A retrospective study based on medical records was conducted by selecting patients who underwent outpatient treatment for anxiety disorders at the Department of Psychiatry at Daegu Catholic University Hospital from March 01, 2016 to December 31, 2020. Before starting treatment, the patients underwent a qEEG examination, and they subsequently received drug treatment for more than 8 weeks. Patients who had been previously diagnosed with neurological conditions such as convulsive disorders, had undergone intracranial surgery or insertion of magnetic material into the head or eyeball, had not received antidepressants for the first treatment, or showed poor-quality EEG findings were excluded from the study. In accordance with a previous report, patients with a CGI-S score of 4 or higher after 8 weeks of sufficient antidepressant treatment were stratified in the treatment resistance group (TRS), and those with a CGI-S score of 3 or less were classified in the treatment response group (TRP).
This study was approved by the Institutional Review Board (IRB) of the Daegu Catholic University Medical Center (DCUMC IRB approval No. CR-21-121) and was performed in accordance with the Declaration of Helsinki (World Medical Association: Ethical Principles for Medical Research Involving Human Subjects, 1964). The ethics committee approved of the waiver for the informed consent because this was a retrospective study.
A total of 86 patients who had undergone diagnoses of the category of anxiety disorders, including generalized anxiety disorder, social anxiety disorder, and panic disorder, by a psychiatrist using the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) during the study period were included. The patient’s medical records were checked to determine their sex, age, type and dose of prescription drugs, and status from the start of treatment to 8 or 12 weeks. Assessments based on the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Symptom Checklist-90-Revised (SCL-90-R) were performed, and the CGI-S scale was used for disease severity assessment by clinicians. To analyze the dose of the prescribed drug, it was converted into an equivalent dose. For antidepressants, fluoxetine was used as the standard, and for benzodiazepines, diazepam was used as the standard[26, 27]. Finally, the results of qEEG examinations performed before starting drug treatment were analyzed.
(1) State-Trait Anxiety Inventory
STAI is a self-reporting tool that has been proven to be useful for measuring anxiety in general populations and clinical samples. It consists of two subscales: the “State,” which evaluates the current state, and the “Trait,” which evaluates the general state. Each subscale includes 20 items that are evaluated on a 4-point Likert scale of 1-4 points, and a score of 40 or higher is considered to be clinically significant. The internal consistency coefficient of the subscales was 0.86 to 0.95; the test repeatability coefficient was 0.65 to 0.75 for 2 months; and the composition and validity of the test are widely known.
(2) Beck Depression Inventory
The BDI is a self-reported test developed by Beck et al., and is the most commonly used tool to measure depressive symptoms. It consists of a total of 21 items that are rated on a 4-point Likert scale with 0-3 points. This scale was used to evaluate depressive symptoms that may be associated with anxiety.
(3) Symptom Checklist-90-Revised
The SCL-90-R is a self-reported test and is commonly used to measure overall psychiatric symptoms. The test evaluates somatization (SOM; 12 items), obsessive-compulsive characteristics (OC; 10 items), interpersonal sensitivity (IS; 9 items), depression (DEP; 13 items), anxiety (ANX; 10 items), hostility (HOS; 6 items), phobic anxiety (PHOB; 7 items), paranoid ideation, (PAR; 6 items), and psychoticism (PSY; 10 items) using symptom-level detailed scales, and each item is scored on a 4-point Likert scale consisting of 0-3 points. This scale was used to evaluate the patient's other psychiatric symptoms.
(4) Clinical Global Impression-Severity
As one of the most commonly used evaluation tools in the field of psychiatry, the CGI-S can be used to directly evaluate patients to measure the severity of symptoms, cure rates, and treatment effectiveness. It consists of a score from 1 to 7, and the severity of the patient's symptoms was evaluated according to standardized scoring guidelines.
(5) EEG recording and pre-processing
For EEG measurement, 19 channels of the international 10-20 system (Fp1, Fp2, F7, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4, P8, O1, O2) were used, and a 64-channel Comet digital EEG unit (Grass, Natus neurology, USA) was used for measurements with a recording frequency of 800 Hz with reference to the ear electrode. EEG measurements were obtained for 5 minutes with eyes open while lying on a comfortable bed, and then for 5 minutes with the eyes closed immediately afterwards. The patient was instructed to keep an eye on the “+” sign in the front when the eyes were open, to refrain from movement as much as possible, to remain in a state of not thinking about anything as much as possible, and to not fall asleep when the eyes were closed. EEG analysis was performed using the fast Fourier transforms (FFT) algorithm for each frequency band for each selected epoch: delta wave (1-4 Hz), theta wave (4-8 Hz), alpha wave (8-12 Hz), and beta wave (12-30 Hz). Beta waves were subdivided into low-beta (12-15 Hz), beta (15-25 Hz), and high-beta (25-30 Hz). MATLAB 7.0.1 (MathWorks, Massachusetts, U.S.A) and EEGLAB toolbox were used for analysis. To calculate the TBR, the theta wave was divided by the beta wave and used for analysis. For analysis, downsampling of EEG data to 250 Hz, detrending, and mean-subtracting were performed to remove the DC component. Then, less than 1 Hz and 60 Hz affected by electrical noise were removed through the filter, and the noise caused by blinking and muscle movement was then removed through independent component analysis (ICA). Finally, an experienced clinician performed a power spectrum analysis on EEG data for at least 2 minutes without noise.
(6) Statistical analysis
The Student t-test was used to compare continuous sociodemographic variables between the two groups (TRS and TRP), and the chi-square test was used for comparison of categorical variables. For each frequency and TBR at each site between the two groups, the total score of sex, age, and BDI, STAI-S, and STAI-T scores was set as a covariate, and then the difference between groups was analyzed using analysis of covariance (ANCOVA). Equality of variance was tested using Levene's test. The p-value was set as 0.05 and all analyses were performed using SPSS Version 25.0 for Windows (IBM Corp., Armonk, NY).