Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06337539
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-29
First Post:
2024-02-27
Brief Title:
Precision Psychiatry for Depression Immune Response and Affective Symptoms as Predictors of Response to Antidepressants
Sponsor:
Germans Trias i Pujol Hospital
Organization:
Germans Trias i Pujol Hospital
Study Overview
Official Title:
Precision Psychiatry for Depression Immune Response and Affective Symptoms as Predictors of Response to Antidepressants
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LYMPHODEP
Brief Summary:
Objectives To identify in patients with major depression different peripheral markers of neuroinflammation in relation to affective symptoms anxiety depression irritability fatigue and cognitive symptoms and its relationship with the response to antidepressant treatment with selective serotonin reuptake inhibitors SSRIs
Methodology This is a prospective observational cohort study in patients with major depression naturally subjected to treatment with SSRIs For this 30 patients with major depression attended in the Outpatient Psychiatry Consultations will be selected All of them will be evaluated at baseline and after 3 months of treatment collecting demographic and clinical variables Diagnostic and Statistical Manual of Mental Disorders 5th edition DSM-5 psychiatric diagnoses psychopathological scales and immunological and biochemical variables The correlation between immunological markers and affective and cognitive symptoms at baseline as well as their variation with treatment will be analyzed A group of 20 healthy subjects will be used as a control group
Subsequently a bivariate comparative analysis will be carried out where the statistically significant or marginally significant variables associated with psychopathological variables will be used to build a multivariate binary logistic regression model
Methodology This is a prospective observational cohort study in patients with major depression naturally subjected to treatment with SSRIs For this 30 patients with major depression attended in the Outpatient Psychiatry Consultations will be selected All of them will be evaluated at baseline and after 3 months of treatment collecting demographic and clinical variables Diagnostic and Statistical Manual of Mental Disorders 5th edition DSM-5 psychiatric diagnoses psychopathological scales and immunological and biochemical variables The correlation between immunological markers and affective and cognitive symptoms at baseline as well as their variation with treatment will be analyzed A group of 20 healthy subjects will be used as a control group
Subsequently a bivariate comparative analysis will be carried out where the statistically significant or marginally significant variables associated with psychopathological variables will be used to build a multivariate binary logistic regression model
Detailed Description:
Depression is the mental disorder that has the highest prevalence affecting approximately 16 of the general population and having a great impact on the global functionality of patients According to the World Health Organization WHO depression will be considered the main cause of disability in 2030 At the end of the last century a large part of the studies on the neurobiological bases of depression evolved from the monoaminergic hypothesis This theory proposes that the etiopathogenesis of depression would be directly related to a reduction in monoaminergic activity noradrenergic serotonergic or both in the central nervous system CNS From there it was postulated that the antidepressant action of various drugs could be due to an enhancement of neurotransmission as a consequence of the increase in the concentration of monoamines at the level of the synaptic space This monoaminergic hypothesis however does not answer some important questions such as what causes these monoaminergic alterations Or how do we explain the existence of 30 of patients refractory to antidepressant treatment For this reason there has been growing interest in recent years in other theories that focus on the immune and endocrine systems
The immune system and the nervous system share the functions of recognizing objects discerning their qualities and generating an adaptive response related to them The inflammatory reflex innate immunity depends on the detection of specific molecular patterns in invaders but not expressed by own tissues One of the first observations on the relationship of the innate immune system to the CNS was the increase in blood concentrations of inflammatory biological markers such as C-reactive protein CRP and fibrinogen in patients with depression Since then and especially in the field of major depression there is a growing body of literature supporting its link with inflammation frequent comorbidity with inflammatory diseases such as coronary heart disease or rheumatoid arthritis presence of elevated levels of proinflammatory cytokines potential of exogenous proinflammatory cytokines to induce depressive symptoms the association of levels of peripheral markers of inflammation with the severity of depression potential of antidepressants to inhibit inflammation antidepressant effects of anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs NSAIDs etc In addition to proinflammatory molecules alterations in the levels of lymphocyte subpopulations such as T helper type 17 Th17 or T regulatory cells Treg have recently been characterized in patients with major depression that could be related to the neuroinflammatory process
The impact of inflammation on behavior however is not only associated with depression itself but with specific dimensions of symptoms such as alterations in motivation and motor activity fatigue psychomotor impairment and with greater sensitivity to the threat anxiety arousal alarm
The results of this project will contribute first of all to a better understanding of the immunological aspects of depressive processes which will favor the possibility of developing new targets for future treatments of this disease Secondly the results will help identify biological and clinical markers that predict response to antidepressant treatment
Hypothesis
1 The combination of immune response biomarkers acute phase inflammation cytokines hypothalamic-pituitary-adrenal HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis symptoms of positive and negative valence systems of Research Domain Criteria RDoC depression anhedonia fatigue anxiety and cognitive dysfunction allows to establish a prediction about the response to treatment with SSRI antidepressants in patients with major depression
