Mouse Anti-Human IMPA2 monoclonal antibody, clone JNQB20

Lithium (Li+) is the mood stabilizer most frequently used in the treatment of bipolar mood disorder; however, its therapeutic mechanism is unknown. In the 1980s, Berridge and colleagues proposed that Li+ treatment acts via inhibition of IMPase (inositol monophosphatase) to deplete the cellular concentration of myoinositol. Inositol depletion is also seen with the alternative mood stabilizers VPA (valproic acid) and CBZ (carbamazepine), suggesting a common therapeutic action. All three drugs cause changes in neuronal cell morphology and cell chemotaxis; however, it is unclear how reduced cellular inositol modulates these changes in cell behaviour. it is often assumed that reduced inositol suppresses Ins(1,4,5)P-3, a major intracellular signal molecule, but there are other important phosphoinostide-based signal molecules in the cell. in the present paper, we discuss evidence that Li+ has a substantial effect on PtdIns(3,4,5)P-3, an important signal molecule within the nervous system. As seen for Ins(1,4,5)P-3 signalling, suppression of PtdIns(3,4,5)P-3 signalling also occurs via an inositol-depletion mechanism. This has implications for the cellular mechanisms controlling phosphoinositide signalling, and offers insight into the genetics underlying risk of bipolar mood disorder.

Introduction: The age at onset of bipolar disorder (BD) has significant implications for severity, duration of affective episodes, response to treatment, and psychiatric comorbidities. It has been suggested that early-onset BD (EO- BD) could represent a clinically distinct subtype with probable genetic risk factors different from those of late-onset BD (LO-BD). To date, several genes have been associated with BD risk but few studies have investigated the genetic differences between EO-BD and LO-BD. The aim of this study was to evaluate if variants of the gene coding for myo-inositol monophosphatase (IMPA2) are linked to age at onset of BD. Method: 235 bipolar patients were recruited and assessed. The final sample consisting of 192 euthymic individuals, was compared according to the age at onset. Polymorphisms were genotyped in the IMPA2 gene (rs669838, rs1020294, rs1250171, and rs630110). Early-onset was defined by the appearance of a first affective episode before the age of 18. Results: The analyses showed that in the genotype distribution rs1020294 (p =.01) and rs1250171 (p =.01) were associated with the age at onset. The significant effect remained only in the rs1020294 SNP in which G carriers were more likely to debut later compared to patients presenting the AA genotype (p =. 002; OR = 9.57, CI95%[ 2.37-38.64]). The results also showed that EO- BD tended to experience more alcohol misuse (p =.003; OR =.197, CI95%[.07-.58]) compared to LO-BD. Conclusions: Our results provide evidence for genetic differences between EO- BD and LO-BD at the IMPA2 gene as well as clinical differences between subgroups with therapeutic implications.