Blier P, Montigny C. Current advances and trends in the treatment of depression. TIPS 15: 220-226
ABSTRACT The pathophysiology of major affective illness is poorly understood. However, several lines of preclinical and clinical evidence indicate that an enhancement of 5-HT-mediated neurotransmission might underlie the therapeutic effect of most antidepressant treatments. This net effect would, however, be obtained via different mechanisms. A better understanding of the neurobiological basis for the delayed onset of action of antidepressant treatments has led to the elaboration of strategies that could accelerate the antidepressant response. These strategies are discussed in this article by Pierre Blier and Claude de Montigny.
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- "3.6. Glial Modulation of IL-DBS-Induced Enhancement of the Spontaneous Activity of Presumed DRN 5-HT Neurons Classical antidepressants are well known to enhance serotoninergic neurotransmission, with a time course that is consistent with the onset of their therapeutic effects (Blier and de Montigny, 1994). In the present study, the firing activity of presumed 5-HT neurons was recorded in the dorsal raphe nucleus (DRN) before and/or after 1 h of stimulation of the IL-PFC (30 and 130 Hz, 150 μA bilaterally) in anesthetized rats (Fig. S3). "
ABSTRACT: Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K+ buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal–glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.
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- "Imaging studies have shown hippocampal volume reduction in patients with depressive disorder, which correlates with disease duration (Koolschijn et al., 2009). Additionally, low levels of monoamines in such regions, and in particular that of 5-HT, have been related to the state of depression (Blier and de Montigny, 1994). Conversely, the increases on brain 5-HT levels are thought to be closely related to the antidepressant effect (Kitaichi et al., 2010). "
ABSTRACT: Atorvastatin is a statin largely used in the treatment of hypercholesterolemia and recently revealed as a neuroprotective agent. The antidepressant-like effect of acute atorvastatin treatment in mice has been previously demonstrated by our laboratory. The purpose of this study was to explore the contribution of the serotonergic system in the antidepressant-like effect of atorvastatin in mice. Data demonstrate that the serotonin (5-HT) depleting agent p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p.) completely abolished atorvastatin (0.1 mg/kg, p.o.) antidepressant-like effect. Besides atorvastatin, fluoxetine (10 mg/kg, p.o.), a serotonin selective reuptake nhibitor (SSRI) was able to exert an antidepressant-like effect, but any of them changed 5-HT content in hippocampus or frontal cortex. The 5H-T1A (WAY100635, 0.1 mg/kg, s.c) or the 5-HT2A/2C (ketanserin, 5 mg/kg, s.c.) receptor antagonists prevented atorvastatin antidepressant-like effect. In addition, a combinatory antidepressant-like effect was observed when mice received the co-administration of sub-effective doses of atorvastatin (0.01 mg/kg, p.o.) and the SSRI fluoxetine (5 mg/kg, p.o.), paroxetine (0.1 mg/kg, p.o.) or sertraline (1 mg/kg, p.o.). Taken together, these results indicate that the antidepressant-like effect of atorvastatin depends on the serotonergic system modulation.Pharmacology Biochemistry and Behavior 07/2014; DOI:10.1016/j.pbb.2014.04.005 · 2.82 Impact Factor
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- "alterations in the 5HT transporter , so far, a primary role for 5HT in the pathophysiology in anxiety disorder has not been established. However, antidepressant treatment is used for anxiety disorders as well and generally targets the reuptake of serotonin and/ or norepinephrine by elevating its availability in the synaptic cleft  . Current antidepressants are effective for about 65% of depressed patients and generally delay the onset of therapeutic effects . "
ABSTRACT: Anxiety and depression are the most frequently diagnosed psychological diseases showing a high co-morbidity. They have a severe impact on the lives of the persons concerned. Many meta-analytical studies suggested a positive anxiolytic and depression-reducing effect of exercise programs. The aim of the present article is to synthesize meta-analyses on the effects of exercise on anxiety and depression and to describe average effect sizes. For this purpose 37 meta-analyses were included reporting 50 effect sizes for anxiety scores of 42,264 participants and depression scores of 48,207 persons. The average documented anxiolytic effect of exercise in these reviews was small, 0.34. In contrast, the effect of exercise on depression was significantly higher and at a moderate level, 0.56. Data of randomized controlled trials suggest higher sizes for the effect of exercise on anxiety and depression leading to increases up to moderate and large effects, respectively. Additionally, exercise seems to be more beneficial for patients compared to participants within a non-clinical, normal range of psychological disease. Especially for the effect of exercise on anxiety, more high quality meta-analyses of randomized controlled trials are needed. Finally, possible neurobiological explanations are suggested for the positive effect of exercise on psychological disorders like anxiety and depression.CNS & neurological disorders drug targets 06/2014; 13(6):1002-1014. DOI:10.2174/1871527313666140612102841 · 2.70 Impact Factor