Post Traumatic Stress Disorder
PTSD Resources

The research showing how exposure to extreme stress affects brain function is making important contributions to understanding the nature of traumatic stress. This includes the notion that traumatized individuals are vulnerable to react to sensory information with subcortically initiated responses that are irrelevant, and often harmful, in the present. Reminders of traumatic experiences activate brain regions that support intense emotions, and decrease activation in the central nervous system (CNS) regions involved in (a) the integration of sensory input with motor output, (b) the modulation of physiological arousal, and (c) the capacity to communicate experience in words.
Source: Clinical Implications of Neuroscience Research in PTSD- New York Academy of Sciences

Childhood abuse and other sources of extreme stress can have lasting effects on the parts of the brain that are involved in memory and emotion. The hippocampus, in particular, seems to be very sensitive to stress. Damage to the hippocampus from stress can not only cause problems in dealing with memories and other effects of past stressful experiences, it can also impair new learning. Exciting recent research has shown that the hippocampus has the capacity to regenerate nerve cells ("neurons") as part of its normal functioning, and that stress impairs that functioning by stopping or slowing down neuron regeneration.

We recently conducted a study to try to see if PTSD symptoms matched up with a measurable loss of neurons in the hippocampus. We first tested Vietnam combat veterans with declaratory memory problems caused by PTSD. Using brain imaging, these combat veterans were found to have an 8% reduction in right hippocampal volume (i.e., the size of the hippocampus), measured with magnetic resonance imaging (MRI), while no differences were found in other areas of the brain.

Our (J. Douglas Bremner, M.D. Yale University School of Medicine, Yale Psychiatric Institute, and National Center for PTSD-VA Connecticut Healthcare System) study showed that diminished right hippocampal volume in the PTSD patients was associated with short-term memory loss. Similar results were found when we looked at PTSD sufferers who were victims of childhood physical or sexual abuse.

More recent studies have since confirmed hippocampal volume reduction in PTSD. These studies also show that hippocampal volume reduction is specific to PTSD and is not associated with disorders such as anxiety or panic disorders.

Further study on the question of memory and the hippocampus may some day shed light on the controversy surrounding delayed recall, or so-called "recovered memories" of childhood abuse. The hippocampus plays an important role in connecting and organizing different aspects of a memory and is thought to be responsible for locating the memory of an event in its proper time, place and context.

We suspect that damage to the hippocampus following exposure to the stress brought on by childhood abuse leads to distortion and fragmentation of memories. For instance, in the case of the PTSD sufferer who was locked in a closet as a child, she had a memory of the smell of old clothes but other parts of her memory of the experience, such as a visual memory of being in the closet or a memory of the feeling of fear, are difficult to retrieve or completely lost. In cases like this, psychotherapy or an event that triggers similar emotions may help the patient restore associations and bring all aspects of the memory together.

This new understanding of the way childhood trauma affects memory and the brain has important implications for public health policy. One example would be the case of inner-city children who have witnessed violent crimes in their neighborhoods and families. If this kind of stress can cause damage to brain areas involved in learning and memory, it would put these children at a serious academic disadvantage in ways and for reasons that programs such as Head Start may be unable to address. Studies confirm this: in war-torn Beirut, traumatized adolescents with PTSD, as compared to non-traumatized adolescents who were without PTSD, lagged behind in academic achievement.

PTSD and Other Brain Areas
Besides the hippocampus, abnormalities of other brain areas, including medial prefrontal cortex, are also associated with PTSD.

The medial prefrontal cortex regulates emotional and fear responses. The medial prefrontal cortex is closely linked to the hippocampus. In several studies we have found dysfunction of both the medial prefrontal cortex and the hippocampus at times when patients were suffering from PTSD symptoms.

We believe that dysfunction in these medial prefrontal regions may underlie pathological emotional responses in patients with PTSD. For example, we sometimes see a failure of extinction of fear responses -- a rape victim who was raped in a dark alley will have fear reactions to dark places for years after the original event, even though there is no threat associated with a particular dark place. In a study using combat-related slides and sounds to provoke PTSD symptoms, combat veterans with PTSD had decreased blood flow in the area of the medial prefrontal cortex. Significantly, this did not occur in combat veterans without PTSD32 We saw similar results when we compared women with PTSD and a history of childhood sexual abuse to women with a history of abuse but no PTSD.

Conclusion
Traumatic stress, such as that caused by childhood sexual abuse, can have far-reaching effects on the brain and its functions. Recent studies indicate that extreme stress can cause measurable physical changes in the hippocampus and medial prefrontal cortex, two areas of the brain involved in memory and emotional response. These changes can, in turn, lead not only to classic PTSD symptoms, such as loss and distortion of memory of events surrounding the abuse, but also to ongoing problems with learning and remembering new information. These findings may help explain the controversial phenomenon of "recovered" or delayed memories. They also suggest that how we educate, rehabilitate and treat PTSD sufferers may need to be reconsidered.
Source: The Invisible Epidemic: Post-Traumatic Stress Disorder, Memory and the Brain

PTSD displays biochemical changes in the brain and body, which are different from other psychiatric disorders such as major depression.

