Functional Magnetic Resonance Imaging (fMRI) Investigation Into Compulsivity in Anorexia

An fMRI Investigation Into Compulsivity in Those Who Have Recovered From Anorexia Nervosa

The investigators will examine compulsivity in those who have recovered from anorexia nervosa, using a multi-modal MRI study. The neural activation of key fronto-striatal areas will be explored using a task which examines set-shifting and reversal-learning, two key components of compulsivity. Additionally, the functional networks displayed during resting-state MRI will be examined between groups, as will the neurochemicals present (using Magnetic Resonance spectroscopy).

Study Overview

• Status: Completed
• Conditions: Compulsive Behavior; Anorexia Nervosa in Remission (Disorder)
• Intervention / Treatment: Other: MRI

Detailed Description

The investigators will perform four different MRI (Magnetic Resonance Imaging) scans during one scanning session on those who have recovered from anorexia nervosa (AN) and healthy controls.

Participants will come to the Warneford hospital for a 2.5 hour screening visit, which will consist of questionnaires and interviews to determine their medical and psychiatric history and current mood, along with a practice of the task they'll do in the scanner. Participants will also complete two tasks which measure compulsivity and can be correlated with their brain activity in the scans. The investigators will also go through a scanning safety form with participants at this time.

Participants will also attend a scanning visit, which will last 1.5 hours. One of the scans will look at how the brain responds to a particular task. This task will examine aspects of compulsivity (which is rigidly repeating actions that aren't rewarding) by using face and house stimuli (see reference 1).

The investigators will also perform a scan when participants are at rest, in order to see if there are differences in the way areas of the brain connect to each other who used to have AN. The scientific literature indicates that there may be differences in the some key brain networks, including one which is thought to be involved in reflection and the self (the default mode network), which might also be linked to compulsivity (see reference 2).

This study will also further investigate some initial pilot findings using Magnetic Resonance Spectroscopy, which allows researchers to examine the levels of different neurochemicals in the brain. It has been found that those with a current diagnosis of AN have lower levels of glutamate (a key brain chemical) compared to healthy controls, which is a finding we seek to extend in those who have recovered from AN (see reference 3).

Aims: The investigators aim to see whether there are differences in the brains of those who have recovered from anorexia compared to those who have never had an anorexia diagnosis. This will be both at rest, and whilst participants are doing a task which measures compulsivity, as compulsivity is thought to be a particular risk factor for eating disorders.

Value: If the investigators are able to identify differences, these might reflect underlying risk factors for eating disorders, which could lead to potential future treatments or prevention schemes.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7JX
      • Department of Psychiatry, University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Able and willing to give informed consent
• BMI over 18.5 and has remained so for the last year
• Score lower than mean+1 standard deviation of global mean scores for young women on the EDE
• Fluent English speaker
• Former diagnosis of anorexia nervosa in relevant group

Exclusion Criteria:

• Any current diagnosis of a psychiatric disorder which in the investigator's opinion could impact study results (e.g. significant depression, anxiety or OCD).
• Any current psychotropic medications.
• Eyesight problems that would prohibit participating in a task-fMRI study.
• Current regular cigarette smoking of over 5 cigarettes per day.
• Recent use of illicit drugs.
• Alcohol intake which indicates an element of alcohol abuse; or unwillingness to refrain from drinking the night before the study visit.
• Any contraindications to MRI scanning (including claustrophobia).
• Participant is pregnant or breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Recovered from anorexia nervosa; Women who have recovered from Anorexia Nervosa for over a year. BMI over 18.5, aged 18-40, scores on Eating Disorder Examination (EDE) within 1 standard deviation of the global mean. All these participants undergo an MRI scan.	Other: MRI; MRI scan, including structural imaging, functional imaging (both task-related and structural), and Magnetic Resonance Spectroscopy.
Experimental: Healthy controls; Healthy control women. BMI over 18.5, aged 18-40, scores on EDE within 1 standard deviation of the global mean. All these participants undergo an MRI scan.	Other: MRI; MRI scan, including structural imaging, functional imaging (both task-related and structural), and Magnetic Resonance Spectroscopy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Oxygen-Level Dependent (BOLD) signal whilst performing set-shifting and reversal-learning	BOLD signal differences between groups during the set-shifting and reversal-learning elements of a task: will be examined in orbitofrontal cortex, dorsolateral prefrontal cortex, and striatum. Analyse using a repeated measures ANOVA with region as within-subject factor and group as between-subject factor. Follow up significant interactions with paired t-tests.	1 day (During MRI scan)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences between groups in the connectivity of the fronto-parietal and default mode networks using independent components analysis, dual regression and permutation testing across the brain.	A resting state scan will be performed, and an Independent Components Analysis will be performed to identify networks. Dual regression using fronto-parietal and default mode network to test whether there are group differences. This procedure regresses the group-spatial-maps into each subject's 4D dataset to give a set of timecourses, then regresses these timecourses into the same 4D dataset to get a subject-specific set of spatial maps. Then, the researchers will compare the spatial maps across groups of subjects to look for group differences in connectivity across the brain, using randomise permutation testing.	1 day (During MRI scan)
The correlation of the default mode network and frontoparietal network activity with perseverative errors on the Wisconsin Card Sorting Task across groups	Correlate perseverative errors on Wisconsin Card Sorting Task with connectivity level of Default Mode Network (DMN) and frontoparietal network	1 day (During MRI scan)
Investigate a difference in levels of glutamate between groups	Concentration of cortical glutamate in those who have recovered from anorexia relative to controls. Will be analysed using LCModel to quantify metabolites, then an independent samples t-test.	1 day (During MRI scan)
Examine differences between groups on an impulsivity measure	Differences between scores on the Affective Go/No-Go Task. Analysed using a independent-samples t-test.	1 day (During MRI scan)

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Philip J Cowen, Prof, University of Oxford

Publications and helpful links

General Publications

• Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, Aitken M, Craig K, Owen AM, Bullmore ET, Robbins TW, Sahakian BJ. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008 Jul 18;321(5887):421-2. doi: 10.1126/science.1154433.
• Boehm I, Geisler D, King JA, Ritschel F, Seidel M, Deza Araujo Y, Petermann J, Lohmeier H, Weiss J, Walter M, Roessner V, Ehrlich S. Increased resting state functional connectivity in the fronto-parietal and default mode network in anorexia nervosa. Front Behav Neurosci. 2014 Oct 2;8:346. doi: 10.3389/fnbeh.2014.00346. eCollection 2014.
• Godlewska BR, Pike A, Sharpley AL, Ayton A, Park RJ, Cowen PJ, Emir UE. Brain glutamate in anorexia nervosa: a magnetic resonance spectroscopy case control study at 7 Tesla. Psychopharmacology (Berl). 2017 Feb;234(3):421-426. doi: 10.1007/s00213-016-4477-5. Epub 2016 Dec 1.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2017
• Primary Completion (Actual): February 7, 2018
• Study Completion (Actual): February 7, 2018

Study Registration Dates

• First Submitted: February 15, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: April 3, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: MRI
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Impulsive Behavior; Anorexia; Anorexia Nervosa; Compulsive Behavior
• Other Study ID Numbers: R47959/RE004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No