How the Brain Responds to Trauma
How the Brain Responds to Trauma
Corticolimbic connectivity, or the connection between neocortex and the brain's primitive structures, in the context of genetic polymorphisms (in this case, 5-HTTLPR) has been studied, with the resultant understanding that possessing short (s) rather than long (l) allele variants for SLC6A4 (the gene coding for the serotonin transporter, the protein that picks up serotonin from the synaptic cleft after neurotransmission) may confer vulnerability or protection. The s allele confers vulnerability for anxiety and depression.
The amygdala is overactive in patients carrying the s allele. The prefrontal cortex helps to regulate the activity of the amygdala when an aversive or stressful stimulus is processed. Functional imaging studies indicate a dysfunctional connectivity between the prefrontal and anterior cingulate cortices and the amygdala in depressed and anxious patients with the s/s or s/l SERT genotype.
In theory, malfunction of frontal inhibitory structures could lead to amygdala hyperactivity and accompanying stress and depressive symptoms. In fact, Hariri and Holmes have proposed a model in which miscommunication between subregions of the prefrontal cortex and the central nucleus of the amygdala occurs, resulting in a diminished ability to integrate, plan, and execute complex behaviors in response to environmental stimuli in individuals with the s/s or s/l genotype.
Early life stress in the form of maternal deprivation or neglect has provided a model for the study of susceptibility to neuropsychiatric disorders. Much work on the genetic and epigenetic consequences of early life stress has yielded important clues about their effects on neurotransmitter systems that subserve emotional tone. Work on the serotonin transporter polymorphisms is one example.
Corticotropin-releasing factor is a key system for understanding the long-term effects of early life stress on emotional regulation. For example, a blunted cortisol response to psychosocial stress is common in individuals who have experienced early life stress, whereas a comparison cohort shows a normal response. A blunted cortisol response points to impaired hypothalamus-pituitary-adrenal (HPA) axis reactivity, which is seen in victims of trauma and has been correlated with PTSD and anxiety disorders. Animal models of early life stress have clarified that changes in HPA and cortisol activity are related at least in part to what happens to its receptors.
In the hippocampus (an important structure for feedback inhibition of the stress response), models of early life stress show down-regulation of corticotropin-releasing factor receptors, which has been linked to excessive glutamate neurotransmission and hippocampal cell death owing to glutamate-mediated excitotoxicity (cell death from excessive oxidation). In other words, adaptive responses to trauma can become maladaptive, at least in part as a result of genetic and molecular changes. These changes lead to alterations in receptor pharmacology that perpetuate the deleterious physiologic and psychological effects of trauma.
Influences on the Development of Mood and Anxiety Disorders
Corticolimbic connectivity, or the connection between neocortex and the brain's primitive structures, in the context of genetic polymorphisms (in this case, 5-HTTLPR) has been studied, with the resultant understanding that possessing short (s) rather than long (l) allele variants for SLC6A4 (the gene coding for the serotonin transporter, the protein that picks up serotonin from the synaptic cleft after neurotransmission) may confer vulnerability or protection. The s allele confers vulnerability for anxiety and depression.
The amygdala is overactive in patients carrying the s allele. The prefrontal cortex helps to regulate the activity of the amygdala when an aversive or stressful stimulus is processed. Functional imaging studies indicate a dysfunctional connectivity between the prefrontal and anterior cingulate cortices and the amygdala in depressed and anxious patients with the s/s or s/l SERT genotype.
In theory, malfunction of frontal inhibitory structures could lead to amygdala hyperactivity and accompanying stress and depressive symptoms. In fact, Hariri and Holmes have proposed a model in which miscommunication between subregions of the prefrontal cortex and the central nucleus of the amygdala occurs, resulting in a diminished ability to integrate, plan, and execute complex behaviors in response to environmental stimuli in individuals with the s/s or s/l genotype.
Early life stress in the form of maternal deprivation or neglect has provided a model for the study of susceptibility to neuropsychiatric disorders. Much work on the genetic and epigenetic consequences of early life stress has yielded important clues about their effects on neurotransmitter systems that subserve emotional tone. Work on the serotonin transporter polymorphisms is one example.
Corticotropin-releasing factor is a key system for understanding the long-term effects of early life stress on emotional regulation. For example, a blunted cortisol response to psychosocial stress is common in individuals who have experienced early life stress, whereas a comparison cohort shows a normal response. A blunted cortisol response points to impaired hypothalamus-pituitary-adrenal (HPA) axis reactivity, which is seen in victims of trauma and has been correlated with PTSD and anxiety disorders. Animal models of early life stress have clarified that changes in HPA and cortisol activity are related at least in part to what happens to its receptors.
In the hippocampus (an important structure for feedback inhibition of the stress response), models of early life stress show down-regulation of corticotropin-releasing factor receptors, which has been linked to excessive glutamate neurotransmission and hippocampal cell death owing to glutamate-mediated excitotoxicity (cell death from excessive oxidation). In other words, adaptive responses to trauma can become maladaptive, at least in part as a result of genetic and molecular changes. These changes lead to alterations in receptor pharmacology that perpetuate the deleterious physiologic and psychological effects of trauma.
