Serotonin transporter and GABA(A) alpha 6 receptor variants are associated with neuroticism
Biological PsychiatryPublished 21 January 2004
Srijan Sen, Sandra Villafuerte, Randolph M. Nesse, Scott F. Stoltenberg, Jeffrey Hopcian, Lillian Gleiberman
Citations121
SJR quartileQ1
SJR score4.68
SNIP2.24
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits and suggest the effect of 5-HTTLPR on neuroticism might be dependent on the Pro385Ser genotype.
Abstract
These findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits.
Keywords
NeuroscienceBiochemistry, Genetics and Molecular Biology
ScienceAssociation of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region
5,178 Citations1996Klaus‐Peter Lesch, Dietmar Bengel +8 more
ScienceGenetic Dissection of Complex Traits
3,453 Citations1994Eric S. Lander, Nicholas J. Schork
This article synthesizes the current state of the genetic dissection of complex traits--describing the methods, limitations, and recent applications to biological problems.
Nature GeneticsReplication validity of genetic association studies
1,826 Citations2001John P. A. Ioannidis, Evangelia Ntzani +2 more
It is concluded that a systematic meta-analytic approach may assist in estimating population-wide effects of genetic risk factors in human disease.
Journal of Personality and Social PsychologyPersonality in adulthood: A six-year longitudinal study of self-reports and spouse ratings on the NEO Personality Inventory.
1,318 Citations1988Paul T. Costa, Robert R. McCrae
Personality in Adulthood
1,278 Citations2003Robert R. McCrae, Paul T. Costa +1 more
This book discusses the search for growth or Decline in Personality, the Influences of Personality on the Life Course, and a Five-Factor Theory of Personality.
The American Journal of Human GeneticsUse of Unlinked Genetic Markers to Detect Population Stratification in Association Studies
1,210 Citations1999Jonathan K. Pritchard, Noah A. Rosenberg
It is shown that the case-control-study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate locus are included in the study, to test for stratification.
The American Journal of Human GeneticsA General Test of Association for Quantitative Traits in Nuclear Families
1,146 Citations2000Gonçalo R. Abecasis, Lon R. Cardon +1 more
A general approach that can accommodate nuclear families of any size, with or without parental information, is constructed, and it is shown that, when siblings are available, the total number of genotypes required in order to achieve comparable power is smaller if parents are not genotyped.
NeuropsychopharmacologyGABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder
1,087 Citations2001Francine M. Beneš
Investigation of the GABA system in rodent, primate and human brain and the characterization of changes in specific phenotypic subclasses of interneurons in schizophrenia and bipolar disorder will undoubtedly provide important new insights into how the integration of this transmitter system may be altered in neuropsychiatric disease.
Journal of PersonalityHeritability of the Big Five Personality Dimensions and Their Facets: A Twin Study
947 Citations1996Kerry L. Jang, W. John Livesley +1 more
The genetic and environmental etiology of the five-factor model of personality as measured by the revised NEO Personality Inventory was assessed using 123 pairs of identical twins and 127 pairs of fraternal twins.
Archives of General PsychiatryA Longitudinal Twin Study of Personality and Major Depression in Women
652 Citations1993Kenneth S. Kendler
In women, the relationship between neuroticism and the liability to major depression is substantial and largely the result of genetic factors that predispose to both neuroticismand major depression.
Archives of General PsychiatryReduced Cortical γ-Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy
618 Citations1999Gerard Sanacora, Graeme F. Mason +7 more
This study provides the first evidence of abnormally low cortical GABA concentrations in the brains of depressed patients through in vivo proton magnetic resonance spectroscopy.
Archives of General PsychiatryA Population-Based Twin Study of Lifetime Major Depression in Men and Women
516 Citations1999Kenneth S. Kendler, Carol A. Prescott
Major depression is equally heritable in men and women, and most genetic risk factors influence liability to MD similarly in the 2 sexes, however, genes may exist that act differently on the risk for MD in men vs women.
American Journal of PsychiatryIncreased Occipital Cortex GABA Concentrations in Depressed Patients After Therapy With Selective Serotonin Reuptake Inhibitors
504 Citations2002Gerard Sanacora, Graeme F. Mason +2 more
SSRI treatment of major depression is associated with increased occipital cortex GABA concentrations which appears to result in a normalization of low pretreatment GABA concentrations, an effect that may contribute to a common mechanism of antidepressant action.
Behavioral and Brain SciencesInsensitivity of the analysis of variance to heredity-environment interaction
477 Citations1990Douglas Wahłsten
If the goal of partitioning variance among mutually exclusive causes and calculating “heritability” coefficients is abandoned, interactive relationships can be examined more seriously and can enhance the understanding of the ways living things develop.
