The relation between GAD1 and PTSD symptoms: Shared risk for depressive symptoms

Bountress, Kaitlin; Sheerin, Christina M.; Amstadter, Ananda B.; Mandel, Howard; Voltin, Joshua; Wang, Zhewu

doi:10.1016/j.psychres.2017.01.010

Cited by 4 publications

(3 citation statements)

References 4 publications

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“…We used human single nucleus RNA-seq data from eight donor brains (15,928 nuclei) from the middle temporal gyrus (MTG) (15) (Figure 3A) where 75 transcriptomically distinct cell types were previously identified, including 45 inhibitory neuron types and 24 excitatory types. All inhibitory types express the GABAergic interneuron maker GAD1 implicated in bipolar disorder ( 41) depression (42), and schizophrenia (43) and excitatory types express the vesicular glutamate transporter SLC17A7, associated with learning and memory disorders (44) (as well as psychiatric diseases), and 6 non-neuronal cell types that express the glutamate transporter SLC1A3; autism (45) and epilepsy (46). A set of 142 genes are used to differentially characterize the MTG clusters (15).…”

Section: Disease Genes and Cell Types Of Middle Temporal Gyrusmentioning

confidence: 99%

Structural and cellular transcriptome foundations of human brain disease

Zeighami

Bakken

Nickl‐Jockschat

et al. 2021

Preprint

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The intersection of human genetics and brain transcriptomics promises to reveal the structural and cellular locus of brain diseases via selective co-expression of risk genes. We find that adult brain-wide transcriptomic profiles of 40 human brain diseases identify four major transcriptional patterns, represented by tumor-related, neurodegenerative, psychiatric and substance abuse, and a mixed group of diseases, with some unexpected disease associations. Based on differential co-expression using bulk transcriptomics, the majority of brain diseases exhibit unique regional transcriptomic signatures that strongly reflect neuronal versus non-neuronal divisions and variation in excitatory and inhibitory neurons across the brain. Single cell transcriptomic data confirms and refines the relationship of different diseases to specific neuronal and non-neuronal subclasses. Disease signatures are largely conserved between mouse and human at the higher cell class level, but with significant species differences emerging at the finer subclass level that may help explain human-specific disease susceptibility.

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Section: Disease Genes and Cell Types Of Middle Temporal Gyrusmentioning

confidence: 99%

Structural and cellular transcriptome foundations of human brain disease

Zeighami

Bakken

Nickl‐Jockschat

et al. 2021

Preprint

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“…Twin studies related to PTSD have addressed the complex genetic relationship between exposure to trauma and disorder risk. Over the last years, there has been an increased interest in identifying genes that increase the risk for PTSD or predict treatment outcome (Sheerin et al 2017). Because of the phenotypic heterogeneity and complexity of defining PTSD for the purposes of genetic studies, many analyses rely on intermediate phenotypes (Meyer-Lindenberg & Weinberger 2006) or endophenotypes (Gottesman & Gould 2003), which are conceptualized as being more directly related to relevant gene action.…”

Section: Introductionmentioning

confidence: 99%

“…Similar findings were obtained in a mixed anxiety (including panic disorder) and mood disorder sample (Hettema et al 2006). With regard to PTSD, only one recent preliminary study documented a significant association between GAD1 polymorphisms and more pronounced PTSD symptoms among American combat veterans (Bountress et al 2017). However, this preliminary work was based on the genetic risk sum score (GRSS), so no information is available for individual SNPs.…”

Section: Introductionmentioning

confidence: 99%

Association of Neuropeptide S Receptor 1 and Glutamate Decarboxylase 1 Gene Polymorphisms With Posttraumatic Stress Disorder

Mclean

Agius

2019

Psychiat Danub

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Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by highly traumatic experiences. The aim of this study was to investigate the influence of single nucleotide polymorphisms (SNPs) in the neuropeptide S receptor 1 (NPSR1) and the glutamate decarboxylase 1(GAD1) gene on PTSD and its psychopathological aspects among individuals affected by the Balkan wars during the 90s.Subjects and methods: This study was conducted as part of the South Eastern Europe (SEE) study on molecular mechanisms of PTSD. It comprised 719 participants (539 males), including those with current PTSD, remitted PTSD and healthy volunteers. Psychometric evaluation was performed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) andthe Brief Symptom Inventory (BSI). We examined NPSR1 single nucleotide polymorphism (SNP) rs324981 and GAD1 variant rs3749034 genotypes. Case-control analyses were carried out using logistical regression to determine genotype differences between all patients that had either current or remitted PTSD and control individuals. To analyse the influence of the analysed SNPs on PTSD severity, we performed linear regression analyses with CAPS and BSI within each of the two patient groups separately. All of the calculations were performed for additive allelic, recessive, dominant and genotypic models.Results: We observed a nominally significant association for the major allele (G) of GAD1 rs3749034 with an increased risk to develop PTSD in a case control analysis in the recessive model (P=0.0315, odds ratio=0.47, SE=0.35). In contrast, a nominally significant association of the minor allele (A) with higher CAPS scores was identified within the patient group with lifetime PTSD in the dominant model (P=0. 0372, =6.29, SE=2.99). None of these results did withstand correction for multiple tests. No nominal significant results of GAD1 rs3749034 were found with regard to the intensity of psychological BSI symptoms. Case-control analyses of NPSR1 rs324981 revealed a nominally significant higher risk for homozygous T allele carriers to develop PTSD (P=0.0452) in the recessive model. On the other hand, the T allele showed a nominally significant association with higher BSI scores in patients suffering from lifetime PTSD in the recessive model (P=0.0434). Again, these results were not significant anymore after correction for multiple tests. No associations of NPSR1 rs324981 and CAPS score was identified. Conclusion:The findings of this study provide some evidence that the NPSR1 and GAD1 polymorphisms might play a role in the development of war-related PTSD and its related psychological expressions. Further research is needed to elucidate the interactions of specific gene variants and environmental factors in the development of PTSD.

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