Association between kynurenine pathway metabolites and psychotropic medications in bipolar disorder: An exploratory...

Abnormalities of the kynurenine pathway (KP) have been described in bipolar disorder (BD). However, the associations between current psychotropic treatments and levels of metabolites remain underexplored.

Peripheral blood levels of tryptophan (TRP), kynurenine (KYN) and metabolites were measured using liquid chromatography-tandem mass spectrometry among 173 individuals with BD. Univariable and multivariable analyses were used to test associations between each metabolite and current use of lithium, valproate, lamotrigine, atypical antipsychotics, and antidepressants.

In univariable analyses, valproate current use was associated with lower levels of TRP (p_adjusted = 0.00006), KYN (p_adjusted = 0.000004), 3-hydroxykynurenine (3OHKYN) (p_adjusted = 0.04), xanthurenic acid (XA) (p_adjusted = 0.00004), and quinolinic acid (QUIN) (p_adjusted = 0.0024). Lithium current use was associated with higher levels of KYN (p_adjusted = 0.002), KYN/TRP ratio (p_adjusted = 0.003), 3OHKYN (p_adjusted = 0.008), and XA (p_adjusted = 0.024). Lamotrigine current use was associated with higher levels of KYN (p_adjusted = 0.03), kynurenic acid (p_adjusted = 0.003), and QUIN (p_adjusted = 0.014). We observed no association between metabolites and current use of atypical antipsychotics or antidepressants. After covariation by age, sex, body mass index, tobacco use, manic and depressive symptoms at inclusion, and BD type, multivariable analyses confirmed most of the associations: lower levels of TRP, KYN, XA, QUIN among valproate users, higher levels of KYN, KYN/TRP ratio, 3OHKYN among lithium users, higher levels of QUIN among lamotrigine users.

The present study is the first to explore whether current use of psychotropic drugs is associated with different levels of kynurenine pathway metabolites in BD. We found that current use of valproate, lithium or lamotrigine was associated with distinct kynurenine pathway profiles. Future studies of the kynurenine pathway in psychiatry should consider current medication exposure as a potential confounder.