Association between glutamic acid decarboxylase genes and anxiety disorders, major depression, and neuroticism.
paper
Cited
Public
Unavailable
- Authors
- Hettema, J M; An, S S; Neale, M C; Bukszar, J; van den Oord, E J C G; Kendler, K S; Chen, X
- Year
- 2006
- Journal
- Molecular psychiatry
- PMID
- 16718280
- DOI
- 10.1038/sj.mp.4001845
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.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| A Proton Magnetic Resonance Spectroscopy (<sup>1</sup>H MRS) Pilot Study Revealing Altered Glutamatergic and Gamma-Aminobutyric Acid (GABA)ergic Neurotransmission in Social Anxiety Disorder (SAD). | Elsaid S et al. | β | 2025 | β |
| Cadmium stress drives remodeling of earthworm mucus metabolism: Hormetic antioxidant response and synergistic amino acid defence mechanisms. | Wu G et al. | β | 2025 | β |
| Network-based mapping and neurotransmitter architecture of gray matter correlates of neuroticism. | Wang S et al. | β | 2025 | β |
| Orphan receptor GPR39: A potential therapeutic target for inflammatory diseases. | Ran S et al. | β | 2025 | β |
| The Comparative Effects Between Long-Term and Short-Term Treatment of Finasteride on Anxiety-Like and Depression-Like Behaviors in Early Senescent Male Rats. | Pintana H et al. | β | 2024 | β |
| Compositional changes and ecological characteristics of earthworm mucus under different electrical stimuli. | Huan H et al. | β | 2023 | β |
| Emotional dysregulation, alexithymia and neuroticism: a systematic review on the genetic basis of a subset of psychological traits. | Castellini G et al. | β | 2023 | β |
| Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs. | Roseberry K et al. | β | 2023 | β |
| Genetics of social anxiety disorder: a systematic review. | Baba A et al. | β | 2022 | β |
| Glutamic Acid Decarboxylase 1 Gene Methylation and Panic Disorder Severity: Making the Connection by Brain Gray Matter Volume. | Wu H et al. | β | 2022 | β |
| Hyperexcitability: From Normal Fear to Pathological Anxiety and Trauma. | Rosen JB et al. | β | 2022 | β |
| Influence of Gestational Chlorpyrifos Exposure on ASD-like Behaviors in an fmr1-KO Rat Model. | Perez-Fernandez C et al. | β | 2022 | β |
| Personality traits as a risk factor for postpartum depression: A systematic review and meta-analysis. | PuyanΓ© M et al. | β | 2022 | β |
| The mediating role of transmembrane protein 132D methylation in predicting the occurrence of panic disorder in physical abuse. | Yu Q et al. | β | 2022 | β |
| Absence seizures and their relationship to depression and anxiety: Evidence for bidirectionality. | Gruenbaum BF et al. | β | 2021 | β |
| Bridging the Metabolic Parallels Between Neurological Diseases and Cancer. | Guo S et al. | β | 2021 | β |
| Childhood heart problems, adulthood emotional stability, and sex associated with self-report heart conditions in adulthood. | Cheng H et al. | β | 2021 | β |
| Experimental Drugs for Panic Disorder: An Updated Systematic Review. | Caldirola D et al. | β | 2021 | β |
| The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour. | Castroflorio E et al. | β | 2021 | β |
| A major role for common genetic variation in anxiety disorders. | Purves KL et al. | β | 2020 | β |
| microRNA-15b contributes to depression-like behavior in mice by affecting synaptic protein levels and function in the nucleus accumbens. | Guo L et al. | β | 2020 | β |
| Ventral Hippocampal Afferents to Nucleus Accumbens Encode Both Latent Vulnerability and Stress-Induced Susceptibility. | Muir J et al. | β | 2020 | β |
| Bidirectional Association between First-Episode Panic Disorder and Major Depressive Disorder in a Nationwide General Population Survey in Korea. | Woo J et al. | β | 2019 | β |
| Leveraging digital technology to intervene on personality processes to promote healthy aging. | Marsch LA et al. | β | 2019 | β |
