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Past Medication Use Continues to Affect Resting-State Connectivity in Obsessive-Compulsive Disorder

Poster No:

550 

Submission Type:

Abstract Submission 

Authors:

Anders Lillevik Thorsen1,2,3, Chris Vriend3,4, Niels de Joode3,4, Petra Pouwels3,4, Feng Liu5, Maria Otaduy6, Bruno Pastorello6, Frances Robertson7, Jonathan Ipser7, Seonjoo Lee5, Dianne Hezel5, Page van Meter5, Marcelo Batistuzzo6, Marcelo Hoexter6, Karthik Sheshachala8, Janardhanan Narayanaswamy8, Ganesan Venkatasubramanian8, Christine Lochner9, Euripedes Miguel6, Y.C. Janardhan Reddy8, Roseli Shavitt6, Dan Stein7, Melanie Wall5, Helen Blair Simpson5, Odile van den Heuvel3,4

Institutions:

1Haukeland University Hospital, Bergen, Norway, 2University of Bergen, Bergen, Norway, 3Amsterdam UMC, Amsterdam, Netherlands, 4Amsterdam Neuroscience, Amsterdam, Netherlands, 5Columbia University, and New York State Psychiatric Institute, New York, NY, 6Universidade de São Paulo, São Paulo, Brazil, 7University of Cape Town, Cape Town, South Africa, 8National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India, 9Stellenbosch University, Stellenbosch, South Africa

First Author:

Anders Lillevik Thorsen, PhD  
Haukeland University Hospital|University of Bergen|Amsterdam UMC
Bergen, Norway|Bergen, Norway|Amsterdam, Netherlands

Co-Author(s):

Chris Vriend, PhD  
Amsterdam UMC|Amsterdam Neuroscience
Amsterdam, Netherlands|Amsterdam, Netherlands
Niels de Joode, MSc  
Amsterdam UMC|Amsterdam Neuroscience
Amsterdam, Netherlands|Amsterdam, Netherlands
Petra Pouwels, PhD  
Amsterdam UMC|Amsterdam Neuroscience
Amsterdam, Netherlands|Amsterdam, Netherlands
Feng Liu, PhD  
Columbia University, and New York State Psychiatric Institute
New York, NY
Maria Otaduy, PhD  
Universidade de São Paulo
São Paulo, Brazil
Bruno Pastorello, PhD  
Universidade de São Paulo
São Paulo, Brazil
Frances Robertson, Phd  
University of Cape Town
Cape Town, South Africa
Jonathan Ipser  
University of Cape Town
Cape Town, South Africa
Seonjoo Lee, PhD  
Columbia University, and New York State Psychiatric Institute
New York, NY
Dianne Hezel, PhD  
Columbia University, and New York State Psychiatric Institute
New York, NY
Page van Meter, PhD  
Columbia University, and New York State Psychiatric Institute
New York, NY
Marcelo Batistuzzo, PhD  
Universidade de São Paulo
São Paulo, Brazil
Marcelo Hoexter, MD, PhD  
Universidade de São Paulo
São Paulo, Brazil
Karthik Sheshachala, PhD  
National Institute of Mental Health & Neurosciences (NIMHANS)
Bangalore, India
Janardhanan Narayanaswamy, MD, PhD  
National Institute of Mental Health & Neurosciences (NIMHANS)
Bangalore, India
Ganesan Venkatasubramanian, MD, PhD  
National Institute of Mental Health & Neurosciences (NIMHANS)
Bangalore, India
Christine Lochner, PhD  
Stellenbosch University
Stellenbosch, South Africa
Euripedes Miguel, MD, PhD  
Universidade de São Paulo
São Paulo, Brazil
Y.C. Janardhan Reddy, MD  
National Institute of Mental Health & Neurosciences (NIMHANS)
Bangalore, India
Roseli Shavitt, MD, PhD  
Universidade de São Paulo
São Paulo, Brazil
Dan Stein  
University of Cape Town
Cape Town, South Africa
Melanie Wall, PhD  
Columbia University, and New York State Psychiatric Institute
New York, NY
Helen Blair Simpson, MD, PhD  
Columbia University, and New York State Psychiatric Institute
New York, NY
Odile van den Heuvel  
Amsterdam UMC|Amsterdam Neuroscience
Amsterdam, Netherlands|Amsterdam, Netherlands

Introduction:

