Data from: Increased breakdown of kynurenine towards its neurotoxic branch in bipolar disorder

Introduction Bipolar disorder (BD) is a chronic psychiatric disease which
can take most different and unpredictable courses. It is accompanied by
unspecific brainstructural changes and cognitive decline. The
neurobiological underpinnings of these processes are still unclear.
Emerging evidence suggests that tryptophan catabolites (TRYCATs), which
involve all metabolites of tryptophan towards the kynurenine (KYN) branch,
are involved in the etiology as well as in the course of BD. They are
proposed to be mediators of immune-inflammation and neurodegeneration. In
this study we measured the levels of KYN and its main catabolites
consisting of the neurotoxic hydroxykynurenine (3-HK), the more
neuroprotective kynurenic acid (KYNA) and anthranilic acid (AA) and
evaluated the ratios between end-products and substrates as proxies for
the specific enzymatic activity (3-HK/KYN, KYNA/KYN, AA/KYN) as well as
3-HK/KYNA as a proxy for neurotoxic vs. neuroprotective end-product
relation in individuals with BD compared to healthy controls (HC). Methods
We took peripheral TRYCAT blood levels of 143 euthymic to mild depressive
BD patients and 101 HC. For statistical analyses MANCOVA's controlled
for age, sex, body mass index, cardiovascular disease and smoking were
performed. Results The levels of KYNA (F=5,579; p<.05) were reduced
in BD compared to HC. The enzymatic activity of the
kynurenine-3-monooxygenase (KMO) reflected by the 3-HK/KYN ratio was
increased in BD individuals compared to HC (F=5,394; p<.05).
Additionally the ratio of 3-HK/KYNA was increased in individuals with BD
compared to healthy controls (F=11,357; p<.01). Discussion In
conclusion our findings subserve the concept of KYN -pathway alterations
in the pathophysiology of BD. We present evidence of increased breakdown
towards the neurotoxic branch in KYN metabolism even in a euthymic to mild
depressive state in BD. From literature we know that depression and mania
are accompanied by inflammatory states which should be capable to produce
an even greater imbalance due to activation of key enzymes in the
neurotoxic direction of KYN -conversion. These processes could finally be
involved in the development of unspecific brain structural changes and
cognitive deficits which are prevalent in BD. Further research should
focus on state dependent changes in TRYCATs and its relation to cognition,
brain structure and staging parameters.