The purpose of this study is to examine the effects of interventional/procedural therapies for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), racemic ketamine infusion and intranasal esketamine insufflation. The investigators will obtain various indicators, or biomarkers, of a depressed individuals' state before, during, and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging, electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and autonomic nervous system measures (i.e. "fight-or-flight" response). The results obtained from this study may provide novel antidepressant treatment response biomarkers, with the future goal of targeting a given treatment to an individual patient ("personalized medicine").
18-99 years of age
English-speaker with a level of understanding sufficient to agree to clinical treatment with a treatment modality offered by the Interventional Psychiatry Service, all required research procedures, and sign an informed consent document
Clinical diagnosis of a major depressive episode in the context of major depressive disorder or bipolar disorder or treatment-resistant OCD evaluated by a provider on the Interventional Psychiatry Service and felt to be an appropriate candidate for clinical treatment with a treatment modality offered by the Interventional Psychiatry Service.
Age less than 18 years
A primary neuropsychiatric diagnosis that is not either major depressive disorder or bipolar disorder
Serious, unstable medical conditions/problems including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, e.g. uncontrolled asthma, uncontrolled hyper/hypothyroidism or active cancer.
Involuntary commitment to psychiatry inpatient units
Adult patients (18-99 years old) in a current major depressive episode in the context of major depressive disorder (MDD) or bipolar disorder (BD) will be recruited for this protocol. Adult patients received TMS for OCD will also be recruited. All treatment will be in addition to the patient's clinical care with the University of Iowa's Interventional Psychiatry Service for treatment-resistant major depression or OCD, and the decision to participate, withdraw from participation or not participate will if not affect clinical care decision-making. We appreciate that minority groups tend to be underrepresented in neuropsychiatric research studies. Therefore, we will make a concerted effort to keep the proportion of racial/ethnic minorities recruited consistent with the demographics of the surrounding communities.
Cohort
Prospective
Electroconvulsive Therapy (ECT)
DeviceECT for the treatment of treatment-resistant depression OR Bipolar Disorder in an active major depressive episode
Transcranial Magnetic Stimulation (TMS)
DeviceTMS for the treatment of treatment-resistant depression in an active major depressive episode
Ketamine
DrugIntravenous ketamine infusion for the treatment of treatment-resistant depression in an active major depressive episode
Esketamine
DrugIntranasal esketamine insufflation for the treatment of treatment-resistant depression in an active major depressive episode
Deep Transcranial Magnetic Stimulation (dTMS)
DeviceTMS for the treatment of OCD
Montgomery-Åsberg Depression Rating Scale (MADRS) Pre-Post Change
For patients with TRD, the MADRS will be administered. The MADRS contains 10 items, and each item is scored 0-6. These item scores are summed to create a scale score; thus, scale scores range from 0 to 60. A scale score of 0 indicates the absence of depressive symptoms, while a score of 60 indicates severe depression. The primary outcome is the mean change in total MADRS score. A decrease in the mean MADRS score indicates a decrease (or improvement) in depressive symptoms, whereas an increase in the mean MADRS score indicates an increase (or worsening) in depressive symptoms.
Yale-Brown Obsessive Compulsive Scale
For patients with OCD, the YBOCS will be administered. Questions on the YBOCS examine the amount of time spent thinking and acting on obsessions and compulsions, how much impairment or distress is caused, and how much resistance and control the participant has over their thoughts or behavior.
Clinical Global Impression/Severity (CGI) Pre-Post Change
The CGI is a clinician-measured scale of 3 items: Severity of Illness (item 1), Global Improvement (item 2), and Efficacy Index (item 3). Items 1 and 2 are rated on a 7-point Likert scale (1=normal, 7=among the most extremely ill patients) with a possible response of "not assessed." Item 3 is rated on a 4-point Likert scale from "none" to "outweighs therapeutic effect." Items 1 and 3 are assessed in relation to last clinical encounter (if possible).
Generalized Anxiety Disorder, 7-item (GAD-7) Pre-Post Change
The GAD-7 is the self-reported anxiety questionnaire which scores each of the 7 symptoms of Generalized Anxiety Disorder in the last two weeks on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("over half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."
Montreal Cognitive Assessment (MoCA) Pre-Post Change
The MoCA is a 30-point screening instrument for detecting cognitive dysfunction. It is used to assess the following cognitive domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed (short-term memory recall), and orientation.
Patient Health Questionnaire, 9-item (PHQ-9) Pre-Post Change
The PHQ-9 is the self-reported depression module of the PHQ, which scores each of the 9 symptoms of a major depressive episode on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("more than half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."
Actigraphy Pre-Post Change
The patient will be asked to continuously wear a Fitbit wristband to monitor gross motor activity, e.g. foot steps. Changes in gross motor activity throughout the day will also provide data on circadian rhythmicity (sleep-wake cycles).
Candidate Gene (DNA) Polymorphisms
The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, and DNA will be isolated and extracted. Data on genetic polymorphisms (differences) that have been demonstrated or hypothesized to play a functional role in major depression, e.g. the brain derived neurotrophic factor (BDNF) rs6265 (val66met) single nucleotide polymorphism, will be obtained. These genotypes (genetic data) will then be correlated with antidepressant response.
Electroencephalography (EEG) Pre-Post Change
The investigators will obtain task-free ("resting state") rs-EEG \[detecting electrical signals in the brain\] at baseline and in response to interventional treatments for treatment-resistant depression.
Epigenetic (Experience-Based) DNA Modifications Pre-Post Change
The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, at baseline and in response to interventional treatments for treatment-resistant depression. DNA will be isolated and extracted. Data on epigenetic (experience-based) modifications to the DNA that have been demonstrated or hypothesized to play a functional role in major depression, e.g. global methylation changes, will be obtained. Changes in epigenetic status, e.g. global DNA methylation changes pre- and post-treatment, will then be correlated with antidepressant response.
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Mark Niciu
Lead sponsor
University of Iowa
Sponsor institution
