P2RX7 Gln460Arg polymorphism is associated with depression among diabetic patients

G, Nagy; Rónai, Zsolt; Somogyi, Anikó; Sasvári-Székely, Mária; Rahman, Omar Abdul; Mate, Attila; Varga, Tímea; Nemoda, Zsófia

doi:10.1016/j.pnpbp.2008.08.021

Cited by 45 publications

(33 citation statements)

References 33 publications

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“…The dimensional analyses of the extended psychiatric patient sample supported our previous results showing association of rs2230912 (P2RX7 Gln460Arg) with severity of depressive symptoms among patients with mood disorders (Hejjas et al, 2009) and in diabetic patients (Nagy et al, 2008). However, in this extended sample of psychiatric patients the genetic effect could be observed only in the BPD subgroup, and not in the MDD subgroup.…”

Section: Discussionsupporting

confidence: 86%

Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms

Halmai

Döme

Vereczkei

et al. 2013

Journal of Affective Disorders

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Section: Discussionsupporting

confidence: 86%

Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms

Halmai

Döme

Vereczkei

et al. 2013

Journal of Affective Disorders

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“…Twelve studies found an association between SNPs in the P2X7 gene and mood disorders: nine with the Gln460Arg allelic variation (rs2230912) (Barden et al, 2006; Lucae et al, 2006; Nagy et al, 2008; Hejjas et al, 2009; McQuillin et al, 2009; Soronen et al, 2011; Backlund et al, 2012; Mantere et al, 2012; Halmai et al, 2013), one with the His155Tyr (rs208294) allelic variation (Soronen et al, 2011), one with a SNP located in the 3′ untranslated region (rs1653625) (Halmai et al, 2013), and one with a trend toward significance with the Thr348Ala allele (rs1718119) (Erhardt et al, 2007). Interestingly, the study by Mantere and colleagues (2012) demonstrated that the P2X7 receptor subunit Gln460Arg polymorphism was specifically associated with neuroticism in the context of mood disorders.…”

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

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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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“…Moreover, significant microgliosis and increased expression of the microglia-specific NMDA agonist quinolinic acid have been observed in depressed patients and patients with schizophrenia who succeeded in suicide [61,62]. Interestingly, specific P2X7 variants have also been associated with both bipolar disorder and depression [63,64]. Importantly, P2X7 receptor knockout mice exhibit an antidepressant-like phenotype and higher responsiveness to subtherapeutic doses of the tricyclic antidepressant imipramine [65].…”

Section: Purinergic Signalingmentioning

confidence: 99%

Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders

Lindberg¹,

Shan²,

Ayers-Ringler³

et al. 2015

CMM

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Purinergic signaling regulates numerous vital biological processes in the central nervous system (CNS). The two principle purines, ATP and adenosine act as excitatory and inhibitory neurotransmitters, respectively. Compared to other classical neurotransmitters, the role of purinergic signaling in psychiatric disorders is not well understood or appreciated. Because ATP exerts its main effect on energy homeostasis, neuronal function of ATP has been underestimated. Similarly, adenosine is primarily appreciated as a precursor of nucleotide synthesis during active cell growth and division. However, recent findings suggest that purinergic signaling may explain how neuronal activity is associated neuronal energy charge and energy homeostasis, especially in mental disorders. In this review, we provide an overview of the synaptic function of mitochondria and purines in neuromodulation, synaptic plasticity, and neuron-glia interactions. We summarize how mitochondrial and purinergic dysfunction contribute to mental illnesses such as schizophrenia, bipolar disorder, autism spectrum disorder (ASD), depression, and addiction. Finally, we discuss future implications regarding the pharmacological targeting of mitochondrial and purinergic function for the treatment of psychiatric disorders.

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P2RX7 Gln460Arg polymorphism is associated with depression among diabetic patients

Cited by 45 publications

References 33 publications

Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms

Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms

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

Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders

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