An Integrated Neuroscience Perspective on Formulation and Treatment Planning for Posttraumatic Stress Disorder


Abstract

Importance  Posttraumatic stress disorder (PTSD) is a common psychiatric illness, increasingly in the public spotlight in the United States due its prevalence in the soldiers returning from combat in Iraq and Afghanistan. This educational review presents a contemporary approach for how to incorporate a modern neuroscience perspective into an integrative case formulation. The article is organized around key neuroscience “themes” most relevant for PTSD. Within each theme, the article highlights how seemingly diverse biological, psychological, and social perspectives all intersect with our current understanding of neuroscience.

Observations  Any contemporary neuroscience formulation of PTSD should include an understanding of fear conditioning, dysregulated circuits, memory reconsolidation, epigenetics, and genetic factors. Fear conditioning and other elements of basic learning theory offer a framework for understanding how traumatic events can lead to a range of behaviors associated with PTSD. A circuit dysregulation framework focuses more broadly on aberrant network connectivity, including between the prefrontal cortex and limbic structures. In the process of memory reconsolidation, it is now clear that every time a memory is reactivated it becomes momentarily labile—with implications for the genesis, maintenance, and treatment of PTSD. Epigenetic changes secondary to various experiences, especially early in life, can have long-term effects, including on the regulation of the hypothalamic-pituitary-adrenal axis, thereby affecting an individual’s ability to regulate the stress response. Genetic factors are surprisingly relevant: PTSD has been shown to be highly heritable despite being definitionally linked to specific experiences. The relevance of each of these themes to current clinical practice and its potential to transform future care are discussed.

Conclusions and Relevance  Together, these perspectives contribute to an integrative, neuroscience-informed approach to case formulation and treatment planning. This may help to bridge the gap between the traditionally distinct viewpoints of clinicians and researchers.

Introduction

In the Clinical Challenge in this issue of JAMA Psychiatry,1 we describe the case of a soldier who experienced multiple life-threatening events during a military deployment and then struggled with a number of problems on his return home.

Although the details of the case are contemporary, the overall arc of the narrative is hardly new. Through much of history there are accounts of similar individuals who, following exposure to a life-threatening event, have struggled to readjust to “normal” life. These accounts include descriptions in The Odyssey of soldiers returning from the Trojan war and of a survivor of the Great Fire of London in the 1600s.2,3 At different times in history, various names have been used to describe the broad phenomenon of difficulty recovering from combat experiences, including nostalgia or soldier’s heart(Civil War), shell shock (World War I), battle exhaustion (World War II), and post-Vietnam syndrome. Although some core features are similar across these entities, each has distinct aspects reflecting the unique time and culture.

In 1980, in part because of political factors, the DSM-IIIintroduced the diagnosis of posttraumatic stress disorder (PTSD). These criteria were held constant until publication of the DSM-5 in 20134 (although experts continue to debate this nosology, including vis-à-vis what constitutes a traumatic experience and the role of complex neuroscience domains in diagnosis).5,6

Phenomenologically, most individuals who are exposed to traumatic events experience transient aftereffects that resolve within the first month (eg, numbness or hyperemotionality, nightmares, anxiety, and hypervigilance). In a minority of individuals (approximately 10%-20%, depending on the type of trauma), these symptoms may persist and cause lasting and potentially debilitating dysfunction.7

With PTSD—perhaps more than with other psychiatric illnesses—it is critical to recognize the context of each individual’s personal history: prior experiences (including trauma or resilience), belief systems, culture, social supports, and myriad other exacerbating and protective factors. As psychiatrists, we aspire to treat people rather than diseases—doing so requires a broad approach that incorporates diverse clinical perspectives. Within this complexity, a range of biological factors play crucial roles. To this end, we review a set of core neuroscience themes relevant to PTSD.

Theme 1: Fear Conditioning

Any conversation about the neurobiology of PTSD needs to begin with what happens in the brain following a traumatic event. How does the brain, from the lowest vertebrates to humans, reflexively respond to a life-threatening event to ensure survival? We study this process through a behavior called fear (or threat) conditioning, a form of classical conditioning in which an innate response to an unconditioned stimulus (eg, a shock or other unexpected painful stimulus) becomes associated with another previously neutral (conditioned) stimulus. From an evolutionary perspective, this form of learning is highly adaptive: it is very beneficial to know—and thereby avoid—contextual cues that may predict dangerous outcomes.

When an individual experiences a traumatic event (eg, as happened to the soldier described in the Clinical Challenge1), the physiologic response to the trauma can become paired with previously neutral environmental cues. Long after the precipitating traumatic event, environmental cues will continue to serve as triggers for a similar physiologic response. This process corresponds to the DSM-5 symptom of intense or prolonged distress after exposure to traumatic reminders4(Table). The patient may be consciously aware of these triggers, such as walking on a city street or being in the desert. Importantly, there may also be subtle contextual cues that induce symptoms of fear and anxiety without conscious awareness of the trigger (eg, fleeting peripheral movement, an unexpected object at the side of the road, or even the aroused emotional response of a sexual partner). The physiologic responses of increased startle, hypervigilance, increased heart rate and respiration, dry mouth, and emotional reactivity and defensive behavior may all be triggered by these experiences, with the most extreme experiences activating a flashback in which the patient has temporary difficulty separating past traumatic experiences from the present. Figure 1 shows a diagram of the basic neural circuits that are relevant to fear conditioning.8

On multiple levels, it is not surprising that individuals exposed to trauma would avoid situations that remind them of these events. This process reflects a form of operant conditioning (Box) known as negative reinforcement, that is, when a behavior that leads to the avoidance or removal of an aversive stimulus is increased in frequency.9 This process correlates with the DSM-5 category C avoidance symptoms of PTSD.4 For example, a patient exposed to an ambush while traveling in a military convoy abroad may subsequently avoid driving on major roads at home so as to prevent the physiologic and affective response that occurs with trauma reminders. As described in the accompanying Clinical Challenge,1 because speaking about traumatic experiences may be a potent trigger of negative affect, the patient may also avoid therapy. This avoidance is a significant barrier to treatment and may underlie recent concerns about certain forms of therapy being less effective in the real world.10,11

Box.

