Bipolar Disorder (BD), Catatonia, Obsessive Compulsive Disorder (OCD), Schizophrenia, Treatment Resistant Depression (TRD)
Conditions
Keywords
biomarkers, treatment resistance, response prediction
Brief summary
The disruption of immune system is a key candidate in the pathogenesis of psychiatric disorders, especially those resistant to traditional treatments. Involving complex processes within the brain and peripheral immune system, inflammation may lead to imbalance of neurotransmitter systems and synaptic plasticity and directly contribute to the psychiatric symptoms observed in conditions such as depression, bipolar disorder (BD) and schizophrenia (SCZ). Studies show that treatment-resistant depression (TRD) is associated with elevated levels of inflammatory markers in the blood, which are linked to a lower response to conventional antidepressants. Interventions that modulate this inflammatory response, such as immunomodulatory treatments or therapies targeting pro-inflammatory cytokines, have demonstrated beneficial effects by reducing symptoms and improving patients' quality of life. A thorough understanding of the links between inflammation and treatment resistance therefore paves the way for innovative therapeutic strategies. These approaches could transform current practices by offering more personalized and effective solutions for patients suffering from chronic and resistant psychiatric disorders.
Interventions
BIOLOGICALBlood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales
the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin
Sponsors
Centre Hospitalier St Anne
GHU Paris Psychiatry & Neurosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Single-center, ambispective, non-randomized, non-controlled study. Exploratory study investigating biomarkers of treatment resistance in adult patients with psychiatric disorders. Patients will be divided into 5 cohorts.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient aged ≥ 18 years old; * Patient suffering from a psychiatric disorder according to DSM-5 criteria; * Patient with drug-resistant disease according to the definition of the protocol * Patient starting a new treatment for his pathology; * Patient informed and having signed an informed consent; * Patient covered by the social security system.
Exclusion criteria
* Patient with major neurocognitive disorder diagnosed (dementia syndrome) * Pregnant, laboring, or breastfeeding female patients * Patient deprived of liberty by judicial or administrative decision. Patient in psychiatric care under constraints may be included. * For patients accepting the lumbar punction: patients who are unable to control themselves and are likely to engage in physical or violent behavior.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3) | Up to 10 weeks | Changes in Positive and Negative Syndrome Scale (PANSS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for Schizophrenia patients. The minimal score is 30. The maximal score is 210. |
| Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3). | Up to 10 weeks | Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : White blood cells, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets in G/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in CRPus from inclusion (V1) to Day 2 (V2) | From enrollment to Day 2 | Variation in CRPus between inclusion (V1) and Day 2 (V2) in mg/L. |
| Changes in immunity markers from inclusion (V1) to Day 2 (V2) | From enrollment to Day 2 | Variation in IL-1β, IL-6, and IL-18 between inclusion (V1) and Day 2 (V2) in pg/mL. |
| Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2) | From enrollment to Day 2 | Changes in Bush-Francis Catatonia Rating Scale (BFCRS) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for catatonia. The minimal score is 0 mm. The maximal score is 69. |
| Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores | through study completion, an average of 2 years | Changes in Positive and Negative Syndrome Scale (PANSS) scores between inclusion (V1) and the end of study EOS (M24). The scale will be used to assess disease severity for Schizophrenia patients. The minimal score is 30. The maximal score is 210. |
| Changes from inclusion (V1) to end of study (M24) in CBC components | through study completion, an average of 2 years | Variation in Complete Blood Count components between inclusion (V1) and End Of Study (M24) : White blood cells, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets in G/L. |
| Changes from inclusion (V1) to end of study (M24) in Folates, Vitamin B6, Vitamin B1, Vitamin D | through study completion, an average of 2 years | Changes in biological parameters measured between inclusion (V1) and the End Of Study (M24). The dosages are : Folates, Vitamins B1, B6, D in nmol/L. |
| Changes from inclusion (V1) to end of study (M24) in Vitamin B12 | through study completion, an average of 2 years | Changes in Vitamin B12 measured between inclusion (V1) and the End Of Study (M24) in pg/mL. |
| Changes from inclusion (V1) to end of study (M24) in TSH, prolactin | through study completion, an average of 2 years | Changes in biological parameters measured between inclusion (V1) and End Of Study (M24). The dosages are : TSH, prolactin in mUI/L |
| Changes from inclusion (V1) to end of study (M24) in drug dosage | through study completion, an average of 2 years | Variation in drug dosage between inclusion (V1) and End Of Study (M24). Unit could be different according to the drug. |
