Lithium has well established regulatory effects on the expression of specific target genes. Gene expression studies on LCLs from patients characterized for response to lithium treatment have identified a series of molecular target directly modulated by this drug. A microarray study (Sun et al., 2004) on LCLs of patients with BD characterized for full response to lithium demonstrated its effect in decreasing the expression of seven genes: somatostatin receptor type 2 (SSTR2), nuclear factor kappa-B DNA binding subunit (NF-kB), alpha1B-adrenoceptor (1B-AR), acetylcholine receptor protein alpha chain precursor (ACHR), cAMP-dependent 3', 5'-cyclic phosphodiesterase 4D (PDE4D), substance-P receptor (SPR), and ras-related protein (RAB7), the latter five being validated by Northern blotting analysis. Recently, using LCLs from three healthy subjects, Sugawara and coworkers (2010) identified 44 genes whose expression was regulated by lithium. Among the ten genes most down-regulated by lithium were Bax, zuotin related factor 1 (ZRF1) and thioredoxin domain containing 13 (TXNDC13), while platelet-activating factor acetylhydrolase, isoform Ib, beta subunit 30 kDa (PAFAH1B2), Synovial sarcoma translocation, chromosome 18 (SS18) and peroxisome biogenesis factor 1 (PEX1) were the most up-regulated. Moreover, Washizuka et al. (2009) showed that valproate, but not lithium, significantly increased the expression of the gene encoding for a subunit of mitochondrial complex I (NDUFV2) in LCLs from Japanese BD patients. In regard to other psychiatric phenotypes, unpublished data from LCLs of BD patients characterized for different risk of suicidal behaviour are showing that in vitro lithium treatment significantly perturbed the expression of the gene coding for the rate limiting enzyme spermidine/spermine N(1)-acethyltransferase (SAT1) (Squassina et al., in preparation).