PTSD Terms and Definitions

Classical Conditioning
  • Classical conditioning is a process wherein an innate response to a specific stimulus (eg, salivating at the sight of food) becomes paired to a neutral stimulus (such as a bell ringing) by repeated presentation of the two stimuli, in the case of appetitive classical conditioning. One prototypical example of aversive conditioning is fear (or threat) conditioning, in which an aversive event (unconditioned stimulus) triggers autonomic arousal and intense fear (the unconditioned response) and contextual cues in the environment (eg, sights, sounds, and smells) become conditionally associated with the trauma. The conditional cues will then trigger the experience of autonomic arousal and intense fear as in the original situation (the conditioned response) as shown in Figure 1.9

Operant Conditioning
  • Operant conditioning, by contrast, is a process by which behaviors are increased or decreased in frequency based on the presence of rewards or noxious stimuli. Reinforcement means that a behavior is increased in frequency based on either the presence of reward (positive reinforcement, as seen in cocaine-seeking behavior) or the removal/avoidance of a noxious stimulus (negative reinforcement, as seen in avoidance of unpleasant situations/circumstances). Punishmentmeans that a behavior is decreased in frequency based on either the addition of a noxious stimulus (positive punishment, such as spanking a child) or the removal of a rewarding stimulus (negative punishment, such as taking away a child’s toys).

Extinction
  • The term extinction was originally coined in a behavioral context: repeated exposure to a conditioned stimulus led to the disappearance of the fear response behavior. Recent work, however, has shown that the conditioned association and response can be brought back (reinstated) by re-exposure to the fear-inducing cue. Thus, it appears that behavioral extinction paradigms are actually teaching individuals to overlearn a safety association on top of the existing fear conditioning. This contrasts with the discussion of reconsolidation that occurs later in this article (a process which may genuinely alter or disrupt the memory of an event). A visual schematic of these opponent processes is shown in Figure 2.

Fear conditioning and the avoidance of conditioned contextual cues are adaptive in a dangerous environment—they support survival. However, the same behaviors become maladaptive when one is returned to a safe environment, where rational, nonreactive, and socially “appropriate” responses are preferred over defensive reflexes. In this regard, ongoing PTSD in the aftermath of trauma exposure may be thought of as a failure to unlearn adaptive thoughts and behaviors on the return to a safe place.12

The best evidence-based treatments for PTSD are forms of psychotherapy that are designed to reverse the lasting impact of fear conditioning (eg, prolonged exposure therapy and cognitive processing therapy).13,14 To do so, patients are encouraged to engage and process traumatic memories in the absence of the feared outcome. Early on in treatment, patients may experience increased anxiety as they engage with these difficult memories. However, over time, exposure to the conditioned stimulus in a safe environment without the expected adverse outcome can lead to habituation (weakening of the intensity of response to a stimulus over time) and extinction (the conditioned stimulus is no longer associated with the aversive unconditioned stimulus) (Box). A visual schematic of these opponent processes is shown in Figure 2. Helping patients understand this process—critically, including the role of negative reinforcement and avoidance in perpetuating symptoms, and that these are robust neurobiological phenomena—may improve patients’ motivation, decrease their self-doubt about recovery, and improve their ability to engage in therapy.

Future Directions

One promising line of inquiry is the use of plasticity-enhancing agents, such as d-cycloserine, a partial agonist of the N-methyl-d-aspartate receptor, to augment the effects of psychotherapy. By increasing the brain’s capacity for learning, these medications may allow patients to complete an exposure-based therapy more rapidly, as shown in studies of acrophobia.15,16 Although d-cycloserine itself has limitations,17enhanced plasticity may be a shared mechanism of action by which other medications benefit patients with PTSD: for example, a known downstream effect of selective serotonin reuptake inhibitors is to increase brain-derived neurotrophic factor and thereby enhance plasticity.18

A different approach to treatment may be to interfere with the initial process of fear conditioning. The strength of an initial memory will depend on many factors (eg, it may be increased in the context of elevated norepinephrine levels, as seen in trauma). There is also a temporal window during which the consolidation of this initial memory occurs. Thus, in some circumstances, it may be possible to disrupt or diminish the strength of the initial encoding. This principle underlies both medication trials (eg, with propranolol and opiates) to potentially prevent the onset of PTSD and, similarly, forms the rationale for early cognitive-behavioral interventions.19,20

Theme 2: Dysregulated Circuits

Some of the earliest research findings with PTSD suggested abnormalities in regulation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis.21 This hypothesis led to clinical trials with adrenergic blockers (eg, clonidine and prazosin) that ultimately were not shown to be effective, although recent research has found prazosin to be effective for treating trauma-related nightmares, in part through its α-1 antagonist properties in normalizing sleep.22The most common HPA dysregulation finding included enhanced cortisol suppression following low-dose dexamethasone treatment.23,24 These data suggested enhanced sensitivity to glucocorticoid activation. More recent work has also suggested that the stress response system may be hyperreactive to triggers, both in the magnitude of response and in the time it takes to return to baseline.25Figure 3 illustrates aspects of the above-described commonly observed aspects of HPA dysregulation seen in individuals with PTSD.

