Current advances in trends in the treatment of depression

Professor, Department of Psychiatry, McGill University, Montréal, Quebec, Canada H3A 1A1
Trends in Pharmacological Sciences (Impact Factor: 9.99). 08/1994; 15(7):220-226. DOI: 10.1016/0165-6147(94)90315-8

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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    • "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). "
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    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 [143], 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 [144] [145]. Current antidepressants are effective for about 65% of depressed patients and generally delay the onset of therapeutic effects [146]. "
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    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
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    • "However, these ligands bind to both 5-HT 1A autoreceptors and heteroreceptors (Yocca 1990), making it difficult to determine which subpopulation mediates specific behavioral effects. Despite this, behavioral models of stress have consistently shown that activation of 5-HT 1A heteroreceptors produce similar changes to conventional antidepressants (Lucki 1991) and several preclinical studies have suggested that 5- HT 1A heteroreceptors are particularly important to the antidepressant response (Blier and de Montigny 1994; De Vry 1995). "
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    ABSTRACT: Serotonin (5-HT) neurotransmission is intimately linked to anxiety and depression and a diverse body of evidence supports the involvement of the main inhibitory serotonergic receptor, the serotonin-1A (5-HT1A) subtype, in both disorders. In this review, we examine the function of 5-HT1A receptor subpopulations and re-interpret our understanding of their role in mental illness in light of new data, separating both spatial (autoreceptor versus heteroreceptor) and the temporal (developmental versus adult) roles of the endogenous 5-HT1A receptors, emphasizing their distinct actions in mediating anxiety and depression-like behaviors. It is difficult to unambiguously distinguish the effects of different populations of the 5-HT1A receptors with traditional genetic animal models and pharmacological approaches. However, with the advent of novel genetic systems and subpopulation-selective pharmacological agents, direct evidence for the distinct roles of these populations in governing emotion-related behavior is emerging. There is strong and growing evidence for a functional dissociation between auto- and heteroreceptor populations in mediating anxiety and depressive-like behaviors, respectively. Furthermore, while it is well established that 5-HT1A receptors act developmentally to establish normal anxiety-like behaviors, the developmental role of 5-HT1A heteroreceptors is less clear, and the specific mechanisms underlying the developmental role of each subpopulation are likely to be key elements determining mood control in adult subjects.
    Psychopharmacology 12/2013; 231(4). DOI:10.1007/s00213-013-3389-x · 3.99 Impact Factor
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