• Young Mania Rating Scale (YMRS),
  
• Bipolar Clinical Global Impression Scale (BP-CGI),
  
• Overt Aggression Scale (OAS),
  
• Child Depression Rating Scale-Revised (CDRS-R),
  
• Brief Psychiatric Rating Scale in Children (BPRS-C),
  
• Child Bipolar Rating Scale- Parent version (subscales: Child Mania Rating Scale,
  
• Child Bipolar Depression Rating Scale,
  
• Child Bipolar Cycling Rating Scale) and Teacher version (subscales: Child Mania Rating Scale,
  
• Child Bipolar Depression Rating Scale)(CBRS-P/T),
  
• Abnormal Involuntary Movements Scale (AIMS),
  
• Pediatric Side Effects Rating Scale (P-SERS),
  
• CAFAS (Child and Adolescent Functional Assessment Scale)
  

Procedure Study 1 This study is planned to be conducted over 18 months, with an average recruitment of 2 subjects per month. Each subject is involved in the study for 18 to 26 weeks. The range of time is necessary to account for factors such as the child’s age, sex, weight, reactions to the medications and side effects. Based on these factors, the time it takes to titrate the medication dose to the optimal amount will vary. Maintaining this flexibility in the protocol is part of good clinical practice where medication is involved. Only children whose medication is not currently improving their symptoms will be recruited. Therefore no children who have been stabilized on a drug will be taken off of it. The initial 2-week screening period includes a diagnostic interview and collection of demographic information. Previous medication will be tapered slowly over this 2-week period. It is an open trial where subjects are aware of the type of medication and the strength (For example, one pill=25 mg strength) of the pill. Research assessment of mood symptoms and side effects will be carried out 5 times over the course of the active trial period. Blood will be collected 3 times: once the subject is washed-out (baseline), once optimal medication dose has been reached, and finally at the end of the 6-week period on full dose.

The dose of Lamotrigine will be 12.5 mg per day beginning the first day. It is increased in 12.5 mg increments every week until it reaches 50 mg and 25 mg per week of increment thereafter until maximum dose of 150 mg in those below 50 kg and 200-400 mg depending on clinical response in those above 50 kg. Increasing the medication to final dose will take approximately 10-18 weeks (depending on age, weight and side-effect profile of each subject on a case-by-case basis) and the response on full and tolerable dose is further monitored for response over 6 weeks. Therefore, this is a 18-26 week trial (2 weeks=screening and wash out; 10-18 weeks=dosing; 6 weeks=acute trial period on full dose).

Study 2 involves adolescent subjects (>10years of age) recruited from the Study 1 sample. This part of the study is a fMRI treatment study to examine how the brain functions before and after receiving lamotrigine medication for bipolar disorder. The goal of study 2 is to understand how and where lamotrigine works in the brain. In order to do this, we will view brain images in a fMRI scanner pre- and post-treatment. This will be done once before subjects begin taking lamotrigine (subjects who require a “wash-out” period, described in study 1, this will occur after the “wash-out.”) The second scan will take place after the medication trial (after the 6-week active treatment period). While in the scanner, subjects will complete tasks related to thinking and emotion. Subjects will be shown pictures of faces with varying expressions including happy, neutral and angry and will be asked to identify the emotions of the faces, remember and identify previously seen faces, and determine the age group of various faces (i.e., above or below 30 years). Subjects will also complete tasks that involve processing words that express different emotions (e.g., happy, angry), and respond to different “go” and “no-go” images that flash on a screen. Brain activity will be recorded during these tasks. Each task will take around 5 minutes. Before the actual fMRI scan, subjects practice lying in a simulator, a machine that looks and sounds like a scanner.