anxiety during abstinence in aud

Conditions: Alcohol Use Disorder

Summary: the goal of this study is to better understand the underlying neurobiological basis of anxiety that emerges during abstinence in patients with alcohol use disorder (aud). the main questions it aims to answer are: 1. to characterize anxiety itself as well as anxiety related-neurobiological circuitry in early abstinence in aud 2. to examine how anxiety and anxiety related-neurobiological circuitry change over the course of abstinence in aud researchers will recruit both participants with aud and healthy volunteers. the participants with aud will be prescribed disulfiram, a medication that helps participants with aud stay abstinent. healthy volunteers will not receive antabuse. patients with aud will undergo fmri scanning both after 1 week and 3 months of disulfiram treatment. healthy volunteers will undergo fmri once.

this study will recruit 40 treatment-seeking participants with aud ("audp") and 20 age matched healthy volunteer participants (hvp). audp will be initiated on disulfiram, a medication fda approved for alcohol use disorder that is a first line treatment for maintenance of abstinence from alcohol, to facilitate and help ensure abstinence from alcohol and will undergo functional mri scanning at two timepoints: 1) 8-14 days after the last drink ("early abstinence") and 2) after three months of abstinence ("protracted abstinence"). hvp will be scanned once. the investigators will examine the functioning of the anterior insula (ai), bed nucleus of the stria terminalis (bnst), and dorsolateral prefrontal cortex (dlpfc) during a task that evokes anxiety while anticipating an uncertain threat ("threat-anxiety") as well as resting state functional connectivity (rsfc) between ai-bnst and ai-dlpfc to measure whether there are neuroplastic changes in these circuits that occur during abstinence. these changes in anxiety circuit activity and connectivity will be related to changes in current anxiety symptoms.

Eligibility criteria:
inclusion criteria (participants with alcohol use disorder): 1. between the ages of 21 and 40 2. right-handed 3. able to perform informed consent and comply with study 4. seeking treatment for aud 5. meets the diagnostic and statistical manual of mental disorders (dsm-5) criteria for aud of at least moderate severity (\>3 symptoms) inclusion criteria (healthy volunteer participants): 1. between the ages of 21 and 40 2. right-handed 3. able to perform informed consent and comply with study 4. report drinking an average of fewer than 8/15 standard drinks per week for women/men and no more than 1 hdd (heavy drinking days) during the previous 28 days. exclusion criteria (participants with alcohol use disorder): 1. neurological, medical or other conditions that would interfere with mri scanning (e.g., history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, non mri-compliant metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight\>300 lbs., wheelchair-bound, tattoos as indicated by the guidelines established by the zuckerman institute mri unit: https://mr.research.columbia.edu/ 2. dsm 5 diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder 3. any non-aud psychiatric disorder that may, according to the investigator's judgment, require treatment over the course of the study 4. significant suicide or violence risk 5. currently taking psychotropic medication 6. current substance use disorder other than aud, tobacco use disorder or mild cannabis use disorder 7. currently pregnant, attempting to become pregnant or nursing 8. sufficiently socially unstable as to preclude participation (e.g. homeless). 9. known history of allergy, intolerance, or hypersensitivity to disulfiram or its derivates 10. contraindications to disulfiram treatment (e.g. liver disease, kidney disease, cardiac disease, seizure disorder, hypothyroidism, diabetes mellitus, pregnancy or lactation, allergy to disulfiram or thiuram derivatives) 11. currently taking medications containing alcohol, metronidazole, isoniazid, paraldehyde, phenytoin, warfarin, or theophylline. 12. treatment with concomitant medications that might interfere with disulfiram 13. a history of alcohol withdrawal seizures, delirium tremens or resistant alcohol withdrawal 14. current moderate or severe alcohol withdrawal (ciwa \>9 with bal\<0.05) 15. history of prior disulfiram treatment failure 16. being abstinent for \> 7 days at the time of screening exclusion criteria (healthy volunteer participants): 1. neurological, medical or other conditions that would interfere with mri scanning (e.g., history of stroke, seizure, brain tumor, brain infection, traumatic brain injury, multiple sclerosis, dementia, non mri-compliant metal device in body, pregnancy, claustrophobia, color blindness, severe hearing impairment, weight\>300 lbs., wheelchair- bound, tattoos as indicated by the guidelines established by the zi mri unit: https://mr.research.columbia.edu/ 2. dsm 5 diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder 3. any psychiatric disorder that may, according to the investigator's judgment, require treatment over the course of the study 4. significant suicide or violence risk 5. currently taking psychotropic medication 6. current substance use disorder other than tobacco use disorder or mild cannabis use disorder 7. currently pregnant, attempting to become pregnant or nursing 8. sufficiently socially unstable as to preclude participation (e.g., homeless). 9. a diagnosis of aud of any severity

Keywords: fmri disulfiram withdrawal anxiety abstinence