American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation q... more R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces. Am J Med Genet Part B 9999:1-10.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation q... more R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces. Am J Med Genet Part B 9999:1-10.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and f... more Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and fear responses. Common antihypertensive medication classes of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) have been associated with lower PTSD symptoms. Here we examine the rs4311 SNP in the ACE gene, previously implicated in panic attacks, in the relationship between ACE-I/ARB medications and PTSD symptoms. Participants were recruited from outpatient wait rooms between 2006 and March 2014 (n ¼ 3803). We examined the interaction between rs4311 genotype and the presence of blood pressure medication on PTSD symptoms and diagnosis. PTSD symptoms were lower in individuals taking ACE-Is or ARBs (N ¼ 776). The rs4311 was associated with PTSD symptoms and diagnosis (N ¼ 3803), as the T-carriers at the rs4311 SNP had significantly greater likelihood of a PTSD diagnosis. Lastly, the rs4311 genotype modified the effect of ACE-Is or ARBs on PTSD symptoms (N ¼ 443; F 1,443 ¼ 4.41, P < 0.05). Individuals with the CC rs4311 genotype showed lower PTSD symptoms in the presence of ACE-Is or ARBs. In contrast, Tcarriers showed the opposite, such that the presence of ACE-Is or ARBs was associated with higher PTSD symptoms. These data suggest that the renin-angiotensin system may be important in PTSD, as ACE-I/ARB usage associates with lower symptoms. Furthermore, we provide genetic evidence that some individuals are comparatively more benefitted by ACE-Is/ARBs in PTSD treatment. Future research should examine the mechanisms by which ACE-Is/ARBs affect PTSD symptoms such that pharmaco-genetically informed interventions may be used to treat PTSD.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and f... more Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and fear responses. Common antihypertensive medication classes of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) have been associated with lower PTSD symptoms. Here we examine the rs4311 SNP in the ACE gene, previously implicated in panic attacks, in the relationship between ACE-I/ARB medications and PTSD symptoms. Participants were recruited from outpatient wait rooms between 2006 and March 2014 (n ¼ 3803). We examined the interaction between rs4311 genotype and the presence of blood pressure medication on PTSD symptoms and diagnosis. PTSD symptoms were lower in individuals taking ACE-Is or ARBs (N ¼ 776). The rs4311 was associated with PTSD symptoms and diagnosis (N ¼ 3803), as the T-carriers at the rs4311 SNP had significantly greater likelihood of a PTSD diagnosis. Lastly, the rs4311 genotype modified the effect of ACE-Is or ARBs on PTSD symptoms (N ¼ 443; F 1,443 ¼ 4.41, P < 0.05). Individuals with the CC rs4311 genotype showed lower PTSD symptoms in the presence of ACE-Is or ARBs. In contrast, Tcarriers showed the opposite, such that the presence of ACE-Is or ARBs was associated with higher PTSD symptoms. These data suggest that the renin-angiotensin system may be important in PTSD, as ACE-I/ARB usage associates with lower symptoms. Furthermore, we provide genetic evidence that some individuals are comparatively more benefitted by ACE-Is/ARBs in PTSD treatment. Future research should examine the mechanisms by which ACE-Is/ARBs affect PTSD symptoms such that pharmaco-genetically informed interventions may be used to treat PTSD.
American Journal of Respiratory and Critical Care Medicine, 2015
Running Head: Stress, ADCYAP1R1, and bronchodilator response 86 87 Descriptor: 1.17 Asthma Epidem... more Running Head: Stress, ADCYAP1R1, and bronchodilator response 86 87 Descriptor: 1.17 Asthma Epidemiology (Pediatric): Risk Factors 88 89 Word count: 3,519 90 91 At a Glance Commentary: 92 Scientific Knowledge on the Subject: Psychosocial stress is both common and associated 93 with asthma morbidity among Puerto Ricans (PRs), who are known to have reduced 94 responsiveness to short-acting inhaled β2-agonists (bronchodilator response [BDR]). Chronic 95 stress has been linked to reduced expression of ADRB2 in leukocytes of children with asthma. 96
... The incision is not sutured in mice, but rather pinched together, as the dam will chew out th... more ... The incision is not sutured in mice, but rather pinched together, as the dam will chew out the sutures. ... 810, 114 (1998). 8 CJ Epstein, KB Avraham, M. Lovett, S. Smith, O. Elroy-Stein, G. Rotman, C. Bry, and Y. Groner, Proc. Natl. Acad. Sci. USA 84, 8044 (1987). ...
