Sociology, Yonsei University, Seoul 03722, South Korea
| | - Yoosik Youm
- Department of Sociology, Yonsei University, Seoul 03722, South Korea
| | - Jeanyung Chey
- Department of Psychology, Seoul National University, Seoul 08826, South Korea
| |
Collapse
|
|
28
|
Hallihan H, Tsai P, Lv N, Xiao L, Peñalver Bernabé B, Wu Y, Pandey GN, Williams LM, Ajilore OA, Ma J. Affective neural circuits and inflammatory markers linked to depression and anxiety symptoms in patients with comorbid obesity. J Psychiatr Res 2023; 160:9-18. [PMID: 36764197 PMCID: PMC10023437 DOI: 10.1016/j.jpsychires.2023.01.044] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 02/05/2023]
Abstract
Although we have effective treatments for depression and anxiety, we lack mechanistic understanding or evidence-based strategies to tailor these treatments in the context of major comorbidities such as obesity. The current feasibility study uses functional neuroimaging and biospecimen data to determine if changes in inflammatory markers, fecal short-chain fatty acids, and neural circuit-based targets can predict depression and anxiety outcomes among participants with comorbid obesity. Blood and stool samples and functional magnetic resonance imaging data were obtained at baseline and 2 months, during the parent ENGAGE-2 trial. From 30 participants with both biospecimen and fMRI data, this subsample study explored the relationship among changes in inflammatory markers and fecal short-chain fatty acids and changes in neural targets, and their joint relationship with depression and anxiety symptoms. Bivariate and partial correlation, canonical correlation, and partial least squares analyses were conducted, with adjustments for age, sex, and treatment group. Initial correlation analyses revealed three inflammatory markers (IL-1RA, IL-6, and TNF-α) and five neural targets (in Negative Affect, Positive Affect, and Default Mode Circuits) with significantly associated changes at 2 months. Partial least squares analyses then showed that changes in IL-1RA and TNF-α and changes in three neural targets (in Negative Affect and Positive Affect Circuits) at 2 months were associated with changes in depression and anxiety symptoms at 6 months. This study sheds light on the plausibility of incorporation of inflammatory and gastrointestinal biomarkers with neural targets as predictors of depression and comorbid anxiety outcomes among patients with obesity.
Collapse
Affiliation(s)
- Hagar Hallihan
- Department of Medicine, University of Illinois at Chicago, Chicago, IL, 60608, USA
| | - Perry Tsai
- Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA
| | - Nan Lv
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, IL, 60608, USA
| | - Lan Xiao
- Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA
| | | | - Yichao Wu
- Department of Mathematics, Statistics, and Computer Science, College of Liberal Arts and Sciences, Chicago, IL, 60607, USA
| | - Ghanshyam N Pandey
- Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA
| | - Leanne M Williams
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Olusola A Ajilore
- Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA
| | - Jun Ma
- Department of Medicine, University of Illinois at Chicago, Chicago, IL, 60608, USA.
| |
Collapse
|
|
29
|
Slavich GM, Roos LG, Mengelkoch S, Webb CA, Shattuck EC, Moriarity DP, Alley JC. Social Safety Theory: Conceptual foundation, underlying mechanisms, and future directions. Health Psychol Rev 2023; 17:5-59. [PMID: 36718584 PMCID: PMC10161928 DOI: 10.1080/17437199.2023.2171900] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 01/19/2023] [Indexed: 02/01/2023]
Abstract
Classic theories of stress and health are largely based on assumptions regarding how different psychosocial stressors influence biological processes that, in turn, affect human health and behavior. Although theoretically rich, this work has yielded little consensus and led to numerous conceptual, measurement, and reproducibility issues. Social Safety Theory aims to address these issues by using the primary goal and regulatory logic of the human brain and immune system as the basis for specifying the social-environmental situations to which these systems should respond most strongly to maximize reproductive success and survival. This analysis gave rise to the integrated, multi-level formulation described herein, which transforms thinking about stress biology and provides a biologically based, evolutionary account for how and why experiences of social safety and social threat are strongly related to health, well-being, aging, and longevity. In doing so, the theory advances a testable framework for investigating the biopsychosocial roots of health disparities as well as how health-relevant biopsychosocial processes crystalize over time and how perceptions of the social environment interact with childhood microbial environment, birth cohort, culture, air pollution, genetics, sleep, diet, personality, and self-harm to affect health. The theory also highlights several interventions for reducing social threat and promoting resilience.
Collapse
Affiliation(s)
- George M Slavich
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | - Lydia G Roos
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | - Summer Mengelkoch
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | - Christian A Webb
- McLean Hospital, Belmont, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Eric C Shattuck
- Institute for Health Disparities Research and Department of Public Health, University of Texas at San Antonio, San Antonio, TX, USA
| | - Daniel P Moriarity
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | - Jenna C Alley
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| |
Collapse
|
|
30
|
Abstract
How do experiences in nature or in spiritual contemplation or in being moved by music or with psychedelics promote mental and physical health? Our proposal in this article is awe. To make this argument, we first review recent advances in the scientific study of awe, an emotion often considered ineffable and beyond measurement. Awe engages five processes-shifts in neurophysiology, a diminished focus on the self, increased prosocial relationality, greater social integration, and a heightened sense of meaning-that benefit well-being. We then apply this model to illuminate how experiences of awe that arise in nature, spirituality, music, collective movement, and psychedelics strengthen the mind and body.
