The Role of Purinergic Signaling in Depressive Disorders.

The role of purinergic signaling in depressive disorders.

Filed under: Depression Treatment

Neuropsychopharmacol Hung. 2012 Dec; 14(4): 231-8
Sperlagh B, Csolle C, Ando RD, Goloncser F, Kittel A, Baranyi M

The purinergic signaling system consists of transporters, enzymes and receptors responsible for the synthesis, release, action and extracellular inactivation of adenosine 5′-triphosphate (ATP) and its extracellular breakdown product adenosine. The actions of ATP are mediated ionotropic P2X and metabotropic P2Y receptor subfamilies, whilst the actions of adenosine are mediated by P1 adenosine receptors. Purinergic signaling pathways are widely expressed in the central nervous system (CNS) and participate in its normal and pathological functions. Among P2X receptors, the P2X7 receptor (P2rx7) has received considerable interest in both basic and clinical neuropsychiatric research because of its profound effects in animal CNS pathology and its potential involvement as a susceptibility gene in mood disorders. Although genetic findings were not always consistently replicated, several studies demonstrated that single nucleotide polymorphisms (SNPs) in the human P2X7 gene (P2RX7) show significant association with major depressive disorder and bipolar disorder. Animal studies revealed that the genetic knock-down or pharmacological antagonism leads to reduced depressive-like behavior, attenuated response in mania-model and alterations in stress reactivity. A potential mechanism of P2rx7 activation on mood related behavior is increased glutamate release, activation of extrasynaptic NMDA receptors and subsequent enduring changes in neuroplasticity. In addition, dysregulation of monoaminergic transmission and HPA axis reactivity could also contribute to the observed changes in behavior. Besides P2rx7, the inhibition of adenosine A1 and A2A receptors also mediate antidepressant-like effects in animal experiments. In conclusion, despite contradictions between existing data, these findings point to the therapeutic potential of the purinergic signaling system in mood disorders.
HubMed – depression

A new clinical evidence-based gene-environment interaction model of depression.

Filed under: Depression Treatment

Neuropsychopharmacol Hung. 2012 Dec; 14(4): 213-20
Bagdy G, Juhasz G, Gonda X

In our current understanding of mood disorders, the role of genes is diverse including the mediation of the effects of provoking and protective factors. Different or partially overlapping gene sets play a major role in the development of personality traits including also affective temperaments, in the mediation of the effects of environmental factors, and in the interaction of these elements in the development of depression. Certain genes are associated with personality traits and temperaments including e.g., neuroticism, impulsivity, openness, rumination and extroversion. Environmental factors consist of external (early and provoking life events, seasonal changes, social support etc.) and internal factors (hormones, biological rhythm generators, comorbid disorders etc). Some of these environmental factors, such as early life events and some prenatal events directly influence the development of personality traits and temperaments. In the NEWMOOD cohort polymorphisms of the genes of the serotonin transporter, 5-HT1A, 5-HT1B and 5-HT2A and endocannabinoid CB1 receptors, tryptophan hydroxylase, CREB1, BDNF and GIRK provide evidence for the involvement of these genes in the development of depression. Based on their role in this process they could be assigned to different gene sets. The role of certain genes, such as promoter polymorphisms of the serotonin transporter (5-HTTLPR) and CB1 receptor has been shown in more than one of the above factors. Furthermore, gene-gene interactions of these promoters associated with anxiety suggest the application of these polymorphisms in personalized medicine. In this review we introduce a new model including environmental factors, genes, trait and temperament markers based on human genetic studies.
HubMed – depression

Factors associated with fear of falling among community-dwelling elderly adults without reduced performance in instrumental activities of daily living.

Filed under: Depression Treatment

Nihon Ronen Igakkai Zasshi. 2012; 49(4): 457-62
Oya T, Uchiyama Y, Shimada H, Makizako H, Doi T, Yoshida D, Uemura K, Suzuki T

Aim: The purpose of this study was to examine factors related to fear of falling (FOF) in elderly adults who showed no reduced performance regarding independent instrumental activities of daily living (IADL). Methods: A total of 119 elderly adults participated in the study (mean age, 75.7±7.2 years, women, n=60). We investigated the prevalence of FOF, anamnesis, medications, body pain, and history of falls, the Geriatric Depression Scale, International Physical Activity Questionnaire, Life-Space Assessment (LSA). The Timed Up and Go test (TUG) and one-legged standing time were measured to evaluate physical performance. Participants were divided into elderly adults with FOF (FOF group) and those without FOF (non-FOF group). The unpaired t-test or chi-square test was used for group comparisons. Multiple logistic regression analysis was then performed to examine the factors associated with FOF. Results: The prevalence of FOF was 51.3% overall. The FOF group had a higher prevalence of anamnesis, body pain, and history of falls than the non-FOF group. The FOF group had lower LSA scores, longer durations on the TUG, and shorter durations on the one-legged standing test than the non-FOF group. On multiple logistic regression analysis, LSA (total score, 120 points) was significantly associated with FOF (odds ratio: 0.96, 95% confidence interval=0.93-0.99). Conclusion: Fear of falling was significantly associated with life space in community-dwelling elderly adults who showed no reduced performance regarding IADL. In future, it will be necessary to clarify any possible causal relationship by longitudinal investigations.
HubMed – depression

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