The etiology of complex traits likely involves the effects of genetic and environmental factors, ... more The etiology of complex traits likely involves the effects of genetic and environmental factors, along with complicated interaction effects between them. Consequently, there has been interest in applying genetic association tests of complex traits that account for potential modification of the genetic effect in the presence of an environmental factor. One can perform such an analysis using a joint test of gene and gene-environment interaction. An optimal joint test would be one that remains powerful under a variety of models ranging from those of strong gene-environment interaction effect to those of little or no gene-environment interaction effect. To fill this demand, we have extended a kernel machine based approach for association mapping of multiple SNPs to consider joint tests of gene and gene-environment interaction. The kernel-based approach for joint testing is promising, because it incorporates linkage disequilibrium information from multiple SNPs simultaneously in analysis...
The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituita... more The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituitary-adrenal axis functioning and has been associated with many stress-related psychiatric disorders. The study of intermediate phenotypes, such as emotionprocessing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates risk for psychiatric disorders.
Objective: Increased systemic inflammation is associated with stress-related psychopathology. Spe... more Objective: Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the proinflammatory marker C-reactive protein (CRP) are elevated in individuals with posttraumatic stress disorder (PTSD). Furthermore, single-nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP level, risk for cardiovascular disease, and obesity. The authors examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a civilian population with high levels of trauma.
Objective: Increased systemic inflammation is associated with stress-related psychopathology. Spe... more Objective: Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the proinflammatory marker C-reactive protein (CRP) are elevated in individuals with posttraumatic stress disorder (PTSD). Furthermore, single-nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP level, risk for cardiovascular disease, and obesity. The authors examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a civilian population with high levels of trauma.
IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), d... more IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), develops only in a subset of trauma-exposed individuals. Genetic risk factors in interaction with trauma exposure have been implicated in PTSD vulnerability. OBJECTIVE To examine the association of 3755 candidate gene single-nucleotide polymorphisms with PTSD development in interaction with a history of childhood trauma. DESIGN, SETTING, AND PARTICIPANTS Genetic association study in an Ohio National Guard longitudinal cohort (n = 810) of predominantly male soldiers of European ancestry, with replication in an independent Grady Trauma Project (Atlanta, Georgia) cohort (n = 2083) of predominantly female African American civilians.
IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), d... more IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), develops only in a subset of trauma-exposed individuals. Genetic risk factors in interaction with trauma exposure have been implicated in PTSD vulnerability. OBJECTIVE To examine the association of 3755 candidate gene single-nucleotide polymorphisms with PTSD development in interaction with a history of childhood trauma. DESIGN, SETTING, AND PARTICIPANTS Genetic association study in an Ohio National Guard longitudinal cohort (n = 810) of predominantly male soldiers of European ancestry, with replication in an independent Grady Trauma Project (Atlanta, Georgia) cohort (n = 2083) of predominantly female African American civilians.