Collapse
Affiliation(s)
- Maria Monroy
- Department of Psychology, University of California,
Berkeley
| | - Dacher Keltner
- Department of Psychology, University of California,
Berkeley
| |
Collapse
|
|
31
|
Slavich GM, Mengelkoch S, Cole SW. Human social genomics: Concepts, mechanisms, and implications for health. LIFESTYLE MEDICINE 2023. [DOI: 10.1002/lim2.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2023] Open
Affiliation(s)
- George M. Slavich
- Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles California USA
| | - Summer Mengelkoch
- Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles California USA
| | - Steven W. Cole
- Department of Psychiatry and Biobehavioral Sciences University of California Los Angeles California USA
- Department of Medicine University of California Los Angeles California USA
| |
Collapse
|
|
32
|
Adolescents' neural reactivity to acute psychosocial stress: dysfunctional regulation habits are linked to temporal gyrus response. Dev Psychopathol 2023; 35:332-344. [PMID: 34365995 DOI: 10.1017/s0954579421000572] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Mid-adolescence is a critical time for the development of stress-related disorders and it is associated with significant social vulnerability. However, little is known about normative neural processes accompanying psychosocial stress at this time. Previous research found that emotion regulation strategies critically influence the relationship between stress and the development of psychiatric symptoms during adolescence. Using functional magnetic resonance imaging (fMRI), we examined neural responses to acute stress and analyzed whether the tendency to use adaptive or maladaptive emotion regulation strategies is related to neural and autonomic stress responses. Results show large linear activation increases from low to medium to high stress levels mainly in medial prefrontal, insulae and temporal areas. Caudate and subgenual anterior cingulate cortex, neural areas related to reward and affective valuations, showed linearly decreasing activation. In line with our hypothesis, the current adolescent neural stress profile resembled social rejection and was characterized by pronounced activation in insula, angular and temporal cortices. Moreover, results point to an intriguing role of the anterior temporal gyrus. Stress-related activity in the anterior temporal gyrus was positively related to maladaptive regulation strategies and stress-induced autonomic activity. Maladaptive coping might increase the social threat and reappraisal load of a stressor, relating to higher stress sensitivity of anterior temporal cortices.
Collapse
|
|
33
|
Hay DE, Bleicher S, Azoulay R, Kivity Y, Gilboa-Schechtman E. Affective and cognitive impact of social overinclusion: a meta-analytic review of cyberball studies. Cogn Emot 2023:1-18. [PMID: 36622872 DOI: 10.1080/02699931.2022.2163619] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Belongingness is a central biopsychosocial system. Challenges to belongingness (i.e. exclusion/ostracism) engender robust negative effects on affect and cognitions. Whether overinclusion - getting more than one's fair share of social attention - favourably impacts affect and cognitions remains an open question. This pre-registered meta-analysis includes twenty-two studies (N = 2757) examining overinclusion in the context of the Cyberball task. We found that the estimated overall effect size of overinclusion on positive affect was small but robust, and the effect on fundamental needs cognitions (belongingness, self-esteem, meaningful existence and control) was moderate in size and positive in direction. Notably, the effect sizes of overinclusion were smaller than the corresponding effects of exclusion. Finally, the effects of overinclusion on positive affect were greater for high, as compared to low, socially anxious individuals. Exploring the sequelae of the full range of inclusion experiences - from exclusion to overinclusion - may enrich our understanding of the functioning of the belongingness system as well as its interaction with another central biosocial system - the social status system.
Collapse
Affiliation(s)
- Dan E Hay
- Department of Psychology, Bar-Ilan University, Ramat Gan, Israel.,Gonda Brain Science Center, Bar-Ilan University, Ramat Gan, Israel
| | - Sun Bleicher
- Department of Psychology, Bar-Ilan University, Ramat Gan, Israel.,Gonda Brain Science Center, Bar-Ilan University, Ramat Gan, Israel
| | - Roy Azoulay
- Department of Psychology, Bar-Ilan University, Ramat Gan, Israel.,Gonda Brain Science Center, Bar-Ilan University, Ramat Gan, Israel
| | - Yogev Kivity
- Department of Psychology, Bar-Ilan University, Ramat Gan, Israel
| | - Eva Gilboa-Schechtman
- Department of Psychology, Bar-Ilan University, Ramat Gan, Israel.,Gonda Brain Science Center, Bar-Ilan University, Ramat Gan, Israel
| |
Collapse
|
|
34
|
Shin SH, Kim YK. Early Life Stress, Neuroinflammation, and Psychiatric Illness of Adulthood. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1411:105-134. [PMID: 36949308 DOI: 10.1007/978-981-19-7376-5_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/24/2023]
Abstract
Stress exposure during early stages of life elevates the risk of developing psychopathologies and psychiatric illness in later life. The brain and immune system are not completely developed by birth and therefore continue develop after birth; this post birth development is influenced by several psychosocial factors; hence, early life stress (ELS) exposure can alter brain structural development and function. A growing number of experimental animal and observational human studies have investigated the link between ELS exposure and increased risk of psychopathology through alternations in the immune system, by evaluating inflammation biomarkers. Recent studies, including brain imaging, have also shed light on the mechanisms by which both the innate and adaptive immune systems interact with neural circuits and neurotransmitters, which affect psychopathology. Herein, we discuss the link between the experience of stress in early life and lifelong alterations in the immune system, which subsequently lead to the development of various psychiatric illnesses.