In PTSD patients, the dexamethasone cortisol suppression is strong, while it is weak in patients with major depression. In most PTSD patients the urine secretion of cortisol is low, at the same time as the catecholamine secretion is high, and the norepinephrine/cortisol ratio is increased. Brain catecholamine levels are low, and corticotropin-releasing factor (CRF) concentrations are high. There is also an increased sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis, with a strong negative feedback of cortisol, due to a generally increased sensitivity of cortisol receptors (Yehuda, 2001).

The response to stress in PTSD is abnormal with long-term high levels of norepinephrine, at the same time as cortisol levels are low, a pattern associated with facilitated learning in animals. Translating this reaction to human conditions gives a pathophysiological explanation for PTSD by a maladaptive learning pathway to fear response (Yehuda 2002). With this deduction follows that the clinical picture of hyperreactivity and hyperresponsiveness in PTSD is consistent with the sensitive HPA-axis.

Swedish United Nations soldiers serving in Bosnia with low pre-service salivary cortisol levels had a higher risk of reacting with PTSD symptoms, following war trauma, than soldiers with normal pre-service levels (Aardal-Eriksson 2001).
Source: US News and World Report

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline (NE) may play roles in the pathophysiology of post-traumatic stress disorder (PTSD).
Source: Nature Journal- Serotonergic and Noradrenergic Markers of Post-Traumatic Stress Disorder with and without Major Depression

The impact of early environment through epigenetic programming by maternal behavior, and glucocorticoid programming of the fetus on the later development of PTSD is discussed in a brief by Jonathan R. Seckl and Michael J. Meaney

Disturbed regulation of both the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenomedullary system in posttraumatic stress disorder (PTSD) suggests that immune function, which is modulated by these systems, may also be dysregulated.
Source:Source: Immune Function in PTSD- A brief by Margaret Altemus, Firdaus S. Dhabhar and Ruirong Yang- New York Academy of Sciences

In animal research as well as human studies, the amygdala has been shown to be strongly involved in the formation of emotional memories, especially fear-related memories. Neuroimaging studies in humans have revealed both morphological and functional aspects of PTSD. The amygdalocentric model of PTSD proposes that it is associated with hyperarousal of the amygdala and insufficient top-down control by the medial prefrontal cortex and the hippocampus. Further animal and clinical research into the c and fear conditioning may suggest additional treatments for the condition.

US News and World Report cites D-Cycloserine (DCS) as an effective and lasting treatment for anxiety disorders without side effects in an article titled DCS- Amygdala and the Hippocampus; The Biological Underpinnings of Paralyzing Fears
Source: US News and World Report

The last decade of neuroimaging research has yielded important information concerning the structure, neurochemistry, and function of the amygdala, medial prefrontal cortex, and hippocampus in posttraumatic stress disorder (PTSD). Neuroimaging research reviewed in this article reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma-unrelated affective information. Importantly, amygdala responsivity is positively associated with symptom severity in PTSD. In contrast, medial prefrontal cortex appears to be volumetrically smaller and is hyporesponsive during symptomatic states and the performance of emotional cognitive tasks in PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD symptom severity. Lastly, the reviewed research suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD.
Source: Amygdala, Medial Prefrontal Cortex, and Hippocampal Function in PTSD, a brief by Lisa M Shin, Scott L Rauch, and Rodger K. Pitman published in the New York Acadamy of Sciences

A study done by Cohen H., Kaplan Z.,Kotler M., Kouperman I. , Moisa R.,Grisaru N. notes that "a number of structural and functional neuroimaging studies which have shown that abnormalities in the prefrontal cortex can be found in patients with PTSD. Low metabolism was found at baseline in temporal and prefrontal cortical areas according to PET scans. PTSD patients showed increased regional cerebral blood flow (rCBF) in the amygdala and decreased rCBF in prefrontal cortex in response to provocation of symptoms by script driven imagery. Also proton magnetic resonance spectroscopy (MRS) measurement of medial cneural density in Vietnam combat veterans with PTSD and in healthy controls showed the ratio of N-acetyl-L-aspartic acid to creatinine ratio was lower in the right hemisphere vs. left as well as in comparison with healthy control subjects. This lower ratio is suggestive of neuronal loss. Additionally, prefrontal and limbic abnormalities is suggested by neuropsychological testing sensitive to frontal lobe damage., which demonstrate impaired performance on tests reflecting abnormalities of the dorsolateral prefrontal cortex, the orbitofrontal cortex as well as the limbic system generally. Taken together these studies suggest that the right limbic and paralimbic structures are involved in the pathophysiology of PTSD and that stimulation of the right dorsolateral prefrontal cortex may result in improvement of symptoms." The study tested Transcortical magnetic stimulation (TMS) "a noninvasive technique for directly stimulating cortical neurons. Electrical energy crosses the brain almost painlessly, without causing convulsions or cognitive impairment but causing depolarization of neurons with resultant changes in monoamines. The authors cite prior pilot studies that lend credence to the idea that repetitive TMS (rTMS) may be an effective alternative for treating patients with PTSD.
Source: Psychiatry and Behavioral Sciences, Duke University