Abstract
Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). The relationship to different psychopathological dimensions within these disorders however remains to be elucidated. We thus investigated potential group differences of tryptophan, kynurenine, kynurenic acid, 3-hydroxy kynurenine and quinolinic acid in the plasma of 19 healthy controls (HC), 45 patients with SZ and 43 patients with MDD and correlated plasma proteins with the “motivation and pleasure” dimension and cognition. After correcting for the covariates age, sex, body mass index, smoking and medication, patients with MDD showed lower kynurenine and 3-hydroxy kynurenine levels compared to HC. Quinolinic acid correlated negatively with composite cognitive score in patients with SZ, indicating that more severe cognitive impairments were associated with increased plasma levels of quinolinic acid. No correlations were found in patients with MDD. These results indicate that MDD and SZ are associated with dysregulation of the kynurenine pathway. Quinolinic acid might be specifically implicated in the pathophysiology of cognitive deficits in patients with SZ. Further studies are needed to determine whether TRYCATs are causally involved in the etiology of these neuropsychiatric disorders.
Highlights
Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD)
Kynurenine can be catabolized along two pathways: Kynurenine aminotransferases produce kynureninc acid (KYNA) and kynurenine monooxygenase (KMO) converts KYN to 3-hydroxykynurenine (3-OHK), which is further catabolized to quinolinic acid (QUIN)
While there were no differences in sex between healthy controls (HC) and patient groups, there were more female participants in the MDD group compared to the SZ group
Summary
Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). Schizophrenia (SZ) and major depressive disorder (MDD) are prevalent neuropsychiatric disorders with high socioeconomic and individual burden[1,2] Despite their significant contribution to the global burden of disabilities[3] our knowledge of the underlying etio-pathophysiological mechanisms are sparse and as a result, treatment options remain limited[4]. There is increasing evidence that the immune system plays a major role in neuropsychiatric disorders, including being causally involved in the pathogenesis of the above discussed symptom dimensions1314. KYNA, 3-OHK and QUIN were shown to exhibit neuroactive properties, including affecting glutamatergic, dopaminergic and nicotinergic neurotransmission[18]
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