IL-33, sST2, and CRP in Panic Disorder

Investigation of IL-33, sST2, and C-Reactive Protein in Panic Disorder: A Cross-Sectional Case-Control Study

Panic disorder (PD) is characterized by recurrent and unexpected panic attacks and is associated with significant functional impairment. Increasing evidence suggests involvement of immune-inflammatory mechanisms in PD. Elevated levels of inflammatory markers such as C-reactive protein (CRP) have been reported in PD; however, interleukin-33 (IL-33) and soluble suppressor tumorogenicity-2 (sST2), components of the IL-33/sST2 signaling axis, have not previously been investigated in PD. This cross-sectional case-control study aims to compare peripheral serum IL-33, sST2, and CRP levels between drug-naïve subjects diagnosed with PD and healthy controls (HCs). The findings may contribute to understanding the inflammatory mechanisms underlying PD.

Study Overview

• Status: Recruiting
• Conditions: Panic Disorder

Detailed Description

This is an observational, cross-sectional, case-control study conducted at the psychiatry outpatient clinic of Elazığ Mental Health and Diseases Hospital. It was planned to include 40 participants in the panic disorder (PD) and healthy controls (HCs) groups. All participants will complete a sociodemographic data form and the DSM-5 Panic Disorder Severity Scale (Adult Form). Venous blood samples (5 mL) will be collected between 08:30-10:00 a.m. after 12-hour fasting. Serum interleukin-33 (IL-33), soluble suppressor tumorogenicity-2 (sST2), and C-reactive protein (CRP) levels will be measured using commercially available ELISA kits. Statistical analyses will include independent samples t-test or Mann-Whitney U test, chi-square test, correlation, regression, and ROC analysis. A p value < 0.05 will be considered statistically significant.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Mehmet Hamdi ÖRÜM, MD, Ass. Prof., Psychiatrist; Phone Number: +905382207558; Email: mhorum@hotmail.com

Study Locations

• Turkey (Türkiye)
  • Elâzığ
    • Elâzığ, Elâzığ, Turkey (Türkiye), 23200
      • Recruiting
      • Elazığ Mental Health and Diseases Hospital Psychiatry Clinic
      • Contact: Mehmet Hamdi ÖRÜM, MD, Assoc. Prof., Psychiatrist; Phone Number: +905382207558; Email: mhorum@hotmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consisted of adult participants aged 18-65 years. The panic disorder (PD) group included consecutive subjects diagnosed with PD according to DSM-5-TR criteria who were admitted to the psychiatry clinic of Elazığ Mental Health and Diseases Hospital (Turkey). The healthy control (HC) group consisted of individuals from the general population who applied to the hospital medical board and had no current or past psychiatric or significant medical disorders. All participants provided informed consent prior to enrollment.

Description

1. For Panic Disorder (PD) Group:

   *Inclusion Criteria:

   • Being between 18-65 years of age
   • Having a diagnosis of panic disorder (PD) according to DSM-5-TR and having presented to the hospital with panic attack symptoms of the disorder
   • Not having previously used any medication for psychiatric purposes (drug-naive)
   • Not having any additional active psychiatric disorders besides PD at the current presentation
   • Absence of hypertension, diabetes mellitus, renal failure, hepatic failure, neurological disease with cognitive impairment, acute infection, pregnancy, autoimmune disease, or cancer
   • Not having taken any medication or supplements in the last month
   • Completing sociodemographic and scale data fully
   • Volunteering to participate in the study

   For PD Group:

   *Exclusion Criteria:

   • Being outside the 18-65 age range

   • Not meeting the diagnostic criteria for PD according to DSM-5-TR or being in good health

   • Having a history of psychiatric medication use

   • Having an additional psychiatric disorder besides PD at the current application

   • Presence of hypertension, diabetes mellitus, renal failure, hepatic failure, neurological disease with cognitive impairment, acute infection, pregnancy, autoimmune disease, cancer

   • Patients with a body mass index (BMI) <18.5 kg/m² and >29.9 kg/m²

   • Taking any medication or supplement in the last month
   • Incomplete completion of sociodemographic and scale data
   • Not volunteering to participate in the study

2. For Healthy Control Group:

   • Inclusion Criteria:

     • Being between 18-65 years of age
     • Not having any active psychiatric disorder
     • Not having previously used any medication for psychiatric purposes (drug-naive)
     • Not having hypertension, diabetes mellitus, kidney failure, liver failure, neurological disease with cognitive impairment, acute infection, pregnancy, autoimmune disease, or cancer
     • Not having taken any medication or supplement in the last month
     • Completing sociodemographic and scale data fully
     • Volunteering to participate in the study

For Healthy Control Group:

*Exclusion Criteria:

• Being outside the 18-65 age range
• Having any active psychiatric disorder
• Having a history of using psychiatric medication
• Having hypertension, diabetes mellitus, renal failure, hepatic failure, neurological disease with cognitive impairment, acute infection, pregnancy, autoimmune disease, or cancer
• Patients with a body mass index (BMI) < 18.5 kg/m² and > 29.9 kg/m²
• Taking any medication or supplement in the last month
• Incomplete completion of sociodemographic and scale data
• Not volunteering to participate in the study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Panic Disorder (PD); Adult participants (18-65 years) diagnosed with panic disorder (PD) according to DSM-5-TR criteria. All of the subjects with PD was drug-naive. Subjects were evaluated at baseline. No intervention was assigned by the study protocol. Blood samples were collected for measurement of serum interleukin-33 (IL-33) and soluble suppressor tumorogenicity-2 (sST2), and C-reactive protein (CRP) levels and complete blood count parameters. Clinical assessments in the PD group included the DSM-5 Panic Disorder Severity Scale (Adult Form). Sociodemographic and clinical data were recorded for all participants.
Healthy Control (HC); Healthy control adult participants (18-65 years) without any current or past psychiatric disorder. No intervention was administered as part of the research protocol. Participants underwent a baseline clinical evaluation and provided a single blood sample for measurement of serum serum interleukin-33 (IL-33) and soluble suppressor tumorogenicity-2 (sST2), and C-reactive protein (CRP) levels and complete blood count parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interleukin-33 (IL-33)	Interleukin-33 (IL-33) levels measured by ELISA (pg/ml).	At hospital admission (baseline)
Soluble Suppressor Tumorogenicity-2 (sST2)	Soluble Suppressor Tumorogenicity-2 (sST2) levels measured by ELISA (pg/ml)	At hospital admission (baseline)
C-Reactive Protein (CRP)	C-Reactive Protein (CRP) levels measured by ELISA (mg/dL)	At hospital admission (baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aggregate Index of Systemic Inflammation (AISI)	Aggregate Index of Systemic Inflammation (AISI) is calculated using the following formula: (neutrophils × monocytes × platelets) / (lymphocytes). All the parameters mentioned here are complete blood count parameters.	At hospital admission (baseline)
DSM-5 Panic Disorder Severity Scale-Adult Form (PDS)	The DSM-5 Panic Disorder Severity Scale-Adult Form (PDS) is a 10-item self-assessment scale developed by the American Psychiatric Association (APA) that uses a five-point Likert scale (0=Never; 1=Sometimes; 2=Halfway through; 3=Most of the time; 4=Always). Participants consider how much their panic disorder has affected their personal lives in the past seven days when completing the scale. Scores obtained from the scale items indicate the severity of the panic disorder. The scale can be scored between 0 and 40, with higher scores indicating a more severe panic disorder. The mean total score is calculated by dividing the total raw score by the number of items on the scale.	At hospital admission (baseline)

Collaborators and Investigators

• Sponsor: Elazığ Mental Health and Diseases Hospital

Publications and helpful links

General Publications

• Quagliato LA,Nardi AE
• Barbosa IG, Morato IB, de Miranda AS, Bauer ME, Soares JC, Teixeira AL. A preliminary report of increased plasma levels of IL-33 in bipolar disorder: further evidence of pro-inflammatory status. J Affect Disord. 2014 Mar;157:41-4. doi: 10.1016/j.jad.2013.12.042. Epub 2014 Jan 11.
• Liu CH, Hua N, Yang HY. Alterations in Peripheral C-Reactive Protein and Inflammatory Cytokine Levels in Patients with Panic Disorder: A Systematic Review and Meta-Analysis. Neuropsychiatr Dis Treat. 2021 Dec 7;17:3539-3558. doi: 10.2147/NDT.S340388. eCollection 2021.
• Wieck A, Grassi-Oliveira R, do Prado CH, Rizzo LB, de Oliveira AS, Kommers-Molina J, Viola TW, Marciano Vieira EL, Teixeira AL, Bauer ME. Pro-inflammatory cytokines and soluble receptors in response to acute psychosocial stress: differential reactivity in bipolar disorder. Neurosci Lett. 2014 Sep 19;580:17-21. doi: 10.1016/j.neulet.2014.07.040. Epub 2014 Aug 1.
• Brunoni AR, Supasitthumrong T, Teixeira AL, Vieira EL, Gattaz WF, Bensenor IM, Lotufo PA, Lafer B, Berk M, Carvalho AF, Maes M. Differences in the immune-inflammatory profiles of unipolar and bipolar depression. J Affect Disord. 2020 Feb 1;262:8-15. doi: 10.1016/j.jad.2019.10.037. Epub 2019 Oct 30.
• Hoppe LJ, Ipser J, Gorman JM, Stein DJ. Panic disorder. Handb Clin Neurol. 2012;106:363-74. doi: 10.1016/B978-0-444-52002-9.00020-6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2025
• Primary Completion (Estimated): March 23, 2026
• Study Completion (Estimated): March 23, 2026

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: C-Reactive Protein; Panic Disorder; IL-33; CRP; sST2; Interleukin-33; Soluble Suppressor Tumorogenicity-2
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Panic Disorder
• Other Study ID Numbers: EMHDH-2025-2026-PD-IL33-ST2-CR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual participant data (IPD) underlying the results reported in this study (including demographic variables, serum interleukin-33 (IL-33) and soluble suppressor tumorogenicity-2 (sST2) and C-reactive protein (CRP) levels, complete blood count parameters, and DSM-5 Panic Disorder Severity Scale-Adult Form (PDS) will be made available to qualified researchers upon reasonable request for academic purposes. Data will be shared after removal of all direct identifiers and in accordance with applicable ethical approvals and data protection regulations. Access to the data will require a methodologically sound research proposal and a data use agreement. Requests should be directed to the corresponding author.
• IPD Sharing Time Frame: Data will be available beginning 6 months after publication and will remain available for 5 years.
• IPD Sharing Access Criteria: Access will be granted to researchers who provide a methodologically sound proposal. Requests must be approved by the principal investigator and may require a data use agreement in accordance with institutional and ethical regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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