Brain Functional Connectivity in Alcohol Use Disorder
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 3/15/2019 |
| Start Date: | February 9, 2017 |
| End Date: | October 2020 |
Brain Functional Connectivity During Early Recovery in Alcohol Use Disorder as a Marker for Relapse
Due to the relapsing nature of alcoholism, excessive alcohol consumption represents a
significant cost to US society ($249 billion in 20101). About 64% of those entering treatment
will relapse within one year. New interventions targeting the underlying brain biomarkers of
relapse vulnerability hold significant promise in reducing this critical public health
problem. Using resting functional magnetic resonance imaging (fMRI) we have identified brain
biomarkers that support long-term abstinence and brain biomarkers that predict relapse. Our
data point to specific brain biomarkers that index higher relapse vulnerability at 11 weeks
of abstinence. Many individuals, however, have already relapsed by this time. It is unknown
whether these biomarkers can be identified earlier during the recovery period. We need to
investigate whether this biomarker of relapse vulnerability can be identified during earlier
stages of abstinence. Earlier identification of this biomarker will give valuable information
for timely targeted interventions (e.g. closer monitoring, longer stay in treatment program,
neuromodulation), increasing the chances of maintaining abstinence. The overall objective of
this study is to identify biomarkers of relapse during early abstinence (2-3 weeks of
abstinence). A secondary objective is to evaluate whether non-imaging measures such as
craving6 and executive function7 add value to prediction models. Findings from this proposal
will provide insight into the neurobiology of relapse vulnerability that will inform new
treatment strategies needed to improve treatment outcome.
significant cost to US society ($249 billion in 20101). About 64% of those entering treatment
will relapse within one year. New interventions targeting the underlying brain biomarkers of
relapse vulnerability hold significant promise in reducing this critical public health
problem. Using resting functional magnetic resonance imaging (fMRI) we have identified brain
biomarkers that support long-term abstinence and brain biomarkers that predict relapse. Our
data point to specific brain biomarkers that index higher relapse vulnerability at 11 weeks
of abstinence. Many individuals, however, have already relapsed by this time. It is unknown
whether these biomarkers can be identified earlier during the recovery period. We need to
investigate whether this biomarker of relapse vulnerability can be identified during earlier
stages of abstinence. Earlier identification of this biomarker will give valuable information
for timely targeted interventions (e.g. closer monitoring, longer stay in treatment program,
neuromodulation), increasing the chances of maintaining abstinence. The overall objective of
this study is to identify biomarkers of relapse during early abstinence (2-3 weeks of
abstinence). A secondary objective is to evaluate whether non-imaging measures such as
craving6 and executive function7 add value to prediction models. Findings from this proposal
will provide insight into the neurobiology of relapse vulnerability that will inform new
treatment strategies needed to improve treatment outcome.
BACKGROUND:
Due to the relapsing nature of alcoholism, excessive alcohol consumption represents a
significant cost to US society ($249 billion in 2010). About 64% of those entering treatment
will relapse within one year. Development of new and improved treatments that could be
personalized to maximize the chance of maintaining abstinence in the first year will require
advancement in understanding the behavioral and neural mechanisms underlying vulnerability to
relapse during early abstinence. New interventions targeting the underlying brain biomarkers
of relapse vulnerability hold significant promise in reducing this critical public health
problem. Using resting functional magnetic resonance imaging (fMRI) we have identified brain
biomarkers that support long-term abstinence and brain biomarkers that predict relapse. Our
cross-sectional and longitudinal findings provide evidence that higher functional
connectivity (FC), particularly between nucleus accumbens (NAcc) and dorsolateral prefrontal
cortex (DLPFC) is a potential brain biomarker that supports abstinence. Resting NAcc-DLPFC FC
is graded depending on abstinence length, with higher FC in long-term abstinent alcoholics (7
years of abstinence) than controls and intermediate FC in short-term abstinent alcoholics (11
weeks of abstinence). Further, lower NAcc-DLPFC FC at 11-weeks of abstinence can be a
predictor of subsequent relapse (with 74% accuracy). Our data point to specific brain
biomarkers that index higher relapse vulnerability at 11 weeks of abstinence. Many
individuals, however, have already relapsed by this time and were not included in the studies
above. It is unknown whether these biomarkers can be identified earlier during the recovery
period. We need to investigate whether this biomarker of relapse vulnerability can be
identified during earlier stages of abstinence. Earlier identification of this biomarker will
give valuable information for timely targeted interventions (e.g. closer monitoring, longer
stay in treatment program, neuromodulation), increasing the chances of maintaining
abstinence.
