drz
10-27-2012, 01:02 PM
Why stress is bad for us.
Social rejection during adolescence hurts more than the psyche. A new study links it to changes in the immune system that could result in negative physical and mental health outcomes down the road.
Among a group of adolescent girls followed for more than 2 years, researchers found evidence that targeted social rejection upregulated proinflammatory signaling molecules, particularly among girls who felt they were at the top of the social ladder.
In a statement, study investigator Michael L. Murphy, PhD, of the Department of Psychology, University of British Columbia, Vancouver, Canada, who worked on the study, noted that targeted rejection is "central to some of life's most distressing experiences — things like getting broken up with, getting fired, and being excluded from your peer group at school. In this study, we aimed to examine processes that may give these experiences the ability to affect health."
The findings support other emerging evidence that "inflammation and the molecular signaling pathways that regulate inflammation are influenced to a significant degree by the external social world," the researchers write.
According to the researchers, the findings have implications for understanding how social conditions increase risk for a variety of inflammation-related diseases, including depression, obesity, diabetes, cardiovascular disease, and cancer.
The study was published online (http://cpx.sagepub.com/content/early/2012/09/07/2167702612455743.abstract) September 7 in Clinical Psychological Science.
Rejection Packs a Proinflammatory Punch
The study included 147 adolescent women between 15 and 19 years old who did not have a personal history of mental health problems but were at risk of developing a first episode of major depression due to family and other personal risk factors.
Every 6 months for roughly 2.5 years, the researchers assessed them for recent episodes of targeted social rejection and psychiatric diagnoses. At each assessment, they drew blood to determine expression levels of key inflammatory signaling molecules and the inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL-6).
Overall, 134 participants (91%) completed at least 3 assessments, and 94 (64%) completed all 6 assessments.
The researchers observed higher mRNA levels for both nuclear factor–kappa B (NF-κB) and inhibitor of kappa B (I-κB), and a lower ratio of NF-κB to I-κB, following visits when a recent targeted rejection life event had occurred compared with visits when no targeted rejection life event had occurred.
Targeted rejection was unrelated to levels of either CRP or IL-6.
"Several studies have now shown that negative social experiences upregulate inflammatory activity," the authors note.
"The present study extends this work by demonstrating for the first time that acute life events involving targeted rejection are associated with increased expression of the genes encoding NF-κB and I-κB, especially for adolescents who perceive themselves to be high in social status," they add.
Dr. Murphy and colleagues speculate that this inflammatory response might be adaptive for individuals at the top of a social hierarchy, giving them a survival advantage. The researchers note, however, that an overly productive immune response can be harmful to mental and physical health in the long run.
Overall, they say the findings "converge with a growing number of transcriptome-wide studies showing enhanced expression of pro-inflammatory immune response genes for individuals confronting a range of adverse social experiences including anticipated bereavement, low socioeconomic status, traumatic life events, and the diagnosis of a life-threatening illness."
The findings "also challenge fundamental notions about the self as a biologically stable entity. For example, although the structure of human DNA changes relatively little over the life course, the activity of our genome is quite fluid and more permeable to external social influence than we realize."
The next step, they add, is to replicate the effects they've seen in a separate study with a "more rigorous experimental design and then, if successful, evaluate their contribution to subsequent mental and physical health problems."
Unique Focus
Commenting on the study for Medscape Medical News, William Copeland, PhD, assistant clinical professor of psychiatry and behavioral sciences at Duke University Medical Center in Durham, North Carolina, said the study adds to the evidence that negative life events, particularly those that involve loss or humiliation, are related to changes in immune function and inflammation.
"What's really interesting about this study is that it kind of gets at the mechanism that really explains how this is all happening by basically looking at the gene products that are related to nuclear factor κB and inhibitor κB.
"In doing so, it kind of shows us how stress may be getting under the skin and affecting inflammation," said Dr. Copeland, who has been involved in research on psychiatric predictors of inflammatory response in adolescence, including some work on peer victimization.
"It's their focus on the messenger RNA which is rather unique," Dr. Copeland added. "There haven't been a lot of studies that have done that; most studies tend focus on levels of cytokines or reactive proteins in cells. This study gets at the messenger RNA."
Dr. Copeland agrees that further study is needed and worthwhile.
"There are a couple good steps the researchers could take for replicating it," he said. "Here they are just looking at single incidences of social rejection and the association of mRNA levels. What we have found and what other people have found is that it seems to be more chronic exposure to these negative types of events like peer rejection but also other types of things like maltreatment which seem to have the most potent effects on inflammation levels and cytokine levels; so really looking at the effects of chronic stress on inflammation is really the way to go forward."
The study was supported by the Canadian Institutes of Health Research, the National Alliance for Research on Schizophrenia and Depression, the Heart and Stroke Foundation of Canada, and the National Institute of Child Health and Human Development. The authors and Dr. Copeland have disclosed no relevant financial relationships.
