Association between glutamic acid decarboxylase genes and anxiety disorders, major depression, and neuroticism.


:Abnormalities in the gamma-aminobutyric acid (GABA) neurotransmitter system have been noted in subjects with mood and anxiety disorders. Glutamic acid decarboxylase (GAD) enzymes synthesize GABA from glutamate, and, thus, are reasonable candidate susceptibility genes for these conditions. In this study, we examined the GAD1 and GAD2 genes for their association with genetic risk across a range of internalizing disorders. We used multivariate structural equation modeling to identify common genetic risk factors for major depression, generalized anxiety disorder, panic disorder, agoraphobia, social phobia and neuroticism (N) in a sample of 9270 adult subjects from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. One member from each twin pair for whom DNA was available was selected as a case or control based on scoring at the extremes of the genetic factor extracted from the analysis. The resulting sample of 589 cases and 539 controls was entered into a two-stage association study in which candidate loci were screened in stage 1, the positive results of which were tested for replication in stage 2. Several of the six single-nucleotide polymorphisms tested in the GAD1 region demonstrated significant association in both stages, and a combined analysis in all 1128 subjects indicated that they formed a common high-risk haplotype that was significantly over-represented in cases (P=0.003) with effect size OR=1.23. Out of 14 GAD2 markers screened in stage 1, only one met the threshold criteria for follow-up in stage 2. This marker, plus three others that formed significant haplotype combinations in stage 1, did not replicate their association with the phenotype in stage 2. Subject to confirmation in an independent sample, our study suggests that variations in the GAD1 gene may contribute to individual differences in N and impact susceptibility across a range of anxiety disorders and major depression.


Mol Psychiatry


Molecular psychiatry


Hettema JM,An SS,Neale MC,Bukszar J,van den Oord EJ,Kendler KS,Chen X




Has Abstract


2006-08-01 00:00:00














  • Nitric oxide in health and disease of the nervous system.

    abstract::Nitric oxide (NO) is a widespread and multifunctional biological messenger molecule. It mediates vasodilation of blood vessels, host defence against infectious agents and tumors, and neurotransmission of the central and peripheral nervous systems. In the nervous system, NO is generated by three nitric oxide synthase (...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审


    authors: Yun HY,Dawson VL,Dawson TM

    更新日期:1997-07-01 00:00:00

  • A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene.

    abstract::Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Papassotiropoulos A,Stefanova E,Vogler C,Gschwind L,Ackermann S,Spalek K,Rasch B,Heck A,Aerni A,Hanser E,Demougin P,Huynh KD,Luechinger R,Klarhöfer M,Novakovic I,Kostic V,Boesiger P,Scheffler K,de Quervain DJ

    更新日期:2013-02-01 00:00:00

  • Depressive-like behavior and stress reactivity are independent traits in a Wistar Kyoto x Fisher 344 cross.

    abstract::Depression is a heritable disorder that is often precipitated by stress. Abnormalities of the stress-reactive hypothalamic-pituitary-adrenal (HPA) axis are also common in depressed patients. In animal models, the forced swim test (FST) is the most frequently used test of depressive-like behavior. We have used a propos...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Solberg LC,Ahmadiyeh N,Baum AE,Vitaterna MH,Takahashi JS,Turek FW,Redei EE

    更新日期:2003-04-01 00:00:00

  • Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.

    abstract::Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions i...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Piton A,Gauthier J,Hamdan FF,Lafrenière RG,Yang Y,Henrion E,Laurent S,Noreau A,Thibodeau P,Karemera L,Spiegelman D,Kuku F,Duguay J,Destroismaisons L,Jolivet P,Côté M,Lachapelle K,Diallo O,Raymond A,Marineau C,Cham

    更新日期:2011-08-01 00:00:00

  • Polymorphisms of the interleukin-1 gene complex in schizophrenia.

    abstract::Activation of the inflammatory response system has been related to the pathophysiology of schizophrenia by several recent studies. Schizophrenic patients have varied levels of proinflammatory cytokines, such as interleukin (IL)-1, -6, and tumor necrosis factor (TNF)alpha in their peripheral blood or cerebrospinal flui...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Katila H,Hänninen K,Hurme M

    更新日期:1999-03-01 00:00:00

  • Connectome-wide network analysis of youth with Psychosis-Spectrum symptoms.

    abstract::Adults with psychotic disorders have dysconnectivity in critical brain networks, including the default mode (DM) and the cingulo-opercular (CO) networks. However, it is unknown whether such deficits are present in youth with less severe symptoms. We conducted a multivariate connectome-wide association study examining ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Satterthwaite TD,Vandekar SN,Wolf DH,Bassett DS,Ruparel K,Shehzad Z,Craddock RC,Shinohara RT,Moore TM,Gennatas ED,Jackson C,Roalf DR,Milham MP,Calkins ME,Hakonarson H,Gur RC,Gur RE

    更新日期:2015-12-01 00:00:00

  • ADORA1-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism.