Collapse
Affiliation(s)
- Sang Ho Shin
- Department of Psychiatry, College of Medicine, Korea University Ansan Hospital, Korea University, Ansan, Republic of Korea
| | - Yong-Ku Kim
- Department of Psychiatry, College of Medicine, Korea University Ansan Hospital, Korea University, Ansan, Republic of Korea.
| |
Collapse
|
|
35
|
Cazassa MJ, Slavich GM, e Silva VHP, de Souza LH, Damasceno ES, Cordeiro RTA, Oliveira MDS. [Instruments for assessing stress in Brazilians: an integrative review]. REVISTA BRASILEIRA DE TERAPIAS COGNITIVAS 2023; 19:122-132. [PMID: 38975642 PMCID: PMC11223748 DOI: 10.5935/1808-5687.20230041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
Introduction Numerous instruments have been developed around the world to assess stress. This study aimed to identify instruments with validation studies that mapping stress in Brazil. Method an integrative review was carried out on databases and the Testing System of the Federal Council of Psychology (SATEPSI) in June 2017 and updated this year. Two independent judges participated in analyzing the results. Results Of the 6,377 articles, 47 articles were selected from the Index Psi, SciELO, LILACS and PubMed databases, and 35 instruments made up the sample, two of which were from SATEPSI. Nine of these tools map stress in a more general way, nine are aimed at specific clinical contexts, 12 are aimed at occupational stress, three at the sports context and another two at other contexts. Discussion Numerous health problems are associated with early and chronic stressors, however it was identified that most instruments access stress in a more recent period of time (last year, month or week). A more accurate analysis of the relationships between longitudinal stress and health outcomes appears limited in this sense. The Stress and Adversity Inventory (STRAIN) appears as an alternative for studying stress throughout life in the Brazilian reality.
Collapse
Affiliation(s)
- Milton José Cazassa
- Pontifícia Universidade Católica do Rio
Grande do Sul (PUCRS), Programa de Pós-graduação em Psicologia
- Porto Alegre - RS - Brasil
| | - George M. Slavich
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
| | | | - Lauren Heineck de Souza
- Pontifícia Universidade Católica do Rio
Grande do Sul (PUCRS), Programa de Pós-graduação em Psicologia
- Porto Alegre - RS - Brasil
| | - Elisa Steinhorst Damasceno
- Pontifícia Universidade Católica do Rio
Grande do Sul (PUCRS), Programa de Pós-graduação em Psicologia
- Porto Alegre - RS - Brasil
| | - Raissa Telesca Arrial Cordeiro
- Pontifícia Universidade Católica do Rio
Grande do Sul (PUCRS), Programa de Pós-graduação em Psicologia
- Porto Alegre - RS - Brasil
| | - Margareth Da Silva Oliveira
- Pontifícia Universidade Católica do Rio
Grande do Sul (PUCRS), Programa de Pós-graduação em Psicologia
- Porto Alegre - RS - Brasil
| |
Collapse
|
|
36
|
Schmitt S, Robjant K, Elbert T, Carleial S, Hoeffler A, Chibashimba A, Hinkel H, Koebach A. Breaking the cycles of violence with narrative exposure: Development and feasibility of NETfacts, a community-based intervention for populations living under continuous threat. PLoS One 2022; 17:e0275421. [PMID: 36534649 PMCID: PMC9762574 DOI: 10.1371/journal.pone.0275421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 08/10/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Interpersonal violence damages mental health and frequently leads to aggressive defence strategies. If survivors are subsequently blamed for the events, both consequences worsen. Stigma flourishes, especially when survivors are silenced so that details of the trauma remain unknown. Breaking the secrecy both at the individual and collective level is key to enable the healing and reconciliation of individuals and communities living under continuous threat. METHOD The NETfacts health system is a stepped care model with three components: (1) Narrative Exposure Therapy (NET), an evidence-based trauma therapy that includes survivor testimony (2) NET for Forensic Offender Rehabilitation (FORNET) acknowledges that perpetrators are frequently also victims and assists in reducing aggression and the attraction to violence, and (3) a community intervention disseminating and discussing Facts derived from NET treatment (NETfacts) to challenge the collective avoidance of atrocities and other traumatic material. The intervention was piloted in a community with 497 adult residents in Eastern Democratic Republic of Congo. The willingness of clients to consent to sharing their anonymised testimonies (with a focus on sexual violence survivors and ex-combatants) was investigated, together with other components of feasibility including security and clinical safety, extent of support of respected local authorities and participation rates. As secondary outcomes, clinical and social measures were assessed before and post NETfacts among 200 village residents of whom 160 self-enrolled and 40 had not participated in any form of treatment. RESULTS Implementation was feasible with 248 clients from a partner project giving consent to use their testimonies and high support of respected local authorities and participation rates (56% of residents self-enrolled in NETfacts). Immediate beneficial effects were shown for posttraumatic stress and rejection of rape myths among NETfacts participants who experienced multiple traumatic events in their own past. Attitudes towards ex-combatants improved and the perceived lack of social acknowledgement after trauma increased independent from participation. No significant change was observed for depressive symptoms. CONCLUSION NETfacts is a feasible and promising approach to challenge the culture of secrecy surrounding trauma, suppression and social exclusion. Long term effectiveness requires further evaluation.