preventing PTSD after traumatic events. may block fear memory consolidation, with implications fo... more preventing PTSD after traumatic events. may block fear memory consolidation, with implications for Oprl1 activation of the NOP receptor encoded by is associated with amygdala function, fear processing, and PTSD symptoms. Furthermore, Oprl1 suggest that fear discrimination and correlates with functional connectivity between the amygdala and insula. Together, these data of associated with PTSD symptoms. The authors show that this SNP is associated with physiological startle measures and may be Oprl1 memories. Additionally, in humans, a single-nucleotide polymorphism (SNP) was found within selective NOP receptor agonist, or injection into the central amygdala of mice impaired the consolidation of fear amygdala, the part of the brain where fear memories are consolidated. Systemic infusion of SR-8993, a new highly in the Oprl1 this process. Using a mouse model of dysregulated fear, the authors found altered expression of gene discovery approach to identify a specific member of the opioid receptor family, Oprl1, which may be involved in use a et al. opioid analgesia, provided shortly after trauma, may decrease the development of PTSD. Here, Andero involved in fear inhibition and may block the consolidation of fear memories. Recent clinical observations suggest that models and humans with PTSD. These findings build on published data showing that opioid activity appears to be (NOP)/orphanin FQ receptor, is involved in stress-mediated enhancement of amygdala-dependent fear in mouse ), encoding the nociceptin Oprl1 like 1 gene ( − now demonstrate that the opioid receptor et al. traumatic event. Andero
preventing PTSD after traumatic events. may block fear memory consolidation, with implications fo... more preventing PTSD after traumatic events. may block fear memory consolidation, with implications for Oprl1 activation of the NOP receptor encoded by is associated with amygdala function, fear processing, and PTSD symptoms. Furthermore, Oprl1 suggest that fear discrimination and correlates with functional connectivity between the amygdala and insula. Together, these data of associated with PTSD symptoms. The authors show that this SNP is associated with physiological startle measures and may be Oprl1 memories. Additionally, in humans, a single-nucleotide polymorphism (SNP) was found within selective NOP receptor agonist, or injection into the central amygdala of mice impaired the consolidation of fear amygdala, the part of the brain where fear memories are consolidated. Systemic infusion of SR-8993, a new highly in the Oprl1 this process. Using a mouse model of dysregulated fear, the authors found altered expression of gene discovery approach to identify a specific member of the opioid receptor family, Oprl1, which may be involved in use a et al. opioid analgesia, provided shortly after trauma, may decrease the development of PTSD. Here, Andero involved in fear inhibition and may block the consolidation of fear memories. Recent clinical observations suggest that models and humans with PTSD. These findings build on published data showing that opioid activity appears to be (NOP)/orphanin FQ receptor, is involved in stress-mediated enhancement of amygdala-dependent fear in mouse ), encoding the nociceptin Oprl1 like 1 gene ( − now demonstrate that the opioid receptor et al. traumatic event. Andero
Proceedings of the National Academy of Sciences, 2014
We have recently found higher circulating levels of pituitary adenylate cyclase-activating polype... more We have recently found higher circulating levels of pituitary adenylate cyclase-activating polypeptide (PACAP) associated with posttraumatic stress disorder (PTSD) symptoms in a highly traumatized cohort of women but not men. Furthermore, a single nucleotide polymorphism in the PACAP receptor gene ADCYAP1R1, adenylate cyclase activating polypeptide 1 receptor type 1, was associated with individual differences in PTSD symptoms and psychophysiological markers of fear and anxiety. The current study outlines an investigation of individual differences in brain function associated with ADCYAP1R1 genotype. Forty-nine women who had experienced moderate to high levels of lifetime trauma participated in a functional MRI task involving passive viewing of threatening and neutral face stimuli. Analyses focused on the amygdala and hippocampus, regions that play central roles in the pathophysiology of PTSD and are known to have high densities of PACAP receptors. The risk genotype was associated with increased reactivity of the amygdala and hippocampus to threat stimuli and decreased functional connectivity between the amygdala and hippocampus. The findings indicate that the PACAP system modulates medial temporal lobe function in humans. Individual differences in ADCYAP1R1 genotype may contribute to dysregulated fear circuitry known to play a central role in PTSD and other anxiety disorders.