PURPOSE OF THE STUDY:
Our long-term goal is to use identified brain and behavioral biomarkers to facilitate the
development of new, personalized treatments that will support enduring abstinence in
addiction. The overall objective of this study is to identify biomarkers of relapse during
early abstinence (2-3 weeks of abstinence). A secondary objective is to evaluate whether
non-imaging measures such as craving and executive function add value to prediction models.
Findings from this study will provide insight into the neurobiology of relapse vulnerability
that will inform new treatment strategies needed to improve treatment outcome.
SPECIFIC AIMS:
SA 1: To evaluate prediction accuracy of FC measures in individuals with alcohol use disorder
(AUD) during early (2-3 weeks) abstinence. To evaluate whether non-imaging measures (e.g.
craving, executive function) add value to FC prediction models we will test prediction models
using (i) only imaging variables (FC during task and rest fMRI), (ii) only non-imaging
variables, and (iii) a combination of imaging and non-imaging variables as predictors of time
to relapse. Hypothesis: Based on compensatory mechanisms hypothesis, we expect that
subsequent abstainers will have stronger NAcc-DLPFC FC when compared to subsequent relapsers
and controls. Pilot data suggests that a combination of imaging and non-imaging variables
will have high prediction accuracy. SA 2. To expand our examination of NAcc-DLPFC FC beyond
resting state we will use the Reversal Learning (RL) task, which involves executive
functioning and reward processing. Hypothesis: Pilot data suggests that subsequent abstainers
will show higher task-related NAcc FC than relapsers and controls. Exploratory Aim: We will
explore whether the strength of resting NAcc-DLPFC FC changes after performing the RL task.
We will collect rest fMRI data before and after RL task performance in the scanner.
Hypothesis: Based on previous findings of increased task-evoked activity in these regions, we
hypothesize that patients will show increased resting NAcc-DLPFC FC after performing the RL
task.
SIGNIFICANCE:
Addiction treatment outcomes are poor. Alcohol use disorder (AUD) in the U.S. remains an
important public health problem with an estimated total annual cost to society of $249.5
billion. The chronic and relapsing nature of AUD is a major obstacle to successful recovery.
We lack tools to subtype in alcohol use disorder (AUD). Subtyping in clinical populations can
be an effective approach to model targeted interventions. For example, targeted treatment for
breast cancer patients based on individual tumor estrogen receptor typing (biomarker) has
improved outcomes from a 25 to 77% survival rate; there has not been a similar improvement in
outcome for AUD treatment. We need to identify biomarkers in AUD that predict relapse and
guide the development and selection of treatment based on subtypes to increase the chances of
achieving long-term abstinence.
Due to the relapsing nature of alcoholism, excessive alcohol consumption represents a
significant cost to US society ($249 billion in 2010). About 64% of those entering treatment
will relapse within one year. Development of new and improved treatments that could be
personalized to maximize the chance of maintaining abstinence in the first year will require
advancement in understanding the behavioral and neural mechanisms underlying vulnerability to
relapse during early abstinence. New interventions targeting the underlying brain biomarkers
of relapse vulnerability hold significant promise in reducing this critical public health
problem. Using resting functional magnetic resonance imaging (fMRI) we have identified brain
biomarkers that support long-term abstinence and brain biomarkers that predict relapse. Our
cross-sectional and longitudinal findings provide evidence that higher functional
connectivity (FC), particularly between nucleus accumbens (NAcc) and dorsolateral prefrontal
cortex (DLPFC) is a potential brain biomarker that supports abstinence. Resting NAcc-DLPFC FC
is graded depending on abstinence length, with higher FC in long-term abstinent alcoholics (7
years of abstinence) than controls and intermediate FC in short-term abstinent alcoholics (11
weeks of abstinence). Further, lower NAcc-DLPFC FC at 11-weeks of abstinence can be a
predictor of subsequent relapse (with 74% accuracy). Our data point to specific brain
biomarkers that index higher relapse vulnerability at 11 weeks of abstinence. Many
individuals, however, have already relapsed by this time and were not included in the studies
above. It is unknown whether these biomarkers can be identified earlier during the recovery
period. We need to investigate whether this biomarker of relapse vulnerability can be
identified during earlier stages of abstinence. Earlier identification of this biomarker will
give valuable information for timely targeted interventions (e.g. closer monitoring, longer
stay in treatment program, neuromodulation), increasing the chances of maintaining
abstinence.