American Journal of PsychiatryCocaine, Ethanol, and Genotype Effects on Human Midbrain Serotonin Transporter Binding Sites and mRNA Levels
385 Citations1998Karley Y. Little, Daniel P. McLaughlin +9 more
Serotonin transporter binding sites were regulated in a region-specific and substance-specific pattern, which was not simply a local response to functional blockade, and it is possible that serotonin transporter promoter genotype may play a complex role in chronic ethanol dependence.
Journal of Affective DisordersGABA and mood disorders: a brief review and hypothesis
377 Citations1995Frederick Petty
Low GABA function is proposed to be an inherited biological marker of vulnerability for development of mood disorders, applicable to a subset of mood disordered persons.
Journal of Personality AssessmentStability and Change in Personality Assessment: The Revised NEO Personality Inventory in the Year 2000
374 Citations1997Paul T. Costa, Robert R. McCrae
The Revised NEO Personality Inventory (NEO-PI-R) consists of 30 facet scales that define the broad domains of the Five-Factor Model of personality.
American Journal of Medical GeneticsAssociation between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample
349 Citations2000Benjamin D. Greenberg, Qian Li +7 more
These results help to define specific personality features reproducibly associated with 5-HTTLPR genotype, enhancing the attractiveness of the five-factor personality model in genetic research on complex behavioral dimensions.
NeuropsychopharmacologyA BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression
331 Citations2002Srijan Sen, Randolph M. Nesse +6 more
To explore the possibility that variation in the BDNF gene is, in part, responsible for the population variation in Neuroticism, a community sample of 441 sub-jects was studied, genotyping a G→A single-nucleotide polymorphism (SNP) responsible for a valine→methionine substitution in the prodomain of BDNF.
Journal of Neural TransmissionFunctional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene
296 Citations1995Armin Heils, Andreas Teufel +6 more
These findings suggest that (1) the 5-HT transporter gene promoter is active in human JAR cells, but inactive in 5- HT transporter-deficient human SK-N-SH neuroblastoma and HeLa cells, (2) the information contained within 1.4kb of 5′-flanking sequence is sufficient to confer its cell-specific expression, and (3) the promoter responds to cAMP induction.
European Journal of Human GeneticsPedigree tests of transmission disequilibrium
295 Citations2000Gonçalo R. Abecasis, William Cookson +1 more
A general approach for scoring allelic transmission that accommodates families of any size and uses all available genotypic information is constructed and used to investigate the relationship between circulating angiotensin-1 converting enzyme levels and polymorphisms in the ACE gene using previously published data.
Biological PsychiatrySelective genotyping for the role of 5-HT2A, 5-HT2C, and GABAα6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study
256 Citations1999Marc A. Schuckit, Chiara Maria Mazzanti +5 more
These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABAA alpha 6 and the serotonin transporter in the reaction to alcohol and the alcoholism risk.
Archives of General PsychiatryRole of the Serotonin Transporter Promoter Polymorphism in Anxiety-Related Traits
255 Citations1998Chiara Maria Mazzanti, Jaakko Lappalainen +7 more
The relationship of SLC6A4*C to anxiety is replicated by sibpair linkage analysis but no evidence of association is found, raising the question of whether SLC8A3*C locus is itself affecting anxiety or is linked to another still unknown functional variant.
Behavior GeneticsFurther Evidence Against the Environmental Transmission of Individual Differences in Neuroticism from a Collaborative Study of 45,850 Twins and Relatives on Two Continents
230 Citations2000Robert I. E. Lake, Lindon J. Eaves +3 more
It is concluded that there is no evidence for environmental transmission as a contribution to individual differences in neuroticism in these replicated samples, drawn from different continents, and that a simple genetic structure underlies familial resemblance for the personality trait of Neuroticism.
Alcoholism Clinical and Experimental ResearchSerotonergic Dysfunction, Negative Mood States, and Response to Alcohol
169 Citations2001Andreas Heinz, Karl Mann +2 more
Several lines of evidence point to a relationship between serotonergic dysfunction, negative mood states, and excessive alcohol intake, which may be mediated in part by reduced alcohol-induced sedation.
The Journal of Comparative NeurologySerotonergic axons in monkey prefrontal cerebral cortex synapse predominantly on interneurons as demonstrated by serial section electron microscopy
167 Citations1996John F. Smiley, Patricia S. Goldman‐Rakic
These are the first results to indicate that interneurons are the major recipient of identifiable 5‐HT synapses in the monkey prefrontal cortex.