2 Symptoms included in RDoC positive and negative valence systems depression anhedonia fatigue anxiety as well as cognitive dysfunction are positively related to biomarkers of acute phase inflammation proinflammatory cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes and negatively related to biomarkers of anti-inflammatory cytokines Treg and neurogenesis in patients with major depression compared to healthy controls
3 The improvement of symptoms included in the positive and negative valence systems of RDoC depression anhedonia fatigue anxiety as well as cognitive dysfunction after antidepressant treatment with SSRIs are related to the reduction of biomarkers of acute phase inflammation proinflammatory cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes and increased anti-inflammatory cytokines Treg and neurogenesis
Primary Objective
1 To assess the combination of immune response biomarkers acute phase inflammation cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis symptoms of positive and negative valence systems of RDoC depression anhedonia fatigue anxiety and cognitive dysfunction as predictors of response to SSRI antidepressant treatment in patients with major depression
Secondary Objectives
2 To evaluate the relationship between biomarkers of immune response acute phase inflammation cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis and symptoms of the positive and negative valence systems of RDoC depression anhedonia fatigue anxiety and cognitive dysfunction in patients with major depression compared to healthy controls
3 To evaluate the relationship between biomarkers of immune response acute phase inflammation cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis and symptoms of the positive and negative valence systems of RDoC depression anhedonia fatigue anxiety and cognitive dysfunction in patients with major depression in relation to response to treatment
4 To define the phenotype and transcriptome of the lymphocyte subpopulations of patients with major depression before and after treatment
5 To evaluate the kinetics of the lymphocyte subpopulations of patients with major depression at different times of treatment
The immune system and the nervous system share the functions of recognizing objects discerning their qualities and generating an adaptive response related to them The inflammatory reflex innate immunity depends on the detection of specific molecular patterns in invaders but not expressed by own tissues One of the first observations on the relationship of the innate immune system to the CNS was the increase in blood concentrations of inflammatory biological markers such as C-reactive protein CRP and fibrinogen in patients with depression Since then and especially in the field of major depression there is a growing body of literature supporting its link with inflammation frequent comorbidity with inflammatory diseases such as coronary heart disease or rheumatoid arthritis presence of elevated levels of proinflammatory cytokines potential of exogenous proinflammatory cytokines to induce depressive symptoms the association of levels of peripheral markers of inflammation with the severity of depression potential of antidepressants to inhibit inflammation antidepressant effects of anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs NSAIDs etc In addition to proinflammatory molecules alterations in the levels of lymphocyte subpopulations such as T helper type 17 Th17 or T regulatory cells Treg have recently been characterized in patients with major depression that could be related to the neuroinflammatory process
The impact of inflammation on behavior however is not only associated with depression itself but with specific dimensions of symptoms such as alterations in motivation and motor activity fatigue psychomotor impairment and with greater sensitivity to the threat anxiety arousal alarm
The results of this project will contribute first of all to a better understanding of the immunological aspects of depressive processes which will favor the possibility of developing new targets for future treatments of this disease Secondly the results will help identify biological and clinical markers that predict response to antidepressant treatment
Hypothesis
1 The combination of immune response biomarkers acute phase inflammation cytokines hypothalamic-pituitary-adrenal HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis symptoms of positive and negative valence systems of Research Domain Criteria RDoC depression anhedonia fatigue anxiety and cognitive dysfunction allows to establish a prediction about the response to treatment with SSRI antidepressants in patients with major depression
2 Symptoms included in RDoC positive and negative valence systems depression anhedonia fatigue anxiety as well as cognitive dysfunction are positively related to biomarkers of acute phase inflammation proinflammatory cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes and negatively related to biomarkers of anti-inflammatory cytokines Treg and neurogenesis in patients with major depression compared to healthy controls
3 The improvement of symptoms included in the positive and negative valence systems of RDoC depression anhedonia fatigue anxiety as well as cognitive dysfunction after antidepressant treatment with SSRIs are related to the reduction of biomarkers of acute phase inflammation proinflammatory cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes and increased anti-inflammatory cytokines Treg and neurogenesis
Primary Objective
1 To assess the combination of immune response biomarkers acute phase inflammation cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis symptoms of positive and negative valence systems of RDoC depression anhedonia fatigue anxiety and cognitive dysfunction as predictors of response to SSRI antidepressant treatment in patients with major depression
Secondary Objectives
2 To evaluate the relationship between biomarkers of immune response acute phase inflammation cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis and symptoms of the positive and negative valence systems of RDoC depression anhedonia fatigue anxiety and cognitive dysfunction in patients with major depression compared to healthy controls
3 To evaluate the relationship between biomarkers of immune response acute phase inflammation cytokines HPA axis oxidative and nitrosative stress activation of microglia and Th17 and Tγδ17 lymphocytes Treg and neurogenesis and symptoms of the positive and negative valence systems of RDoC depression anhedonia fatigue anxiety and cognitive dysfunction in patients with major depression in relation to response to treatment
4 To define the phenotype and transcriptome of the lymphocyte subpopulations of patients with major depression before and after treatment
5 To evaluate the kinetics of the lymphocyte subpopulations of patients with major depression at different times of treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None