Collapse
Affiliation(s)
- Sabine Schmitt
- Department of Clinical and Neuropsychology, University of Konstanz, Konstanz, Germany
- Non-Governmental Organization Vivo International e.V., Konstanz, Germany
| | - Katy Robjant
- Department of Clinical and Neuropsychology, University of Konstanz, Konstanz, Germany
- Non-Governmental Organization Vivo International e.V., Konstanz, Germany
| | - Thomas Elbert
- Department of Clinical and Neuropsychology, University of Konstanz, Konstanz, Germany
- Non-Governmental Organization Vivo International e.V., Konstanz, Germany
| | - Samuel Carleial
- Department of Clinical and Neuropsychology, University of Konstanz, Konstanz, Germany
| | - Anke Hoeffler
- Department of Politics and Public Administration, University of Konstanz, Konstanz, Germany
| | - Amani Chibashimba
- Non-Governmental Organization Vivo International e.V., Konstanz, Germany
| | | | - Anke Koebach
- Department of Clinical and Neuropsychology, University of Konstanz, Konstanz, Germany
- Non-Governmental Organization Vivo International e.V., Konstanz, Germany
| |
Collapse
|
|
37
|
Hill KR, Hsu DT, Taylor SF, Ogden RT, Parsey RV, DeLorenzo C. Mu Opioid Receptor Dynamics in Healthy Volunteers with a History of Childhood Maltreatment. JOURNAL OF CHILD & ADOLESCENT TRAUMA 2022; 15:1105-1112. [PMID: 36439668 PMCID: PMC9684394 DOI: 10.1007/s40653-022-00463-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/31/2022] [Indexed: 06/16/2023]
Abstract
Evidence suggests that adults with a history of childhood maltreatment, the experience of emotional or physical neglect and/or abuse within the family during childhood, have blunted reward and stress processing, and higher risk of depression. The mu opioid receptor rich nucleus accumbens and amygdala are critical to reward and stress processing respectively. We hypothesized that nucleus accumbens and amygdala mu opioid receptor densities and activity (change in receptor binding due to endogenous opioid release or receptor conformation change) were negatively associated with childhood maltreatment in healthy young adults. Maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Healthy participants, n = 75 (52% female) completed [11C]carfentanil positron emission tomography imaging labeling mu opioid receptors. The relationship between CTQ score and binding potential (BPND, proportional to density of unoccupied receptors) was evaluated with a linear mixed effects model. No significant relationship was found between CTQ score and BPND (f = 3.28; df = 1, 73; p = 0.074) or change in BPND (activity) (t = 1.48; df = 198.3; p = 0.14). This is the first investigation of mu opioid receptors in those with childhood maltreatment. We did not identify a significant relationship between mu opioid receptor dynamics and severity of maltreatment in those without psychopathology. Because this cohort has a low CTQ score average, this may indicate that those with low severity of maltreatment may not have associated changes in mu opioid receptor dynamics. Future directions include evaluating a cohort with increased severity of childhood maltreatment.
Collapse
Affiliation(s)
- Kathryn R. Hill
- Department of Psychiatry, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794 United States
| | - David T. Hsu
- Department of Psychiatry, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794 United States
- Department of Psychiatry, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109 USA
| | - Stephan F. Taylor
- Department of Psychiatry, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109 USA
| | - R. Todd Ogden
- Department of Biostatistics, Columbia University Mailman School of Public Health, NY, NY 10032 USA
| | - Ramin V. Parsey
- Department of Psychiatry, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794 United States
| | - Christine DeLorenzo
- Department of Psychiatry, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794 United States
| |
Collapse
|
|
38
|
Uy JP, Dieffenbach M, Leschak CJ, Eisenberger NI, Fuligni AJ, Galván A. Sleep duration moderates the associations between immune markers and corticolimbic function during stress in adolescents. Neuropsychologia 2022; 176:108374. [PMID: 36167192 PMCID: PMC12050106 DOI: 10.1016/j.neuropsychologia.2022.108374] [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: 03/21/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 11/28/2022]
Abstract
Adolescence is characterized by biological changes in hormonal and circadian systems that, with concurrent psychosocial changes, result in increased sleep disturbances and stress sensitivity. Sleep disturbance has been associated with heightened stress sensitivity and elevated levels of inflammation in adults and adolescents, yet the neural correlates are unknown in adolescents. The current study investigated whether and how individual differences in peripheral immune markers (IL-6, TNF-α) related to neural response to stress in adolescents and whether these immune-brain associations were moderated by adolescents' sleep duration. Thirty-seven adolescents (14-15 years) who met quality control criteria for fMRI reported daily sleep duration for 7 days and performed a fMRI stressor task. A subsample of 23 adolescents additionally provided blood samples that were assayed for inflammatory markers using a multiplex assay. Results revealed that average sleep duration moderated associations between TNF-α and medial frontolimbic circuitry (amygdala, medial prefrontal cortex) during the stressor task such that, among adolescents who reported shorter sleep duration, higher levels of TNF-α were associated with greater deactivation in those regions during stress, which was associated with greater self-reported anxiety. These findings suggest that insufficient sleep duration coupled with greater levels of peripheral inflammation may promote a neural profile characterized by alterations in frontolimbic circuitry during stress, which can exacerbate sleep disturbances and/or peripheral inflammation.
