iTBS-DCS in Obsessive Compulsive Disorder

Clinical Remission

score ≤12 on the YBOCs

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Clinical Response

≥30% reduction in YBOCS scores from baseline

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Montgomery-Asberg Depression Rating Scale (MADRS)

Change in severity of depressive symptoms as measured by the MADRS, a clinician-rated instrument. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes. The overall score ranges from 0 - 60. Cutoff points are 0-6 = normal, 7-9 = mild depression, 20-34 = moderate depression, \>34 = severe depression.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Change in self reported anxiety symptoms

Anxiety symptoms will be assessed using the 7 item Generalized Anxiety Disorder (GAD-7) questionnaire. The GAD-7 measures self-reported feelings of anxiety within the last 2 weeks. Scores range from 0-21. Scores of 5, 10, and 15 represent cut points for mild, moderate, and severe anxiety, respectively.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Change in quality of Life as measured by the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire

The WHOQOL-BREF is a self-reported questionnaire which assesses individual's perception of their quality of life across 4 domains; physical health, psychological, social relationships and environment. Domains scores are calculated to range from 0-20 and scaled in a positive direction (ie. higher scores denote higher quality of life).

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Change in self reported depressive symptoms as measured by The Quick Inventory of Depressive Symptomatology (QIDS)

The Quick Inventory of Depressive Symptomatology (QIDS) rates depression symptoms via self-assessment.Severity of depression can be judged based on the total score. 1-5 = No depression 6-10 = Mild depression 11-15 = Moderate depression 16-20 = Severe depression 21-27 = Very severe depression

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Change in self reported measures of workplace productivity

Productivity will be assessed using the Lam Employment Absence and Disability Scale (LEAPS). The LEAPS is a 10-item, self-rated scale and provides information on how participants are functioning at work. Scores range from 0 - 28, with higher scores representing more severe work impairment.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Clinical Global Impression- Severity

The CGI-Severity scale is clinician rated from 1-7 representing 'Not at all ill' to 'Severely ill'.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Clinical Global Impression- Improvement

The CGI-Improvement scale is a clinician rated 1-7, representing the range between 'Very much improved' and 'Very much worse' from the baseline visit.

Time frame: Administered at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Stool samples- microbiome analysis

Microbiome analysis will include α-diversity metrics for each sample and β-diversity measures (weighted and unweighted unifrac, Bray-Curtis, nonmetric multidimensional scaling) and other statistical analysis using QIIME and PhyloSeq. Association of specific taxa and co-occurrence of taxa with sample groups will be examined with ANOVA, the G test of independence, or a paired t-test in QIIME. Sequence data will be assembled and analyzed with the QIIME package. Statistical significance of depression-associated signature profiles will be identified by multivariate statistics (PC-ORD software, R statistical package). Microbial 16S rRNA gene sequence libraries will be compared for distinct microbial patterns.

Time frame: Samples will be collected at baseline, after TMS treatment (week 4) and 4 weeks after completion of TMS (week 8)

Stool samples- metabolomics

Changes in fecal metabolomics will be assessed. Fecal supernatants will be removed and filtered through 0.2 μm membrane filters. The fecal sample will be transferred to a standard NMR tube for 1H-NMR spectral analysis on a 500 MHz Inova spectrometer. Spectral fitting for metabolites will be done using the standard Chenomx 500 MHz metabolite library. Typically, 90% of visible peaks are assigned to a compound and more than 90% of the spectral area can be routinely fit using the Chenomx spectral analysis software.

Time frame: Samples will be collected at baseline, after TMS treatment (week 4) and 4 weeks after completion of TMS (week 8)

Change in Cognitive Function - THINC-it- PDQ-5

Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire. The cognitive questionnaire is called the Perceived Deficits Questionnaire - 5 item scale (PDQ-5). The questionnaire assesses self perceived cognition by asking questions about attention/concentration, retrospective memory, prospective memory, and planning/organization. Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Change in Cognitive Function - THINC-it- Choice Reaction Time

Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire. The first objective cognitive test is called "spotter" and measures choice reaction time by calculating the total time that elapses between the presentation of a stimulus and the occurrence of a response in a task that requires a participant to make one of two different responses depending on which stimuli is presented. Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Change in Cognitive Function - THINC-it- Working Memory

Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire. The second objective cognitive test is called "Symbol Check" and is an n-back test. N-back tests measure working memory by presenting the subject with a sequence of stimuli, and the task consists of selecting the stimuli that was presented n steps earlier in the sequence. Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Change in Cognitive Function - THINC-it- Digit Symbol Substitution

Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire. The third objective cognitive test is called "CodeBreaker" and is a Digit Symbol Substitution Test (DSST). DSST involves a key consisting of the numbers 1-6, each paired with a unique symbol. Below the key are a series of the numbers 1-6 in random order and repeated several times. Subjects must select the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Change in Cognitive Function - THINC-it- Trail Making Test part B

Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire. The fourth objective cognitive test is called "Trails" and is a version of the Trail Making Test part B (TMT-B). The subject is presented with numbers and letters in circles placed in random array on the screen. The subject must draw a line from one circle to the next in ascending order; however, s/he must alternate the circles with numbers in them and circles with letters in them (ie, 1-A-2-B-3-C etc). The TMT is a timed test and the goal is to complete the tests accurately and as quickly as possible. Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Implicit Suicidality

Death Implicit Association Test (D-IAT) is a behavioral test that measures the strength of automatic (implicit) associations between concepts in people's minds relying on latency measures in a simple sorting task. The strength of an association between concepts of "death" and "ones self" is measured by the standardized mean difference score of the 'hypothesis-inconsistent' pairings and 'hypothesis-consistent' pairings

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Wisconsin Card Sorting Task (WCST)

The WCST is a neuropsychological instrument used to measure the executive functions, reportedly sensitive to brain dysfunction affecting the frontal lobes.

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Stop Signal Task

The stop-signal reaction time in the Stop-Signal Task. The stop signal reaction time ranges from 50 to 250, where greater values represent worse outcome (i.e, increased motor impulsivity).

Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)

Change in self reported cognitive failures as measured by The Cognitive Failures Questionnaire (CFQ)

The Cognitive Failures Questionnaire (CFQ) is used to assess the frequency with which people experienced cognitive failures, such as absent-mindedness, in everyday life -- slips and errors of perception, memory, and motor functioning. Individuals are asked to rate how often in the past 6 months they have experienced different cognitive failures from "never "(0) to "very often" (4). The sum of the ratings of the 25 individual items yields a score from 0-100, with higher scores indicating more cognitive failures.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

VAS for General Health

A Visual Analog Scale (VAS) will ask participants how good or bad their health is today. This scale is numbered from 0 to 100. 100 indicates the best health they can imagine. 0 indicates the worst health they can imagine.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Change in suicidal intentions

The Scale for Suicide Ideation (SSI) is a brief 19-item scale that assesses the person's current intensity of attitudes, plans, and behaviors to commit suicide. Each question has 3 answer choices. The answer choice suggesting the least suicide intentions is scored as 0, and answer choice suggesting the most suicide intentions are scored as 2. Total score is determined based on the sum of all individual scores.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Change in severity of skin-picking symptoms

The Yale-Brown Obsessive Compulsive Scale Modified for Neurotic Excoriation (NE-YBOCS) is a 10-item instrument used to assess severity of skin picking disorder symptoms during the preceding seven days. Responses to the 10 items are coded on a 4-point scale and summed to produce a composite score ranging from 0 to 40, with higher scores reflecting greater illness severity.

Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)