Serum uric acid levels and the clinical characteristics of depression

Wen, Shi Wu; Cheng, Mingwang; Wang, Houliang; Yue, Jihui; Wang, Hong; Li, Guanying; Zheng, Liang; Zhong, Zhaohui; Peng, Fuhua

doi:10.1016/j.clinbiochem.2011.10.010

Cited by 86 publications

(68 citation statements)

References 21 publications

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“…As indicated by clinical studies, inosine may also partially act via its breakdown product, uric acid [30,29]. Lowered uric acid levels were found in depressive patients [58], a compound that exerts antioxidant and neuroprotective proprieties in different pathological conditions including Parkinson's disease [30,29]. The antidepressant potential of inosine is in agreement with clinical data showing decreased levels of inosine in the serum of patients diagnosed with MDD [7].…”

Section: Discussionsupporting

confidence: 76%

Signaling pathways underlying the antidepressant-like effect of inosine in mice

Gonçalves

Neis

Rieger

et al. 2016

Purinergic Signalling

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Inosine is a purine nucleoside formed by the breakdown of adenosine that elicits an antidepressant-like effect in mice through activation of adenosine A 1 and A 2A receptors. However, the signaling pathways underlying this effect are largely unknown. To address this issue, the present study investigated the influence of extracellular-regulated protein kinase (ERK)1/2, Ca 2+ /calmoduline-dependent protein kinase (CaMKII), protein kinase A (PKA), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase 3beta (GSK-3β) modulation in the antiimmobility effect of inosine in the tail suspension test (TST) in mice. In addition, we attempted to verify if inosine treatment was capable of altering the immunocontent and phosphorylation of the transcription factor cyclic adenosine monophosphatate (cAMP) responsebinding element protein (CREB) in mouse prefrontal cortex and hippocampus. Intracerebroventricular administration of U0126 (5 μg/mouse, MEK1/2 inhibitor), KN-62 (1 μg/ mouse, CaMKII inhibitor), H-89 (1 μg/mouse, PKA inhibitor), and wortmannin (0.1 μg/mouse, PI3K inhibitor) prevented the antiimmobility effect of inosine (10 mg/kg, intraperitoneal (i.p.)) in the TST. Also, administration of a subeffective dose of inosine (0.1 mg/kg, i.p.) in combination with a sub-effective dose of AR-A014418 (0.001 μg/mouse, GSK-3β inhibitor) induced a synergic antidepressant-like effect. None of the treatments altered locomotor activity of mice. Moreover, 24 h after a single administration of inosine (10 mg/kg, i.p.), CREB phosphorylation was increased in the hippocampus. Our findings provided new evidence that the antidepressant-like effect of inosine in the TST involves the activation of PKA, PI3K/Akt, ERK1/2, and CaMKII and the inhibition of GSK-3β. These results contribute to the comprehension of the mechanisms underlying the purinergic system modulation and indicate the intracellular signaling pathways involved in the antidepressant-like effect of inosine in a preclinical test of depression.

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Section: Discussionsupporting

confidence: 76%

Signaling pathways underlying the antidepressant-like effect of inosine in mice

Gonçalves

Neis

Rieger

et al. 2016

Purinergic Signalling

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“…Additionally, they also found that uric acid levels of MDD patients were lower than healthy subjects. Another study found uric acid levels significantly reduced in MDD patients compared to controls (Wen et al, 2012), suggesting that purinergic dysfunctions might affect the whole spectrum of affective disorders.…”

Section: Discussionmentioning

confidence: 98%

“…To be enrolled in the control group, patients had to have an Axis I diagnosis other than bipolar disorder (DSM-IV-TR, SCID-I) and they had to have never been exposed to mood stabilizers in their life. We included in the present study controls with Major Depressive Disorder only if in euthymic state for at least two months because it was found that patients during major depressive episodes have lower serum uric acid levels (Wen et al, 2012). Subjects with severe or unstable medical illnesses were excluded from the study; patients with gout, chronic inflammatory disease, diabetes, renal failure or serum creatinine value 41.5 mg/dL, or other diseases associated with hyperuricemia were also excluded.…”

Section: Subjectsmentioning

confidence: 99%

Increased uric acid levels in bipolar disorder subjects during different phases of illness

Albert

Cori

Aguglia

et al. 2015

Journal of Affective Disorders

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“…However, at least one study found no differences in uric acid levels between BD subjects and healthy controls (Wen et al, 2012). Uric acid, as one of a cluster of urinary metabolites, was correlated with first depressive episode in drug-naïve MDD subjects (Zheng et al, 2013).…”

Section: Human Studiesmentioning

confidence: 99%

Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics

Ortiz

Ulrich

Zarate

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

105

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Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system particularly the modulation of P1 and P2 receptor subtypes—plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects.

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Serum uric acid levels and the clinical characteristics of depression

Cited by 86 publications

References 21 publications

Signaling pathways underlying the antidepressant-like effect of inosine in mice

Signaling pathways underlying the antidepressant-like effect of inosine in mice

Increased uric acid levels in bipolar disorder subjects during different phases of illness

Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics

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