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.

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.

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

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.

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.

Data will be available beginning 6 months after publication and will remain available for 5 years.

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.