A Biological Signature for the Early Differential Diagnosis of Psychosis

July 17, 2024 updated by: Francesco Benedetti, IRCCS San Raffaele

A Biological Signature for the Early Differential Diagnosis of Psychosis: Unveiling the Differences Between Mood Disorders and Schizophrenia With Multimodal Machine Learning Techniques

Schizophrenia (SZ) and mood disorders (BD, MDD) are among the most disabling disorders worldwide, with a relevant social, functional, and economic burden. Although they are identified as distinct disorders, the potential overlapping symptomatology poses important challenges for the differential diagnosis. A consistent literature affirms that brain structure, and function reflect an intermediate phenotype of an underlying genetic vulnerability for the disorders, shaped by interaction with environmental experiences. Such experiences include early life stress and trauma which seem to characterize psychiatric patients and have been associated with brain abnormalities. Further, early life experiences have been associated with inflammation in a subpopulation of psychiatric patients However imaging, inflammatory, and genetic group-level differences, albeit consistent, do not impact clinical practice since they have not been translated into individual prediction. To address these issues, a rapidly growing body of scientific literature implemented computational techniques, such as machine learning (ML). In this project we will develop cutting-edge ML algorithms to predict the differential diagnosis between mood disorders and SZ from genetic, neuroimaging, inflammatory and environmental data in a unique cohort of 1850 patients and 1000 healthy controls recruited in 4 different centers in Italy. The project will address three different aims: in aim 1 we will develop algorithms for the differential diagnosis between SZ and MD combining multimodal neuroimaging and genetic data; in aim 2 we will predict the differential diagnosis between SZ and MD from immuno-inflammatory and environmental data; finally, with aim three we will exploit an animal model to identify the underlying mechanisms of brain alterations associated with exposure to early life stress. Machine learning analyses will include algorithms for data harmonization and feature reduction, as well as for generating normative models. Finally. different classifying models will be compared considering the specific features to achieve the best performance.The definition of reliable and objective biomarkers, combined with cutting-edge computational methodology, could help clinicians in providing more precise diagnoses and early interventions, also considering dimensional constructs & factors influencing outcomes such as affective vs non-affective psychosis and breadth of exposure to traumatic events

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1850

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Psychiatric patients with a diagnosis of Schizophrenia or Bipolar disorder or Major depressive disorder, neuroimaging data and peripheral blood sampling.

Healthy controls with neuroimaging data and peripheral blood sampling

Description

Inclusion Criteria:

  1. Aged 18-65
  2. diagnosed with Schizophrenia, Bipolar Disorder or Major depressive disorder.
  3. For Bipolar and Major depressive disorder, Hamilton Depression Rating Scale scores >8
  4. Multimodal 3 T MRI acquisition available (*)
  5. Genetic and serum inflammatory data available, or serum and whole blood available for genotyping and inflammatory markers determination.

Exclusion Criteria:

  1. Presence of major medical or neurological disorders
  2. Alcohol or drugs abuse or dependence
  3. Conditions known to alter immune-inflammatory status, such as rheumatic diseases, malignancies,
  4. ongoing treatment with drugs acting on the immune system, such as corticosteroids, NSAIDs and other immunomodulatory drugs.
  5. Pregnancy or lactating

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Controls
healthy controls
Other: differential diagnosis
this is a retrospective observational study. no intervention has been or will be performed
Schizophrenia
All patients with schizophrenia recruited from 2007 and 2023
Other: differential diagnosis
this is a retrospective observational study. no intervention has been or will be performed
Mood disorders
All patients with bipolar or major depressive disorders recruited from 2007 and 2023
Other: differential diagnosis
this is a retrospective observational study. no intervention has been or will be performed

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Schizophrenia vs Mood disorders
Time Frame: baseline
Predicting the differential diagnosis between Schizophrenia and Mood Disorders combining multimodal neuroimaging, immuno-inflammatory and genetic data
baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Bipolar vs major depressive disorder
Time Frame: baseline
Predicting the differential diagnosis between major depression and bipolar disorder, and the presence or absence of psychotic symptoms combining multimodal neuroimaging, immuno-inflammatory and genetic data
baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS San Raffaele

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ministry of Health, Italy

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Francesco Benedetti, Prof, IRCCS Ospedale San Raffaele

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 31, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 17, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 23, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PNRR-MCNT2-2023-12378015

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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