    abstract::It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripher...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Zhang J,Hou Y,Du XL,Chen D,Sui G,Qi Y,Licinio J,Wong ML,Yang Y

    更新日期:2020-10-16 00:00:00

  • Educational attainment and drinking behaviors: Mendelian randomization study in UK Biobank.

    abstract::Educational attainment has been associated with drinking behaviors in observation studies. We performed Mendelian randomization analysis to determine whether educational attainment causally affected drinking behaviors, including amount of alcohol intakes (in total and various types), drinking frequency, and drinking w...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Zhou T,Sun D,Li X,Ma H,Heianza Y,Qi L

    更新日期:2019-11-25 00:00:00

  • Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain.

    abstract::Polymorphic variants of the dopamine D(4) receptor have been consistently associated with attention-deficit hyperactivity disorder (ADHD). However, the functional significance of the risk polymorphism (variable number of tandem repeats in exon 3) is still unclear. Here, we show that whereas the most frequent 4-repeat ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: González S,Rangel-Barajas C,Peper M,Lorenzo R,Moreno E,Ciruela F,Borycz J,Ortiz J,Lluís C,Franco R,McCormick PJ,Volkow ND,Rubinstein M,Floran B,Ferré S

    更新日期:2012-06-01 00:00:00

  • Tph2 gene variants modulate response control processes in adult ADHD patients and healthy individuals.

    abstract::Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Baehne CG,Ehlis AC,Plichta MM,Conzelmann A,Pauli P,Jacob C,Gutknecht L,Lesch KP,Fallgatter AJ

    更新日期:2009-11-01 00:00:00

  • Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

    abstract::Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it wit...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Anazi S,Maddirevula S,Faqeih E,Alsedairy H,Alzahrani F,Shamseldin HE,Patel N,Hashem M,Ibrahim N,Abdulwahab F,Ewida N,Alsaif HS,Al Sharif H,Alamoudi W,Kentab A,Bashiri FA,Alnaser M,AlWadei AH,Alfadhel M,Eyaid W,Has

    更新日期:2017-04-01 00:00:00

  • Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder.

    abstract::Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not ju...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Dean KR,Hammamieh R,Mellon SH,Abu-Amara D,Flory JD,Guffanti G,Wang K,Daigle BJ Jr,Gautam A,Lee I,Yang R,Almli LM,Bersani FS,Chakraborty N,Donohue D,Kerley K,Kim TK,Laska E,Young Lee M,Lindqvist D,Lori A,Lu L,M

    更新日期:2020-12-01 00:00:00

  • The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior.

    abstract::Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognit...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Arentsen T,Qian Y,Gkotzis S,Femenia T,Wang T,Udekwu K,Forssberg H,Diaz Heijtz R

    更新日期:2017-02-01 00:00:00

  • Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes.

    abstract::Although disrupted in schizophrenia 1 (DISC1) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Carless MA,Glahn DC,Johnson MP,Curran JE,Bozaoglu K,Dyer TD,Winkler AM,Cole SA,Almasy L,MacCluer JW,Duggirala R,Moses EK,Göring HH,Blangero J

    更新日期:2011-11-01 00:00:00

  • Dissecting bipolar disorder complexity through epigenomic approach.

    abstract::In recent years, numerous studies of gene regulation mechanisms have emerged in neuroscience. Epigenetic modifications, described as heritable but reversible changes, include DNA methylation, DNA hydroxymethylation, histone modifications and noncoding RNAs. The pathogenesis of psychiatric disorders, such as bipolar di...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审


    authors: Ludwig B,Dwivedi Y

    更新日期:2016-11-01 00:00:00

  • A transcript map encompassing a susceptibility locus for bipolar affective disorder on chromosome 4q35.

    abstract::Bipolar affective disorder is one of the most common mental illnesses with a population prevalence of approximately 1%. The disorder is genetically complex, with an increasing number of loci being implicated through genetic linkage studies. However, the specific genetic variations and molecules involved in bipolar sus...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Blair IP,Adams LJ,Badenhop RF,Moses MJ,Scimone A,Morris JA,Ma L,Austin CP,Donald JA,Mitchell PB,Schofield PR

    更新日期:2002-01-01 00:00:00

  • Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.

    abstract::Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Martinez ME,Duarte CW,Stohn JP,Karaczyn A,Wu Z,DeMambro VE,Hernandez A

    更新日期:2020-05-01 00:00:00

  • Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities.

    abstract::Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions a...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,多中心研究


    authors: Hodge JC,Mitchell E,Pillalamarri V,Toler TL,Bartel F,Kearney HM,Zou YS,Tan WH,Hanscom C,Kirmani S,Hanson RR,Skinner SA,Rogers RC,Everman DB,Boyd E,Tapp C,Mullegama SV,Keelean-Fuller D,Powell CM,Elsea SH,Morton CC

    更新日期:2014-03-01 00:00:00

  • Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families.

    abstract::A recent report showed significant associations between several SNPs in a previously unknown EST cluster with schizophrenia. (1). The cluster was identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence database comparisons and homology with mouse DTNBP1. (2). However, the linkage disequilibriu...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: van den Oord EJ,Sullivan PF,Jiang Y,Walsh D,O'Neill FA,Kendler KS,Riley BP

