Non-Coding RNAs Gene Expression in Psychiatric Disorders (PsiRNA26)

Gene Expression Analysis of Non-coding RNAs in Psychiatric Disorders

This study aims to investigate whether specific non-coding RNAs, molecules involved in the regulation of gene expression, are altered in individuals with psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, panic disorder, and obsessive-compulsive disorder. Researchers will compare the expression levels of these molecules in patients who are drug-naïve or have been free from psychiatric treatment for at least six months with those observed in healthy volunteers.

The study will also evaluate whether the expression of these non-coding RNAs changes after approximately five months of standard psychiatric treatment. Blood samples collected during routine clinical care will be used to measure the expression levels of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR), a laboratory technique used to assess gene expression.

This is an observational study and does not assign specific treatments. All therapies will be prescribed according to standard clinical practice.

The main objective is to determine whether alterations in non-coding RNA expression may serve as biological markers of psychiatric disorders and whether these markers may help monitor treatment-related changes over time. The findings may contribute to a better understanding of the biological mechanisms underlying major psychiatric disorders and support the future development of more accurate diagnostic and therapeutic approaches.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depression; Bipolar Affective Disorders; Schizophrenia Disorders; Obsessive Compulsive Disorder (OCD); Anxiety Disorder (Panic Disorder or GAD)
• Intervention / Treatment: Genetic: Reverse Transcription Quantitative Polymerase Chain Reaction

Detailed Description

This is a multicenter, prospective, observational case-control study designed to evaluate the expression of selected non-coding RNAs in psychiatric disorders. The study will include adult drug-naïve or drug-free patients diagnosed with Bipolar Disorder type I or II, Panic Disorder, Major Depressive Disorder, Obsessive-Compulsive Disorder or Schizophrenia, as well as healthy volunteers recruited from transfusion services.

Patients will be assessed at baseline (T0) and again after at least five months of pharmacological treatment (T1). Healthy controls will be assessed at baseline only. No treatments will be assigned for the purposes of the study. All pharmacological therapies will be prescribed according to routine clinical practice.

Peripheral blood serum samples will be collected from patients and healthy controls. For patients, residual peripheral venous blood collected during routine laboratory investigations will be used for study purposes. Serum samples will be centrifuged, stored at -80 °C, and subsequently transferred on dry ice to the Cellular and Molecular Biology Laboratories of the University of Messina.

Total RNA will be extracted from serum samples and reverse-transcribed into cDNA. Expression levels of selected miRNAs and lncRNAs will be analyzed using RT-qPCR. Relative expression levels will be quantified using the 2^-ΔΔCt method.

The study aims to identify possible ncRNA expression abnormalities in major psychiatric disorders, evaluate treatment-related changes over time, and explore the potential role of ncRNAs as biomarkers for diagnosis and treatment monitoring.

• Study Type: Observational
• Enrollment (Estimated): 384

Contacts and Locations

• Study Contact: Name: Professor Maria Salvina Signorelli, PhD, MD; Phone Number: +39 095 3782791; Email: maria.signorelli@unict.it

Study Locations

• Italy
  • Sicily
    • Catania, Sicily, Italy, 95123
      • Psychiatry Unit, Via Santa Sofia 78
      • Contact: Professor Maria Salvina Signorelli, PhD, MD; Phone Number: +39 095 3782791; Email: maria.signorelli@unict.it
      • Sub-Investigator: Dr Fabrizio Bella, MD
      • Sub-Investigator: Professor Antonino Petralia, PhD, MD
      • Sub-Investigator: Professor Carmen Concerto, PhD, MD
      • Sub-Investigator: Dr Ludovico Mineo, PhD, MD
      • Sub-Investigator: Dr Lucia Basile, MD
      • Sub-Investigator: Professor Cinzia Santa Di Pietro, PhD
    • Enna, Sicily, Italy, 94100
      • Psychiatry Unit, Contrada Ferrante SNC
      • Contact: Professor Antonino Messina, PhD, MD; Phone Number: +39 0935 516044; Email: antonino.messina2@unikore.it
    • Messina, Sicily, Italy, 98125
      • Cellular and Molecular Biology Laboratory, Tower of Biological Laboratories, 5th Floor Via Consolare Valeria 1
      • Contact: Professor Angela D'Ascola, PhD; Phone Number: +39 090 221 3389; Email: adascola@unime.it
      • Sub-Investigator: Professor Michele Scuruchi, PhD
      • Sub-Investigator: Professor Salvatore Campo, PhD
      • Sub-Investigator: Professor Giuseppe Maurizio Campo, PhD
      • Sub-Investigator: Dr Angela Avenoso, PhD
    • Messina, Sicily, Italy, 98125
      • Psychiatry Unit, Via Consolare Valeria 1
      • Contact: Professor Maria Rosaria Anna Muscatello, PhD, MD; Phone Number: +39 090 2217384; Email: maria.muscatello@unime.it
    • Palermo, Sicily, Italy, 90127
      • Psychiatry Unit, Via del Vespro 129
      • Contact: Professor Diego Quattrone, PhD, MD; Phone Number: +39 091 238 93011; Email: diego.quattrone@unipa.it
      • Sub-Investigator: Dr Giovanna Marrazzo, PhD, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of adult psychiatric inpatients and day-hospital/day-service patients recruited from the Psychiatry Units of the University Hospitals of Catania, Messina, Palermo, and the Psychiatry Unit of Umberto I Hospital in Enna. Eligible participants will include drug-naive or drug-free subjects diagnosed with Bipolar Disorder type I or II, Major Depressive Disorder, Panic Disorder, Obsessive-Compulsive Disorder, or Schizophrenia. Healthy controls will consist of volunteer blood donors recruited from the transfusion services of the participating university hospitals.