Collapse
Affiliation(s)
- Jessica P Uy
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
| | - Macrina Dieffenbach
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Carrianne J Leschak
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Naomi I Eisenberger
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Andrew J Fuligni
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA
| | - Adriana Galván
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA
| |
Collapse
|
|
39
|
Wijaya MT, Jin R, Liu X, Zhang R, Lee TM. Towards a multidimensional model of inflamed depression. Brain Behav Immun Health 2022; 26:100564. [DOI: 10.1016/j.bbih.2022.100564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 11/10/2022] [Accepted: 11/13/2022] [Indexed: 11/21/2022] Open
|
|
40
|
Chen Y, Liu Y, Gao Y, Wu X, Mo L. The relationship between self-esteem and self-concept clarity is modulated by spontaneous activities of the dACC. Front Psychol 2022; 13:926181. [PMID: 36275295 PMCID: PMC9581283 DOI: 10.3389/fpsyg.2022.926181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 09/09/2022] [Indexed: 11/13/2022] Open
Abstract
Although it has been found that self-esteem and self-concept clarity are positively correlated, self-determination theory shows that the positive relationship might be lowered for individuals whose basic psychological needs are chronically thwarted. The exact neural mechanisms underlying the relationship between self-esteem and self-concept clarity are still not fully understood. The dorsal anterior cingulate cortex (dACC) plays an important role in monitoring basic psychological needs, considering that it is more active when some basic psychological needs are actually or potentially thwarted. To better understand the neural mechanisms underlying the relationship between self-esteem and self-concept clarity, we investigated the differences in the relationship between self-esteem and self-concept clarity among healthy adults with different levels of spontaneous activities of the dACC using rs-fMRI combined with amplitude of low-frequency fluctuation (ALFF). As expected, the results showed that the positive relationship between self-esteem and self-concept clarity was modulated by the ALFF value of the right dACC, which indicated that the positive relationship was significant when the ALLF value of the right dACC was lower, but the positive relationship was not significant when the ALFF value of the right dACC was higher. The modulating roles of right dACC might also reflect that the individuals with higher ALFF value of dACC might experience chronically thwarted relatedness of basic psychological needs, which means the more disturbed by thwarting relatedness information in individuals, the lower positive relationship emerged.
Collapse
Affiliation(s)
- Yujie Chen
- School of Psychology, South China Normal University, Guangzhou, China
- Centre for Studies of Psychological Applications, South China Normal University, Guangzhou, China
- Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China
- Key Laboratory of Brain Cognition and Educational Science, Ministry of Education, South China Normal University, Guangzhou, China
| | - Yanchi Liu
- School of Psychology, South China Normal University, Guangzhou, China
- Centre for Studies of Psychological Applications, South China Normal University, Guangzhou, China
- Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China
- Key Laboratory of Brain Cognition and Educational Science, Ministry of Education, South China Normal University, Guangzhou, China
| | - Yuan Gao
- School of Psychology, South China Normal University, Guangzhou, China
- Centre for Studies of Psychological Applications, South China Normal University, Guangzhou, China
- Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China
- Key Laboratory of Brain Cognition and Educational Science, Ministry of Education, South China Normal University, Guangzhou, China
| | - Xin Wu
- School of Psychology, Xinxiang Medical University, Xinxiang, China
- *Correspondence: Lei Mo
| | - Lei Mo
- School of Psychology, South China Normal University, Guangzhou, China
- Centre for Studies of Psychological Applications, South China Normal University, Guangzhou, China
- Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, China
- Key Laboratory of Brain Cognition and Educational Science, Ministry of Education, South China Normal University, Guangzhou, China
- Xin Wu
| |
Collapse
|
|
41
|
Jackson NA, Jabbi MM. Integrating biobehavioral information to predict mood disorder suicide risk. Brain Behav Immun Health 2022; 24:100495. [PMID: 35990401 PMCID: PMC9388879 DOI: 10.1016/j.bbih.2022.100495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 08/04/2022] [Accepted: 08/05/2022] [Indexed: 11/25/2022] Open
Abstract
The will to live and the ability to maintain one's well-being are crucial for survival. Yet, almost a million people die by suicide globally each year (Aleman and Denys, 2014), making premature deaths due to suicide a significant public health problem (Saxena et al., 2013). The expression of suicidal behaviors is a complex phenotype with documented biological, psychological, clinical, and sociocultural risk factors (Turecki et al., 2019). From a brain disease perspective, suicide is associated with neuroanatomical, neurophysiological, and neurochemical dysregulations of brain networks involved in integrating and contextualizing cognitive and emotional regulatory behaviors. From a symptom perspective, diagnostic measures of dysregulated mood states like major depressive symptoms are associated with over sixty percent of suicide deaths worldwide (Saxena et al., 2013). This paper reviews the neurobiological and clinical phenotypic correlates for mood dysregulations and suicidal phenotypes. We further propose machine learning approaches to integrate neurobiological measures with dysregulated mood symptoms to elucidate the role of inflammatory processes as neurobiological risk factors for suicide.
Collapse
Affiliation(s)
- Nicholas A. Jackson
- Department of Psychiatry and Behavioral Sciences, Dell Medical School, The University of Texas at Austin, USA
- Institute for Neuroscience, The University of Texas at Austin, USA
| | - Mbemba M. Jabbi
- Department of Psychiatry and Behavioral Sciences, Dell Medical School, The University of Texas at Austin, USA
- Mulva Clinics for the Neurosciences
- Institute for Neuroscience, The University of Texas at Austin, USA
- Department of Psychology, The University of Texas at Austin, USA
- Center for Learning and Memory, The University of Texas at Austin, USA
| |
Collapse
|
|
42
|
Park J, Kang Y, Han KM, Tae WS, Kang UB, Chu H, Ham BJ. Association Between the C4 Binding Protein Level and White Matter Integrity in Major Depressive Disorder. Psychiatry Investig 2022; 19:703-711. [PMID: 36202105 PMCID: PMC9536885 DOI: 10.30773/pi.2022.0100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 06/02/2022] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE Considerable evidence suggests that neuroinflammation plays an important role in the pathophysiology of major depressive disorder (MDD). However, the relationship between serum C4 binding protein (C4BP) and white matter (WM) tract integrity in MDD has not been investigated. METHODS We obtained diffusion tensor images of 44 patients with MDD and 44 healthy controls and performed TRActs Constrained by UnderLying Anatomy (TRACULA) analysis to assess WM tract integrity. Serum C4-binding protein alpha chain (C4BPA) and C4- binding protein beta chain (C4BPB) levels were measured and in-between group comparisons were obtained. The correlation between serum C4BP levels and WM tract integrity was examined. RESULTS In comparison to healthy controls, both serum C4BPA and C4BPB were higher in MDD. Also, fractional anisotropy (FA) was increased in the left cingulum-angular bundle (CAB) in MDD, but not healthy controls (HCs). A significant correlation was found between serum C4BP and FA levels in the right cingulum-cingulate gyrus bundle (CCG) in MDD. CONCLUSION This study is the first to investigate the correlation between serum C4BP levels and WM tract integrity in MDD. We identified an increase in WM integrity in the left CAB region in MDD. Furthermore, serum C4BP levels were higher in MDD, and this finding correlated with increased WM integrity in the right CCG region.
Collapse
Affiliation(s)
- Jihoon Park
- Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Youbin Kang
- Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Kyu-Man Han
- Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Woo-Suk Tae
- Brain Convergence Research Center, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Un-Beom Kang
- Bertis R&D Division, Bertis Inc., Seongnam, Republic of Korea
| | - Hyosub Chu
- Bertis R&D Division, Bertis Inc., Seongnam, Republic of Korea
| | - Byung-Joo Ham
- Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
43
|
Lin X, Zhuo S, Liu Z, Fan J, Peng W. Autistic traits heighten sensitivity to rejection-induced social pain. Ann N Y Acad Sci 2022; 1517:286-299. [PMID: 35976662 DOI: 10.1111/nyas.14880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Autistic traits-subclinical forms of characteristics associated with autism spectrum disorders-are associated with poor social interactions and high risks for mental health disorders. We hypothesized that altered sensitivity to social rejection is an important contributor to psychological distress observed among individuals with high autistic traits. Experiment 1 adopted a social-judgment task and compared behavioral and neural activity in response to social rejection between participants exhibiting either high or low autistic traits (HAT and LAT, respectively). Rejection-induced hurt feelings, P3 amplitudes, and θ-oscillation magnitudes were greater in the HAT group than in the LAT group. Mediation analysis indicated that autistic traits heighten rejection-induced social pain through increasing frontal-midline θ-oscillations. Responses to nonsocial feedback in the age-judgment task were comparable, confirming that the between-group differences were specific to social negative feedback. Experiment 2 assessed the association between autistic traits, rejection sensitivity, and psychological distress among randomly recruited participants. Results showed that autistic traits affected depressive/anxious symptomatology partially through heightened rejection sensitivity. Therefore, autistic traits heighten sensitivity to rejection-induced social pain that leads to psychological distress. This finding will help facilitate the development of strategies for coping with social pain and improving mental health for individuals with high autistic traits.
Collapse
Affiliation(s)
- Xinxin Lin
- School of Psychology, Shenzhen University, Shenzhen, China
| | - Shiwei Zhuo
- School of Psychology, Shenzhen University, Shenzhen, China
| | - Zhouan Liu
- School of Psychology, Shenzhen University, Shenzhen, China
| | - Junsong Fan
- School of Psychology, Shenzhen University, Shenzhen, China
| | - Weiwei Peng
- School of Psychology, Shenzhen University, Shenzhen, China
| |
Collapse
|
|
44
|
Pharmacological Strategies for Suicide Prevention Based on the Social Pain Model: A Scoping Review. PSYCH 2022. [DOI: 10.3390/psych4030038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Suicidal behaviour is a public health problem whose magnitude is both substantial and increasing. Since many individuals seek medical treatment following a suicide attempt, strategies aimed at reducing further attempts in this population are a valid and feasible secondary prevention approach. An evaluation of the available evidence suggests that existing treatment approaches have a limited efficacy in this setting, highlighting the need for innovative approaches to suicide prevention. Existing research on the neurobiology of social pain has highlighted the importance of this phenomenon as a risk factor for suicide, and has also yielded several attractive targets for pharmacological strategies that could reduce suicidality in patients with suicidal ideation or a recent attempt. In this paper, the evidence related to these targets is synthesized and critically evaluated. The way in which social pain is related to the “anti-suicidal” properties of recently approved treatments, such as ketamine and psilocybin, is examined. Such strategies may be effective for the short-term reduction in suicidal ideation and behaviour, particularly in cases where social pain is identified as a contributory factor. These pharmacological approaches may be effective regardless of the presence or absence of a specific psychiatric diagnosis, but they require careful evaluation.