| Changes from inclusion in levels of pro-inflammatory cytokines and other immune biomarkers in cerebrospinal fluid, skin biopsies and/or stool, at end of acute treatment (V3), 6-month follow-up (V4), 12-month follow-up (V5) and 24-month follow-up (V6) | At inclusion (V1), 10 weeks, 6 months-, 12 months- and 24 months after end of acute treatment | Change in levels of pro-inflammatory cytokines and other immune biomarkers in other biological samples (cerebrospinal fluid (CSF), skin biopsies, stool) between inclusion (V1) , end of acute treatment (V3), 6-month follow-up (V4), 12-month follow-up (V5) and 24-month follow-up (V6). This will enable direct assessment of the efficacy of interventions on immune processes. |
| Changes from inclusion (V1) in functional (Clinical Global Impression, CGI-S and CGI-I) scores to end of acute treatment (V3) | Up to 10 weeks | Variation in Clinical Global Impression (CGI-S and CGI-I) questionnaire scores between inclusion (V1) and end of acute treatment (V3): * CGI-Severity (CGI-S) assess global disease severity. The Score min is 1 and Score max is 7. * CGI-Improvement (CGI-I) : assess the improvement or deterioration of the disease compared to initial state. The Score min is 1 (highly improved). The Score max is 7 (Highly deteriorated). |
| Changes from inclusion (V1) in quality of life (by WHOQOL-BREF questionnaire) scores to end of acute treatment (V3) | Up to 10 weeks | Variation in WHOQOL-BREF questionnaire scores between inclusion (V1) and end of acute treatment (V3). The minimum score is 16 and the maximum is 80. The higher the score, the better the perceived quality of life in the relevant area. |
| Changes from inclusion in quality of life (by WHOQOL-BREF scores), to End Of Study (M24) | through study completion, an average of 2 years | Variation in quality-of-life questionnaire scores (WHOQOL-BREF) between inclusion (V1) and End Of Study (M24). The minimal score is 16 and the maximal is 80. The higher the score, the better the perceived quality of life in the relevant area. |
| Changes from inclusion in functional score (by Clinical Global Impression scale), to End Of Study (M24) | through study completion, an average of 2 years | Variation in Clinical Global Impression (CGI-S and CGI-I) questionnaire scores between inclusion (V1) and end of study (M24): * CGI-Severity (CGI-S) assess global disease severity. The Score min is 1 and Score max is 7. * CGI-Improvement (CGI-I) : assess the improvement or deterioration of the disease compared to initial state. The Score min is 1 (highly improved). The Score max is 7 (Highly deteriorated). |
| Number of side-effects (type, intensity, severity) in total population and by cohort between study inclusion (V1) and end of study (M24) | through study completion, an average of 2 years | Side-effects (type, intensity, severity) in total population and by cohort between study inclusion and End Of Study (M24) |
| Number and characteristics of biomarkers identified in the retrospectively and prospectively included populations | through study completion, an average of 2 years | The number and characteristics of biomarkers identified in the retrospectively and prospectively included populations throughout the study |
| Changes from inclusion (V1) in fibrinogen, C3, C4 to End Of Study (M24) | through study completion, an average of 2 years | Changes in biological parameters measured between inclusion (V1) and the end of study (M24). The dosages are : C3, C4, fibrinogen in g/L. |
| Changes from inclusion (V1) to End Of Study (M24) in IL-1β, IL-6, IL-18 | through study completion, an average of 2 years | Changes in biological parameters measured between inclusion (V1) and the End Of Study (M24). The dosages are : IL-1β, IL-6, IL-18 in pg/mL. |
| Changes from inclusion (V1) to End Of Study (M24) in cortisol dosage | through study completion, an average of 2 years | Changes in cortisol measured between inclusion (V1) and the end of study (M24) in nmol/L. |
| Changes from inclusion (V1) to End Of Study (M24) in CRPus, β2 microglobulin, C1q | through study completion, an average of 2 years | Changes in biological parameters measured between inclusion (V1) and End Of Study (M24). The dosages are : CRPus, β2 microglobulin, C1q in mg/L. |
| Changes from inclusion (V1) to End Of Study (M24) in anti-TPO Ab, anti-TG Ab, CH50 | through study completion, an average of 2 years | Changes in biological parameters measured between inclusion (V1) and the End Of Study (M24). The dosages are : anti-Peroxidase Antibodies, anti-thyroglobulin Antibodies, Hemolytic Complement 50 in UI/mL. |
| Changes from inclusion (V1) to End Of Study (M24) in anti-TRAK Ab | through study completion, an average of 2 years | Variation in anti TSH receptor specific Antibodies (anti-TRAK Ab) between inclusion (V1) and End Of Study (M24) |
| Changes from inclusion (V1) to End Of Study (M24) in neuronal Ab | through study completion, an average of 2 years | Number of positive neuronal antibodies between inclusion (V1) and End Of Study (M24) |
| Changes from inclusion (V1) to End Of Study (M24) in interferon signature score | through study completion, an average of 2 years | Variation in interferon signature score between inclusion (V1) and End Of Study (M24) |
Countries
France
Contacts
CONTACTIolanda PALIMARU, MD
STUDY_DIRECTORAnne-Cécile PETIT, MD, PhD
GHU Paris Psychiatry & Neurosciences
Outcome results
None listed