Treatment Resistance in Psychiatric Disorders: the Search for Biological Markers Predictive of Response to Treatment (BIO-INM)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia; Catatonia; Obsessive Compulsive Disorder (OCD); Bipolar Disorder (BD); Treatment Resistant Depression (TRD)
• Intervention / Treatment: Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Iolanda PALIMARU, MD; Phone Number: +33145658798; Email: iolanda.palimaru@ghu-paris.fr

Study Locations

• France
  • Paris, France, 75014
    • GHU Paris - Psychiatrie et Neurosciences
    • Contact: Cécile MICHEL; Phone Number: +331 80 52 70 19; Email: cecile.bultez@ghu-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: OCD cohort; Patients suffering from OCD resistant to treatments	Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales; the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin
Other: Catatonia cohort; Patients suffering from resistant catatonia	Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales; the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin
Other: TRD cohort; Patients suffering from treatment resistant depression (TRD)	Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales; the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin
Other: BD cohort; Patients suffering from treatment resistant bipolar disorders (BD)	Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales; the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin
Other: Schizophrenia cohort; Patients suffering from schizophrenia resistant to treatments	Biological: Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales; the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 10 weeks
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.	Up to 10 weeks
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.	Up to 10 weeks
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.	Up to 10 weeks
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.	Up to 10 weeks
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.	Up to 10 weeks
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	Up to 10 weeks
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.	Up to 10 weeks
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.	Up to 10 weeks
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.	Up to 10 weeks
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	Up to 10 weeks
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.	Up to 10 weeks
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.	Up to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in CRPus from inclusion (V1) to Day 2 (V2)	Variation in CRPus between inclusion (V1) and Day 2 (V2) in mg/L.	From enrollment to Day 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.	From enrollment to Day 2
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.	From enrollment to Day 2
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.	From enrollment to Day 2
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.	From enrollment to Day 2
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.	From enrollment to Day 2
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.	From enrollment to Day 2
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.	From enrollment to Day 2
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	At inclusion (V1), 10 weeks, 6 months-, 12 months- and 24 months after end of acute treatment
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).	Up to 10 weeks
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.	Up to 10 weeks
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.	through study completion, an average of 2 years
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).	through study completion, an average of 2 years
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)	through study completion, an average of 2 years
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	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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.	through study completion, an average of 2 years
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)	through study completion, an average of 2 years
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)	through study completion, an average of 2 years
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)	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier St Anne
• Collaborators: GHU Paris Psychiatry & Neurosciences
• Investigators: Study Director: Anne-Cécile PETIT, MD, PhD, GHU Paris Psychiatry & Neurosciences

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): October 1, 2036
• Study Completion (Estimated): August 1, 2038

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: July 27, 2026
• First Posted (Actual): August 3, 2026

Study Record Updates

• Last Update Posted (Actual): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 27, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: biomarkers; treatment resistance; response prediction
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Neurologic Manifestations; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavioral Symptoms; Neurobehavioral Manifestations; Mood Disorders; Anxiety Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Schizophrenia; Bipolar Disorder; Depressive Disorder, Treatment-Resistant; Catatonia; Obsessive-Compulsive Disorder; Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Biopsy; Diagnostic Techniques, Neurological; Spinal Puncture; Blood Specimen Collection
• Other Study ID Numbers: D25-P041; N°ID-RCB: 2026-A00433-48 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No