Clinical trial NCT01882023: Comparing Neural Responses to Food Images in EDNOS Patients and Healthy Controls Using fMRI
Official title: Comparing Neural Responses to Explicit and Subliminal Food Images in EDNOS Patients and Healthy Controls Using fMRI
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Eating Disorders
Keywords: EDNOS
adolescents
eating disorder
anorexia nervosa
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2013-06-20
Enrollment: 150
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Half of the cohort are patients recruited from the eating disorder clinic. All subjects in the study are adolescent females residing in the Uppsala area.

Brief summary: Currently, there is not a robust, testable neural model available that sufficiently explains the development and maintenance of anorexia nervosa (AN) a severe, often fatal, adolescent-onset eating disorder. Using state of the art neuroimaging and neuropsychological techniques, our objective is to identify neural mechanisms in the adolescent brain underlying AN. This is of high clinical relevance in as much as it will provide a robust platform for a diagnostic battery so that physicians can identify those who are prone to develop AN at a very early stage of life.

The aim of this research plan is: 1) To develop knowledge of cognitive dysfunction in adolescents who have recently been diagnosed with AN, with a battery of cognitive tests during a series of clinical visits. 2) To provide a scientific basis for our knowledge about how the brain of an adolescent with an eating disorder differs from that of a healthy adolescent, by conducting functional and structural magnetic resonance imaging on adolescent females with AN.

Detailed description: Adolescents with eating disorders have debilitating cognitive disturbances that impact on their social, educational and physical health. One cognitive trait that is found to form core cognitive disturbances in AN is superior working memory (WM). WM is the ability to ruminate on a cognitive strategy while attending to the details of another task, excluding non-relevant stimuli, and is linked to activation of the dorsolateral prefrontal cortex (DLPFC). By administering functional Magnetic Resonance Imaging (fMRI) we have recently found that females with AN have increased activation in the DLPFC and reduced appetitive brain responses when thinking about eating food shown in visual images. This suggests that the increased WM capacity in AN may serve to suppress food intake, but this has not yet been clarified. In line with this assumption, we have also shown that restraint of appetite in those with AN was linked to greater plasticity in the DLPFC. Furthermore, Transcranial Magnetic Stimulation (TMS) of the DLPFC reduces appetitive responses to food stimuli in adults with eating disorders. Conversely, we have shown that being obese is linked to reduced structure and abnormal function in the DLPFC, as well as reduced attentional control/WM performance. Therefore, it is likely that DLPFC-related WM function is associated with eating disorders, particularly cognitive restraint of appetite.

It is likely that the interaction between appetitive brain regions and specific prefrontal cortex (PFC) cognitions determines whether an adolescent develops anorexia nervosa. We aim to provide neuropsychological and brain imaging measures showing how a specific cognitive function is linked to early-onset disordered eating behaviour, and we will do this before and after standard clinical treatment. We suggest that such understanding could enable school nurses to use the unique paradigm we use in our fMRI study, to detect illness before it damages the child's life and becomes difficult to treat.

The study has now been increased to include genetic components to examine the genetic and epigenetic variation for genes found to be linked with eating disorders.

Eligibility criteria: Inclusion Criteria:

* Females
* Age 13 - 18 yrs
* Right handed
* For controls: BMI within the "normal" range
* For patients: Be admitted to treatment for an eating disorder

Exclusion Criteria:

* On medication
* Suffering from any other illnesses
* Left handed
* Metal implants which can impact the fMRI image
* Severe claustrophobia
* Pregnancy
* Smoker
* Regular alcohol drinker

