Fig. 1

Sequence of assessment of clinical, structural, functional and metabolic markers (see text for details). Pre-initiation refers to the time period between agreement to commence a trial of lithium and actual initiation of medication, and it is expected to average about 2 weeks; most post-initiation measures will be undertaken at approximately week 12 (allowing for titration of lithium dosage & stabilization of plasma levels); neuropsychology assessment will be undertaken in individuals with 4 consecutive weeks of euthymia; actigraphy will ideally be include some days pre-lithium initiation, as some analyses will be feasible with a minimum of 3 days of continuous recording; post-lithium initiation actigraphy may be extended for prolonged periods in patients who consent to this; any program for optimizing adherence will commence after approximately 12 weeks (after stabilization of lithium treatment), when repeated ratings of levels of adherence are available; home-based salivary lithium assessments will only be undertaken in a small subsample of patients who agree to participate in an exploratory pilot study (during the second year of follow-up)