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

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

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.

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