Collapse
|
|
45
|
Lucero MM, Satz S, Miceli R, Swartz HA, Manelis A. The effects of mood disorders and childhood trauma on fear of positive and negative evaluation. Acta Psychol (Amst) 2022; 227:103603. [PMID: 35523082 PMCID: PMC9189689 DOI: 10.1016/j.actpsy.2022.103603] [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: 08/23/2021] [Revised: 04/18/2022] [Accepted: 04/26/2022] [Indexed: 11/28/2022] Open
Abstract
Fear of positive and negative evaluation is maladaptive and may result in psychosocial dysfunction. Although being diagnosed with mood disorders or experiencing childhood trauma may potentially affect fear of evaluation, previous studies examined this phenomenon mostly in social anxiety disorders. To fill this gap, we investigated the relationship between childhood trauma and fear of positive and negative evaluation in individuals with bipolar disorder (BD), depressive disorders (DD), and healthy controls (HC). 43 individuals with BD, 89 with DD, and 65 HC completed clinical interviews and self-report assessments. The relationship between participants’ diagnoses and presence of trauma on fear of positive and negative evaluation was examined using ANCOVA. Independently of experiencing childhood trauma, fear of positive evaluation was significantly higher in individuals with mood disorders vs. HC. Fear of negative evaluation was significantly associated with diagnosis-by-trauma interaction. Significantly lower scores were observed in individuals with BD without childhood trauma compared to those with childhood trauma and individuals with DD. Compared to HC, more individuals with mood disorders experienced childhood trauma. While experiencing childhood trauma may increase vulnerability to mood disorders in general, it is especially detrimental for individuals with BD by increasing the risk for developing a fear of negative evaluation.
Collapse
|
|
46
|
Kornienko O, Riis J, Davila M, White NS, Garner PW. Preliminary insights into associations between C-reactive protein and social network dynamics. Psychoneuroendocrinology 2022; 139:105690. [PMID: 35193045 DOI: 10.1016/j.psyneuen.2022.105690] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 02/11/2022] [Accepted: 02/13/2022] [Indexed: 11/19/2022]
Abstract
Recent social psychoneuroimmunology models suggest bidirectional associations between social experiences and the immune system. This work posits that social relationships and networks may influence the functioning of the immune system, but we know little about the role that the immune system plays in how social networks are created and maintained. We examine how salivary C-reactive protein (CRP), as an inflammatory protein, is associated with making new and keeping existing friendship and conflicted relationships among young adult members of a social group. Participants (n = 37; 67.6% female; M age = 18.18 years, 56.81% white/non-Hispanic) provided nominations of friends and individuals with whom they have conflict at wave 1 and two months later at wave 2. At wave 1, in a group setting, participants donated saliva, later assayed for CRP. Stochastic actor-based models revealed that CRP levels were negatively associated with keeping existing friends and positively associated with developing new friendships. We also found that CRP levels were negatively associated with creating new conflicted relationships and predicted an increased likelihood that group members continue conflicted relationships with the focal individual. These preliminary results support the premises of recent social psychoneuroimmunology models by suggesting that inflammation can also serve as a signal to seek new supportive relationships such as friendships and avoid creating new relationships characterized by threat and/or conflict. Findings provide new insights into the theorized function of the immune system for social approach and withdrawal patterns through which our social connections are constructed.
Collapse
Affiliation(s)
- Olga Kornienko
- Department of Psychology, George Mason University, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, USA.
| | - Jenna Riis
- Department of Psychological Science, University of California, Irvine, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, USA.
| | | | | | - Pamela W Garner
- School of Integrative Studies and Human Development and Family Science, George Mason University, USA.
| |
Collapse
|
|
47
|
A cross-sectional healthy-control study of serum inflammatory biomarkers interleukin (IL)-1B and IL-2R in panic disorder patients and their offspring. J Psychiatr Res 2022; 149:260-264. [PMID: 35303615 DOI: 10.1016/j.jpsychires.2022.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 03/02/2022] [Accepted: 03/04/2022] [Indexed: 01/13/2023]
Abstract
Alterations in the immune system have been associated with a variety of mental illnesses. An increase in circulating inflammatory cytokines is observed not only in people with mental disorders but also in their first-degree relatives. A considerable amount of data support the link between immune system activation and panic disorder (PD) pathogenesis, while it is still unclear whether differential immunological reactivity represents a propensity, a measure of disease activity, or both. To better understand the role of cytokines in PD pathophysiology, we compared the levels of serum inflammatory biomarkers interleukin (IL)-1B and IL-2R among PD patients, offspring of PD patients and healthy controls. The offspring of PD patients were evaluated by a psychiatrist and were considered unaffected by any mental disorder at the time of the evaluation. Concentrations of the cytokines IL-1B and IL-2R were assessed using the Immulite System (Diagnostic Products Corporation). The levels of proinflammatory markers IL-1B and IL-2R were increased in PD patients compared to those of controls, but offspring of PD patients and healthy controls demonstrated no differences regarding peripheral interleukin levels. Our findings suggest that interleukins might represent a disease-dependent marker in PD.