Connecting this work back to the basic circuit diagrammed in Figure 1, a core aspect of normal functioning is the reciprocal inhibition between the medial prefrontal cortex (mPFC) and the amygdala: during stress, limbic activation inhibits PFC functioning; conversely, PFC activity is able to inhibit the amygdala and, resultantly, decrease the stress response. Individuals with PTSD may have a regulatory imbalance in which amygdala activation is exaggerated while the function of the PFC is diminished. Much work on the output of amygdala activation has led to a greater understanding of many of the downstream neural pathways that mediate the enhanced startle response, hyperarousal, increased heart rate, and other core aspects of response to fear and threats.26– 30

From this perspective, a wide range of treatments for PTSD may share a central therapeutic mechanism of restoring balance between PFC and amygdala function. Selective serotonin reuptake inhibitors may exert their benefit by decreasing hyperreactivity in the amygdala.31 In addition, different forms of psychotherapy may help individuals restore top-down (PFC) control to regulate arousal and anxiety. A helpful line of inquiry comes from research into the phenomenon of resilience. This area of work aims to identify factors that protect individuals from developing PTSD. Resilient individuals have been shown to have better regulation of their stress response, mediated by a number of possible pathways, including neuropeptide Y.32 It has also been shown that early exposure to manageable stress may confer resilience toward future trauma—a process known as stress inoculation.7

Future Directions

As described above, many current treatments align well with a circuit-based model of PTSD including, most notably, forms of psychotherapy that may help to restore balance between PFC and limbic structures.

In recent years, considerable research in psychiatry has explored the role of a wide range of interventional approaches to help regulate circuits. These interventions include electroconvulsive therapy, deep brain stimulation, vagal nerve stimulation, and, more recently, repetitive transcranial magnetic stimulation and transcranial direct current stimulation. To date, research findings with interventional approaches for PTSD have been limited.33 However, one might hope that these methods may eventually prove to be able to restore balance to dysregulated circuits by altering function in specific regions.

Theme 3: Memory Reconsolidation

Autobiographical memories are formed when stimuli that represent an experience are encoded in working and short-term memory and then consolidated into long-term memory. At one time, it was thought that such memories were indelible and reflected the initial information that was encoded. Recent research, including examining the accuracy of “flashbulb memories” for major events (eg, the assassination of President Kennedy or the 9/11 terrorist attacks), has suggested a different story.34

The concept of memory reconsolidation is that every time a memory is recalled it is momentarily made labile and then needs to be reconsolidated. During this process, the memory may be updated or changed based on new experience. From this perspective, any particular memory may be thought of as being only as old as the last time it was recalled (Figure 2).35,36

This process has clear implications in PTSD. For better or for worse, each time a traumatic experience is recalled, the patient’s memory may be updated. Returning to our Clinical Challenge patient1: left to his own, one imagines that each time he recalls the trauma there is a high potential that the reconsolidation process may reinforce prior beliefs and interpretations (likely including cognitive distortions around guilt, responsibility, and self-blame); in contrast, in the context of therapy one might view this as an opportunity for a combination of fear extinction, as outlined above, along with updating the memory to incorporate new data and perspectives into a more adaptive overall representation.

Future Directions

There is considerable interest in developing treatments that may capitalize on this process. Some behavioral therapies have been explicitly designed to leverage the reconsolidation process.36 Other studies have sought to combine therapy with pharmacologic agents that may help to block the reconsolidation of traumatic memories (eg, propranolol37 or xenon gas, the latter of which is thought to inhibit the N-methyl-d-aspartate receptor38). A recent study also demonstrated the possibility of using the globally amnestic properties of electroconvulsive therapy to disrupt the reconsolidation of memories.39

Theme 4: Epigenetic Considerations

Epigenetics refers to mechanisms (eg, DNA methylation or histone acetylation) by which environmental exposures may influence the functional expression of genes. A large amount of literature has demonstrated that early childhood neglect or trauma can epigenetically program the stress system, leading to aberrant regulation of the HPA axis and maladaptive, prolonged responses to stressors encountered later in life. This effect appears to occur by the inhibition of the expression of hippocampal glucocorticoid receptors (GRs) via DNA methylation along the GR gene promoter.

As illustrated in Figure 4, GRs in the hippocampus are central to effective regulation of the HPA axis. Under ideal conditions, the body is able to mount a cortisol stress response that quickly shuts off once the danger has passed. This response occurs through negative feedback at the level of the GR (with increased density of receptors correlating with improved regulation). Studies of rodents and humans suggest that GR expression is significantly reduced by childhood abuse or neglect and that this difference persists into adulthood. These individuals then have inefficient negative HPA feedback and a prolonged stress response, similar to that in patients with PTSD.41,42

From this perspective, for the veteran we have been discussing, it is clinically important to recognize that his history of childhood trauma is itself a risk factor for developing PTSD43,44 and other psychiatric illnesses (including depression and substance use disorders),45 perhaps in part through a dysregulated stress response system.46 Of interest, this same process of dysregulated stress response may also be associated with a range of other health problems, including heart disease and stroke, thus giving cause for increased vigilance in routine health monitoring.45

Recent work has also provided evidence that epigenetic mechanisms may be able to act across generations, possibly being transmitted through gametes. Thus, environmental exposures experienced by an individual may even affect gene expression in offspring, with potentially broad influences including susceptibility to trauma.47,48 In this regard, clinicians should be thoughtful in obtaining a family history and also in considering supports and resources that may be appropriate for patients’ children and other family members.

Future Directions

Several researchers are exploring the potential value of an epigenetic perspective for the diagnosis and treatment of PTSD. Major areas of inquiry include whether epigenetic data could be used to identify populations at risk for developing PTSD, to help diagnose PTSD, and as biomarkers to predict who will respond to specific types of treatment. Early positive findings for each of these ideas have been shown in studies that examined military service members before and after deployment.49,50 Of particular interest, some patterns of methylation that are associated with PTSD were shown to be reversed during the course of psychotherapy, thus suggesting that, although epigenetic changes are enduring, they are not immutable.50

There is also interest in developing pharmacotherapies that could help modify epigenetic changes. The best-explored line of inquiry has examined histone deacetylase inhibitors. In animal models, these medications have been shown to augment fear extinction through multiple complex pathways, including brain-derived neurotrophic factor and N-methyl-d-aspartate receptor signaling.51 To date, these ideas have not translated into clinical populations, although sodium valproate seems to have some action as a histone deacetylase inhibitor, possibly accounting for some of its efficacy in a broad range of psychiatric disorders.52

Of course, the ideal intervention from an epigenetic perspective would be to implement interventions that either prevent early trauma and/or minimize its long-term impact.53Improved public health measures would be invaluable.

Theme 5: Genetic Considerations

As alluded to above, a central research question is why, in the face of trauma, only some individuals develop PTSD. Despite the disease being definitionally linked to an external event, research studies (eTable in the Supplement) have consistently shown that PTSD is highly heritable (approximately 40%-50%). Here, we would continue to emphasize that there are many nonbiological factors that may also confer risk or resilience. As far as identifying specific risk genes, findings to date have been mixed, likely reflecting methodological challenges, including the difficulty of achieving adequate sample sizes in which cases can be compared with trauma-exposed controls. The most promising findings have involved genes influencing molecules that are associated with neural plasticity (eg, brain-derived neurotrophic factor), neural inhibition (γ-aminobutyric acid), and stress response (glucocorticoids).54 A large, recent genome-wide association study reflecting more than 13 000 trauma exposed soldiers found no genome-wide significant loci in their main analysis. The investigators found the association of a single nucleotide polymorphism at genome wide significance in the ANKRD55gene (known to be involved in inflammatory and autoimmune disorders) only in African American participants. The authors of that study noted that their sample size may not have been adequately powered to detect other significant findings. The eTable in the Supplement highlights key findings pertaining to the recent genome-wide association study of unbiased genetic approaches to understanding PTSD.

As discussed above, and as with all patients, it is important to take a careful family history. Given the frequent role of guilt and self-blame as a core aspect of PTSD (now acknowledged in the DSM-5 criterion of “persistent, distorted cognitions about the cause or consequences of the traumatic event(s) that lead the individual to blame himself/herself or others”),4 discussing biological predisposing factors may be a valuable tool in the process of therapeutic communication.

Future Directions

A major obstacle in psychiatric practice today is that clinical diagnoses are based on behaviorally defined criteria that may encompass heterogeneous populations at a neurobiological level. The Research Domain Criteria project was created with the goal of understanding psychiatric illness based on relevant neurobiological domains.55 This parallels broader efforts—most notably in oncology—to move toward precision medicine.

From this perspective, understanding relevant genetic contributions serves 2 purposes. First, identifying genes implicated in PTSD may help researchers better understand underlying molecular mechanisms, which could inform the development of future treatments. Second, it is possible that patterns in gene expression may allow us to identify subgroups that are either at risk for PTSD or are more likely to respond to a specific treatment.

Caveats and Additional Perspectives

Throughout this article, we have discussed PTSD in a relatively generic manner, as if it were a single diagnostic entity. Of course, in psychiatry every case is unique, as is especially true with trauma. Factors that may affect both the incidence and severity of PTSD include type of trauma (eg, natural disasters vs assault vs motor vehicle accidents vs combat related), severity of the trauma (in conjunction with an individual’s pre-existing resilience/vulnerability), the cultural context of the event, and the individual’s perception and interpretation of the event. This last idea is especially relevant for cognitive models of PTSD (consider, as an example, the literature on “moral injury”56) and is also reflected in the considerable controversy regarding the update made to DSM-5 criteria.57

In addition, although we have generally discussed PTSD as a discrete condition, it is highly comorbid with other psychiatric illnesses, including depression and substance use disorders. Each of these possible diagnoses would carry its own implications for formulation and treatment planning.

Another important caveat with respect to neuroscience is that much of our understanding comes from animal models. Although useful in many ways, these models are also intrinsically limited. This point may be especially relevant to our discussion of fear conditioning, wherein the protocols used to induce fear conditioning in animals may differ greatly from the types of experiences that cause PTSD in our patients.

Finally, although we have selected 5 key themes to discuss, there are obviously other relevant domains. One especially important area relates to sleep, in which there is extensive literature on rapid eye movement disturbances that occur following trauma. Although findings have been variable, it is plausible that sleep disruption plays a central role in the development and/or persistence of PTSD symptoms.58

Conclusions

Modern neuroscience is leading to dramatic shifts in how we understand psychiatric illness. Amid this revolution, PTSD is one of the disorders (along with substance use disorders) for which we have the most compelling evidence relating to the underlying neurobiology.

In this article, we have highlighted 5 compelling neuroscience themes relevant to PTSD: the role of fear conditioning and associated processes (including extinction and negative reinforcement); a circuit-based perspective, with a central emphasis on the reciprocal inhibitory connections between the mPFC and the amygdala; the new concept of memory reconsolidation, suggesting that any time a memory is reactivated it becomes briefly labile and thereby amenable to strengthening or weakening; the role of epigenetics, including extensive data on how early traumatic experiences may lead to long-term dysregulation in the HPA axis; and the role of genetic factors in this highly heritable disease, opening doors for new research approaches and, perhaps, someday leading to a precision medicine–based approach.

Posttraumatic stress disorder reveals imbalance between signalling systems in the brain


PTSD
Regions of the brain associated with stress and posttraumatic stress disorder. 

Experiencing a traumatic event can cause life-long anxiety problems, called posttraumatic stress disorder. Researchers from Uppsala University and Karolinska Institutet now show that people with posttraumatic stress disorder have an imbalance between two neurochemical systems in the brain, serotonin and substance P. The greater the imbalance, the more serious the symptoms patients have.

Many people experience traumatic events in life, e.g. robbery, warfare, a serious accident or sexual assault. Approximately 10 percent of people subjected to trauma suffer long-lasting symptoms in the form of disturbing flashbacks, insomnia, hyperarousal and anxiety. If these problems lead to impairment, the person is said to suffer from , PTSD.

It has previously been shown that people with PTSD have altered brain anatomy and function. A new study by researchers from the Department of Psychology at Uppsala University and Clinical Neuroscience at Karolinska Institutet shows that people with PTSD have an imbalance between two neurochemical signalling systems of the brain, serotonin and substance P. Professors Mats Fredrikson and Tomas Furmark led the study using a so-called PET scanner to measure the relationship between these systems.

The study, which has been published in the renowned scientific journal Molecular Psychiatry, shows that it is the imbalance between the two signalling systems which determines the severity of the symptoms suffered by the individual rather than the degree of change in a single system. Others have previously speculated that the biological basis of psychiatric disorders such as PTSD includes a shift in the balance between different signalling systems in the brain but none has yet proved it. The results of the study are a great leap forward in our understanding of PTSD. It will contribute new knowledge which can be used to design improved treatments for traumatised individuals.

“At present, PTSD is often treated with selective serotonin re-uptake inhibitors (SSRIs) which have a direct effect on the serotonin system. SSRI drugs provide relief for many but do not help everybody. Restoring the balance between the and substance P systems could become a new treatment strategy for individuals suffering from traumatic incidents,” says lead author Andreas Frick, researcher at the Department of Psychology, Uppsala University.

PET/CT neuroimaging reveals pituitary abnormalities in veterans with PTSD


Hybrid neuroimaging of the pituitary region of the brain could help distinguish military veterans with posttraumatic stress disorder from those with mild traumatic brain injury, according to research presented at the annual meeting of the Radiological Society of North America.

Besides the utility of PET/CT in differential diagnosis, the findings support the notion that pituitary gland damage from blast injuries are causing hormonal irregularities affecting veterans diagnosed with posttraumatic stress disorder(PTSD).

“It’s important that providers as well as patients are aware of what might be causing these PTSD-like symptoms and that there are therapeutics that can help them if current therapies, such as antidepressants, anxiolytics and group therapy, aren’t helping,” Thomas M. Malone, a research associate at Saint Louis University School of Medicine, told Endocrine Today.

Malone and colleagues focused on 18F-fluorodeoxyglucose (18F-FDG) PET/CT, which measures uptake of the radiopharmaceutical FDG to show metabolism, in a retrospective review of 159 brain exam records; all PET images were obtained in the morning and adhered to standard brain PET/CT protocol. MRI scans of the brain were subsequently taken and given a structurally normal interpretation by a fellowship-trained neuroradiologist.

Cases were divided into three groups — normal control, traumatic brain injury(TBI) and TBI+PTSD — matched for age and sex. Based on criteria from the 2009 Department of Defense and Department of Veterans Affairs consensus definition of TBI, patients were further stratified by severity.

Two board certified nuclear medicine physicians masked to the groups read the PET/CT scans.

Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) of the pituitary gland and the hypothalamus were log-recorded. With approximately normal distributions and sufficiently large sample sizes, parametric tests were performed.

The SUVmax from the hypothalamus was lower in patients with TBI only vs. normal controls (5.78 vs. 6.46; P=.04). With TBI stratified by severity and limited to military veterans, the SUVmean from the pituitary was higher among patients with mild TBI+PTSD compared with those with mild TBI only (3.08 vs. 2.54; P=.04).

The higher FDG uptake demonstrated in the pituitary glands of patients with PTSD points to the possibility that some PTSD cases may actually be hypopituitarism masked, according to the researchers, in which case screening and treatment could help.

“I really hope it helps remove the stigma that many soldiers feel is attached to a PTSD diagnosis,” Malone said. “Being able to see that there is a physical, neurological injury caused by blast or a car accident should help remove any moral judgment about someone feeling depressed, anxious or continuing to experience fatigue or cognitive difficulties after a [TBI].” – by Allegra Tiver

PET/CT neuroimaging reveals pituitary abnormalities in veterans with PTSD


Hybrid neuroimaging of the pituitary region of the brain could help distinguish military veterans with posttraumatic stress disorder from those with mild traumatic brain injury, according to research presented at the annual meeting of the Radiological Society of North America.

Besides the utility of PET/CT in differential diagnosis, the findings support the notion that pituitary gland damage from blast injuries are causing hormonal irregularities affecting veterans diagnosed with posttraumatic stress disorder(PTSD).

“It’s important that providers as well as patients are aware of what might be causing these PTSD-like symptoms and that there are therapeutics that can help them if current therapies, such as antidepressants, anxiolytics and group therapy, aren’t helping,” Thomas M. Malone, a research associate at Saint Louis University School of Medicine, told Endocrine Today.

Malone and colleagues focused on 18F-fluorodeoxyglucose (18F-FDG) PET/CT, which measures uptake of the radiopharmaceutical FDG to show metabolism, in a retrospective review of 159 brain exam records; all PET images were obtained in the morning and adhered to standard brain PET/CT protocol. MRI scans of the brain were subsequently taken and given a structurally normal interpretation by a fellowship-trained neuroradiologist.

Cases were divided into three groups — normal control, traumatic brain injury(TBI) and TBI+PTSD — matched for age and sex. Based on criteria from the 2009 Department of Defense and Department of Veterans Affairs consensus definition of TBI, patients were further stratified by severity.

Two board certified nuclear medicine physicians masked to the groups read the PET/CT scans.

Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) of the pituitary gland and the hypothalamus were log-recorded. With approximately normal distributions and sufficiently large sample sizes, parametric tests were performed.

The SUVmax from the hypothalamus was lower in patients with TBI only vs. normal controls (5.78 vs. 6.46; P=.04). With TBI stratified by severity and limited to military veterans, the SUVmean from the pituitary was higher among patients with mild TBI+PTSD compared with those with mild TBI only (3.08 vs. 2.54; P=.04).

The higher FDG uptake demonstrated in the pituitary glands of patients with PTSD points to the possibility that some PTSD cases may actually be hypopituitarism masked, according to the researchers, in which case screening and treatment could help.

“I really hope it helps remove the stigma that many soldiers feel is attached to a PTSD diagnosis,” Malone said. “Being able to see that there is a physical, neurological injury caused by blast or a car accident should help remove any moral judgment about someone feeling depressed, anxious or continuing to experience fatigue or cognitive difficulties after a [TBI].” – by Allegra Tiver

New Study Validates EFT’s Effectiveness.


Story at-a-glance

  • Energy psychology uses a form of psychological acupressure, based on the same energy meridians used in traditional acupuncture to treat physical and emotional ailments for over 5,000 years, but without the invasiveness of needles
  • Recent research found that, compared to the control group, it significantly increased positive emotions, such as hope and enjoyment, and decreased negative emotional states like anger and shame
  • Another recent review found statistically significant benefits in using energy psychology for anxiety, depression, weight loss, PTSD, phobias, athletic performance, cravings, pain, and more
  • A review published in the American Psychological Association’s journal found that EFT “consistently demonstrated strong effect sizes and other positive statistical results that far exceed chance after relatively few treatment sessions”

Although frequently overlooked, emotional health is critical for your physical health and healing. No matter how devoted you are to the proper diet and lifestyle, you’re unlikely to achieve optimal health if emotional barriers stand in your way.

Energy psychology uses a psychological acupressure technique based on the same energy meridians used in traditional acupuncture (which has been used to treat physical and emotional ailments for over 5,000 years) but without the invasiveness of needles.

The Emotional Freedom Techniques (EFT) is the most popular form of energy psychology and was developed in the 1990s by Gary Craig, a Stanford engineering graduate specializing in healing and self-improvement. I routinely used EFT in my practice, and highly recommend it to optimize your emotional health.

The method involves tapping specific points on your head and chest with your fingertips while thinking about your specific problem—be it a traumatic event, an addiction, pain, etc.—and voicing positive affirmations. This can be done alone or under the supervision of a qualified therapist.1

The combination of tapping the energy meridians and voicing positive affirmation works to clear the emotional block from your body’s bioenergy system, thus restoring your mind and body’s balance.

Clinical trials have shown that EFT is able to rapidly reduce the emotional impact of memories and incidents that trigger emotional distress. Once the distress is reduced or removed, your body can often rebalance itself, and accelerate healing.

While some still view energy psychology with suspicion, EFT has actually met the criteria for evidence-based treatments set by the American Psychological Association for a number of conditions, including post-traumatic distress syndrome (PTSD).2

Research Validates EFT’s Effectiveness

In a critical review published in the American Psychological Association’s (APA) journal Review of General Psychology3 last year, researchers found that EFT “consistently demonstrated strong effect sizes and other positive statistical results that far exceed chance after relatively few treatment sessions.”

Other recent studies demonstrate how EFT can accomplish remarkable progress in a very short amount of time for people with a history of trauma. For example:

1.    A 2009 study4 of 16 institutionalized adolescent boys with histories of physical or psychological abuse showed substantially decreased intensity of traumatic memories after just ONE session of EFT.

2.    An EFT study5 involving 30 moderately to severely depressed college students was conducted. The depressed students were given four 90-minute EFT sessions. Students who received EFT showed significantly less depression than the control group when evaluated three weeks later.

Most recently, a study published in the Energy Psychology Journal6 confirmed that the benefits from EFT are the result of the tapping process and not a placebo effect. The study included 20 college students who were divided into two groups. One group did EFT while the control group received mindfulness training. Before and after the sessions, positive and negative emotions were assessed.

This included enjoyment, hope, pride, anger, anxiety, shame, hopelessness, boredom, and mindfulness. Overall, the EFT group experienced significantly greater increases in positive emotions, such as hope and enjoyment, along with greater decreases in negative emotional states like anger and shame. The study concluded that:

“No significant change was found for mindfulness. Tapping on acupoints, combined with the vocalization of self-affirming statements, appears to be an active ingredient in EFT rather than an inert placebo. The results were consistent with other published reports demonstrating EFTs efficacy for addressing psychological conditions in students.”

Tapping Alters Conditioned Responses

Such findings come as no great surprise to other researchers in the field, such as Dr. Dawson Church, Ph.D., founder of the National Institute for Integrative Healthcare. Dr. Church told the Examiner:

“We learn early on to disassociate from our emotions. EFT is a way that people can feel safe and empowered to process their emotions. When we tap and use affirmative statements, we can actually change our old conditioned responses.”

Earlier this year, Dr. Church published a review7 of more than 40 different EFT studies evaluating the effectiveness of the method. In his paper, he cites studies demonstrating the method’s effectiveness for a wide range of emotional problems, including:

Phobias

Post-traumatic stress disorder (PTSD)

Anxiety

Depression

Pain

Weight loss and food cravings

Athletic and academic performance

Test anxiety

 

Dr. Church’s website, ResearchEFTUniverse.com,8 is a great resource if you want to learn more about EFT and the research that has been done on each of these ailments, as well as other problems. According to Dr. Church:

“EFT has been researched in more than 10 countries, by more than 60 investigators, whose results have been published in more than 20 different peer-reviewed journals… EFT research includes investigators affiliated with many different institutions.”

It’s worth noting that as a general rule, the research being done on EFT is done using the techniques originally developed by Gary Craig.9 An expanding list of similar techniques has sprung up since then, and while they might provide similar benefits, EFT is the only empirically validated treatment version. (The APA defines an empirically validated treatment as one for which there are two different controlled trials conducted by independent research teams.)

Operation Emotional Freedom

EFT has shown particular promise in the treatment of war veterans with post-traumatic stress.10 I want to highlight this aspect of its use as PTSD is hard to treat, and studies have shown drugs like antidepressants and antipsychotics to be on par with placebo for the treatment of this condition.

The documentary film entitled Operation: Emotional Freedom,11 directed by Eric Huurre, follows a number of veterans and their families who went through intensive therapy using EFT. Gary Craig, along with other EFT practitioners worked very closely with veterans who were all suffering from PTSD, depression, anxiety and a few were suicidal. The results were truly astounding. At the end of treatment, each one of them describes a new feeling of peace and hope that there is help and they were able to overcome emotional traumas experienced in combat.

The film offers a close look at the current state of health care for combat veterans diagnosed with PTSD, and examines the myths and misconceptions surrounding the chemical approach to treating emotional conditions and why drugs are not “the answer” that pharmaceuticals promise. (You can learn more about the efforts to assist veterans and their families through energy psychology on the film’s website, operation-emotionalfreedom.com.12)

Research performed by the Iraq Vets Stress Project13 also demonstrates the effectiveness of EFT. In a study that included 100 veterans with severe PTSD,14 90 percent of the veterans had such a reduction in symptoms that they no longer met the clinical criteria for PTSD after six one-hour EFT sessions! Sixty percent no longer met PTSD criteria after just three EFT sessions. At the three-month follow-up, the gains remained stable, suggesting lasting and potentially permanent resolution of the problem.

How to Perform EFT

For a demonstration of how to perform EFT, please view the video below featuring EFT practitioner Julie Schiffman. This is a general demonstration that can be tailored to just about any problem. You can also find text instructions and photographs of where to tap on my EFT page. For when you’re on the go, there are at least four different EFT applications available in the iTunes store. The apps range from a simple recap of the EFTs Basic Recipe to a sophisticated virtual coaching app for specific mental health problems like anxiety and depression.

Bear in mind that while EFT is quite easy to learn and perform, I strongly encourage you to seek out a qualified therapist for more serious or complex issues. It is an art, and tapping for deep-seated issues typically require the kind of skill that only a well-seasoned practitioner will have. If you try to self-treat, you may end up falsely concluding that EFT doesn’t work, when nothing could be further from the truth… This is particularly pertinent if you’re trying to address trauma-based stress such as PTSD or grief following the loss of a loved one.

 

Mice can ‘warn’ sons, grandsons of dangers via sperm .


Lab mice trained to fear a particular smell can transfer the impulse to their unborn sons and grandsons through a mechanism in their sperm, a study reveals.

The research claims to provide evidence for the concept of animals “inheriting” a memory of their ancestors’ traumas, and responding as if they had lived the events themselves.

It is the latest find in the study of epigenetics, in which environmental factors are said to cause genes to start behaving differently without any change to their underlying DNA encoding.

“Knowing how ancestral experiences influence descendant generations will allow us to understand more about the development of neuropsychiatric disorders that have a transgenerational basis,” says study co-author Brian Dias of the Emory University School of Medicine in Atlanta, Georgia.

And it may one day lead to therapies that can soften the memory “inheritance”.

For the study, Dias and co-author Kerry Ressler trained mice, using foot shocks, to fear an odour that resembles cherry blossoms.

Later, they tested the extent to which the animals’ offspring startled when exposed to the same smell. The younger generation had not even been conceived when their fathers underwent the training, and had never smelt the odour before the experiment.

The offspring of trained mice were “able to detect and respond to far less amounts of odour… suggesting they are more sensitive” to it, says Ressler co-author of the study published in the journal Nature Neuroscience.

They did not react the same way to other odours, and compared to the offspring of non-trained mice, their reaction to the cherry blossom whiff was about 200 percent stronger, he says.

The scientists then looked at a gene (M71) that governs the functioning of an odour receptor in the nose that responds specifically to the cherry blossom smell.

Epigenetic marks

The gene, inherited through the sperm of trained mice, had undergone no change to its DNA encoding, the team found.

But the gene did carry epigenetic marks that could alter its behaviour and cause it to be “expressed more” in descendants, says Dias.

This in turn caused a physical change in the brains of the trained mice, their sons and grandsons, who all had a larger glomerulus – a section in the olfactory (smell) unit of the brain.

“This happens because there are more M71 neurons in the nose sending more axons” into the brain, says Dias.

Similar changes in the brain were seen even in offspring conceived with artificial insemination from the sperm of cherry blossom-fearing fathers.

The sons of trained mouse fathers also had the altered gene expression in their sperm.

“Such information transfer would be an efficient way for parents to ‘inform’ their offspring about the importance of specific environmental features that they are likely to encounter in their future environments,” says Ressler.

Happening in humans?

Commenting on the findings, British geneticist Marcus Pembrey says they could be useful in the study of phobias, anxiety and post-traumatic stress disorders.

“It is high time public health researchers took human transgenerational responses seriously,” he said in a statement issued by the Science Media Centre.

Focal point sperm cell entering a human egg depicting conception of child birth.

“I suspect we will not understand the rise in neuropsychiatric disorders or obesity, diabetes and metabolic disruptions generally without taking a multigenerational approach.”

Wolf Reik, epigenetics head at the Babraham Institute in England, says such results were “encouraging” as they suggested that transgenerational inheritance does exist, but cannot yet be extrapolated to humans.