American Journal of PsychiatrySerotonin Transporter Protein Gene Polymorphism and Personality Measures in African American and European American Subjects
167 Citations1998Joel Gelernter, Henry R. Kranzler +3 more
There was no main effect of genotype on harm avoidance and neuroticism scores in subjects with diagnoses of a personality disorder or substance dependence, and interactions were observed between sex and promoter system genotype and between race and promoterSystem genotype.
Biological PsychiatryFrequency of long allele in serotonin transporter gene is increased in depressed suicide victims
166 Citations1999Lisheng Du, Gábor Faludi +6 more
A significantly higher frequency of the 5-HT transporter gene long (L) allele in depressed suicides is found, providing the first evidence suggesting that a functional polymorphism in the regulatory region of serotonin transporter gene may be associated with suicide in depressed subjects.
Journal of Affective DisordersNeuroticism: a vulnerability marker for depression evidence from a family study
154 Citations1995Conor Duggan, Pak C. Sham +3 more
Recurrent episodes of major depression in the recovered MD relatives were significantly associated with increased N scores, suggesting that raised N may be a vulnerability marker for major depression.
Alcoholism Clinical and Experimental ResearchSerotonergic Dysfunction, Negative Mood States, and Response to Alcohol
153 Citations2001Andreas Heinz, Karl Mann +2 more
NeuropsychopharmacologySerotonin Transporter and Seasonal Variation in Blood Serotonin in Families with Obsessive-Compulsive Disorder
150 Citations1998Gregory L. Hanna
There was a significant interaction between HTT promoter genotype and seasonal variation in blood 5- HT content, with significant seasonal differences in 5-HT occurring only in the subjects with thel/l genotype.
American Journal of Medical GeneticsSerotonin transporter gene polymorphisms are associated with anxiety‐related personality traits in women
142 Citations2001Jonas Melke, Mikael Landén +7 more
An association was found between the intron 2 polymorphism and one anxiety-related personality trait (somatic anxiety), and subjects being homozygous for the short allele displaying higher anxiety scores than those of the long/long or long/short genotype.
Molecular PsychiatryAn association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms
133 Citations1998Anthony F. Jorm, A. S. Henderson +6 more
A functional polymorphism in the regulatory region of the serotonin transporter gene has been reported to be associated with anxiety-related personality traits, but an association study involving 759 Caucasians selected from the general Australian population found no associations.
Critical Reviews in NeurobiologyImpairment of GABAergic Transmission in Depression: New Insights from Neuroimaging Studies
133 Citations2000Gerard Sanacora, Graeme F. Mason +1 more
Molecular PsychiatryNeuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism
129 Citations1999J.D. Flory, Stephen B. Manuck +4 more
It is indicated that the reproducibility of the association between the 5-HTTLPR polymorphism and neuroticism must be regarded as questionable and the need for a replication attempt in a large, normative sample that is stratified by ethnicity and sex is suggested.
American Journal of PsychiatryRelationship Between a GABA<sub>A</sub>α6 Pro385Ser Substitution and Benzodiazepine Sensitivity
85 Citations1999Nakao Iwata, Deborah S. Cowley +3 more
The authors detected a Pro385Ser [1236C>T] amino acid substitution in the human GABAAa6 that may influence alcohol sensitivity and found it associated with less diazepam-induced impairment of saccadic velocity but not with smooth pursuit gain.
Journal of Personality DisordersRole of the Serotonin Transporter Gene in Temperament and Character
72 Citations1999Dean H. Hamer, Benjamin D. Greenberg +2 more
It is suggested that there is no fundamental mechanistic distinction between character and temperament in regard to the serotonin transporter gene, and that a single neurotransmitter can influence multiple personality traits.
Journal of Personality and Social PsychologyCovariance structure of neuroticism and agreeableness: A twin and molecular genetic analysis of the role of the serotonin transporter gene.
70 Citations2001Kerry L. Jang, W. John Livesley +7 more
In all four samples, genetic influences contributed to the covariance of Neuroticism and Agreeableness, with the serotonin transporter gene accounting for 10% of the relationship between these domains.
American Journal of HypertensionA Genome-Wide Linkage Analysis Investigating the Determinants of Blood Pressure in Whites and African Americans
68 Citations2003Bonnie Thiel
The results support the idea that BP regulation is most likely governed by multiple genetic loci, each with a relatively weak effect on BP in the population at large.
Psychological MedicineGABA and mood disorders
50 Citations2003Matthew Taylor, Zubin Bhagwagar +2 more
Increasing biochemical and pharmacological evidence from animal and human studies has supported the hypothesis that mood disorders are associated with abnormalities in brain GABA function.