Multimodal Neuroimaging Genetic Biomarkers of Nicotine AddictionSeverity

Exclusion Criteria

• •Participants will be excluded if they:
• •1. are not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.
• •2. have coagulopathies, history of, current superficial, or deep vein thrombosis, musculoskeletal
• •abnormalities restricting an individual s ability to lie flat for extended periods of time. Justification: MR scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately two hours. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) or dangerous (e.g. familial hypercoagulability syndrome, history of thrombosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort issues.
• •3. have HIV or Syphilis. Justification: HIV and Syphilis both can have central nervous system (CNS) sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): Oral HIV blood test if oral test is + and STS+ without adequate prior treatment
• •4. regularly use any prescription (e.g., benzodiazepines, antipsychotics, anticonvulsants, barbiturates), over-the-counter (e.g., cold medicine) or herbal medication (e.g., Kava, Gingko biloba, St. John s wort) that may alter CNS function, cardiovascular function, or neuronal-vascular coupling. Antidepressant use will be allowed if an individual is on a stable dose of an SSRI or SNRI for \~6 weeks. As needed, benzodiazepine use is also allowed, but the individual must test negative for benzodiazepines on the drug screen. Justification: The use of some medications may alter the fMRI signal and/or neural functions of interest in the current study. Consistent antidepressant use or infrequent use of benzodiazepines is unlikely to drive study-related changes in brain function. Allowing such medication use will also make it possible to study nicotine dependent individuals who continue to smoke despite receiving treatment for a mood disorder. Assessment tool(s): History and comprehensive urine drug screening to detect antidepressants, benzodiazepines, antipsychotics, anticonvulsants, and barbiturates.
• •5. have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor. Justification: Neurological diseases alter CNS function and, possibly, the neuronalvascular coupling that forms the basis of the fMRI signal. Assessment tool(s): History and physical examination by a qualified IRP clinician, urine drug screening for anticonvulsants not disclosed by history. History of head trauma with loss of consciousness of more than 30 minutes or with postconcussive sequelae lasting more than two days, regardless of loss of consciousness, will be exclusionary. The MAI who will also retain discretion to exclude based on a history of neurological illness that may compromise data integrity.
• •6. Have current major psychiatric disorders to include, but not limited to psychotic disorders, or substance-induced psychiatric disorders, or risk of suicide or currently on antipsychotic medication treatment. Individuals with current major depressive disorder (MDD) and related anxiety will be allowed if currently stable, as assessed by the MAI. The MAI will reserve the right to exclude on the basis of psychiatric history not explicitly described in this criterion. Justification: Psychiatric disorders involve the central neural system (CNS) and, therefore, can be expected to alter the fMRI measures being used in this study. However, mood disorders such as MDD are highly comorbid with nicotine dependence. Including this population will generate results that are more representative of nicotine dependent individuals. Assessment tool(s): Computerized SCID or M.I.N.I., Beck Depression Inventory, Beck Anxiety Inventory, Adult ADHD Self-Report Scales and clinical interview confirmation by clinician.
• •7. Are cognitively impaired or learning disabled. Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited during laboratory task performance. Cognitive impairment may affect one s ability to give informed consent. Assessment tool(s): History examination and validated IQ test, such as the Wechsler Abbreviated Scale of Intelligence (WASI) or Shipley-2. IQ estimate must be 80 or over.
• •8. have significant cardiovascular, cerebrovascular, or respiratory conditions. Justification: Such conditions may alter blood flow, the fMRI signal and other autonomic signals, and increase risks associated with nicotine patch and/or e-cigarette use. Assessment tool(s): History and physical exam, including 12-lead EKG.
• •9. have any other major medical condition that in the view of the investigators would compromise the safety of an individual during participation. Justification: Many illnesses not explicitly covered here may increase risk or alter important outcome measures. Assessment tool(s): History and physical examination by a qualified IRP clinician and CBC, urinalysis, NIDA chemistry panel (liver function tests, electrolytes, kidney function). The following lab values will result in exclusion from the study:
• •i. Hemoglobin \< 10 g/dl
• •ii. White Blood Cell Count \< 2400/ l
• •iii. Liver Function Tests \> 3X normal
• •iv. Serum glucose \> 200 mg/dl
• •v. Urine protein \> 2+
• •vi. Serum creatinine \> 2 mg/dl
• •vii. Estimated creatinine clearance \<60ml/min
• •The MAI will retain discretion to exclude based on less extreme lab results. After the screening process has been completed, the MAI will take into account all data collected in order to decide if there is an existing medical illness that would compromise participation in this research.
• •10. are pregnant, planning to become pregnant, or breastfeeding. Females are instructed in the consent to use effective forms of birth control during the study period. Justification: study procedures and drugs used in the current protocol may complicate pregnancy or be transferred to nursing children. Assessment tool(s): Urine and/or serum pregnancy tests, and clinical interview. Urine pregnancy tests will also be conducted at the beginning of each imaging visit.
• •11. Are non-English speaking. Justification: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify, given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI procedures. The inability to effectively communicate MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants. Assessment tool(s): self-report....