Collapse
|
|
48
|
Rudzki S. Is PTSD an Evolutionary Survival Adaptation Initiated by Unrestrained Cytokine Signaling and Maintained by Epigenetic Change? Mil Med 2022; 188:usac095. [PMID: 35446412 DOI: 10.1093/milmed/usac095] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 03/01/2022] [Accepted: 03/24/2022] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Treatment outcomes for PTSD with current psychological therapies are poor, with very few patients achieving sustained symptom remission. A number of authors have identified physiological and immune disturbances in Post Traumatic Stress Disorder (PTSD) patients, but there is no unifying hypothesis that explains the myriad features of the disorder. MATERIALS AND METHODS The medical literature was reviewed over a 6-year period primarily using the medical database PUBMED. RESULTS The literature contains numerous papers that have identified a range of physiological and immune dysfunction in association with PTSD. This paper proposes that unrestrained cytokine signaling induces epigenetic changes that promote an evolutionary survival adaptation, which maintains a defensive PTSD phenotype. The brain can associate immune signaling with past threat and initiate a defensive behavioral response. The sympathetic nervous system is pro-inflammatory, while the parasympathetic nervous system is anti-inflammatory. Prolonged cholinergic withdrawal will promote a chronic inflammatory state. The innate immune cytokine IL-1β has pleiotropic properties and can regulate autonomic, glucocorticoid, and glutamate receptor functions, sleep, memory, and epigenetic enzymes. Changes in epigenetic enzyme activity can potentially alter phenotype and induce an adaptation. Levels of IL-1β correlate with severity and duration of PTSD and PTSD can be prevented by bolus administration of hydrocortisone in acute sepsis, consistent with unrestrained inflammation being a risk factor for PTSD. The nervous and immune systems engage in crosstalk, governed by common receptors. The benefits of currently used psychiatric medication may arise from immune, as well as synaptic, modulation. The psychedelic drugs (3,4-Methylenedioxymethamphetamine (MDMA), psilocybin, and ketamine) have potent immunosuppressive and anti-inflammatory effects on the adaptive immune system, which may contribute to their reported benefit in PTSD. There may be distinct PTSD phenotypes induced by innate and adaptive cytokine signaling. CONCLUSION In order for an organism to survive, it must adapt to its environment. Cytokines signal danger to the brain and can induce epigenetic changes that result in a persistent defensive phenotype. PTSD may be the price individuals pay for the genomic flexibility that promotes adaptation and survival.
Collapse
Affiliation(s)
- Stephan Rudzki
- Canberra Sports Medicine, Deakin, Australian Capital Territory 2600, Australia
| |
Collapse
|
|
49
|
Cytokine profile in drug-naïve panic disorder patients. Transl Psychiatry 2022; 12:75. [PMID: 35194013 PMCID: PMC8863842 DOI: 10.1038/s41398-022-01835-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 01/31/2022] [Accepted: 02/03/2022] [Indexed: 12/20/2022] Open
Abstract
Although accumulating evidence suggests that inflammatory processes play a role in the pathophysiology of mental disorders, few studies have investigated this matter in panic disorder (PD). Furthermore, no studies to date have evaluated cytokine levels in drug-naïve patients with PD. Therefore, little is known about the presence of inflammation at the onset of this disorder. The aim of the present study was to determine the levels of the proinflammatory interleukins IL-1B and IL-2R and the anti-inflammatory cytokine IL-10 in drug-naïve PD patients. Analysis of serum chemokine levels revealed increased proinflammatory activity in the early phase of PD through increased IL-2R and IL-1B levels and a decrease in IL-10 levels in drug-naïve PD patients compared to matched healthy controls. Neurotransmitters and neurocircuits that are targets of inflammatory responses are discussed, followed by an examination of brain-immune interactions as risk factors for PD. This study is the first to identify a proinflammatory cytokine response in drug-naïve PD subjects. These findings indicate that treatments targeting proinflammatory markers may ameliorate anxiety symptoms in PD patients.
Collapse
|
|
50
|
Zhang Y, Jiang S, Liao F, Huang Z, Yang X, Zou Y, He X, Guo Q, Huang C. A transcriptomic analysis of neuropathic pain in the anterior cingulate cortex after nerve injury. Bioengineered 2022; 13:2058-2075. [PMID: 35030976 PMCID: PMC8973654 DOI: 10.1080/21655979.2021.2021710] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
The anterior cingulate cortex (ACC) is a core brain region processing pain emotion. In this study, we performed RNA sequencing analysis to reveal transcriptomic profiles of the ACC in a rat chronic constriction injury (CCI) model. A total of 1628 differentially expressed genes (DEGs) were identified by comparing sham-operated rats with rats of 12 hours, 1, 3, 7, and 14 days after surgery, respectively. Although these inflammatory-related DEGs were generally increased after CCI, different kinetics of time-series expression were observed with the development of neuropathic pain affection. Specifically, the expression of Ccl5, Cxcl9 and Cxcl13 continued to increase following CCI. The expression of Ccl2, Ccl3, Ccl4, Ccl6, and Ccl7 were initially upregulated after CCI and subsequently decreased after 12 hours. Similarly, the expression of Rac2, Cd68, Icam-1, Ptprc, Itgb2, and Fcgr2b increased after 12 hours but reduced after 1 day. However, the expression of the above genes increased again 7 days after CCI, when the neuropathic pain affection had developed. Furthermore, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment and interaction network analyses further showed a high connectivity degree among these chemokine targeting genes. Similar expressional changes in these genes were found in the rat spinal dorsal horn responsible for nociception processing. Taken together, our results indicated chemokines and their targeting genes in the ACC may be differentially involved in the initiation and maintenance of neuropathic pain affection. These genes may be a target for not only the nociception but also the pain affection following nerve injury.
Collapse
Affiliation(s)
- Yu Zhang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Shiwei Jiang
- Medical College of Xiangya, Central South University, Changsha, China
| | - Fei Liao
- Department of Anesthesiology, People's Hospital of Yuxi City, Yuxi, China
| | - Zhifeng Huang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Xin Yang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Yu Zou
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Xin He
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Qulian Guo
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Changsheng Huang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|