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RecruitingNCT07741981BIO-INMUpdated Sep 21, 2026

Treatment Resistance in Psychiatric Disorders: the Search for Biological Markers Predictive of Response to Treatment

An interventional study of Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales in Schizophrenia, Treatment Resistant Depression (TRD) and Bipolar Disorder (BD), sponsored by Centre Hospitalier St Anne. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by Centre Hospitalier St Anne · Not applicable, Interventional, and Other

Phase
Not applicable
Study type
Interventional
Enrollment
700
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Schizophrenia
  • Treatment Resistant Depression (TRD)
  • Bipolar Disorder (BD)
  • Catatonia
  • Obsessive Compulsive Disorder (OCD)

Keywords

  • biomarkers
  • treatment resistance
  • response prediction
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
700 participants (estimated)

Study arms

  • Other
    OCD cohort

    Patients suffering from OCD resistant to treatments

    Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

  • Other
    Catatonia cohort

    Patients suffering from resistant catatonia

    Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

  • Other
    TRD cohort

    Patients suffering from treatment resistant depression (TRD)

    Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

  • Other
    BD cohort

    Patients suffering from treatment resistant bipolar disorders (BD)

    Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

  • Other
    Schizophrenia cohort

    Patients suffering from schizophrenia resistant to treatments

    Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

Interventions

  • BiologicalBlood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

    the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin

05

What researchers measure

Primary outcomes

  1. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    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.

    Time frame: Up to 10 weeks

  2. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for depression. The minimal score is 0. The maximal score is 60.

    Time frame: Up to 10 weeks

  3. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Changes in Young Mania Rating Scale (YMRS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for bipolar troubles. The minimal score is 0. The maximal score is 60.

    Time frame: Up to 10 weeks

  4. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Changes in Obsessive-Compulsive Inventory-Revised (OCI-R) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0. The maximal score is 72.

    Time frame: Up to 10 weeks

  5. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Changes in Visual analogic scale for obsessive compulsive disorder (VAS-OCD) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0 mm. The maximal score is 100 mm.

    Time frame: Up to 10 weeks

  6. Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3)

    Changes in Bush-Francis Catatonia Rating Scale (BFCRS) scores between inclusion (V1) and the end of acute phase therapy (V3). The scale will be used to assess disease severity for catatonia. The minimal score is 0 mm. The maximal score is 69.

    Time frame: Up to 10 weeks

  7. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    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

    Time frame: Up to 10 weeks

  8. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : C3, C4, fibrinogen in g/L.

    Time frame: Up to 10 weeks

  9. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : Vitamin B12, IL-1β, IL-6, IL-18 in pg/mL.

    Time frame: Up to 10 weeks

  10. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : Folate, Vitamin B1, B6, D, cortisol in nmol/L.

    Time frame: Up to 10 weeks

  11. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : TSH, prolactin in mUI/L

    Time frame: Up to 10 weeks

  12. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : CRPus, β2 microglobulin, C1q in mg/L.

    Time frame: Up to 10 weeks

  13. Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3).

    Changes in biological parameters measured between inclusion (V1) and the end of acute phase therapy (V3). The dosages are : anti-TPO Ab, anti-TG Ab, CH50 in UI/mL.

    Time frame: Up to 10 weeks

Secondary outcomes

  1. Changes in CRPus from inclusion (V1) to Day 2 (V2)

    Variation in CRPus between inclusion (V1) and Day 2 (V2) in mg/L.

    Time frame: From enrollment to Day 2

  2. Changes in immunity markers from inclusion (V1) to Day 2 (V2)

    Variation in IL-1β, IL-6, and IL-18 between inclusion (V1) and Day 2 (V2) in pg/mL.

    Time frame: From enrollment to Day 2

  3. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    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.

    Time frame: From enrollment to Day 2

  4. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Changes in Positive and Negative Syndrome Scale (PANSS) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for Schizophrenia patients. The minimal score is 30. The maximal score is 210.

    Time frame: From enrollment to Day 2

  5. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores between inclusion (V1) and day 2 (V2). The scale will be used to assess disease severity for depression. The minimal score is 0. The maximal score is 60.

    Time frame: From enrollment to Day 2

  6. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Changes in Young Mania Rating Scale (YMRS) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for bipolar troubles. The minimal score is 0. The maximal score is 60.

    Time frame: From enrollment to Day 2

  7. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Changes in Visual analogic scale for obsessive compulsive disorder (VAS-OCD) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0 mm. The maximal score is 100 mm.

    Time frame: From enrollment to Day 2

  8. Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2)

    Changes in Obsessive-Compulsive Inventory-Revised (OCI-R) scores between inclusion (V1) and Day 2 (V2). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0. The maximal score is 72.

    Time frame: From enrollment to Day 2

  9. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    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.

    Time frame: through study completion, an average of 2 years

  10. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for depression. The minimal score is 0. The maximal score is 60.

    Time frame: through study completion, an average of 2 years

  11. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Variation in standardized clinical disease scale scores between inclusion (V1) and EOS (M24). Changes in Young Mania Rating Scale (YMRS) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for bipolar troubles. The minimal score is 0. The maximal score is 60.

    Time frame: through study completion, an average of 2 years

  12. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Changes in Obsessive-Compulsive Inventory-Revised (OCI-R) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0. The maximal score is 72.

    Time frame: through study completion, an average of 2 years

  13. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Variation in standardized clinical disease scale scores between inclusion (V1) and EOS (M24). Changes in Visual analogic scale for obsessive compulsive disorder (VAS-OCD) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for obsessive compulsive disorder. The minimal score is 0 mm. The maximal score is 100 mm.

