In a double-blind, randomized and placebo-controlled trial, adjuvant allopurinol improved symptoms of mania in in-patients suffering from bipolar disorder

Jahangard, Leila; Soroush, Sara; Haghighi, Mohammad; Ghaleiha, Ali; Bajoghli, Hafez; Holsboer‐Trachsler, Edith; Brand, Serge

doi:10.1016/j.euroneuro.2014.05.013

Cited by 49 publications

(46 citation statements)

References 21 publications

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“…Uric acid has been linked with a variety of psychological conditions, including neurodegenerative conditions and emotion-related psychopathology (Albert et al, 2015; Bowman et al, 2010; Fang et al, 2013; Jahangard et al, 2014; Kesebir et al, 2014; Lyngdoh et al, 2013; Machado-Vieira et al, 2008). Although variations in uric acid level alters neural transmission (Ortiz et al, 2015; Ozten et al, 2015), the brain functions that link uric acid and mental health have yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…The role of uric acid in mental health is also an emerging area of research. For example, uric acid levels are associated with emotion-related psychopathology, such as anxiety and mood disorders (Albert et al, 2015; Jahangard et al, 2014; Kesebir et al, 2014; Lyngdoh et al, 2013; Machado-Vieira et al, 2008). Within non-clinical populations, individuals with elevated uric acid levels are more likely to be impulsive (Sutin et al, 2014), hyperactive (Barrera et al, 1988; Johnson et al, 2011), and disinhibited (Lorenzi et al, 2010).…”

mentioning

confidence: 99%

“…Specifically, patients with bipolar disorder show higher uric acid levels during manic episodes (characterized by disinhibition), and therapeutic reductions in uric acid concentrations via allopurinol (a xanthine oxidase inhibitor) significantly reduce manic symptoms (Machado-Vieira et al, 2008). Furthermore, the degree of uric acid reduction correlates with improvement in manic symptom severity (Jahangard et al, 2014). Even within non-clinical populations, baseline uric acid has been linked to psychosocial behavioral tendencies (Lorenzi et al, 2010; Sutin et al, 2014).…”

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confidence: 99%

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The hippocampal response to psychosocial stress varies with salivary uric acid level

et al. 2016

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Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid’s impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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The hippocampal response to psychosocial stress varies with salivary uric acid level

et al. 2016

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“…Unfortunately, the authors provided no information on the number of concomitant medications, dose, or even the duration of treatment with mood stabilizers and antipsychotic medications during the follow-up period (Weiser et al, 2014), which prevents consistent conclusions from being drawn. More recently, a four-week, double-blind, placebo-controlled trial with allopurinol (300mg/day) as an add-on treatment to valproate showed significant antimanic effects compared to placebo (Jahangard et al, 2014). Echoing our previous findings, this study also found an association between lower uric acid levels and symptom improvement at endpoint (Jahangard et al, 2014).…”

Section: Treatment-related Studies and Clinical Trialsmentioning

confidence: 99%

“…More recently, a four-week, double-blind, placebo-controlled trial with allopurinol (300mg/day) as an add-on treatment to valproate showed significant antimanic effects compared to placebo (Jahangard et al, 2014). Echoing our previous findings, this study also found an association between lower uric acid levels and symptom improvement at endpoint (Jahangard et al, 2014). Finally, a recent systematic review and meta-analysis of adenosine modulators—with a special focus on allopurinol—supported the efficacy of these agents as adjuvant therapy in bipolar mania compared to placebo (Hirota and Kishi, 2013).…”

Section: Treatment-related Studies and Clinical Trialsmentioning

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

104

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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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Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Kumar

Joshi

Kler

et al. 2017

Medicinal Research Reviews

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Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases' binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.

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In a double-blind, randomized and placebo-controlled trial, adjuvant allopurinol improved symptoms of mania in in-patients suffering from bipolar disorder

Cited by 49 publications

References 21 publications

The hippocampal response to psychosocial stress varies with salivary uric acid level

The hippocampal response to psychosocial stress varies with salivary uric acid level

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

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

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