Biological predictors of lithium response in bipolar disorder

Abstract

In order to prescribe lithium appropriately to patients with bipolar disorder, predictors of lithium response are helpful. The present paper reviews the biological predictors of lithium response. As a positive predictor of lithium response, the following have been reported: strong loudness dependence of the auditory-evoked N1/P2-response; higher brain lithium concentration; lower inositol monophosphatase (IMPase) mRNA expression; higher serotonin-induced calcium mobilization; increased N -acetyl-aspartate peak and decreased myo-inositol peak; white matter hyperintensity; decreased intracellular pH; higher frequency of phospholipase C g -1 ( PLCG1 )-5 repeat and PLCG1 -8 repeat; and C973A polymorphism in the inositol polyphosphate 1-phosphatase gene. In contrast the following have been reported as a predictor of negative lithium response: epileptiform abnormality of electroencephalography; human leukocyte antigen type A3; decreased phosphocreatine peak area after photic stimulation; and homozygotes for the short variant of the serotonin transporter gene. Most of the possible biological predictors of better lithium response, such as lower IMPase mRNA levels, white matter hyperintensity, lower brain intracellular pH, enhanced calcium response, and PLCG1 -5 repeat had been detected as risk factors for bipolar disorder, suggesting that bipolar disorder responding well to maintenance lithium treatment is a distinct category having a certain neurobiological basis, although these findings need further replication. The search for biological predictors of lithium response is still in its infancy. Most of the laboratory or neuroimaging techniques used in these studies are not easily performed in clinical settings, so the development of an easy and useful laboratory test is needed.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Responsiveness may also be a familial trait, with a study showing that patients who have a lithium‐responsive relative have a 67% likelihood of also being lithium responsive, versus 35% of those without a responsive relative 417. Among biological measures, lack of electroencephalogram (EEG) abnormalities, higher brain lithium concentration, increased N ‐acetyl aspartate and lower myo‐inositol peaks on magnetic resonance spectroscopy, as well as several variants in candidate gene studies, may predict response,418 but these studies require confirmation. Response to lithium in particular seems to be quite specific, as shown in a study of neurons derived from induced pluripotent stem cells.…”

Stargazin involvement with bipolar disorder and response to lithium treatment

“…Numerous genes have been tested for association with lithium response, but most yielded nonreplicable or negative results [14][15][16]. The relatively few genes, in which association with lithium response was found and did not fail to be replicated, include phospholipase C g (PLCG1) [17,18], tryptophan hydroxylase [19] and serotonin transporter genotype (5HTTLPR) [20][21][22][23].…”

Physiological Correlates of Bipolar Spectrum Disorders and their Treatment

“…Within the EEG and ERP literature, there has been one review examining correlates of lithium treatment effect (Ikeda and Kato 2003). Here, we updated this review and review other treatments (Table 4).…”