Clinical Psychological Science. Published online September 7, 2012. Abstract (http://cpx.sagepub.com/content/early/2012/09/07/2167702612455743.abstract)
Social rejection during adolescence hurts more than the psyche. A new study links it to changes in the immune system that could result in negative physical and mental health outcomes down the road.
Among a group of adolescent girls followed for more than 2 years, researchers found evidence that targeted social rejection upregulated proinflammatory signaling molecules, particularly among girls who felt they were at the top of the social ladder.
In a statement, study investigator Michael L. Murphy, PhD, of the Department of Psychology, University of British Columbia, Vancouver, Canada, who worked on the study, noted that targeted rejection is "central to some of life's most distressing experiences — things like getting broken up with, getting fired, and being excluded from your peer group at school. In this study, we aimed to examine processes that may give these experiences the ability to affect health."
The findings support other emerging evidence that "inflammation and the molecular signaling pathways that regulate inflammation are influenced to a significant degree by the external social world," the researchers write.
According to the researchers, the findings have implications for understanding how social conditions increase risk for a variety of inflammation-related diseases, including depression, obesity, diabetes, cardiovascular disease, and cancer.
The study was published online (http://cpx.sagepub.com/content/early/2012/09/07/2167702612455743.abstract) September 7 in Clinical Psychological Science.
Rejection Packs a Proinflammatory Punch
The study included 147 adolescent women between 15 and 19 years old who did not have a personal history of mental health problems but were at risk of developing a first episode of major depression due to family and other personal risk factors.
Every 6 months for roughly 2.5 years, the researchers assessed them for recent episodes of targeted social rejection and psychiatric diagnoses. At each assessment, they drew blood to determine expression levels of key inflammatory signaling molecules and the inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL-6).
Overall, 134 participants (91%) completed at least 3 assessments, and 94 (64%) completed all 6 assessments.
The researchers observed higher mRNA levels for both nuclear factor–kappa B (NF-κB) and inhibitor of kappa B (I-κB), and a lower ratio of NF-κB to I-κB, following visits when a recent targeted rejection life event had occurred compared with visits when no targeted rejection life event had occurred.
Targeted rejection was unrelated to levels of either CRP or IL-6.
"Several studies have now shown that negative social experiences upregulate inflammatory activity," the authors note.
"The present study extends this work by demonstrating for the first time that acute life events involving targeted rejection are associated with increased expression of the genes encoding NF-κB and I-κB, especially for adolescents who perceive themselves to be high in social status," they add.
Dr. Murphy and colleagues speculate that this inflammatory response might be adaptive for individuals at the top of a social hierarchy, giving them a survival advantage. The researchers note, however, that an overly productive immune response can be harmful to mental and physical health in the long run.
Overall, they say the findings "converge with a growing number of transcriptome-wide studies showing enhanced expression of pro-inflammatory immune response genes for individuals confronting a range of adverse social experiences including anticipated bereavement, low socioeconomic status, traumatic life events, and the diagnosis of a life-threatening illness."
The findings "also challenge fundamental notions about the self as a biologically stable entity. For example, although the structure of human DNA changes relatively little over the life course, the activity of our genome is quite fluid and more permeable to external social influence than we realize."
The next step, they add, is to replicate the effects they've seen in a separate study with a "more rigorous experimental design and then, if successful, evaluate their contribution to subsequent mental and physical health problems."
Unique Focus
Commenting on the study for Medscape Medical News, William Copeland, PhD, assistant clinical professor of psychiatry and behavioral sciences at Duke University Medical Center in Durham, North Carolina, said the study adds to the evidence that negative life events, particularly those that involve loss or humiliation, are related to changes in immune function and inflammation.
"What's really interesting about this study is that it kind of gets at the mechanism that really explains how this is all happening by basically looking at the gene products that are related to nuclear factor κB and inhibitor κB.
"In doing so, it kind of shows us how stress may be getting under the skin and affecting inflammation," said Dr. Copeland, who has been involved in research on psychiatric predictors of inflammatory response in adolescence, including some work on peer victimization.
"It's their focus on the messenger RNA which is rather unique," Dr. Copeland added. "There haven't been a lot of studies that have done that; most studies tend focus on levels of cytokines or reactive proteins in cells. This study gets at the messenger RNA."
Dr. Copeland agrees that further study is needed and worthwhile.
"There are a couple good steps the researchers could take for replicating it," he said. "Here they are just looking at single incidences of social rejection and the association of mRNA levels. What we have found and what other people have found is that it seems to be more chronic exposure to these negative types of events like peer rejection but also other types of things like maltreatment which seem to have the most potent effects on inflammation levels and cytokine levels; so really looking at the effects of chronic stress on inflammation is really the way to go forward."
The study was supported by the Canadian Institutes of Health Research, the National Alliance for Research on Schizophrenia and Depression, the Heart and Stroke Foundation of Canada, and the National Institute of Child Health and Human Development. The authors and Dr. Copeland have disclosed no relevant financial relationships.
Clinical Psychological Science. Published online September 7, 2012. Abstract (http://cpx.sagepub.com/content/early/2012/09/07/2167702612455743.abstract)