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. 2018 Jul 24;12:499. doi: 10.3389/fnins.2018.00499

Table 1.

Studies investigating antidepressant interventions targeting inflammation, kynurenine or BH4 pathways.

Population/model Treatment Main outcomes
Clinical trials
Akhondzadeh et al., 2009 n = 40 Depressed patients COX-2 inhibitor (celecoxib) Improvement of antidepressant treatment
Müller et al., 2006 n = 40 Depressed patients COX-2 inhibitor (celecoxib) Improvement of antidepressant treatment
Kappelmann et al., 2018 (review and meta-analysis) Chronic inflammatory conditions Anti-cytokines ↙Depressive symptoms
Arisoy et al., 2013 n = 9 patients Ankylosing spondylitis TNFα blockers (infliximab) ↙Depression and anxiety scores
Fleming et al., 2015 (databases review) n = 464 patients Psoriasis TNFα blockers ↙Depressive symptoms
Raison et al., 2013 n = 60 Depressed patients TNFα blockers (infliximab) ↙Depressive symptoms
Emery et al., 2007 n = 13 Obese women Weight loss (gastric bypass) ↙Depressive symptoms
↙Inflammatory blood markers (CRP levels)
Pan et al., 2011 Case report (treatment refractory suicidal ideation) Sapropterin Mood improvement
Curtius et al., 1983 Case report BH4 Mood improvement
Woggon et al., 1984 Case report BH4 No mood change
Preclinical studies
Norden et al., 2015 Mice (Cancer-related fatigue) Ibuprofen ↙Depressive-like behavior and fatigue-like (FST/wheel running)
↙IL-1b and IL-6 in hippocampus
Zaminelli et al., 2014 Rats (rotenone Parkinson model) Ibuprofen ↙Depressive-like behavior (FST)
Fu et al., 2016 Stressed rats (UCMS) TNFα blockers (infliximab) ↙Depressive-like behavior
↙Brain IDO and HAAO mRNA expression
Bayramgürler et al., 2013 Rats TNFα blockers (etanercept) ↙Depressive-like behavior (FST)
Laumet et al., 2017 Mice (spared nerve injury) (IL-1RA KMO inhibitor (Ro 61-8048) ↙Depressive-like behavior (FST)
↙Brain KMO mRNA expression
↙Depressive-like behavior (FST)
Dobos et al., 2012 Mice (LPS) 1-MT ↙Depressive-like behavior
Corona et al., 2013 Mice (LPS) 1-MT ↙Depressive-like behavior (TST)
Xie et al., 2014 Rat (pilocarpine) 1-MT ↙Depressive-like behavior (FST)
↙Brain IDO mRNA expression and activity
O’Connor et al., 2009c Mice 1-MT ↙Depressive-like behavior
Gibney et al., 2014 (LPS) Minocycline (TST/FST)
Rats (restraint stress) Allopurinol Brain IDO mRNA expression and activity
↙Depressive-like behavior (FST)
↙Circulating kyn/tryp

COX-2, cyclo-oxygenase-2; UCMS, unpredictable chronic mild stress; FST, forced swim test; TST, tail suspension test; IL-1RA, interleukin-1 receptor antagonist; KMO, kynurenine 3-hydroxylase; 1-MT, 1-methyl tryptophan (IDO inhibitor); LPS, lipopolysaccharide; IDO, indolamine 2,3-dioxygenase; HAAO, hydroxyanthranilic acid oxygenase.