DOI: 10.5061/dryad.2358m
title: Data from: Increased breakdown of kynurenine towards its neurotoxic branch in bipolar disorder

description: 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&lt;.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&lt;.05).
 Additionally the ratio of 3-HK/KYNA was increased in individuals with BD
 compared to healthy controls (F=11,357; p&lt;.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.
description: DATA FOR Increased
 breakdown of kynurenine towards its neurotoxic branch in bipolar disorder
 PLOS ONEThe study was conducted
 at the Medical University of Graz, Department of Psychiatry. All patients
 took part in the ongoing single centre BIPFAT study, that assesses
 demographic parameters, complete actual and lifetime psychiatric history
 using the Structured Clinical Interview according to DSM-IV (SCID I),,
 history of medication, anthropometric measure, blood pressure, fasting
 blood, cognitive testing, EEG, stool sample, different lifestyle
 questionnaires and magnetic resonance imaging (MRI) of the brain. All
 patients included were former in- or outpatients of the Medical University
 of Graz and had a diagnosis of BD I or BD II according to the DSM-IV
 criteria. Patients needed to be in the state of euthymia or mild
 depression (HAM-D score &lt;14 and YMRS &lt;9) and had given written
 informed consent prior to participating in the study. The study has been
 approved by the local ethics committee (Medical University of Graz,
 Austria) in compliance with the current revision of the Declaration of
 Helsinki, ICH guideline for Good Clinical Practice and current regulations
 (EK-number: 24-123 ex 11/12). Exclusion criteria were the presence of
 chronic obstructive pulmonary disease, rheumatoid arthritis, systemic
 lupus erythematosus, inflammatory bowel disease, neurodegenerative and
 neuroinflammatory disorders (i.e. Alzheimer's, Huntington's and
 Parkinson's disorder, multiple sclerosis), hemodialysis and
 interferon-α-based immunotherapy. Further exclusion criteria for controls
 were the presence of lifetime psychiatric diagnoses (verified by SCID I)
 and first and second grade relationship to relatives with psychiatric
 disorders. We took peripheral TRYCAT blood levels of 143 euthymic and mild
 depressive BD patients and 101 healthy controls. Targeted parameters were
 the levels of KYN, KYNA, 3-HK and AA, the ratio 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. Because of technical issues AA could
 only be evaluated in 113 BD and 88 HC. The analyzation took place at the
 Institute of Laboratory Medicine, Medical Center of Ludwig Maximilian
 University, Munich, Germany.