New frontiers in the neuropsychopharmacology of mental illness

Abstract

This Research Topic aims to cover recent progress in research studying how genetic make-up and environmental factors can contribute to the development of mental disorders such as anxiety, depression, schizophrenia, and psychoactive substances abuse. It has brought together leading experts in the field to address these questions from different angles in eleven reviews, seven original research articles and two theoretic/opinion papers.The first three articles describe several techniques which are valuable tools to study the role of neurotransmitters such as serotonin (5-HT) in the pathophysiology and the treatment of psychiatric disorders. First, Prof. Gardier (2013) nicely summarizes the main advantages as well as some limitations of using microdialysis in wildtype (WT) and knockout (KO) mice. His team showed that paroxetine-induced increased in cortical 5-HT extracellular level was enhanced in 5-HT 1A receptor KO mice compared to WT animals. Then, by performing loose-seal cell-attached electrophysiological recordings in 5-HT transporter knockout (Sert −/− ) and tryptophan hydroxylase-2 knockout (Tph2 −/− ) mice, Araragi et al. (2013) demonstrate that the sensitivity of somatodendritic 5-HT 1A receptors does not predict the magnitude of 5-HT neuron auto-inhibition. Finally, Mendez-David et al.'s (2013) results suggest that isolation of peripheral blood mononuclear cells (PBMCs) from mice by submandibular bleeding is a useful technique to screen putative biomarkers relevant to the pathophysiology of mood disorders such as β-arrestin 1. They found that the reduced β-arrestin 1 levels found in PBMCs from anxious/depressed mice was restored to normal levels following chronic treatment with fluoxetine.The following eleven articles provide excellent insights into the interaction between gene and environment in mental disorders as well as the role of several transmitters/neuropeptides and the different therapeutic strategies. El-Hage et al. (2013) elegantly expose the potential predictors of response/non-response to antidepressants and discuss their clinical and practical implications. Alongside with reviewing several markers that can be used to predict response to pharmacotherapy, they also describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. Then, focusing mainly on the impact of polymorphisms on anxiety-like and depression-like behavior in rodents, Armario and Nadal (2013) discuss how individual differences can contribute to explain differential susceptibility to develop behavioral alterations. They also emphasize methodological problems that can lead to inappropriate or over-simplistic interpretations. Olivier et al. (2013) review the role of the GABAA receptor and the serotonergic system in drug discovery for anxiety disorders. They elegantly highlight how genetic studies aiming to unravel the neurobiology of anxiety have proven to be challenging, and describe how the development of animal models (including genetically modified rodents) ...