Childhood Trauma in Schizophrenia: Exploration of Links Between Gene Expression, Cerebral Morphology and Symptomatology

Study Overview
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Brief Summary
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Childhood trauma is known as a vulnerability factor in schizophrenia. In healthy volunteers, these adversities are linked to a decrease of grey matter of the brain, similar to those observed in schizophrenia. In a previous study based on Voxel-Based Morphometry (VBM), including 21 schizophrenic patients and 30 healthy volunteers, the investigators shown a negative correlation between emotional neglect (important dimension in childhood trauma) and grey matter decrease. This strong correlation was significantly higher in schizophrenic patients than in healthy volunteers, suggesting a higher genetic predisposition to environmental factors in schizophrenic people. Currently, interaction between genetic predisposition and environmental stress factors is the major model for understanding in schizophrenia. In order to analyze both effects on human body, particularly on brain, several studies currently focus on the product of genetic expression, the ribonucleic acid (ARN). The purpose of this study is to provide an explanatory model of links between childhood trauma, candidate gene for schizophrenia expression, cerebral morphology and schizophrenic symptomatology. Using conceptual framework of stress vulnerability, structural equation modeling (SEM) will allow testing causal link between these different variables.

Official Title
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Childhood Trauma in Schizophrenia: Exploration of Links Between Gene Expression, Cerebral Morphology and Symptomatology. SCHIZO' TRAUMA

