Eating Disorder
Conditions
Brief summary
This study will use brain imaging technologies to measure several neurotransmitters (serotonin and dopamine) that contribute to our abilities to respond to reward or inhibit our impulses, and which are known to be altered in the brain of people with anorexia nervosa (AN) and bulimia nervosa (BN). Because palatable food stimulates dopamine secretion, we propose to use a challenge with brain imaging that will stimulate dopamine release which we hypothesize will generate anxiety rather than pleasure in AN, and will help explain why AN restrict eating in order to reduce anxiety. This study will help to understand the unique puzzling symptoms in eating disorders and contribute to finding better methods for identifying effective treatments for these often relapsing and sometimes chronic disorders.
Detailed description
Alterations of serotonin (5-HT) and dopamine (DA) activity may contribute to extremes of appetitive behaviours in anorexia nervosa (AN) and bulimia nervosa (BN), through effects on inhibitory and reward neural pathways. To avoid the confounding effects of malnutrition, and because they have behaviours and neural circuit alterations relevant for this study, we will study 25 recovered (REC) restricting-type AN, 25 REC bulimic-type AN (AN-BN), 25 REC BN, and 25 control women (CW). This 5 year study, of women 18 to 45 years old, will employ positron emission tomography (PET) imaging with radioligands for the 5-HT transporter (\[11C\]DASB) and DA D2/D3 receptors (\[11C\]raclopride).
Interventions
DRUG[11C]raclopride
1.\[11C\]raclopride -The change (Δ) in BPND (the difference between the \[11C\]raclopride BPND at baseline and post-AMPH treatment normalized to the baseline BPND
DRUG[11C]DASB
BPND of \[11C\]DASB.
DRUGamphetamine
The change (Δ) in BPND (the difference between the \[11C\]raclopride BPND at baseline and post-AMPH treatment normalized to the baseline BPND.
Sponsors
National Institute of Mental Health (NIMH)
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion * history of Diagnostic and Statistical Manual (DSM-IV) diagnosis of anorexia or bulimia. * AN women have history of average body weight (ABW) below 85% for height. * AN-BN subjects have history of ABW below 85% ABW. * AN-BN subjects have history of binging/purging behaviors during a period of low weight. * Subjects must be right-handed. * Subjects have been recovered for 12 months or more. Exclusion * Diagnosis of alcohol or drug abuse or dependence in the 3 months. * Alcohol or substance use within 30 days. * Current diagnosis of an Axis I disorder. * Organic brain syndromes, dementia, psychotic disorders, or mental retardation. * Neurological or medical disorders such as seizure disorder, renal disease, diabetes, thyroid disease, EKG indicative of electrolyte imbalance * BN subjects whose purging methods were the use of laxatives, diuretics * Use of psychoactive medication in the 3 months. * Pregnancy or lactation. * Tobacco use in the 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 5-HT Transporter Binding as Measured During the PET Scan | 90 minute PET scan | Use PET and \[11C\]DASB to explore 5-HTT receptor binding potential midbrain and striatal regions of interest in eating disorder subtypes. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. \[VT = distribution volume in tissue; VND = non-displaceable distribution volume\]. The binding of the 5-HTT on PET presumably reflects 5-HTT density and/or affinity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | 90 min PET scan | Use PET and \[11C\]raclopride to explore Dopamine D2/D3 receptor binding potential (BPND) in striatal regions of interest in eating disorder subtypes after amphetamine administration. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. \[VT = distribution volume in tissue; VND = non-displaceable distribution volume\]. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| [11C]Raclopride, [11C]DASB, Amphetamine 1. healthy control women (CW);
2. women recovered from restricting type anorexia nervosa (REC AN);
3. women recovered from bulimic type anorexia nervosa (REC AN-BN)
4. women recovered from from bulimia nervosa (REC BN) | 85 |
| Total | 85 |
Baseline characteristics
| Characteristic | [11C]Raclopride, [11C]DASB, Amphetamine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 72 Participants |
| Region of Enrollment United States | 85 participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 85 |
| other Total, other adverse events | 2 / 85 |
| serious Total, serious adverse events | 0 / 85 |
Outcome results
Primary
5-HT Transporter Binding as Measured During the PET Scan
Use PET and \[11C\]DASB to explore 5-HTT receptor binding potential midbrain and striatal regions of interest in eating disorder subtypes. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. \[VT = distribution volume in tissue; VND = non-displaceable distribution volume\]. The binding of the 5-HTT on PET presumably reflects 5-HTT density and/or affinity.
