We have developed a strategy for measuring total medication load in bipolar individuals by coding the dose of each antidepressant, mood stabilizer, antipsychotic and anxiolytic medication as absent = 0, low = 1, or high = 2. For antidepressants and mood stabilizers, we converted each medication into low- or high-dose groupings using a previously employed approach (35 (link), 51 , 52 (link)). Individuals on Levels 1 and 2 of these criteria were coded as low dose, those with Levels 3 and 4 as high dose. We added a no-dose subtype for those not taking these medications. We converted antipsychotic doses into chlorpromazine dose equivalents, and coded as 0, 1, or 2, for no medication, chlorpromazine equivalents dose equal or below, or above the mean effective daily dose (ED50) of chlorpromazine as defined by Davis and Chen (53 (link)). Lorazepam dose was similarly coded as, 0, 1 or 2, with reference to the midpoint of the Physician's Desk Reference-recommended daily dose range. We generated a composite measure of total medication load, reflecting dose and variety of different medications taken, by summing all individual medication codes for each medication category for each individual bipolar participant. We used Spearman rank correlational analyses to examine associations between total medication load and magnitude of BOLD signal change in a-priori neural regions showing significant group-by-condition interactions and/or a significant main effect of group.
To examine potential effects of illness duration, age of illness onset and current (subthreshold) depression severity, we conducted post hoc correlational analyses between these variables and BOLD signal change in a-priori neural regions (i.e., subcortical limbic regions, including amygdala and striatum, and DLPFC). Since 11 out of 19 patients had multiple comorbid diagnoses, and seven of these had comorbid anxiety disorders, we additionally compared BOLD signal change in our a-priori neural regions of interest in bipolar individuals with comorbid diagnoses versus those without any such diagnoses.
For the above analyses, we used an adjusted statistical threshold of p = 0.05/(number of comparisons plus number of regions examined) to allow for multiple between-group comparisons.
To examine potential effects of illness duration, age of illness onset and current (subthreshold) depression severity, we conducted post hoc correlational analyses between these variables and BOLD signal change in a-priori neural regions (i.e., subcortical limbic regions, including amygdala and striatum, and DLPFC). Since 11 out of 19 patients had multiple comorbid diagnoses, and seven of these had comorbid anxiety disorders, we additionally compared BOLD signal change in our a-priori neural regions of interest in bipolar individuals with comorbid diagnoses versus those without any such diagnoses.
For the above analyses, we used an adjusted statistical threshold of p = 0.05/(number of comparisons plus number of regions examined) to allow for multiple between-group comparisons.
