Abstract
ObjectiveTryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.MethodsA systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.ResultsTwenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.ConclusionThe TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.
Highlights
Bipolar disorder (BD) is a chronic psychiatric disorder characterized by alternating periods of depression and abnormally elevated moods
More recent studies point towards the imbalance supposedly neurotoxic [including 3-hydroxy kynurenine (3-HK) and quinolinic acid (QA)) and neuroprotective (kynurenic acid (KA)] TRP catabolites (TRYCAT) as a central mechanism in the pathophysiology of mood disorders (7, 8)
The analysis of TRP in cerebrospinal fluid (CSF) and five TRYCATs (TRP, KYN, KA, 3-HK, QA) in peripheral blood were included in the meta-analyses based on the minimal requirement of three studies for each meta-analysis
Summary
Bipolar disorder (BD) is a chronic psychiatric disorder characterized by alternating periods of depression and abnormally elevated moods. In response to inflammation or psychosocial stress (3), TRP is primarily metabolized into kynurenine (KYN) following an upregulation of indoleamine 2,3‐deoxygenase (IDO‐1) and hereby leading to a reduction in availability of serotonin (for a graphical illustration of the KYN Pathway, see Figure 1). This depletion of serotonin has been assumed to play a major role in the pathophysiology of depression (5, 6). In patients with Major Depressive Disorder (MDD), a consistent increase in 3-HK and QA and a decrease in KA in blood and cerebrospinal fluid has been found (8, 9). BD patients with a history of psychosis have shown elevated KA levels in cerebrospinal fluid (CSF) but not in the periphery, analogous to schizophrenia patients (13–16)
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