User login
LAS VEGAS – Despite recent advances in the diagnosis and treatment of posttraumatic stress disorder, researchers have yet to fully understand its pathophysiology.
“We don’t know whether there is just one type of pathophysiology or if there are different mechanisms and different etiologies that contribute to the symptomatic heterogeneity that we see,” Murray B. Stein, MD, MPH, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Many theories currently being studied are inflammatory theories, looking at autonomic dysregulation, glucocorticoid sensitivity, hippocampal volume/dysfunction, and cortical-amygdala circuit dysregulation.”
Dr. Stein expects clinicians to gain an improved understanding of PTSD and a myriad of other conditions in the coming years as the Million Veteran Program (MVP) gets underway. MVP researchers are building one of the world’s largest medical databases by asking 1 million veteran volunteers to provide a blood sample and complete surveys about their health, military experience, lifestyle, and other topics that might contribute to health and disease. They will study how genes influence diseases such as diabetes and cancer, and military-related illnesses, such as PTSD. “It’s an amazing study, where over the next decade, you’re going to hear research findings not just on PTSD but in other areas of mental health and physical health,” said Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego. So far, he said, 700,000 veterans are enrolled.
Dr. Stein shared preliminary findings from one component of the MVP study, in which participants complete the PTSD Checklist (PCL-17), a widely used 17-item self-report measure of PTSD symptoms in the past month. Using Manhattan plot analysis, Dr. Stein and his colleagues conducted a PTSD genomewide association study based on PCL-17 total scores. They found several genes significantly associated with PTSD, including LRRIQ3, TRAIP, KCNIP4, PCDHA1, MAD1L1, TSNARE1, EXD3, MGC57346-CRHR1, and TCF4. “This is the first study in the world to find this many genes [associated with PTSD],” said Dr. Stein, a staff psychiatrist with the VA San Diego Healthcare System. “The MAD1L1 gene is also one that’s come up in schizophrenia and in major depression. In fact, if we look at genetic correlations of how PTSD is genetically associated to other disorders that have been studied in this way, like major depression and schizophrenia, we find that there is shared variation. However, there are also unique features, so we are learning what we think is true about mental disorders overall, that in some ways comorbidity is explained by genetic risk, but there are also individual specific risk factors that go with specific disorders.
“We’re exploring each of those genes.”
of any of the genes in the genome. “One of the prominent theories of PTSD is that there is an increase in CRHR1 in the brain of individuals with the disorder,” Dr. Stein said. “More than by chance, it looks like the genes that are popping up in PTSD seem to be expressed in the frontal cortex, the anterior cingulate, the cortex, the hypothalamus, the amygdala, the hippocampus, the basal ganglia, and the substantia nigra. So all of a sudden, we go from having a list of genes to knowing there’s something going on in the brain of people with PTSD that involves expression in these particular regions that we might be able to target.”
In related work using the same genetic information, Dr. Stein and his colleagues have demonstrated an association between PTSD and medium spiny neurons, which are located in the basal ganglia and make up 95% of neurons in the striatum. “They also have GABAergic projection to other parts of the brain and play a key role in motivation, reward, enforcement, and aversion,” Dr. Stein said.
Dr. Stein disclosed that he has received research support from the National Institute of Mental Health, the National Institute of Alcoholism and Alcohol Abuse, the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. He also has received consulting fees from Aptinyx, Bionomics, Janssen, Neurocrine, Oxeia Biopharmaceuticals, and Resilience Therapeutics.
LAS VEGAS – Despite recent advances in the diagnosis and treatment of posttraumatic stress disorder, researchers have yet to fully understand its pathophysiology.
“We don’t know whether there is just one type of pathophysiology or if there are different mechanisms and different etiologies that contribute to the symptomatic heterogeneity that we see,” Murray B. Stein, MD, MPH, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Many theories currently being studied are inflammatory theories, looking at autonomic dysregulation, glucocorticoid sensitivity, hippocampal volume/dysfunction, and cortical-amygdala circuit dysregulation.”
Dr. Stein expects clinicians to gain an improved understanding of PTSD and a myriad of other conditions in the coming years as the Million Veteran Program (MVP) gets underway. MVP researchers are building one of the world’s largest medical databases by asking 1 million veteran volunteers to provide a blood sample and complete surveys about their health, military experience, lifestyle, and other topics that might contribute to health and disease. They will study how genes influence diseases such as diabetes and cancer, and military-related illnesses, such as PTSD. “It’s an amazing study, where over the next decade, you’re going to hear research findings not just on PTSD but in other areas of mental health and physical health,” said Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego. So far, he said, 700,000 veterans are enrolled.
Dr. Stein shared preliminary findings from one component of the MVP study, in which participants complete the PTSD Checklist (PCL-17), a widely used 17-item self-report measure of PTSD symptoms in the past month. Using Manhattan plot analysis, Dr. Stein and his colleagues conducted a PTSD genomewide association study based on PCL-17 total scores. They found several genes significantly associated with PTSD, including LRRIQ3, TRAIP, KCNIP4, PCDHA1, MAD1L1, TSNARE1, EXD3, MGC57346-CRHR1, and TCF4. “This is the first study in the world to find this many genes [associated with PTSD],” said Dr. Stein, a staff psychiatrist with the VA San Diego Healthcare System. “The MAD1L1 gene is also one that’s come up in schizophrenia and in major depression. In fact, if we look at genetic correlations of how PTSD is genetically associated to other disorders that have been studied in this way, like major depression and schizophrenia, we find that there is shared variation. However, there are also unique features, so we are learning what we think is true about mental disorders overall, that in some ways comorbidity is explained by genetic risk, but there are also individual specific risk factors that go with specific disorders.