Time frame: 90 minute PET scan
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [11C]DASB Binding Potential Control Women | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anteroventral striatum | 1.68 binding potential (BPND) | Standard Deviation 0.26 |
| [11C]DASB Binding Potential Control Women | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND post dorsal caudate | 0.44 binding potential (BPND) | Standard Deviation 0.15 |
| [11C]DASB Binding Potential Control Women | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND posterior putamen | 1.36 binding potential (BPND) | Standard Deviation 0.25 |
| [11C]DASB Binding Potential Control Women | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND predorsal caudate | 1.08 binding potential (BPND) | Standard Deviation 0.19 |
| [11C]DASB Binding Potential Control Women | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anterior putamen | 1.70 binding potential (BPND) | Standard Deviation 0.26 |
| [11C]DASB Binding Potential Control Women | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND midbrain | 2.21 binding potential (BPND) | Standard Deviation 0.31 |
| [11C]DASB Binding Potential in REC AN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND midbrain | 2.06 binding potential (BPND) | Standard Deviation 0.3 |
| [11C]DASB Binding Potential in REC AN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND predorsal caudate | 0.99 binding potential (BPND) | Standard Deviation 0.32 |
| [11C]DASB Binding Potential in REC AN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anteroventral striatum | 1.54 binding potential (BPND) | Standard Deviation 0.32 |
| [11C]DASB Binding Potential in REC AN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND posterior putamen | 1.27 binding potential (BPND) | Standard Deviation 0.18 |
| [11C]DASB Binding Potential in REC AN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND post dorsal caudate | 0.35 binding potential (BPND) | Standard Deviation 0.18 |
| [11C]DASB Binding Potential in REC AN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anterior putamen | 1.59 binding potential (BPND) | Standard Deviation 0.26 |
| [11C]DASB Binding Potential in REC ANBN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND post dorsal caudate | 0.39 binding potential (BPND) | Standard Deviation 0.16 |
| [11C]DASB Binding Potential in REC ANBN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND posterior putamen | 1.17 binding potential (BPND) | Standard Deviation 0.39 |
| [11C]DASB Binding Potential in REC ANBN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND predorsal caudate | 0.99 binding potential (BPND) | Standard Deviation 0.34 |
| [11C]DASB Binding Potential in REC ANBN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND midbrain | 1.98 binding potential (BPND) | Standard Deviation 0.6 |
| [11C]DASB Binding Potential in REC ANBN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anterior putamen | 1.49 binding potential (BPND) | Standard Deviation 0.48 |
| [11C]DASB Binding Potential in REC ANBN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anteroventral striatum | 1.46 binding potential (BPND) | Standard Deviation 0.47 |
| [11C]DASB Binding Potential in REC BN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anterior putamen | 1.57 binding potential (BPND) | Standard Deviation 0.28 |
| [11C]DASB Binding Potential in REC BN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND midbrain | 2.17 binding potential (BPND) | Standard Deviation 0.19 |
| [11C]DASB Binding Potential in REC BN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND post dorsal caudate | 0.37 binding potential (BPND) | Standard Deviation 0.19 |
| [11C]DASB Binding Potential in REC BN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND predorsal caudate | 0.98 binding potential (BPND) | Standard Deviation 0.3 |
| [11C]DASB Binding Potential in REC BN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND anteroventral striatum | 1.60 binding potential (BPND) | Standard Deviation 0.34 |
| [11C]DASB Binding Potential in REC BN | 5-HT Transporter Binding as Measured During the PET Scan | [11C]DASB BPND posterior putamen | 1.32 binding potential (BPND) | Standard Deviation 0.29 |
p-value: >0.05ANOVA
Secondary
Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration
Use PET and \[11C\]raclopride to explore Dopamine D2/D3 receptor binding potential (BPND) in striatal regions of interest in eating disorder subtypes after amphetamine administration. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. \[VT = distribution volume in tissue; VND = non-displaceable distribution volume\].
Time frame: 90 min PET scan
Population: Due to technical problems and temporary closure of the PET Facility during the study and consequent lack of time and funding for additional scanning, we were unable to recruit a sufficient number of women recovered from bulimia nervosa (BN) for the AMPHETAMINE CHALLENGE STUDY and therefore no data for this outcome measure were collected in REC BN.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [11C]DASB Binding Potential Control Women | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND posterior putamen | 2.53 binding potential (BPND) | Standard Deviation 0.32 |
| [11C]DASB Binding Potential Control Women | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND anterior putamen | 2.71 binding potential (BPND) | Standard Deviation 0.26 |
| [11C]DASB Binding Potential Control Women | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND anteroventral striatum | 2.09 binding potential (BPND) | Standard Deviation 0.22 |
| [11C]DASB Binding Potential Control Women | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND post dorsal caudate | 1.69 binding potential (BPND) | Standard Deviation 0.27 |
| [11C]DASB Binding Potential Control Women | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND predorsal caudate | 2.48 binding potential (BPND) | Standard Deviation 0.3 |
| [11C]DASB Binding Potential in REC AN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND anterior putamen | 2.65 binding potential (BPND) | Standard Deviation 0.22 |
| [11C]DASB Binding Potential in REC AN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND anteroventral striatum | 2.01 binding potential (BPND) | Standard Deviation 0.15 |
| [11C]DASB Binding Potential in REC AN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND post dorsal caudate | 1.62 binding potential (BPND) | Standard Deviation 0.19 |
| [11C]DASB Binding Potential in REC AN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND posterior putamen | 2.46 binding potential (BPND) | Standard Deviation 0.26 |
| [11C]DASB Binding Potential in REC AN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND predorsal caudate | 2.40 binding potential (BPND) | Standard Deviation 0.14 |
| [11C]DASB Binding Potential in REC ANBN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND predorsal caudate | 2.47 binding potential (BPND) | Standard Deviation 0.47 |
| [11C]DASB Binding Potential in REC ANBN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND posterior putamen | 2.47 binding potential (BPND) | Standard Deviation 0.4 |
| [11C]DASB Binding Potential in REC ANBN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND anteroventral striatum | 1.94 binding potential (BPND) | Standard Deviation 0.37 |
| [11C]DASB Binding Potential in REC ANBN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND anterior putamen | 2.60 binding potential (BPND) | Standard Deviation 0.4 |
| [11C]DASB Binding Potential in REC ANBN | Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | [11C]raclopride BPND post dorsal caudate | 1.69 binding potential (BPND) | Standard Deviation 0.34 |
Comparison: A General Linear Model using log(\[11C\]raclopride BPND) after amphetamine administration as dependent variable and Diagnostic Group as independent variable was used. Baseline (before amphetamine administration) \[11C\]raclopride BPND was used as covariate.p-value: <0.05General Linear Model