Table 2 Overview of the R-LiNK work packages

1

Project administration

2

Set-up, ethical approval, database development

3

Identification of baseline & follow-up assessment of clinical symptoms, neuropsychological and social functioning, illness activity, etc

Characterisation of the clinical response phenotype for lithium treatment according to pre-defined outcome measures (categorical/continuous)

Assessment & optimization of medication adherence

Economic modelling of using a stratified approach to prescribing lithium; Qualitative & quantitative assessment of the digital phenotype

Development of a prototype device for salivary lithium measurement

4

Examination of neuro-imaging (MRI and ¹H-spectroscopy) signature before & after lithium initiation to allow repeated assessment of e.g. architecture of the amygdala, etc

5

Assessment of 7Li-MRI signature (i.e. distribution of lithium in the brain measured 12 weeks after initiation of treatment)

6

Blood sampling to measure omics (e.g. putative transcriptomic, mirnomic, methylomic and proteomic biomarkers) before & after lithium initiation to explore potential molecular signatures

7

Data management infrastructure for e.g. data collection of heterogeneous data (imaging, genetics, clinical) across different institutions & countries; Quality control of data processing; controlled data sharing; etc

Data analysis

8

Evaluation of laboratory to bedside transferability of study findings according to e.g. clinical feasibility, technical feasibility, utility of markers when employed alone or in combination (i.e. additivity or redundancy), acceptability & cost effectiveness

9

Communication & dissemination of findings