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation q... more R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces. Am J Med Genet Part B 9999:1-10.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation q... more R, Marmar CR, Ressler KJ. 2015. A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces. Am J Med Genet Part B 9999:1-10.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and f... more Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and fear responses. Common antihypertensive medication classes of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) have been associated with lower PTSD symptoms. Here we examine the rs4311 SNP in the ACE gene, previously implicated in panic attacks, in the relationship between ACE-I/ARB medications and PTSD symptoms. Participants were recruited from outpatient wait rooms between 2006 and March 2014 (n ¼ 3803). We examined the interaction between rs4311 genotype and the presence of blood pressure medication on PTSD symptoms and diagnosis. PTSD symptoms were lower in individuals taking ACE-Is or ARBs (N ¼ 776). The rs4311 was associated with PTSD symptoms and diagnosis (N ¼ 3803), as the T-carriers at the rs4311 SNP had significantly greater likelihood of a PTSD diagnosis. Lastly, the rs4311 genotype modified the effect of ACE-Is or ARBs on PTSD symptoms (N ¼ 443; F 1,443 ¼ 4.41, P < 0.05). Individuals with the CC rs4311 genotype showed lower PTSD symptoms in the presence of ACE-Is or ARBs. In contrast, Tcarriers showed the opposite, such that the presence of ACE-Is or ARBs was associated with higher PTSD symptoms. These data suggest that the renin-angiotensin system may be important in PTSD, as ACE-I/ARB usage associates with lower symptoms. Furthermore, we provide genetic evidence that some individuals are comparatively more benefitted by ACE-Is/ARBs in PTSD treatment. Future research should examine the mechanisms by which ACE-Is/ARBs affect PTSD symptoms such that pharmaco-genetically informed interventions may be used to treat PTSD.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2015
Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and f... more Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and fear responses. Common antihypertensive medication classes of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) have been associated with lower PTSD symptoms. Here we examine the rs4311 SNP in the ACE gene, previously implicated in panic attacks, in the relationship between ACE-I/ARB medications and PTSD symptoms. Participants were recruited from outpatient wait rooms between 2006 and March 2014 (n ¼ 3803). We examined the interaction between rs4311 genotype and the presence of blood pressure medication on PTSD symptoms and diagnosis. PTSD symptoms were lower in individuals taking ACE-Is or ARBs (N ¼ 776). The rs4311 was associated with PTSD symptoms and diagnosis (N ¼ 3803), as the T-carriers at the rs4311 SNP had significantly greater likelihood of a PTSD diagnosis. Lastly, the rs4311 genotype modified the effect of ACE-Is or ARBs on PTSD symptoms (N ¼ 443; F 1,443 ¼ 4.41, P < 0.05). Individuals with the CC rs4311 genotype showed lower PTSD symptoms in the presence of ACE-Is or ARBs. In contrast, Tcarriers showed the opposite, such that the presence of ACE-Is or ARBs was associated with higher PTSD symptoms. These data suggest that the renin-angiotensin system may be important in PTSD, as ACE-I/ARB usage associates with lower symptoms. Furthermore, we provide genetic evidence that some individuals are comparatively more benefitted by ACE-Is/ARBs in PTSD treatment. Future research should examine the mechanisms by which ACE-Is/ARBs affect PTSD symptoms such that pharmaco-genetically informed interventions may be used to treat PTSD.
American Journal of Respiratory and Critical Care Medicine, 2015
Running Head: Stress, ADCYAP1R1, and bronchodilator response 86 87 Descriptor: 1.17 Asthma Epidem... more Running Head: Stress, ADCYAP1R1, and bronchodilator response 86 87 Descriptor: 1.17 Asthma Epidemiology (Pediatric): Risk Factors 88 89 Word count: 3,519 90 91 At a Glance Commentary: 92 Scientific Knowledge on the Subject: Psychosocial stress is both common and associated 93 with asthma morbidity among Puerto Ricans (PRs), who are known to have reduced 94 responsiveness to short-acting inhaled β2-agonists (bronchodilator response [BDR]). Chronic 95 stress has been linked to reduced expression of ADRB2 in leukocytes of children with asthma. 96
... The incision is not sutured in mice, but rather pinched together, as the dam will chew out th... more ... The incision is not sutured in mice, but rather pinched together, as the dam will chew out the sutures. ... 810, 114 (1998). 8 CJ Epstein, KB Avraham, M. Lovett, S. Smith, O. Elroy-Stein, G. Rotman, C. Bry, and Y. Groner, Proc. Natl. Acad. Sci. USA 84, 8044 (1987). ...
