The interaction of serotonin transporter gene polymorphisms and early adverse life events on vulnerability for major depression.
ABSTRACT Considerable literature supports the hypothesis of dysfunction in central nervous system serotonergic circuits in the pathophysiology of mood disorders, specifically major depression. Since the development of the selective serotonin (5-HT) reuptake inhibitors, a putative role for the 5-HT transporter (SERT) in the etiology of depression has been explored. The discovery of a functional SERT polymorphism has provided a novel tool to further scrutinize the role of serotonergic neurons in depression. This article reviews the burgeoning evidence of an interaction between early life stress and an SERT polymorphism on vulnerability to depression.
Full-textDOI: · Available from: Charles B Nemeroff, May 30, 2015
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ABSTRACT: Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene--dosage effects on language development at 7q11.23 have been hypothesized. Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined. The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production. Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype--phenotype correlations, possible gene--environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism.Molecular Autism 08/2013; 4(1):29. DOI:10.1186/2040-2392-4-29 · 5.49 Impact Factor
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ABSTRACT: Psychiatric disorders are often considered as simple imbalances between a limited number of cerebral neurotransmitters. In fact, it is more complicated than this “simple approach” and each psychiatric disorder constitutes network dysfunction within which several agents and factors are implicated. Thus, the therapeutical perspectives and implications are as vast and as numerous as the diversity of those network dysfunctions. Furthermore, the description of factors influencing diseases prognoses and treatment efficacy indicates new elements to consider both in therapies and drug researches.Saudi Pharmaceutical Journal 04/2014; 22(2):95–100. DOI:10.1016/j.jsps.2013.01.008 · 1.00 Impact Factor
Frontiers in Public Health 01/2015; 3:4. DOI:10.3389/fpubh.2015.00004