“We’re exploring each of those genes.”
of any of the genes in the genome. “One of the prominent theories of PTSD is that there is an increase in CRHR1 in the brain of individuals with the disorder,” Dr. Stein said. “More than by chance, it looks like the genes that are popping up in PTSD seem to be expressed in the frontal cortex, the anterior cingulate, the cortex, the hypothalamus, the amygdala, the hippocampus, the basal ganglia, and the substantia nigra. So all of a sudden, we go from having a list of genes to knowing there’s something going on in the brain of people with PTSD that involves expression in these particular regions that we might be able to target.”
In related work using the same genetic information, Dr. Stein and his colleagues have demonstrated an association between PTSD and medium spiny neurons, which are located in the basal ganglia and make up 95% of neurons in the striatum. “They also have GABAergic projection to other parts of the brain and play a key role in motivation, reward, enforcement, and aversion,” Dr. Stein said.
Dr. Stein disclosed that he has received research support from the National Institute of Mental Health, the National Institute of Alcoholism and Alcohol Abuse, the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. He also has received consulting fees from Aptinyx, Bionomics, Janssen, Neurocrine, Oxeia Biopharmaceuticals, and Resilience Therapeutics.
LAS VEGAS – Despite recent advances in the diagnosis and treatment of posttraumatic stress disorder, researchers have yet to fully understand its pathophysiology.
“We don’t know whether there is just one type of pathophysiology or if there are different mechanisms and different etiologies that contribute to the symptomatic heterogeneity that we see,” Murray B. Stein, MD, MPH, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Many theories currently being studied are inflammatory theories, looking at autonomic dysregulation, glucocorticoid sensitivity, hippocampal volume/dysfunction, and cortical-amygdala circuit dysregulation.”
Dr. Stein expects clinicians to gain an improved understanding of PTSD and a myriad of other conditions in the coming years as the Million Veteran Program (MVP) gets underway. MVP researchers are building one of the world’s largest medical databases by asking 1 million veteran volunteers to provide a blood sample and complete surveys about their health, military experience, lifestyle, and other topics that might contribute to health and disease. They will study how genes influence diseases such as diabetes and cancer, and military-related illnesses, such as PTSD. “It’s an amazing study, where over the next decade, you’re going to hear research findings not just on PTSD but in other areas of mental health and physical health,” said Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego. So far, he said, 700,000 veterans are enrolled.
Dr. Stein shared preliminary findings from one component of the MVP study, in which participants complete the PTSD Checklist (PCL-17), a widely used 17-item self-report measure of PTSD symptoms in the past month. Using Manhattan plot analysis, Dr. Stein and his colleagues conducted a PTSD genomewide association study based on PCL-17 total scores. They found several genes significantly associated with PTSD, including LRRIQ3, TRAIP, KCNIP4, PCDHA1, MAD1L1, TSNARE1, EXD3, MGC57346-CRHR1, and TCF4. “This is the first study in the world to find this many genes [associated with PTSD],” said Dr. Stein, a staff psychiatrist with the VA San Diego Healthcare System. “The MAD1L1 gene is also one that’s come up in schizophrenia and in major depression. In fact, if we look at genetic correlations of how PTSD is genetically associated to other disorders that have been studied in this way, like major depression and schizophrenia, we find that there is shared variation. However, there are also unique features, so we are learning what we think is true about mental disorders overall, that in some ways comorbidity is explained by genetic risk, but there are also individual specific risk factors that go with specific disorders.
“We’re exploring each of those genes.”
of any of the genes in the genome. “One of the prominent theories of PTSD is that there is an increase in CRHR1 in the brain of individuals with the disorder,” Dr. Stein said. “More than by chance, it looks like the genes that are popping up in PTSD seem to be expressed in the frontal cortex, the anterior cingulate, the cortex, the hypothalamus, the amygdala, the hippocampus, the basal ganglia, and the substantia nigra. So all of a sudden, we go from having a list of genes to knowing there’s something going on in the brain of people with PTSD that involves expression in these particular regions that we might be able to target.”
In related work using the same genetic information, Dr. Stein and his colleagues have demonstrated an association between PTSD and medium spiny neurons, which are located in the basal ganglia and make up 95% of neurons in the striatum. “They also have GABAergic projection to other parts of the brain and play a key role in motivation, reward, enforcement, and aversion,” Dr. Stein said.
Dr. Stein disclosed that he has received research support from the National Institute of Mental Health, the National Institute of Alcoholism and Alcohol Abuse, the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. He also has received consulting fees from Aptinyx, Bionomics, Janssen, Neurocrine, Oxeia Biopharmaceuticals, and Resilience Therapeutics.
REPORTING FROM NPA 2019