The etiology of complex traits likely involves the effects of genetic and environmental factors, ... more The etiology of complex traits likely involves the effects of genetic and environmental factors, along with complicated interaction effects between them. Consequently, there has been interest in applying genetic association tests of complex traits that account for potential modification of the genetic effect in the presence of an environmental factor. One can perform such an analysis using a joint test of gene and gene-environment interaction. An optimal joint test would be one that remains powerful under a variety of models ranging from those of strong gene-environment interaction effect to those of little or no gene-environment interaction effect. To fill this demand, we have extended a kernel machine based approach for association mapping of multiple SNPs to consider joint tests of gene and gene-environment interaction. The kernel-based approach for joint testing is promising, because it incorporates linkage disequilibrium information from multiple SNPs simultaneously in analysis...
The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituita... more The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituitary-adrenal axis functioning and has been associated with many stress-related psychiatric disorders. The study of intermediate phenotypes, such as emotionprocessing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates risk for psychiatric disorders.
Objective: Increased systemic inflammation is associated with stress-related psychopathology. Spe... more Objective: Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the proinflammatory marker C-reactive protein (CRP) are elevated in individuals with posttraumatic stress disorder (PTSD). Furthermore, single-nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP level, risk for cardiovascular disease, and obesity. The authors examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a civilian population with high levels of trauma.
Objective: Increased systemic inflammation is associated with stress-related psychopathology. Spe... more Objective: Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the proinflammatory marker C-reactive protein (CRP) are elevated in individuals with posttraumatic stress disorder (PTSD). Furthermore, single-nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP level, risk for cardiovascular disease, and obesity. The authors examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a civilian population with high levels of trauma.
IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), d... more IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), develops only in a subset of trauma-exposed individuals. Genetic risk factors in interaction with trauma exposure have been implicated in PTSD vulnerability. OBJECTIVE To examine the association of 3755 candidate gene single-nucleotide polymorphisms with PTSD development in interaction with a history of childhood trauma. DESIGN, SETTING, AND PARTICIPANTS Genetic association study in an Ohio National Guard longitudinal cohort (n = 810) of predominantly male soldiers of European ancestry, with replication in an independent Grady Trauma Project (Atlanta, Georgia) cohort (n = 2083) of predominantly female African American civilians.
IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), d... more IMPORTANCE Posttraumatic stress disorder (PTSD), while highly prevalent (7.6% over a lifetime), develops only in a subset of trauma-exposed individuals. Genetic risk factors in interaction with trauma exposure have been implicated in PTSD vulnerability. OBJECTIVE To examine the association of 3755 candidate gene single-nucleotide polymorphisms with PTSD development in interaction with a history of childhood trauma. DESIGN, SETTING, AND PARTICIPANTS Genetic association study in an Ohio National Guard longitudinal cohort (n = 810) of predominantly male soldiers of European ancestry, with replication in an independent Grady Trauma Project (Atlanta, Georgia) cohort (n = 2083) of predominantly female African American civilians.