| A translational approach to the genetics of anxiety disorders. | McGregor NW et al. | β | 2018 | β |
| GAD65 Promoter Polymorphism rs2236418 Modulates Harm Avoidance in Women via Inhibition/Excitation Balance in the Rostral ACC. | Colic L et al. | β | 2018 | β |
| Glutamate Concentration in the Superior Temporal Sulcus Relates to Neuroticism in Schizophrenia. | Balz J et al. | β | 2018 | β |
| High anxiety trait: A vulnerable phenotype for stress-induced depression. | Weger M et al. | β | 2018 | β |
| Panic disorders: The role of genetics and epigenetics. | Kim EJ et al. | β | 2018 | β |
| Prefrontal cortex-dependent innate behaviors are altered by selective knockdown of Gad1 in neuropeptide Y interneurons. | Corder KM et al. | β | 2018 | β |
| Review: Amino acid concentration of high protein food products and an overview of the current methods used to determine protein quality. | Huang S et al. | β | 2018 | β |
| A Major Role for Common Genetic Variation in Anxiety Disorders | Purves KL et al. | β | 2017 | β |
| A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score. | Ciuculete DM et al. | β | 2017 | β |
| GABAergic neurons in nucleus accumbens are correlated to resilience and vulnerability to chronic stress for major depression. | Zhu Z et al. | β | 2017 | β |
| Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties. | Zarei I et al. | β | 2017 | β |
| The Neurobiology of Panic: A Chronic Stress Disorder. | Goddard AW | β | 2017 | β |
| A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder. | Milak MS et al. | β | 2016 | β |
| Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways. | Howe AS et al. | β | 2016 | β |
| Cortical and subcortical gamma amino acid butyric acid deficits in anxiety and stress disorders: Clinical implications. | Goddard AW | β | 2016 | β |
| Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia. | Chen YW et al. | β | 2016 | β |
| Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia. | Lee SA et al. | β | 2016 | β |
| Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress. | Ma K et al. | β | 2016 | β |
| Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress. | Xu A et al. | β | 2016 | β |
| Meta-analysis of genome-wide association studies of anxiety disorders. | Otowa T et al. | β | 2016 | β |
| Neuroanatomical correlates of individual differences in social anxiety in a non-clinical population. | Tian X et al. | β | 2016 | β |
| The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders. | Smoller JW | β | 2016 | β |
| Direct, indirect and pleiotropic effects of candidate genes on internalizing disorder psychopathology. | Hettema JM et al. | β | 2015 | β |
| Genetics of anxiety disorders: Genetic epidemiological and molecular studies in humans. | Shimada-Sugimoto M et al. | β | 2015 | β |
| Molecular signatures of mood stabilisers highlight the role of the transcription factor REST/NRSF. | Warburton A et al. | β | 2015 | β |
| Novel investigational therapeutics for panic disorder. | Perna G et al. | β | 2015 | β |
| The Association between Neuroticism and Heart Rate Variability Is Not Fully Explained by Cardiovascular Disease and Depression. | ΔukiΔ I et al. | β | 2015 | β |
| The GAD65 knock out mouse - a model for GABAergic processes in fear- and stress-induced psychopathology. | MΓΌller I et al. | β | 2015 | β |
| Validation of candidate anxiety disorder genes using a carbon dioxide challenge task. | Savage JE et al. | β | 2015 | β |
| Applications of blood-based protein biomarker strategies in the study of psychiatric disorders. | Chan MK et al. | β | 2014 | β |
| Are there depression and anxiety genetic markers and mutations? A systematic review. | Lacerda-Pinheiro SF et al. | β | 2014 | β |
| Etiology, triggers and neurochemical circuits associated with unexpected, expected, and laboratory-induced panic attacks. | Johnson PL et al. | β | 2014 | β |