Primary outcomes:
measure: Measure functional differences in adolescents with eating disorders and healthy controls.
timeFrame: This is measured during scanning shortly after patient admittance to treatment, and one year later. Controls have their scans shortly after being recruited to the study, then again 1 year later.
Secondary outcomes:
measure: Measure structural differences in adolescents with eating disorders and healthy controls.
timeFrame: This is measured during scanning shortly after patient admittance to treatment, and one year later. Controls have their scans shortly after being recruited to the study, then again 1 year later.
measure: Develop knowledge of cognitive dysfunction in adolescents with eating disorders.
timeFrame: The cognitive measures are conducted shortly after recruitment of the study. The subjects are given the questionnaires upon their first meeting, and are posted back to us shortly after.
measure: To examine whether clinical variables can predict neural activity.
timeFrame: The neural activity is measured during scanning shortly after subject recruitment, and one year later. The clinical measurements are measured with questionnaires given to them on their first meeting after recruitment, which are later posted back to us.
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Röntgenavdelningen, Uppsala Academic Hospital
state: Uppsala Län
Study officials:
affiliation: Uppsala University
name: Christina Zhukovsky, MMed
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brooks SJ, O'Daly OG, Uher R, Schioth HB, Treasure J, Campbell IC. Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa. Conscious Cogn. 2012 Jun;21(2):751-63. doi: 10.1016/j.concog.2012.02.006. Epub 2012 Mar 11.
citation: Andrews SC, Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB. Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimul. 2011 Apr;4(2):84-9. doi: 10.1016/j.brs.2010.06.004. Epub 2010 Jul 11.
citation: Brooks SJ, O'Daly OG, Uher R, Friederich HC, Giampietro V, Brammer M, Williams SC, Schioth HB, Treasure J, Campbell IC. Differential neural responses to food images in women with bulimia versus anorexia nervosa. PLoS One. 2011;6(7):e22259. doi: 10.1371/journal.pone.0022259. Epub 2011 Jul 20.
citation: Brooks SJ, O'Daly O, Uher R, Friederich HC, Giampietro V, Brammer M, Williams SC, Schioth HB, Treasure J, Campbell IC. Thinking about eating food activates visual cortex with reduced bilateral cerebellar activation in females with anorexia nervosa: an fMRI study. PLoS One. 2012;7(3):e34000. doi: 10.1371/journal.pone.0034000. Epub 2012 Mar 27.
citation: Brooks SJ, Barker GJ, O'Daly OG, Brammer M, Williams SC, Benedict C, Schioth HB, Treasure J, Campbell IC. Restraint of appetite and reduced regional brain volumes in anorexia nervosa: a voxel-based morphometric study. BMC Psychiatry. 2011 Nov 17;11:179. doi: 10.1186/1471-244X-11-179.
citation: Van den Eynde F, Claudino AM, Mogg A, Horrell L, Stahl D, Ribeiro W, Uher R, Campbell I, Schmidt U. Repetitive transcranial magnetic stimulation reduces cue-induced food craving in bulimic disorders. Biol Psychiatry. 2010 Apr 15;67(8):793-5. doi: 10.1016/j.biopsych.2009.11.023. Epub 2010 Jan 8.
citation: Brooks SJ, Benedict C, Burgos J, Kempton MJ, Kullberg J, Nordenskjold R, Kilander L, Nylander R, Larsson EM, Johansson L, Ahlstrom H, Lind L, Schioth HB. Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study. Int J Obes (Lond). 2013 Feb;37(2):230-6. doi: 10.1038/ijo.2012.13. Epub 2012 Jan 31.
citation: Olivo G, Wiemerslage L, Swenne I, Zhukovsky C, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Correction: Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders. PLoS One. 2017 Apr 20;12(4):e0176646. doi: 10.1371/journal.pone.0176646. eCollection 2017.
citation: Olivo G, Wiemerslage L, Swenne I, Zhukowsky C, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders. PLoS One. 2017 Mar 1;12(3):e0172129. doi: 10.1371/journal.pone.0172129. eCollection 2017.
citation: Olivo G, Zhou W, Sundbom M, Zhukovsky C, Hogenkamp P, Nikontovic L, Stark J, Wiemerslage L, Larsson EM, Benedict C, Schioth HB. Resting-state brain connectivity changes in obese women after Roux-en-Y gastric bypass surgery: A longitudinal study. Sci Rep. 2017 Jul 26;7(1):6616. doi: 10.1038/s41598-017-06663-5.
citation: Gaudio S, Carducci F, Piervincenzi C, Olivo G, Schioth HB. Altered thalamo-cortical and occipital-parietal- temporal-frontal white matter connections in patients with anorexia and bulimia nervosa: a systematic review of diffusion tensor imaging studies. J Psychiatry Neurosci. 2019 Sep 1;44(5):324-339. doi: 10.1503/jpn.180121.
citation: Olivo G, Swenne I, Zhukovsky C, Tuunainen AK, Saaid A, Salonen-Ros H, Larsson EM, Brooks SJ, Schioth HB. Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa. Int J Eat Disord. 2019 Feb;52(2):166-174. doi: 10.1002/eat.23012. Epub 2019 Jan 24.
citation: Olivo G, Swenne I, Zhukovsky C, Tuunainen AK, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa. Transl Psychiatry. 2018 Dec 13;8(1):275. doi: 10.1038/s41398-018-0333-1.
citation: Gaudio S, Olivo G, Beomonte Zobel B, Schioth HB. Altered cerebellar-insular-parietal-cingular subnetwork in adolescents in the earliest stages of anorexia nervosa: a network-based statistic analysis. Transl Psychiatry. 2018 Jul 6;8(1):127. doi: 10.1038/s41398-018-0173-z.
citation: Olivo G, Solstrand Dahlberg L, Wiemerslage L, Swenne I, Zhukovsky C, Salonen-Ros H, Larsson EM, Gaudio S, Brooks SJ, Schioth HB. Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients. Int J Eat Disord. 2018 Jan;51(1):39-45. doi: 10.1002/eat.22805. Epub 2017 Dec 7.