Obsessive-compulsive disorder (OCD) is associated with altered functional connectivity (FC) within and between key brain networks (Stein et al., 2019; Thorsen & van den Heuvel, 2023). However, the magnitude and direction of these alterations is inconsistent and likely influenced by medication use, age, data acquisition and processing procedures (Stein et al., 2019). A notable limitation of most previous studies is low sample size. ENIGMA-OCD attempted to address this through a mega-analysis which found less somatomotor network FC in adults with OCD vs healthy controls (HC), which was driven by patients using selective serotonin reuptake inhibitors (SSRI) or serotonin norepinephrine reuptake inhibitors (SNRI, Bruin et al., 2023). However, such mega-analyses are limited by lack of harmonized data collection. Here, we present findings from the Global OCD study (Pouwels et al. 2023; Simpson et al., 2020), which compares network FC in adult individuals with OCD and HC using harmonized data acquisition and processing procedures across five sites and continents based on a preregistered analysis plan (https://osf.io/b3vz5).

Methods:

FC between and within the visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal and default mode networks was compared between 259 currently unmedicated (for a minimum of 6 weeks) adults with OCD and 251 age, sex matched HC (mean age 29.79 (SD 8.03), 56% female). Connectivity was estimated in grayordinate fsLR32k space, providing optimal spatial resolution and minimized blurring between regions (Coalson et al., 2018). Denoising included ICA-AROMA noise components, mean cerebrospinal fluid and white matter signals, detrending, and bandpass filtering (0.009-0.08 Hz). FC was estimated between regions of the Schaefer 400 cortical parcellation and 36 subcortical regions from the Brainnetome atlas. ComBat was used to adjust for site differences in FC, permutation-based linear models adjusted for age, sex and years of education were used for statistical analyses, and the false discovery rate was used to adjust for multiple comparisons.

Results:

No significant differences in FC were found between adults with OCD and HC. Among individuals with OCD, those with previous use of medication (n=112, including n=99 SSRI, n=4 SNRI, n=9 both), compared to 147 medication naive patients, showed significantly weaker FC between the ventral attention and default mode network and between the ventral attention and limbic network (pFDR<.03, d≥0.43). Post-hoc tests showed that more days since last SSRI/SNRI use was related to stronger FC between the ventral attention and default mode network (uncorrected p<.03, r=.12). Furthermore, previously medicated, but not medication naive, patients also showed significantly weaker FC between the ventral attention and limbic network and between the ventral attention and default mode network compared to HC (uncorrected p<.02, d≥-0.35). Medication naive patients showed less severe symptoms of OCD (Yale-Brown Obsessive-Compulsive Scale), depression (Hamilton Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale) than previously medicated patients (uncorrected p<.04, d≥0.28), but the difference in ventral attention-limbic and ventral attention-default mode FC versus medication naïve patients remained after adjusting for these variables.
Supporting Image: Med_status_combined_no_caption.png
   ·Difference between 251 healthy controls, 147 medication naïve individuals with OCD, and 112 previously medicated individuals with OCD in DMN-VAN and limbic-VAN functional connectivity
Supporting Image: between_Default_SalVentAttn_ComBat_TxHis_SRI_orSNRI_days_no_caption.png
   ·Linear relation between days since last SSRI/SNRI use and DMN-VAN functional connectivity in 112 previously medicated individuals with OCD
 

Conclusions:

The overall difference in network FC between unmedicated adults with OCD and HC is small and not significant in this relatively large multicenter study with harmonized data collection and processing. Comparions between previously medicated and medication naïve individuals with OCD suggests that previous use of SSRI/SNRI continues to be associated with network FC after a minimum of a six-week wash-out period.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural) 2

Novel Imaging Acquisition Methods:

BOLD fMRI

Keywords:

FUNCTIONAL MRI
Obessive Compulsive Disorder
Other - functional connectivity; serotonin reuptake inhibitor

1|2Indicates the priority used for review

Provide references using author date format

Bruin, W. B. (2023). The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium. Molecular Psychiatry, 1-13.
Coalson, T. S. (2018). The impact of traditional neuroimaging methods on the spatial localization of cortical areas. Proceedings of the National Academy of Sciences, 115(27)
Pouwels, P. J. (2023). Global multi‐center and multi‐modal magnetic resonance imaging study of obsessive‐compulsive disorder: Harmonization and monitoring of protocols in healthy volunteers and phantoms. International Journal of Methods in Psychiatric Research, 32(1), e1931.
Simpson, H. B. (2020). Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative. BMC Ppsychiatry, 20, 1-14
Stein, D. J. (2019). Obsessive–compulsive disorder. Nature reviews Disease Primers, 5(1)
Thorsen, A. L. (2023). Neuroanatomy of obsessive-compulsive and related disorders. In Tolin, D. (Ed.) Oxford Handbook of Obsessive Compulsive and Related Disorders, Second Edition. Oxford University Press.