The MIND Study: The MGH/MIT Investigation of NAC on Dysregulation

This is a double-blind randomized controlled study. The study will last up to 16 weeks from the initial phone screen (it could take up to eight weeks to schedule and complete the initial screening process and schedule the 2 MRI visits). Once subjects have completed the screening process, they will begin the 8-week trial phase. Subjects will be assessed weekly throughout the study for efficacy and tolerability. The investigators plan to recruit 80 participants with emotional dysregulation (ED) in the treatment arm. In addition, the investigators will aim to recruit 40age-, sex-, and parental-education matched participants without emotional dysregulation, and major psychopathology as Typically Developing (TD) control participants in the control arm. Upon scheduling the baseline visit, only the emotional dysregulation (ED) participants will be randomized 1:1 to be exposed to NAC or placebo treatment for 8 weeks. Participants will complete baseline and post-treatment (endpoint) brain MRI acquisition. TD participants will complete the same screening and characterization process as the ED group and then will be invited to complete MRI eligibility screening and to be scanned twice, separated by an eight-week interval, but the TD will not complete the NAC treatment or receive a placebo. See Table 1 (Study Schema) for a complete list of characterization measures to be completed by each group.

The investigators will enroll 120 subjects. Participants will be 80 children with emotion dysregulation, 6-12 years of age. In addition, the investigators will include 40 children without emotion dysregulation as healthy controls to provide a normative comparison group for neuroimaging analyses. All subjects that enter the study will undergo standard screening and diagnostic procedures. Individuals who express interest in the study, either by responding to advertising or by giving a referring clinician explicit permission to be contacted for research, will be screened for eligibility by the study coordinator or a research assistant via phone. If the interested youth meet criteria for either the ED or TD group, the parent/guardian will be asked to complete the Child Behavior Checklist (CBCL) online via RedCap, a secure online data capture system. The study coordinator will send a link to complete the CBCL electronically to the parent/guardian via email. An online consent statement will appear, prompting parents to indicate their agreement to participate in the online questionnaire portion of the study. If the parent/guardian indicates their agreement, the data capture system will proceed to the CBCL. After completing the CBCL, eligible participants based on inclusion and exclusion criteria will either be assigned to the ED or TD group. Eligible participants will be scheduled to speak with a study clinician via phone or secure Zoom call to obtain informed consent prior to completing further screening and baseline study procedures. Written informed consent will be obtained from subjects' parent/guardian prior to initiation of the study protocol. Subjects aged 7 and older will sign age-appropriate assent forms. The study subjects and their parent may take as much time as they feel necessary to consider their participation in the study as well as consult with their family members or physician. Subjects may remain on most current treatments while participating in this study. Participation in this study is voluntary, and subjects may withdraw from the study at any time. Informed consent will be obtained virtually. Study staff will send the consent form and assent form (when applicable) to subjects in PDF form ready for Adobe eSignature via email with a brief statement explaining why they are receiving this form and further instructions. Study staff will schedule a time for the subject and their parent(s)/guardian to meet with a study clinician via phone or secure Zoom to complete consent. For the ED group, the study clinician will have a conversation over the phone or Zoom with the subject and their parent(s)/guardian to obtain consent in the usual fashion: review the consent form, review inclusion and exclusion criteria, review risks and benefits of the study, review alternatives to participation, and answer any questions subjects and their parent(s)/guardian may have. If the subject and their parent(s)/guardian decide to participate, they will si Покажи пълното описание...

Inclusion Criteria: \- Emotional Dysregulation Group 1. Male or female subjects, 6-12 years of age. 2. Current symptoms of emotional dysregulation as indicated by combined T-scores on the Child Behavior Checklist \> 180 on the Anxiety/Depression + Aggression + Attention subscales. 3. Score 15 or above on the clinician YMRS 4. Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol. 5. Subjects and their legal representative must be considered reliable. 6. Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must provide written consent and the subject must provide written assent. 7. Subject must have access to a computer with a camera, speaker, microphone, and internet connection. 8. Subject must be willing to refrain from treatment changes during the study protocol. Typically Developing Control Group 1. Age-, sex-matched with ED participants. 2. No significant traits of ED as screened by parent and clinician YMRS both under scores of 6 3. No previous psychiatric history as confirmed by clinician interview 4. No significant psychopathology as screened on the CBCL (Subdomain T-scores \<60). 5. Participant weight is above the 5th percentile and below the 95th percentile, per CDC child BMI categories (https://www.cdc.gov/obesity/basics/childhood-defining.html) Exclusion Criteria: 1. Investigator and his/her immediate family (defined as the investigator's spouse, parent, child, grandparent, or grandchild). 2. Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 3. History of bleeding diathesis, including those with von Willebrand disease. 4. Uncorrected hypothyroidism or hyperthyroidism. 5. History of sensitivity to N-acetylcysteine, a history of intolerance to N-acetylcysteine or a non-responder after 2 months of treatment at adequate doses as determined by the clinician. 6. Severe allergies or multiple adverse drug reactions. 7. Current or past history of seizures. 8. DSM-IV substance use, abuse, or dependence 9. Any concomitant medication with primary central nervous system activity other than specified in the Concomitant Medication portion of the protocol. 10. Current diagnosis of schizophrenia or psychosis. 11. Females who have started menstruating. 12. Pregnant or nursing. 13. Judged to clinically be at serious suicidal risk or C-SSRS score ≥ 4. 14. History of intellectual disability as reported by parent