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

Schizophrenia Clinical Trial

— SCHIZO'TRAUMA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03355781
• Other study ID #: 1608039
• Secondary ID: 2017-A00408-45
• Status: Completed
• Start date: November 14, 2018
• Est. completion date: November 30, 2023

Study information

• Verified date: January 2024
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: November 30, 2023
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Device:
• magnetic resonance imaging (MRI)
brain imaging : structural anatomy, emotional congruence, anatomic connectivity, functional connectivity

Procedure:
• Blood sample
27,5 ml of blood sample : genetic analysis and biobank

Other:
• Clinical psychiatric evaluation
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)

Locations

Country	Name	City	State
France	CHU de Saint Etienne	Saint-Étienne

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Quantitative measurement of RNAs	development of an etiopathogenic model characteristic of schizophrenia	5 days
Primary	Voxel-based morphometry (VBM) for total gray matter	development of an etiopathogenic model characteristic of schizophrenia	5 days
Primary	Voxel-based morphometry (VBM) for regional gray matter density.	development of an etiopathogenic model characteristic of schizophrenia	5 days
Secondary	Connectivity in the cortico-limbic circuit		5 days
Secondary	Volumetry of the brain		5 days
Secondary	Correlation of BOLD activity in the cortico-limbic circuit in patients with patients with symptomatic variables	symptomatic variables : PANSS scale	5 days
Secondary	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
Secondary	Correlation of BOLD activity in the cortico-limbic circuit with personality characteristics	personality characteristics : EPQ-R scale, SPQ scale	5 days
Secondary	Correlation of BOLD activity in the cortico-limbic circuit with history of trauma in childhood	history of trauma in childhood : CTQ scale	5 days