| FT-IR spectroscopy as a sentinel technology in earthworm toxicology. | Aja M et al. | β | 2014 | β |
| Genetic influences on alcohol use across stages of development: GABRA2 and longitudinal trajectories of drunkenness from adolescence to young adulthood. | Dick DM et al. | β | 2014 | β |
| Glutamic acid decarboxylase 65: a link between GABAergic synaptic plasticity in the lateral amygdala and conditioned fear generalization. | Lange MD et al. | β | 2014 | β |
| Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy. | Rosso IM et al. | β | 2014 | β |
| Long-term behavioral programming induced by peripuberty stress in rats is accompanied by GABAergic-related alterations in the Amygdala. | Tzanoulinou S et al. | β | 2014 | β |
| Personality and diabetes mellitus incidence in a national sample. | CukiΔ I et al. | β | 2014 | β |
| The self-liking brain: a VBM study on the structural substrate of self-esteem. | Agroskin D et al. | β | 2014 | β |
| Anxiety genetics - findings from cross-species genome-wide approaches. | Sokolowska E et al. | β | 2013 | β |
| Epigenetic signature of panic disorder: a role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation? | Domschke K et al. | β | 2013 | β |
| Genetic association between RGS1 and internalizing disorders. | Hettema JM et al. | β | 2013 | β |
| The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders. | Olivier JD et al. | β | 2013 | β |
| TMPRSS9 and GRIN2B are associated with neuroticism: a genome-wide association study in a European sample. | Aragam N et al. | β | 2013 | β |
| An animal model of panic vulnerability with chronic disinhibition of the dorsomedial/perifornical hypothalamus. | Johnson PL et al. | β | 2012 | β |
| Anxiety in liver X receptor Ξ² knockout female mice with loss of glutamic acid decarboxylase in ventromedial prefrontal cortex. | Tan XJ et al. | β | 2012 | β |
| Behavioral genetics of affective and anxiety disorders. | Domschke K et al. | β | 2012 | β |
| Can the neuroeconomics revolution revolutionize psychiatry? | Hasler G | β | 2012 | β |
| Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder. | Weber H et al. | β | 2012 | β |
| Genome-wide association uncovers shared genetic effects among personality traits and mood states. | Luciano M et al. | β | 2012 | β |
| Support for involvement of glutamate decarboxylase 1 and neuropeptide Y in anxiety susceptibility. | Donner J et al. | β | 2012 | β |
| Altered GABA transmission in a mouse model of increased trait anxiety. | Tasan RO et al. | β | 2011 | β |
| Discovering imaging endophenotypes for major depression. | Hasler G et al. | β | 2011 | β |
| Four potential criteria for deciding when to use antidepressants or psychotherapy for unipolar depression: a literature review. | Sharpley CF et al. | β | 2011 | β |
| Neuroticism explained? From a non-informative vulnerability marker to informative person-context interactions in the realm of daily life. | Jacobs N et al. | β | 2011 | β |
| Schizophrenia in the internalizing-externalizing framework: a third dimension? | Kotov R et al. | β | 2011 | β |
| The AVPR1A gene and substance use disorders: association, replication, and functional evidence. | Maher BS et al. | β | 2011 | β |
| The genetic basis of panic disorder. | Na HR et al. | β | 2011 | β |
| The role of glutamate on the action of antidepressants. | Hashimoto K | β | 2011 | β |
| Advances in molecular genetics of panic disorder. | Maron E et al. | β | 2010 | β |
| An association analysis of circadian genes in anxiety disorders. | SipilΓ€ T et al. | β | 2010 | β |
| An association between Epac-1 gene variants and anxiety and depression in two independent samples. | Middeldorp CM et al. | β | 2010 | β |
| A population-based association study of candidate genes for depression and sleep disturbance. | Utge S et al. | β | 2010 | β |