    更新日期:2003-05-01 00:00:00

  • Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis.

    abstract::Patients with psychotic disorders are at high risk for type 2 diabetes mellitus, and there is increasing evidence that patients display glucose metabolism abnormalities before significant antipsychotic medication exposure. In the present study, we examined insulin action by quantifying insulin sensitivity in first-epi...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Chouinard VA,Henderson DC,Dalla Man C,Valeri L,Gray BE,Ryan KP,Cypess AM,Cobelli C,Cohen BM,Öngür D

    更新日期:2019-10-01 00:00:00

  • Neuropsychosocial markers of binge drinking in young adults.

    abstract::Binge drinking is associated with disease and death, and developing tools to identify risky drinkers could mitigate its damage. Brain processes underlie risky drinking, so we examined whether neural and psychosocial markers could identify binge drinkers. Reward is the most widely studied neural process in addiction, b...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Gowin JL,Manza P,Ramchandani VA,Volkow ND

    更新日期:2020-05-12 00:00:00

  • Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors.

    abstract::The glutamate hypothesis of schizophrenia derived from evidence that phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is defici...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Brody SA,Dulawa SC,Conquet F,Geyer MA

    更新日期:2004-01-01 00:00:00

  • MicroRNA regulation of persistent stress-enhanced memory.

    abstract::Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Sillivan SE,Jamieson S,de Nijs L,Jones M,Snijders C,Klengel T,Joseph NF,Krauskopf J,Kleinjans J,Vinkers CH,Boks MPM,Geuze E,Vermetten E,Berretta S,Ressler KJ,Rutten BPF,Rumbaugh G,Miller CA

    更新日期:2020-05-01 00:00:00

  • Direct conversion of human fibroblasts to induced serotonergic neurons.

    abstract::Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly convert...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Xu Z,Jiang H,Zhong P,Yan Z,Chen S,Feng J

    更新日期:2016-01-01 00:00:00

  • Dysthymia in neurological disorders.

    abstract::Dysthymia is characterized by long-lasting periods of lowered mood. Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Its pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is its ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审


    authors: Akiskal HS,Bolis CL,Cazzullo C,Costa e Silva JA,Gentil V,Lecrubier Y,Licinio J,Linden M,Lopez-Ibor JJ,Ndiaye IP,Pani L,Prilipko L,Robertson MM,Robinson RG,Starkstein SE,Thomas P,Wang Y,Wong ML

    更新日期:1996-12-01 00:00:00

  • HPA axis genetic variation, cortisol and psychosis in major depression.

    abstract::Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depres...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Schatzberg AF,Keller J,Tennakoon L,Lembke A,Williams G,Kraemer FB,Sarginson JE,Lazzeroni LC,Murphy GM

    更新日期:2014-02-01 00:00:00

  • Variants in Apaf-1 segregating with major depression promote apoptosome function.

    abstract::APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 ac...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Harlan J,Chen Y,Gubbins E,Mueller R,Roch JM,Walter K,Lake M,Olsen T,Metzger P,Dorwin S,Ladror U,Egan DA,Severin J,Johnson RW,Holzman TF,Voelp K,Davenport C,Beck A,Potter J,Gopalakrishnan M,Hahn A,Spear BB,Halb

    更新日期:2006-01-01 00:00:00

  • Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system.

    abstract::Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hypera...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Clements CC,Castro VM,Blumenthal SR,Rosenfield HR,Murphy SN,Fava M,Erb JL,Churchill SE,Kaimal AJ,Doyle AE,Robinson EB,Smoller JW,Kohane IS,Perlis RH

    更新日期:2015-06-01 00:00:00

  • Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder.

    abstract::Significant heterogeneity across aetiologies, neurobiology and clinical phenotypes have been observed in individuals with autism spectrum disorder (ASD). Neuroimaging-based neuroanatomical studies of ASD have often reported inconsistent findings which may, in part, be attributable to an insufficient understanding of t...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Bedford SA,Park MTM,Devenyi GA,Tullo S,Germann J,Patel R,Anagnostou E,Baron-Cohen S,Bullmore ET,Chura LR,Craig MC,Ecker C,Floris DL,Holt RJ,Lenroot R,Lerch JP,Lombardo MV,Murphy DGM,Raznahan A,Ruigrok ANV,Smith E

    更新日期:2020-03-01 00:00:00

  • Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits.

    abstract::The urocortin (Ucn) family of neuropeptides is suggested to be involved in homeostatic coping mechanisms of the central stress response through the activation of corticotropin-releasing factor receptor type 2 (CRFR2). The neuropeptides, Ucn1 and Ucn2, serve as endogenous ligands for the CRFR2, which is highly expresse...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章


    authors: Neufeld-Cohen A,Evans AK,Getselter D,Spyroglou A,Hill A,Gil S,Tsoory M,Beuschlein F,Lowry CA,Vale W,Chen A

    更新日期:2010-04-01 00:00:00