Effect of Coping With Stress Program to Depression, Anxiety, Brain Functions in Adolescent at High-Risk for Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional

Summary: 
      Depression is one of the leading diseases that cause disability, disease burden and threaten
      public health all over the world. In addition to the economic burdens brought on by
      depression, it also leads to many individual problems such as deterioration in education,
      increased psychiatric illnesses in the future, self-harm and suicide. For these reasons, it
      is important to prevent depression or delay the onset of depression. One of the depression
      prevention programs, "Coping with Stress Program", is a psychoeducational group program based
      on cognitive-behavioral therapy and researches shows that the program reduces the rate of
      diagnosing depression and depressive symptoms in adolescents. Although it is an important
      mental health problem, studies on adolescent depression are limited in Turkey and existing
      studies are descriptive and there are no randomized controlled trials. It is believed that
      this research will encourage studies to prevent depression in Turkey.

      The primary aim of this research is to determine the effect of coping with stress program on
      adolescents' depression and anxiety symptoms, which is applied to adolescents with high risk
      for depression. The second aim is to examine the changes in brain functions of adolescents
      participating in the coping with stress program. In the first step, high school students will
      be screened for depression and adolescents with high levels of depression will be identified.
      In the second step, randomized controlled experimental design will be used. At the first
      stage of the study, adolescents with high levels of depression and volunteering to
      participate in the study will be randomly assigned to the experimental and control groups.
      After pre-test measurements (determination of depression and anxiety level, functional
      magnetic resonance imaging (fMRI)), the Coping with Stress Program will be applied to the
      adolescents in the experimental group. Post-test measures (determination of depression and
      anxiety level, fMRI) will be performed. The amygdala stimulation test will be used for the
      fMRI experiment and the data obtained from the fMRI before and after the program will be
      investigated using the general linear model with Statistical Parametric Mapping (SPM).
    

Detailed description: 
      Study Type: The study was designed as a randomized controlled trial. Site and Date of the
      Study: The study will be conducted between October 2018 and January 2020 with the first-year
      high school students who are registered in the high schools under the governance of Izmir
      Balcova District National Education Directorate.

      Participants: The calculation of the sampling size was based on the Brain Functions outcome.
      It was recommended that at least 20 subjects should be included in each group for brain
      imaging studies. Taking into consideration the parametric characteristics of the data, which
      will be obtained with the scale, the investigators planned to include a total of 60 subjects
      (30 subjects in each group) in the study. The investigators also planned that 6-10 subjects
      should be adolescents in each group in experimental group. Experimental group will be
      evaluated with the help of the Coping with Stress Program.

      The sampling process of the study: During the initial phase of the study, adolescents, who
      will score 19 or more in the Children's Depression Scale, will be determined. The
      adolescents, who will fulfill the inclusion criteria, will be evaluated by the investigator
      with the help of the Hamilton Depression Scale. Adolescents, who will have a score equal to
      or more than 29 will be referred by the investigator to the Outpatient Department of the
      Children/Adolescent Mental Health at Dokuz Eylül University.

      The adolescents, who will fulfill the inclusion criteria, will be informed about the study's
      objective and methodology during a face-to-face conversation and their families will be
      informed by phone. The consent form will be handed to the adolescents in order that
      participants forward it to the parents for signing if they approve the participation of their
      children in the study. The adolescents, who will accept to participate, will be numbered
      starting from 1 and they will be randomized in the experimental and control groups with the
      help of a simple table of randomized numbers (experimental group: 30 subjects; control group:
      30 subjects).

      In the school, the subjects will undergo pre-test evaluation with Children Depression Scale,
      The Center for Epidemiological Studies Depression Scale, and Beck's Anxiety Scale after the
      obtainment of their verbal and written consent. Then 20 adolescents from the experimental
      group and 20 healthy adolescents will undergo fMRI examination. The individual
      characteristics of the groups (age, gender, socio-economic status, history of depression in
      parents) will be compared regarding the significant differences.

      Instruments At this phase of the study, the investigators plan to use the following forms,
      scales, and examinations: Information Questionnaire, Children Depression Scale, The Center
      for Epidemiological Studies Depression Scale, Beck's Anxiety Scale, Hamilton Depression
      Rating Scale, 3 Tesla Magnetic Resonance Imaging Device and Functional Magnetic Resonance
      Imaging (fMRI).

      Magnetic Resonance Imaging (MRI) Technique The MRI examinations will be conducted with 3.0
      Tesla magnet (Siemens, Erlangen, Germany) using a 12-channel head coil. First, the
      investigators will obtain structural images with the axial turbo spin echo (TSE) T2-weighted,
      coronary 3D-SPACE FLAIR (Dark fluid) and 3D-MPRAGE sequences. The obtained images will be
      immediately examined by the radiologist and interpreted for the presence of a brain
      anomaly/pathology considered among the inclusion criteria. Subjects without any
      radio-pathological finding will also be referred to the fMRI examination. The blood oxygen
      level-dependent (BOLD) technique, which is previously designed in concordance with the task
      design will be used for the fMRI.

      fMRI Task Meta-analyses which are focused on the evaluation of the structural and functional
      MRI studies of the depression patients, demonstrated anomalies in the amygdala, hippocampus,
      and subcortical regions. Therefore, the investigators decided to use an fMRI task, which will
      stimulate these structures. The amygdala stimulation test developed by Hariri, Bookheimer &
      Mazziotta is widely used in the studies and it was demonstrated that it could strongly and
      consistently stimulate amygdala.