preventing PTSD after traumatic events. may block fear memory consolidation, with implications fo... more preventing PTSD after traumatic events. may block fear memory consolidation, with implications for Oprl1 activation of the NOP receptor encoded by is associated with amygdala function, fear processing, and PTSD symptoms. Furthermore, Oprl1 suggest that fear discrimination and correlates with functional connectivity between the amygdala and insula. Together, these data of associated with PTSD symptoms. The authors show that this SNP is associated with physiological startle measures and may be Oprl1 memories. Additionally, in humans, a single-nucleotide polymorphism (SNP) was found within selective NOP receptor agonist, or injection into the central amygdala of mice impaired the consolidation of fear amygdala, the part of the brain where fear memories are consolidated. Systemic infusion of SR-8993, a new highly in the Oprl1 this process. Using a mouse model of dysregulated fear, the authors found altered expression of gene discovery approach to identify a specific member of the opioid receptor family, Oprl1, which may be involved in use a et al. opioid analgesia, provided shortly after trauma, may decrease the development of PTSD. Here, Andero involved in fear inhibition and may block the consolidation of fear memories. Recent clinical observations suggest that models and humans with PTSD. These findings build on published data showing that opioid activity appears to be (NOP)/orphanin FQ receptor, is involved in stress-mediated enhancement of amygdala-dependent fear in mouse ), encoding the nociceptin Oprl1 like 1 gene ( − now demonstrate that the opioid receptor et al. traumatic event. Andero
preventing PTSD after traumatic events. may block fear memory consolidation, with implications fo... more preventing PTSD after traumatic events. may block fear memory consolidation, with implications for Oprl1 activation of the NOP receptor encoded by is associated with amygdala function, fear processing, and PTSD symptoms. Furthermore, Oprl1 suggest that fear discrimination and correlates with functional connectivity between the amygdala and insula. Together, these data of associated with PTSD symptoms. The authors show that this SNP is associated with physiological startle measures and may be Oprl1 memories. Additionally, in humans, a single-nucleotide polymorphism (SNP) was found within selective NOP receptor agonist, or injection into the central amygdala of mice impaired the consolidation of fear amygdala, the part of the brain where fear memories are consolidated. Systemic infusion of SR-8993, a new highly in the Oprl1 this process. Using a mouse model of dysregulated fear, the authors found altered expression of gene discovery approach to identify a specific member of the opioid receptor family, Oprl1, which may be involved in use a et al. opioid analgesia, provided shortly after trauma, may decrease the development of PTSD. Here, Andero involved in fear inhibition and may block the consolidation of fear memories. Recent clinical observations suggest that models and humans with PTSD. These findings build on published data showing that opioid activity appears to be (NOP)/orphanin FQ receptor, is involved in stress-mediated enhancement of amygdala-dependent fear in mouse ), encoding the nociceptin Oprl1 like 1 gene ( − now demonstrate that the opioid receptor et al. traumatic event. Andero
Proceedings of the National Academy of Sciences, 2014
We have recently found higher circulating levels of pituitary adenylate cyclase-activating polype... more We have recently found higher circulating levels of pituitary adenylate cyclase-activating polypeptide (PACAP) associated with posttraumatic stress disorder (PTSD) symptoms in a highly traumatized cohort of women but not men. Furthermore, a single nucleotide polymorphism in the PACAP receptor gene ADCYAP1R1, adenylate cyclase activating polypeptide 1 receptor type 1, was associated with individual differences in PTSD symptoms and psychophysiological markers of fear and anxiety. The current study outlines an investigation of individual differences in brain function associated with ADCYAP1R1 genotype. Forty-nine women who had experienced moderate to high levels of lifetime trauma participated in a functional MRI task involving passive viewing of threatening and neutral face stimuli. Analyses focused on the amygdala and hippocampus, regions that play central roles in the pathophysiology of PTSD and are known to have high densities of PACAP receptors. The risk genotype was associated with increased reactivity of the amygdala and hippocampus to threat stimuli and decreased functional connectivity between the amygdala and hippocampus. The findings indicate that the PACAP system modulates medial temporal lobe function in humans. Individual differences in ADCYAP1R1 genotype may contribute to dysregulated fear circuitry known to play a central role in PTSD and other anxiety disorders.
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Papers by Lynn Almli