Response to Zhang et al., (2005) Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression. Neuron 45, 11–16

Department of Psychiatry, Columbia University, New York, New York, United States
Neuron (Impact Factor: 15.05). 01/2006; 48(5):702-3; author reply 705-6. DOI: 10.1016/j.neuron.2005.11.018
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    ABSTRACT: A substantial body of research has developed concerning the role of serotonin (5-HT) in the etiology and treatment of major depressive disorder (MDD). The first section of this chapter summarizes the clinical evidence implicating alterations of the serotonergic system in the etiology of MDD. A general serotonin vulnerability has been proposed as a major risk factor in MDD, consisting of the composite risk factors from different components of 5-HT transmission. The effects of abnormal 5-HT synthesis, receptor function and genetic polymorphisms are discussed. The second section reviews some of the preclinical models and tests that are used to measure depressive behaviors and the efficacy of antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs). This section is focused on models that are commonly used in rodent species. Models and tests that require either acute or chronic antidepressant administration to achieve behavioral alterations are covered. The third section reviews the preclinical (rodent) literature concerning the role of individual 5-HT receptors in the development and pharmacological treatment of depressive behaviors. The effects of 5-HT depletion and of manipulation of the 5-HT transporter are also discussed. Although identifying the 5-HT receptors that support the therapeutic effects of SSRIs may lead to the development of more effective antidepressant drugs with fewer side effects, it is unclear whether the complete antidepressant effect of SSRIs can be reproduced by a single selective 5-HT receptor agonist or antagonist.
    No preview · Article · Feb 1990 · Annals of the New York Academy of Sciences
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    Full-text · Article · Dec 2005 · Neuron
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    ABSTRACT: Psychiatric disorders, including affective disorders (AD) and schizophrenia (SZ) are among the most common disabling brain diseases in Western populations and result in high costs in terms of morbidity as well as mortality. Although their etiology and pathophysiology is largely unknown, family-, twin-, and adoption studies argue for a strong genetic determination of these disorders. These studies indicate that there is between 40 and 85% heritability for these disorders but point also to the importance of environmental factors. Therefore, any research strategy aiming at the identification of genes involved in the development of AD and SZ should account for the complex nature (multifactorial) of these disorders. During the last decade, molecular genetic studies have contributed a great deal to the identification of genetic factors involved in complex disorders. Here we provide a comprehensive review of the most promising genes for AD and SZ, and the methods and approaches that were used for their identification. Also, we discuss the current knowledge and hypotheses that have been formulated regarding the effect of variations on protein functioning as well as recent observations that point to common molecular mechanisms.
    No preview · Article · Sep 2006 · Human Mutation
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