Current advances and 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; 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.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Enhancing cerebral serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is a common property of antidepressant treatments and the basis for their efficacy. 5-HT1A receptors located on the cell body and dendrites of 5-HT neurons (autoreceptors) play a key role in this regard. Because they normally mediate an inhibition of neuronal firing, their desensitization is a prerequisite to the delayed enhancement of 5-HT neurotransmission upon treatment with monoamine oxidase (MAOI) inhibitors or specific serotonin reuptake inhibitors (SSRI). Using β-sensitive microprobes in vivo, we measured a significant decrease (−30%) in binding sites for the 5-HT1A PET radioligand [18F]MPPF associated with an equivalent reduction (−34%) in the cell surface density of 5-HT1A receptor immunoreactivity (internalization), in the nucleus raphe dorsalis (autoreceptors), but not hippocampus (heteroreceptors), of rats given a single dose of the specific 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, iv). This effect was completely blocked by pretreatment with the selective 5-HT1A antagonist WAY 100635. Having ruled out that this decreased density of [18F]MPPF binding in the nucleus raphe dorsalis of 8-OH-DPAT-treated rats resulted from a local blood flow effect, we obtained autoradiographic evidence indicating that the total amount of specific binding of [18F]MPPF in tissue sections was unaffected by the 8-OH-DPAT treatment in either NRD or hippocampus. It was therefore concluded that the internalization of 5-HT1A autoreceptors accounted for the decreased binding in vivo of [18F]MPPF in the nucleus raphe dorsalis of rats treated with 8-OH-DPAT. Thus, PET imaging might provide a mean to measure 5-HT1A receptor internalization in human brain and thus assess responsiveness to antidepressant treatment.
    NeuroImage 05/2004; DOI:10.1016/S1053-8119(04)00175-2 · 6.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of silicon dioxide nanoparticles on the expression of key genes of the brain serotonergic (5-HT) system has been studied in specific pathogen-free mice chronically exposed to Tarkosil nanoaerosol (25-nm particles). Males of the Balb/c and C57Bl/6 strains are used to reveal genetic differences in the response to the nanomaterial. The animals are exposed to aerosol with a mean particle size of 107 nm for 10 days. After exposure, their midbrains, hippocampi, and frontal cortices are examined. The expression rates of genes for 5-HT1A and 5-HT2A receptors; tryptophan hydroxylase (TPH2), the key enzyme in 5-HT production; serotonin transporter (5-HTT); and interleukin 6 (IL6) as a marker of inflammation in the brain are assayed by quantitative reverse transcription PCR. The expression of 5-HT1A is notably elevated in the hippocampus of Balb/c mice, but it tends to decrease in C57Bl/6. No changes in the expression of the genes for 5-HT2A, TPH2, 5-HTT, or IL6 are noted in any brain divisions. Thus, the chronic inhalation of silicon dioxide nanoparticles does not activate nonspecific immunity in the brain, but it exerts contrasting genotype-specific effects on the expression of the 5-HT1A receptor in the hippocampus.
    Nanotechnologies in Russia 03/2014; 9(3-4):213-218. DOI:10.1134/S1995078014020177
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Major Depressive Disorder is a debilitating and increasingly prevalent psychiatric condition (Compton et al., 2006; Andersen et al., 2011). At present, its primary treatments are antidepressant medications and psychotherapy. Curiously, although the pharmacological effects of antidepressants manifest within hours, remission of clinical symptoms takes a number of weeks-if at all. Independently, support has grown for an idea-proposed as early as Helmholtz (von Helmholtz, 1924)-that the brain is a prediction machine, holding generative models for the purpose of inferring causes of sensory information (Dayan et al., 1995; Rao and Ballard, 1999; Knill and Pouget, 2004; Friston et al., 2006; Friston, 2010). If the brain does indeed represent a collection of beliefs about the causal structure of the world, then the depressed phenotype may emerge from a collection of depressive beliefs. These beliefs are modified gradually through successive combinations of expectations with observations. As a result, phenotypic remission ought to take some time as the brain's relevant statistical structures become less pessimistic.
    Frontiers in Psychology 02/2015; 6:153. DOI:10.3389/fpsyg.2015.00153 · 2.80 Impact Factor