    Time frame: through study completion, an average of 2 years

  14. Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores

    Changes in Bush-Francis Catatonia Rating Scale (BFCRS) scores between inclusion (V1) and the end of study (M24). The scale will be used to assess disease severity for catatonia. The minimal score is 0 mm. The maximal score is 69.

    Time frame: through study completion, an average of 2 years

  15. Changes from inclusion (V1) to end of study (M24) in CBC components

    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.

    Time frame: through study completion, an average of 2 years

  16. Changes from inclusion (V1) to end of study (M24) in Folates, Vitamin B6, Vitamin B1, Vitamin D

    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.

    Time frame: through study completion, an average of 2 years

  17. Changes from inclusion (V1) to end of study (M24) in Vitamin B12

    Changes in Vitamin B12 measured between inclusion (V1) and the End Of Study (M24) in pg/mL.

    Time frame: through study completion, an average of 2 years

  18. Changes from inclusion (V1) to end of study (M24) in TSH, prolactin

    Changes in biological parameters measured between inclusion (V1) and End Of Study (M24). The dosages are : TSH, prolactin in mUI/L

    Time frame: through study completion, an average of 2 years

  19. Changes from inclusion (V1) to end of study (M24) in drug dosage

    Variation in drug dosage between inclusion (V1) and End Of Study (M24). Unit could be different according to the drug.

    Time frame: through study completion, an average of 2 years

  20. 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)

    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.

    Time frame: At inclusion (V1), 10 weeks, 6 months-, 12 months- and 24 months after end of acute treatment

  21. Changes from inclusion (V1) in functional (Clinical Global Impression, CGI-S and CGI-I) scores to end of acute treatment (V3)

    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).

    Time frame: Up to 10 weeks

  22. Changes from inclusion (V1) in quality of life (by WHOQOL-BREF questionnaire) scores to end of acute treatment (V3)

    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.

    Time frame: Up to 10 weeks

  23. Changes from inclusion in quality of life (by WHOQOL-BREF scores), to End Of Study (M24)

    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.

    Time frame: through study completion, an average of 2 years

  24. Changes from inclusion in functional score (by Clinical Global Impression scale), to End Of Study (M24)

    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).

    Time frame: through study completion, an average of 2 years

  25. Number of side-effects (type, intensity, severity) in total population and by cohort between study inclusion (V1) and end of study (M24)

    Side-effects (type, intensity, severity) in total population and by cohort between study inclusion and End Of Study (M24)

    Time frame: through study completion, an average of 2 years

  26. Number and characteristics of biomarkers identified in the retrospectively and prospectively included populations

    The number and characteristics of biomarkers identified in the retrospectively and prospectively included populations throughout the study

    Time frame: through study completion, an average of 2 years

  27. Changes from inclusion (V1) in fibrinogen, C3, C4 to End Of Study (M24)

    Changes in biological parameters measured between inclusion (V1) and the end of study (M24). The dosages are : C3, C4, fibrinogen in g/L.

    Time frame: through study completion, an average of 2 years

  28. Changes from inclusion (V1) to End Of Study (M24) in IL-1β, IL-6, IL-18

    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.

    Time frame: through study completion, an average of 2 years

  29. Changes from inclusion (V1) to End Of Study (M24) in cortisol dosage

    Changes in cortisol measured between inclusion (V1) and the end of study (M24) in nmol/L.

    Time frame: through study completion, an average of 2 years

  30. Changes from inclusion (V1) to End Of Study (M24) in CRPus, β2 microglobulin, C1q

    Changes in biological parameters measured between inclusion (V1) and End Of Study (M24). The dosages are : CRPus, β2 microglobulin, C1q in mg/L.

    Time frame: through study completion, an average of 2 years

  31. Changes from inclusion (V1) to End Of Study (M24) in anti-TPO Ab, anti-TG Ab, CH50

    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.

    Time frame: through study completion, an average of 2 years

  32. Changes from inclusion (V1) to End Of Study (M24) in anti-TRAK Ab

    Variation in anti TSH receptor specific Antibodies (anti-TRAK Ab) between inclusion (V1) and End Of Study (M24)

    Time frame: through study completion, an average of 2 years

  33. Changes from inclusion (V1) to End Of Study (M24) in neuronal Ab

    Number of positive neuronal antibodies between inclusion (V1) and End Of Study (M24)

    Time frame: through study completion, an average of 2 years

  34. Changes from inclusion (V1) to End Of Study (M24) in interferon signature score

    Variation in interferon signature score between inclusion (V1) and End Of Study (M24)

    Time frame: through study completion, an average of 2 years

06

Study locations

1 of 1 sites recruiting
  • GHU Paris - Psychiatrie et Neurosciences
    Paris, 75014, France
    Recruiting
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
NCT07741981
Lead sponsor
Centre Hospitalier St Anne
Collaborators
GHU Paris Psychiatry & Neurosciences
Responsible party
Sponsor
First posted
Aug 3, 2026
Start date
Aug 20, 2026
Primary completion
Nov 1, 2036 (estimated)
Completion
Sep 1, 2038 (estimated)
Last update
Sep 21, 2026

Study contacts

Iolanda PALIMARU, MD
Contact
iolanda.palimaru@ghu-paris.fr
+33145658798
Anne-Cécile PETIT, MD, PhD
study director · GHU Paris Psychiatry & Neurosciences

Oversight

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