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CompletedNCT03355781SCHIZO'TRAUMAUpdated Jan 17, 2024

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

An observational study in Schizophrenia, sponsored by Centre Hospitalier Universitaire de Saint Etienne. Completed at 1 site in France. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-01-17.

Sponsored by Centre Hospitalier Universitaire de Saint Etienne · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
78
Ages
18 Years to 50 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Schizophrenia

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Keywords

  • childhood trauma
  • candidate gene expression
  • cerebral morphology
  • schizophrenic symptomatology
  • conceptual framework of stress vulnerability
03

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Schizophrenic patients, related volunteers (first degree relative of patient) and healthy volunteers

Eligibility criteria

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

04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
78 participants (actual)
Patient registry
No

Groups and cohorts

  • Schizophrenic patients

    Patients will have clinical psychiatric evaluation, brain imaging and blood sample

    Device: magnetic resonance imaging (MRI) · Procedure: Blood sample · Other: Clinical psychiatric evaluation

  • Related volunteers (first degree relative of patient)

    Related volunteers will have clinical psychiatric evaluation, brain imaging and blood sample

    Device: magnetic resonance imaging (MRI) · Procedure: Blood sample · Other: Clinical psychiatric evaluation

  • Healthy volunteers

    Healthy volunteers will have clinical psychiatric evaluation, brain imaging and blood sample

    Device: magnetic resonance imaging (MRI) · Procedure: Blood sample · Other: Clinical psychiatric evaluation

Interventions

  • Devicemagnetic resonance imaging (MRI)

    brain imaging : structural anatomy, emotional congruence, anatomic connectivity, functional connectivity

  • ProcedureBlood sample

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

  • OtherClinical 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)

05

What researchers measure

Primary outcomes

  1. 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 : 1. Emotional neglect 2. physical abuse 3. emotional abuse 4. physical neglect 5. sexual abuse Each item being rated in 5 answer choice from 1 to 5 (never, rarely, sometimes, often or very often)

    Time frame: 5 days

  2. Quantitative measurement of RNAs

    development of an etiopathogenic model characteristic of schizophrenia

    Time frame: 5 days

  3. Voxel-based morphometry (VBM) for total gray matter

    development of an etiopathogenic model characteristic of schizophrenia

    Time frame: 5 days

  4. Voxel-based morphometry (VBM) for regional gray matter density.

    development of an etiopathogenic model characteristic of schizophrenia

    Time frame: 5 days

Secondary outcomes

  1. Connectivity in the cortico-limbic circuit

    Time frame: 5 days

  2. Volumetry of the brain

    Time frame: 5 days

  3. Correlation of BOLD activity in the cortico-limbic circuit in patients with patients with symptomatic variables

    symptomatic variables : PANSS scale

    Time frame: 5 days

  4. 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

    Time frame: 5 days

  5. Correlation of BOLD activity in the cortico-limbic circuit with personality characteristics

    personality characteristics : EPQ-R scale, SPQ scale

    Time frame: 5 days

  6. Correlation of BOLD activity in the cortico-limbic circuit with history of trauma in childhood

    history of trauma in childhood : CTQ scale

    Time frame: 5 days

06

Study locations

1 site
  • CHU de Saint Etienne
    Saint-Étienne, 42055, France
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03355781
Lead sponsor
Centre Hospitalier Universitaire de Saint Etienne
Responsible party
Sponsor
First posted
Nov 28, 2017
Start date
Nov 14, 2018
Primary completion
Nov 30, 2023
Completion
Nov 30, 2023
Last update
Jan 17, 2024

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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