Clinical trial NCT06515522: A Biological Signature for the Early Differential Diagnosis of Psychosis
Official title: A Biological Signature for the Early Differential Diagnosis of Psychosis: Unveiling the Differences Between Mood Disorders and Schizophrenia With Multimodal Machine Learning Techniques
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Schizophrenia
Bipolar Disorder
Major Depressive Disorder
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Italy
First posted: 2024-07-23
Enrollment: 1850
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
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

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Schizophrenia vs Mood disorders
timeFrame: baseline
Secondary outcomes:
measure: Bipolar vs major depressive disorder
timeFrame: baseline
Other outcomes:
Locations:
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Francesco Benedetti, Prof
role: PRINCIPAL_INVESTIGATOR
References: