The Relationship of Alcohol Use Disorders and Depressive Symptoms to Tryptophan Metabolism: Cross-Sectional Data from a Nepalese Alcohol Treatment Sample

Abstract

Background Activation of the kynurenine pathway of tryptophan metabolism results in increased production of potentially depressogenic tryptophan catabolites and a reduction in tryptophan availability for serotonin synthesis. Since alcohol consumption affects tryptophan metabolism and disposition, we determined serum levels of kynurenine, tryptophan and the kynurenine/tryptophan ratio (KT ratio) in alcohol-use disorder (AUD) patients and compared their levels considering abstinence duration, AUD severity and comorbid depression. Methods The study sample included 169 AUD inpatients from eight alcohol treatment facilities in Kathmandu, Nepal. The Composite International Diagnostic Interview was administered to generate the AUD diagnosis. The Alcohol Use Disorder Identification Test (AUDIT) captured AUD severity and patterns of alcohol use. The Hopkins Symptom Checklist-25 was used to reveal current depressive symptoms. Serum kynurenine and tryptophan levels were determined by high-performance liquid chromatography and tryptophan degradation was measured by KT ratio (kynurenine/tryptophan × 103). Results Patients with above average AUDIT scores had higher mean serum levels of kynurenine (2.1μM±0.7 vs 1.8 μM ±0.6, p= 0.006) and KT ratios (48.6±17.6 vs 40.4±14.3, p=0.002) than those with below average scores. Patients with current depressive symptoms had higher mean tryptophan concentrations (49.9 μM ±13 vs 45.7 μM±14.1, p= 0.047) and lower KT ratios (41.4 μM ±14 vs 47.5 μM ±17.6, p=0.028) compared to patients whose reported depressive symptoms were below the standard cut-off. Higher tryptophan levels and lower KT ratios in the depressed group was specific to patients with longer abstinence and higher AUD severity. Conclusions Depression-related deregulation in tryptophan metabolism was found to depend on length of abstinence and on AUD severity. Together, results suggest that in AUD populations, peripheral tryptophan metabolism is subject to interactions between AUD severity and depressive symptoms.

Role of Kynurenine pathway and its metabolites in mood disorders: A systematic review and meta-analysis of clinical studies

“…Fourteen studies were identified and eleven met inclusion criteria (Baranyi et al, 2017; Bradley et al, 2015; Dahl et al, 2015; Krause et al, 2017; Meier et al, 2016; Myint et al, 2013; Myint et al, 2007b; Neupane et al, 2015; Quak et al, 2014; Savitz et al, 2015b; Sorgdrager et al, 2017; Sublette et al, 2011; Umehara et al, 2017; Wood et al, 1978) (Table 1) having excluded the study by Myint and colleagues, 2013 (Myint et al, 2013) because cases and controls were not fully matched at baseline, Myint and colleagues, 2007 (Myint et al, 2007b) which enrolled patients with BD, and Neupane and colleagues (Neupane et al, 2015) which included participants with alcohol-related disorders. The studies by Meier and colleagues (2015) and by Savitz and colleagues (2015) (Savitz et al, 2015b) contained the same participants and were included in separate analyses.…”

Comorbid post-traumatic stress disorder in alcohol use disorder: relationships to demography, drinking and neuroimmune profile

“…In the studied population, we have earlier shown lifetime MD to be related to higher inflammatory cytokine levels [ 20 ], whereas, recent depressive symptoms were related to lower BDNF levels [ 36 ] as well as altered tryptophan metabolism parameters [ 37 ] in the serum. Despite being highly associated with MD history, lifetime PTSD was not related to any of the assessed cytokines, CRP, or other neuroimmune factors.…”

Neuroimmune Interface in the Comorbidity between Alcohol Use Disorder and Major Depression

“…This could well be explained in terms of hyperactive stress response in concert with negative reinforcement, craving, and relapse. We reported increased tryptophan turnover with increased duration of abstinence (104). However, another study (105) showed that AUD individuals who abstained from alcohol for longer than two weeks, regardless of background variables, had much higher tryptophan levels compared to healthy controls.…”

“…However, another study (105) showed that AUD individuals who abstained from alcohol for longer than two weeks, regardless of background variables, had much higher tryptophan levels compared to healthy controls. Literature also indicates a contradictory higher tryptophan and lower tryptophan degradation in depression, alongside activated pro-inflammatory pathway (104, 106, 107), but these findings are based on peripherally measured mediators and may not reflect brain levels. An overview of the few studies that have investigated neuroimmune mediators in the context of AUD–MD comorbidity are shown in Table 1.…”