| Childhood adversities are associated with shorter telomere length at adult age both in individuals with an anxiety disorder and controls. | Kananen L et al. | β | 2010 | β |
| Classical neurotransmitters and neuropeptides involved in major depression: a review. | Werner FM et al. | β | 2010 | β |
| Cortical inhibition, gamma-aminobutyric acid, and major depression: there is plenty of smoke but is there fire? | Sanacora G | β | 2010 | β |
| Genetic modulation of GABA levels in the anterior cingulate cortex by GAD1 and COMT. | Marenco S et al. | β | 2010 | β |
| Genetics of panic disorder: focus on association studies and therapeutic perspectives. | Jacob C et al. | β | 2010 | β |
| Is depression "evolutionary" or just "adaptive"? A comment. | Sharpley CF et al. | β | 2010 | β |
| Joining the dots: neurobiological links in a functional analysis of depression. | Sharpley CF et al. | β | 2010 | β |
| Nature and nurture in neuropsychiatric genetics: where do we stand? | Dick DM et al. | β | 2010 | β |
| The future of mental health care and the limits of the behavioral neurosciences. | Luchins DJ | β | 2010 | β |
| Twin studies and their implications for molecular genetic studies: endophenotypes integrate quantitative and molecular genetics in ADHD research. | Wood AC et al. | β | 2010 | β |
| Association study between GABA receptor genes and anxiety spectrum disorders. | Pham X et al. | β | 2009 | β |
| Association study of CREB1 with Major Depressive Disorder and related phenotypes. | Hettema JM et al. | β | 2009 | β |
| Linkage and association studies of anxiety disorders. | Hamilton SP | β | 2009 | β |
| Polymorphisms in the GAD2 gene-region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders. | Unschuld PG et al. | β | 2009 | β |
| Public health significance of neuroticism. | Lahey BB | β | 2009 | β |
| Self-esteem, negative emotionality, and depression as a common temperamental core: a study of mid-adolescent twin girls. | Neiss MB et al. | β | 2009 | β |
| Sociodemographic and psychopathologic predictors of first incidence of DSM-IV substance use, mood and anxiety disorders: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. | Grant BF et al. | β | 2009 | β |
| The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders. | Thoeringer CK et al. | β | 2009 | β |
| Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence. | Chen X et al. | β | 2009 | β |
| Association study between the serotonin 1A receptor (HTR1A) gene and neuroticism, major depression, and anxiety disorders. | Hettema JM et al. | β | 2008 | β |
| A whole genome association study of neuroticism using DNA pooling. | Shifman S et al. | β | 2008 | β |
| Cannabinoid receptor 1 gene association with nicotine dependence. | Chen X et al. | β | 2008 | β |
| Catechol-O-methyltransferase contributes to genetic susceptibility shared among anxiety spectrum phenotypes. | Hettema JM et al. | β | 2008 | β |
| Experiential and genetic contributions to depressive- and anxiety-like disorders: clinical and experimental studies. | Anisman H et al. | β | 2008 | β |
| Genetics of anxiety: would the genome recognize the DSM? | Smoller JW et al. | β | 2008 | β |
| Lack of association between the amiloride-sensitive cation channel 2 (ACCN2) gene and anxiety spectrum disorders. | Hettema JM et al. | β | 2008 | β |
| Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample. | Agrawal A et al. | β | 2008 | β |
| Molecular genetics of anxiety in mice and men. | Hovatta I et al. | β | 2008 | β |
| The genetic basis of panic and phobic anxiety disorders. | Smoller JW et al. | β | 2008 | β |
| What is the genetic relationship between anxiety and depression? | Hettema JM | β | 2008 | β |
| Genetic and environmental factors in complex neurodevelopmental disorders. | van Loo KM et al. | β | 2007 | β |
| Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. | Huang HS et al. | β | 2007 | β |