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: magnetic resonance imaging (MRI)
* Procedure: Blood sample
* Other: Clinical psychiatric evaluation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria of patients : For women with reproductively active age period: suitable contraceptive method and negative pregnancy test Schizophrenia diagnosis (according to DSM 5) Regular follow-up care at hospital No change in antipsychotic medication (medication AND dosage) within at least six weeks Patient into remission : constant dosage, out-patient and meeting Andreassen criteria Who have given their informed consent before participating in the study. Physical examination without significant clinical physical anomaly No serious somatic pathology Affiliates or entitled to a social security scheme Exclusion Criteria of patients : For women with reproductively active age period: no suitable contraceptive method (oral, hormonal, intramuscular, intrauterine device, or surgical) Pregnancy or breastfeeding Not meeting schizophrenic criteria according to DSM 5 or presenting resistant schizophrenic criteria according Kane criteria Presenting a serious somatic disorder or neurological (particularly Parkinson disease, epilepsy, tardive dyskinesia) Cardiovascular, hepatic or serious renal diseases Contraindication to MRI examination, particularly ocular or intracranial metallic foreign object,pacemaker, artificial heart valve, surgical clip Claustrophobia, significant tatoo in the high part of the body, IUD incompatible with MRI 3Tesla Alcohol or drug addiction, within the last year Recruited in other clinical trial or exclusion period from previous trial. Susceptibility to self-harm behaviour according to investigator Inclusion Criteria of Related volunteers : Age, gender and socio-educational level similar to recruited patients Who have given their informed consent before participating in the study. First degree relative of schizophrenic patient diagnosed according DSM IV criteria No schizophrenia diagnosis according DSM IV criteria No psychiatric history and free of psychotropic drugs/treatment Physical examination without significant clinical anomaly Affiliates or entitled to a social security scheme Exclusion Criteria of Related volunteers : For women with reproductively active age period: no suitable contraceptive method (oral, hormonal, intramuscular, intrauterine device, or surgical) Pregnancy or breastfeeding Presenting somatic, neurological or psychiatric disorder Alcohol or drug addiction, within the last year Recruited in other clinical trial or exclusion period from previous trial. Contraindication to MRI examination, particularly ocular or intracranial metallic foreign object, pacemaker, artificial heart valve, surgical clip Claustrophobia, significant tatoo in the high part of the body, IUD incompatible with MRI 3Tesla Inclusion Criteria of Healthy volunteers : Age, gender and socio-educational level similar to recruited patients Who have given their informed consent before participating in the study. No schizophrenia diagnosis according DSM IV criteria No personal or family history of psychiatric disorders Free of psychotropic drugs/treatment Physical examination without significant clinical anomaly Affiliates or entitled to a social security scheme Exclusion Criteria of Healthy volunteers : Beside the absence of schizophrenia diagnosis, healthy volunteers should meet the same exclusion criteria as patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Schizophrenic patients<br>Patients will have clinical psychiatric evaluation, brain imaging and blood sample | Device: magnetic resonance imaging (MRI)<br>* brain imaging : structural anatomy, emotional congruence, anatomic connectivity, functional connectivity<br>Procedure: Blood sample<br>* 27,5 ml of blood sample : genetic analysis and biobank<br>Other: Clinical psychiatric evaluation<br>* Global Assessment Scale(GAS),Mini International Neuropsychiatric Interview(MINI),Positive and Negative Symptoms Scale(PANSS),Family Interview for Genetic Studies(FIGS),Calgary Depression Scale for Schizophrenia(CDSS),extrapyramidal side effects evaluation or Simpson-Angus scale evaluation(ESRS),Apathy Evaluation Scale(AES-C),State-Trait Anxiety Inventory(STAI),Beck Depression Inventory(BDI-13),Eysenck Personality Questionnaire-Revised(EPQ-R),Assessment of Schizotypal Personality(SPQ),Emotion Regulation Questionnaire(ERQ),Emotional Reactivity Scale(ERS),Toronto Alexithymia Scale(TAS-20),social anhedonia scale(SAS),Childhood Trauma Questionnaire(CTQ),Clinical-administered Post Traumatic Stress Disorder Scale(CAPS),Wechsler Adult Intelligence Scale(WAIS-III),Trail Making Test(TMT),Pen and paper visuospatial working memory(DOT-test),impulsivity test(GoStop),Stroop test,National Adult Reading Test(NART),Wechsler Adult Intelligence Scale(WAIS-III),Facial Emotion Recognition task(FER)<br>|
| Related volunteers (first degree relative of patient)<br>Related volunteers will have clinical psychiatric evaluation, brain imaging and blood sample | Device: magnetic resonance imaging (MRI)<br>* brain imaging : structural anatomy, emotional congruence, anatomic connectivity, functional connectivity<br>Procedure: Blood sample<br>* 27,5 ml of blood sample : genetic analysis and biobank<br>Other: Clinical psychiatric evaluation<br>* Global Assessment Scale(GAS),Mini International Neuropsychiatric Interview(MINI),Positive and Negative Symptoms Scale(PANSS),Family Interview for Genetic Studies(FIGS),Calgary Depression Scale for Schizophrenia(CDSS),extrapyramidal side effects evaluation or Simpson-Angus scale evaluation(ESRS),Apathy Evaluation Scale(AES-C),State-Trait Anxiety Inventory(STAI),Beck Depression Inventory(BDI-13),Eysenck Personality Questionnaire-Revised(EPQ-R),Assessment of Schizotypal Personality(SPQ),Emotion Regulation Questionnaire(ERQ),Emotional Reactivity Scale(ERS),Toronto Alexithymia Scale(TAS-20),social anhedonia scale(SAS),Childhood Trauma Questionnaire(CTQ),Clinical-administered Post Traumatic Stress Disorder Scale(CAPS),Wechsler Adult Intelligence Scale(WAIS-III),Trail Making Test(TMT),Pen and paper visuospatial working memory(DOT-test),impulsivity test(GoStop),Stroop test,National Adult Reading Test(NART),Wechsler Adult Intelligence Scale(WAIS-III),Facial Emotion Recognition task(FER)<br>|
| Healthy volunteers<br>Healthy volunteers will have clinical psychiatric evaluation, brain imaging and blood sample | Device: magnetic resonance imaging (MRI)<br>* brain imaging : structural anatomy, emotional congruence, anatomic connectivity, functional connectivity<br>Procedure: Blood sample<br>* 27,5 ml of blood sample : genetic analysis and biobank<br>Other: Clinical psychiatric evaluation<br>* Global Assessment Scale(GAS),Mini International Neuropsychiatric Interview(MINI),Positive and Negative Symptoms Scale(PANSS),Family Interview for Genetic Studies(FIGS),Calgary Depression Scale for Schizophrenia(CDSS),extrapyramidal side effects evaluation or Simpson-Angus scale evaluation(ESRS),Apathy Evaluation Scale(AES-C),State-Trait Anxiety Inventory(STAI),Beck Depression Inventory(BDI-13),Eysenck Personality Questionnaire-Revised(EPQ-R),Assessment of Schizotypal Personality(SPQ),Emotion Regulation Questionnaire(ERQ),Emotional Reactivity Scale(ERS),Toronto Alexithymia Scale(TAS-20),social anhedonia scale(SAS),Childhood Trauma Questionnaire(CTQ),Clinical-administered Post Traumatic Stress Disorder Scale(CAPS),Wechsler Adult Intelligence Scale(WAIS-III),Trail Making Test(TMT),Pen and paper visuospatial working memory(DOT-test),impulsivity test(GoStop),Stroop test,National Adult Reading Test(NART),Wechsler Adult Intelligence Scale(WAIS-III),Facial Emotion Recognition task(FER)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Childhood Trauma Questionnaire (CTQ) for childhood trauma. | development of an etiopathogenic model characteristic of schizophrenia Childhood Trauma Questionnaire : to assess five types of childhood trauma : Emotional neglect physical abuse emotional abuse physical neglect sexual abuse Each item being rated in 5 answer choice from 1 to 5 (never, rarely, sometimes, often or very often) | 5 days | 
| Quantitative measurement of RNAs | development of an etiopathogenic model characteristic of schizophrenia | 5 days | 
| Voxel-based morphometry (VBM) for total gray matter | development of an etiopathogenic model characteristic of schizophrenia | 5 days | 
| Voxel-based morphometry (VBM) for regional gray matter density. | development of an etiopathogenic model characteristic of schizophrenia | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Connectivity in the cortico-limbic circuit |  | 5 days | 
| Volumetry of the brain |  | 5 days | 
| Correlation of BOLD activity in the cortico-limbic circuit in patients with patients with symptomatic variables | symptomatic variables : PANSS scale | 5 days | 
| Correlation of BOLD activity in the cortico-limbic circuit with emotional variables | emotional variables : ERS scale, ERQ scale, TAS-20 scale, SAS scale, AES-C scale | 5 days | 
| Correlation of BOLD activity in the cortico-limbic circuit with personality characteristics | personality characteristics : EPQ-R scale, SPQ scale | 5 days | 
| Correlation of BOLD activity in the cortico-limbic circuit with history of trauma in childhood | history of trauma in childhood : CTQ scale | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood trauma, candidate gene expression, cerebral morphology, schizophrenic symptomatology, conceptual framework of stress vulnerability