PURPOSE OF THE STUDY:
Our long-term goal is to use identified brain and behavioral biomarkers to facilitate the
development of new, personalized treatments that will support enduring abstinence in
addiction. The overall objective of this study is to identify biomarkers of relapse during
early abstinence (2-3 weeks of abstinence). A secondary objective is to evaluate whether
non-imaging measures such as craving and executive function add value to prediction models.
Findings from this study will provide insight into the neurobiology of relapse vulnerability
that will inform new treatment strategies needed to improve treatment outcome.
SPECIFIC AIMS:
SA 1: To evaluate prediction accuracy of FC measures in individuals with alcohol use disorder
(AUD) during early (2-3 weeks) abstinence. To evaluate whether non-imaging measures (e.g.
craving, executive function) add value to FC prediction models we will test prediction models
using (i) only imaging variables (FC during task and rest fMRI), (ii) only non-imaging
variables, and (iii) a combination of imaging and non-imaging variables as predictors of time
to relapse. Hypothesis: Based on compensatory mechanisms hypothesis, we expect that
subsequent abstainers will have stronger NAcc-DLPFC FC when compared to subsequent relapsers
and controls. Pilot data suggests that a combination of imaging and non-imaging variables
will have high prediction accuracy. SA 2. To expand our examination of NAcc-DLPFC FC beyond
resting state we will use the Reversal Learning (RL) task, which involves executive
functioning and reward processing. Hypothesis: Pilot data suggests that subsequent abstainers
will show higher task-related NAcc FC than relapsers and controls. Exploratory Aim: We will
explore whether the strength of resting NAcc-DLPFC FC changes after performing the RL task.
We will collect rest fMRI data before and after RL task performance in the scanner.
Hypothesis: Based on previous findings of increased task-evoked activity in these regions, we
hypothesize that patients will show increased resting NAcc-DLPFC FC after performing the RL
task.
SIGNIFICANCE:
Addiction treatment outcomes are poor. Alcohol use disorder (AUD) in the U.S. remains an
important public health problem with an estimated total annual cost to society of $249.5
billion. The chronic and relapsing nature of AUD is a major obstacle to successful recovery.
We lack tools to subtype in alcohol use disorder (AUD). Subtyping in clinical populations can
be an effective approach to model targeted interventions. For example, targeted treatment for
breast cancer patients based on individual tumor estrogen receptor typing (biomarker) has
improved outcomes from a 25 to 77% survival rate; there has not been a similar improvement in
outcome for AUD treatment. We need to identify biomarkers in AUD that predict relapse and
guide the development and selection of treatment based on subtypes to increase the chances of
achieving long-term abstinence.
Alcohol Use Disorder
INCLUSION CRITERIA:
- Age 18-60
- Ability to provide written consent and comply with study procedures
- Meet Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for
Alcohol Use Disorder
- May have current comorbid drug use, but primary substance use disorder diagnosis needs
to be based on alcohol use
- Must be enrolled in Lodging Plus (Fairview Riverside) treatment program
- Must have the intention to remain in program until the end of the study
EXCLUSION CRITERIA:
- Any medical condition or treatment with neurological sequelae (i.e. stroke, tumor,
loss of consciousness>30 min, HIV)
- Any MRI scanning contraindications (i.e., metal implants, pacemakers, etc.)
- DSM-V criteria for psychiatric disorder, may have a lifetime but not current diagnosis
of depression
- Primary current substance use disorder diagnosis on a substance other than alcohol
except for caffeine or nicotine
- Clinical evidence for Wernicke-Korsakoff syndrome
Healthy controls
INCLUSION CRITERIA:
- Age 18-60
- Ability to provide written consent and comply with study procedures
EXCLUSION CRITERIA:
- Any medical condition or treatment with neurological sequelae (i.e. stroke, tumor,
loss of consciousness>30 min, HIV)
- Any MRI scanning contraindications (i.e., metal implants, pacemakers, etc.)
- DSM-V criteria for psychiatric disorder, may have a lifetime but not current diagnosis
of depression
- Primary current substance use disorder diagnosis on any substance such as alcohol,
stimulant, opioids, etc. except for caffeine or nicotine
We found this trial at
1
site
Minneapolis, Minnesota 55455
(612) 625-5000
Principal Investigator: Jazmin Camchong, PhD
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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