Description

Inclusion Criteria (patients):

• Age between 18 and 55 years;
• Male sex or female sex in the mid-luteal phase of the menstrual cycle;
• Clinical presentation consistent with diagnostic criteria for:
• Bipolar Disorder type I or II,
• Panic Disorder,
• Major Depressive Disorder,
• Obsessive-Compulsive Disorder,
• Schizophrenia;
• First diagnosis and drug-naive status, or absence of psychopharmacological treatment for at least 6 months prior to enrollment.

Inclusion Criteria (Healthy Control):

• Age between 18 and 55 years;
• Male sex or female sex in the mid-luteal phase of the menstrual cycle;
• No treatment with psychotropic medications;
• Absence of clinical elements supporting a diagnosis of Bipolar Disorder, Panic Disorder, Major Depressive Disorder, Obsessive-Compulsive Disorder, Schizophrenia;
• Absence of clinical or laboratory evidence of infectious or internal medicine diseases;
• Absence of autoimmune diseases;
• HAM-D score < 8;
• MRS score < 11;
• Y-BOCS score < 7;
• BPRS score = 18;
• No significant stressful life events during the previous 6 months.

Exclusion Criteria (patients):

• Current immunosuppressive, antibiotic, or hormone replacement therapy;
• Relevant medical comorbidities, including autoimmune or internal medicine disorders;
• Active infectious diseases or infections resolved less than 3 weeks before enrollment;
• Relevant psychiatric comorbidities;
• Current psychopharmacological treatment or discontinuation of psychopharmacological therapy less than 6 months before enrollment.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Major Depressive Disorder Cohort; Drug-naïve or drug-free patients diagnosed with Major Depressive Disorder, assessed at baseline (T0) and after at least five months of standard pharmacological treatment (T1).	Genetic: Reverse Transcription Quantitative Polymerase Chain Reaction; Gene expression analysis of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Schizophrenia Cohort; Drug-naïve or drug-free patients diagnosed with Schizophrenia, assessed at baseline (T0) and after at least five months of standard pharmacological treatment (T1).	Genetic: Reverse Transcription Quantitative Polymerase Chain Reaction; Gene expression analysis of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Obsessive-Compulsive Disorder Cohort; Drug-naïve or drug-free patients diagnosed with Obsessive-Compulsive Disorder, assessed at baseline (T0) and after at least five months of standard pharmacological treatment (T1).	Genetic: Reverse Transcription Quantitative Polymerase Chain Reaction; Gene expression analysis of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Panic Disorder Cohort; Drug-naïve or drug-free patients diagnosed with Panic Disorder, assessed at baseline (T0) and after at least five months of standard pharmacological treatment (T1).	Genetic: Reverse Transcription Quantitative Polymerase Chain Reaction; Gene expression analysis of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Bipolar Disorder Cohort; Drug-naïve or drug-free patients diagnosed with Bipolar Disorder type I or II, assessed at baseline (T0) and after at least five months of standard pharmacological treatment (T1).	Genetic: Reverse Transcription Quantitative Polymerase Chain Reaction; Gene expression analysis of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Healthy Control Cohort; Healthy volunteers without current psychiatric disorders or psychotropic medication use, assessed at baseline only.	Genetic: Reverse Transcription Quantitative Polymerase Chain Reaction; Gene expression analysis of selected non-coding RNAs using reverse transcription quantitative polymerase chain reaction (RT-qPCR).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential Expression of Selected Non-Coding RNAs in Psychiatric Disorders	Assessment of relative expression levels of a predefined panel of circulating non-coding RNAs (miRNAs and lncRNAs) in peripheral blood serum of drug-naive/drug-free psychiatric patients compared with healthy controls, using real-time PCR (RT-qPCR) and quantified through the 2^-ΔΔCt method.	Baseline (T0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Non-Coding RNA Expression After Pharmacological Treatment	Evaluation of changes in expression levels of circulating non-coding RNAs in psychiatric patients after at least 5 months of standard pharmacological treatment, comparing baseline (T0) and follow-up (T1) samples through RT-PCR analysis.	Baseline (T0) and 5 months (T1)
Differences in ncRNA Expression Between Psychiatric Patients and Healthy Controls	Comparison of expression levels of ncRNAs involved in synaptogenesis, synaptic plasticity, glial activation, and stress-response pathways between psychiatric patients at baseline and healthy control subjects.	Baseline (T0)
Differences in ncRNA Expression Between Manic and Depressive Episodes in Bipolar Disorder	Evaluation of differential expression of selected ncRNAs in patients with Bipolar Disorder during manic episodes compared with depressive episodes at baseline assessment.	Baseline (T0)

Collaborators and Investigators

• Sponsor: Carmen Concerto

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: June 10, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Mood Disorders; Depressive Disorder; Schizophrenia; Anxiety Disorders; Depressive Disorder, Major; Obsessive-Compulsive Disorder; Panic Disorder; Generalized Anxiety Disorder; Investigative Techniques; Genetic Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Real-Time Polymerase Chain Reaction
• Other Study ID Numbers: 10/2026/CL-PAR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared.

Drug and device information, study documents

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