      This test will be performed in a single session and the subjects will be asked to fulfill two
      different tasks. The first task consists of 3 blocks of cognitive face processing task and
      the second task consists of 4 blocks of sensorimotor control task. Facial expressions of
      anger, fear, surprise, and neutral faces from the FACES stimulus set will be used for this
      purpose (with equal numbers of male and female faces). Face-matching blocks will exhibit
      three faces, with one on the top and two at the bottom. The expressions will consist of
      anger, fear, surprise, and neutral outlook. The participant will be asked to match the face
      on the top with one of the faces at the bottom, which he/she will consider having the same
      expression. For each face expression (e.g. fear) there will be 6 trials which are equalized
      for the gender distribution. Each test will last 6 seconds. There will be an interval of 3
      seconds between each test (inter-stimulus interval). Each block lasts 54 seconds. In the
      sensorimotor control blocks, the participant will have 3 geometric shapes (circle,
      horizontal, and vertical ellipses), one on the top and two at the bottom and will be asked to
      match the shape on the top with one at the bottom, which he/she will consider as same. Each
      control block contains 6 different shapes matching and each test lasts 6 seconds. There will
      be a 3-second inter-stimulus interval between each test. Each block lasts 54 seconds. The
      blocks will start after a short instruction ("match the shapes" or "match the faces"). The
      total duration of the fMRI task is 399 seconds. Responses and the response time will be
      recorded.

      Data Collection Implementation 9th grader high school students will be screened during the
      2018-2019 school year and the Coping with Stress Program will be implemented in the
      experimental group, which will consist of 30 students. The demographic data of each student
      in the experimental and control groups will be collected with a data collection questionnaire
      before the start of the study (pre-test measurements).

      After the pre-test measurements, 20 volunteers from the control group will be scheduled for
      the fMRI examination. The adolescents and their family will be instructed about the measures,
      which are to be considered at the examination day and the adolescents will be informed that
      he/she should not fasten before the examination. On the examination day, the adolescents will
      be interviewed in the room of the Standardization of Computational Anatomy Techniques fıor
      Cognitive and Behavioral Sciences (SoCAT) research group in the Ege University, Department of
      Mental Health, and Psychiatry. During the interview, the adolescents will receive
      instructions about the fMRI task. During this instruction, which will last approx. 15
      minutes, a facial expression set, a shorter version of the set used during the fMRI
      examination, will be implemented. The adolescents, who have completed the instruction, will
      be referred to the 3 Tesla MRI unit of the Radiology Department in Ege University and will
      undergo MRI examination. The fMRI examination will be performed between 10:00-14:00 in
      weekends, as the unit is overloaded in weekdays. The adolescents will be asked not to move in
      the MRI device and will be informed that the fMRI process will start just after the
      structural imaging is completed. The structural imaging will last approx. 5 minutes and will
      be followed by the fMRI. During the whole process, the investigator Burcu Özkul and the
      radiology technician will be present in the MRI unit. Healthy adolescents will also undergo
      fMRI.

      The subjects in the experimental group will undergo the Coping with Stress Program. There
      will be no intervention in the control group; only pre-test, final test and monitoring
      measurements will be performed. After the completion of the program implemented in the
      experimental group (final test), all measurements will be repeated in the 3rd, 6th and 12th
      months in both experimental and control groups. fMRI imaging will be repeated for the
      subjects in the experimental group in the 2nd month.

      Data Analysis The data obtained during the study will be analyzed with the Statistical
      Package for the Social Sciences (SPSS) v.22 software package. Demographic data will be
      expressed with descriptive statistics, such as percentage, mean, and standard deviation. The
      distribution of the continuous data will be analyzed with the Kolmogorov-Smirnov Test and the
      homogeneity of the groups will be evaluated with Chi-square test. Regarding the repeated
      comparative measurements performed before the start of the program, they will be evaluated
      after the instruction, in the 3rd, 6th and 12th months with the variance analysis.

      fMRI Analysis: The images in DICOM format will be uploaded in the SPM 12 software and the
      standard pre-processing will be carried out. This process constitutes of a re-alignment
      process (aligning of the images in the time sequence in a 3D format), the normalization to
      the standard space (MNI) and finally the smoothing process. A general linear model (GLM) will
      be used for the statistical analysis. Therefore, the common and different neural circuits
      between the groups will be determined. The p-value of 0.05 will be considered as
      statistically significant for the intergroup comparisons (after the correction according to
      the multiple comparisons with the family-wise error correction). The minimum cluster
      threshold will be limited to 5 voxels.
    

Intervention name(s): Coping with Stress Course
Intervention type(s): Behavioral
Intervention description(s): The Coping with Stress Program is a group program, which is developed by Clarke and Lewinson (1995) for the prevention of depression in high-risk adolescents. It is based on cognitive-behavioral therapy principles and contains psychoeducation and cognitive-behavioral therapy interventions. There are handbooks available for the group leader of the program and the participating adolescents. In the handbook developed for the group leader, there is detailed information about the objective of each session and the implemented interventions. The adolescents will find lists organized for the fulfillment of the tasks in the handbook prepared for them. The handbooks of the program were translated in Turkish and experts were consulted for their validity.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: Depression; High-Risk; Adolescent; fMRI