Molecular Signatures of Lithium Treatment: Current Knowledge

Abstract

Lithium (Li) is the key mood stabilizer in the prevention of mood recurrences and suicide in bipolar disorders. However, only one-third of patients become asymptomatic with Li treatment, and to date, no clinical markers can predict this response variability. Li is a multitargeting drug, complicating an understanding of its mechanisms of action. The present article reviews Li's various biological effects, including those obtained in transcriptomic and epigenetic studies, in both humans and animal models. A molecular signature of the therapeutic response to Li is urgently required, including possibly from the circulation. This would better clarify the therapeutic mechanism of Li's action as well as the development of clinical biomarkers. As such, the biological underpinnings of Li's beneficial effects should provide clearer understanding of the varying pathophysiological processes in bipolar disorder presentations, with implications for classification and clinical management, possibly leading to a personalized prescription.

Lithium Content of 160 Beverages and Its Impact on Lithium Status in Drosophila melanogaster

“…Although Li has not yet been considered to be an essential trace element, it mediates important functions in humans and animals [ 22 , 27 ]. Schrauzer recommended a provisional dietary Li intake of 1000 µg per day [ 21 ].…”

“…One soft drink, namely, Acai 28 Black (105 µg Li/L), exhibited Li values comparable to the mean Li values found in mineral water ( Table 5). Although Li has not yet been considered to be an essential trace element, it mediates important functions in humans and animals [22,27]. Schrauzer recommended a provisional dietary Li intake of 1000 µg per day [21].…”

Effects of chronic lithium treatment on anxious behaviors and serotonergic genes expression in the midbrain raphe nuclei in defeated male mice

“…Therefore, there is a great need for the tools that would guide the clinicians in selecting a correct treatment strategy. Our data may be useful for understanding the variability of response to lithium in the medicine practice across individuals shown in many works [36,37,59]. We agree that important questions regarding the mechanism of lithium action on anxiety and depression remain open [61] despite much practice in application.…”

“…It was similarly shown that patients with bipolar disorder demonstrate lithium responsiveness of two types: they are good responders or poor responders [41]. Lithium is obviously a multitarget drug, which complicates understanding of its mechanism of action [59]. Lithium as a monotherapy or in combination with other drugs is effective in 60% of chronically treated patients, but response remains heterogeneous, and a large number of patients require a change in therapy after several weeks or months [60].…”

Metabolomics Analyses of 14 Classical Neurotransmitters by GC-TOF with LC-MS Illustrates Secretion of 9 Cell–Cell Signaling Molecules from Sympathoadrenal Chromaffin Cells in the Presence of Lithium

“…The adrenal medulla is involved in stress-related disorders which impact mental health conditions including bipolar disorder and other related illnesses (43)(44)(45)(46). Lithium, a widely used drug for the treatment of bipolar disorder (47)(48)(49)(50), modulates sodium and calcium channels of chromaffin cells (51)(52)(53). Regulation of sodium and calcium channels, essential for neurotransmitter secretion, suggested that lithium may modulate neurotransmitter secretion from chromaffin cells.…”