 

‘Memories’ pass between generations


Generations of a family

Behaviour can be affected by events in previous generations which have been passed on through a form of genetic memory, animal studies suggest.

Experiments showed that a traumatic event could affect the DNA in sperm and alter the brains and behaviour of subsequent generations.

A Nature Neuroscience study shows mice trained to avoid a smell passed their aversion on to their “grandchildren”.

Experts said the results were important for phobia and anxiety research.

The animals were trained to fear a smell similar to cherry blossom.

The team at the Emory University School of Medicine, in the US, then looked at what was happening inside the sperm.

They showed a section of DNA responsible for sensitivity to the cherry blossom scent was made more active in the mice’s sperm.

Both the mice’s offspring, and their offspring, were “extremely sensitive” to cherry blossom and would avoid the scent, despite never having experiencing it in their lives.

Changes in brain structure were also found.

“The experiences of a parent, even before conceiving, markedly influence both structure and function in the nervous system of subsequent generations,” the report concluded.

Family affair

The findings provide evidence of “transgenerational epigenetic inheritance” – that the environment can affect an individual’s genetics, which can in turn be passed on.

One of the researchers Dr Brian Dias told the BBC: “This might be one mechanism that descendants show imprints of their ancestor.

“There is absolutely no doubt that what happens to the sperm and egg will affect subsequent generations.”

Prof Marcus Pembrey, from University College London, said the findings were “highly relevant to phobias, anxiety and post-traumatic stress disorders” and provided “compelling evidence” that a form of memory could be passed between generations.

He commented: “It is high time public health researchers took human transgenerational responses seriously.

“I suspect we will not understand the rise in neuropsychiatric disorders or obesity, diabetes and metabolic disruptions generally without taking a multigenerational approach.”

In the smell-aversion study, is it thought that either some of the odour ends up in the bloodstream which affected sperm production or that a signal from the brain was sent to the sperm to alter DNA.

Concurrent Naltrexone and Prolonged Exposure Therapy for Patients With Comorbid Alcohol Dependence and PTSDA Randomized Clinical Trial.


Importance   Alcohol dependence comorbid with posttraumatic stress disorder (PTSD) has been found to be resistant to treatment. In addition, there is a concern that prolonged exposure therapy for PTSD may exacerbate alcohol use.

Objective   To compare the efficacy of an evidence-based treatment for alcohol dependence (naltrexone) plus an evidence-based treatment for PTSD (prolonged exposure therapy), their combination, and supportive counseling.

Design, Setting, and Participants   A single-blind, randomized clinical trial of 165 participants with PTSD and alcohol dependence conducted at the University of Pennsylvania and the Philadelphia Veterans Administration. Participant enrollment began on February 8, 2001, and ended on June 25, 2009. Data collection was completed on August 12, 2010.

Interventions   Participants were randomly assigned to (1) prolonged exposure therapy plus naltrexone (100 mg/d), (2) prolonged exposure therapy plus pill placebo, (3) supportive counseling plus naltrexone (100 mg/d), or (4) supportive counseling plus pill placebo. Prolonged exposure therapy was composed of 12 weekly 90-minute sessions followed by 6 biweekly sessions. All participants received supportive counseling.

Main Outcomes and Measures   The Timeline Follow-Back Interview and the PTSD Symptom Severity Interview were used to assess the percentage of days drinking alcohol and PTSD severity, respectively, and the Penn Alcohol Craving Scale was used to assess alcohol craving. Independent evaluations occurred prior to treatment (week 0), at posttreatment (week 24), and at 6 months after treatment discontinuation (week 52).

Results   Participants in all 4 treatment groups had large reductions in the percentage of days drinking (mean change, −63.9% [95% CI, −73.6% to −54.2%] for prolonged exposure therapy plus naltrexone; −63.9% [95% CI, −73.9% to −53.8%] for prolonged exposure therapy plus placebo; −69.9% [95% CI, −78.7% to −61.2%] for supportive counseling plus naltrexone; and −61.0% [95% CI, −68.9% to −53.0%] for supportive counseling plus placebo). However, those who received naltrexone had lower percentages of days drinking than those who received placebo (mean difference, 7.93%; P = .008). There was also a reduction in PTSD symptoms in all 4 groups, but the main effect of prolonged exposure therapy was not statistically significant. Six months after the end of treatment, participants in all 4 groups had increases in percentage of days drinking. However, those in the prolonged exposure therapy plus naltrexone group had the smallest increases.

Conclusions and Relevance   In this study of patients with alcohol dependence and PTSD, naltrexone treatment resulted in a decrease in the percentage of days drinking. Prolonged exposure therapy was not associated with an exacerbation of alcohol use disorder.

Source: JAMA

Decriminalisation of psilocybin could help millions.


Previous studies have shown that low doses of psilocybin produce no consciousness state altering effects. Administered in the correct amount, psilocybin could therefore be assumed to safely treat PTSD with minimal risk of adverse side effects. Magic mushrooms could help millions recover from the debilitating cycles of fight and flight and other conditioned biological responses caused by extreme trauma, if only they weren’t listed as a dangerous Schedule 1 drug with no medical benefits.
Meanwhile, doctors are authorised to dispense powerful, side-effect laden pharmaceutical drugs to army vets and others suffering from the symptoms of PTSD without any evidence that these treatments actually work, according to a major review by the committee of the Institute of Medicine on the topic.

The situation is so bad that an average of 18 American veterans commits suicide every day (http://www.naturalnews.com), linked to the sharp rise in prescription drugs, depression, and other psychological conditions. Safe, natural alternatives to pharmaceuticals such as homeopathic and herbal remedies have been found to alleviate symptoms (http://www.naturalnews.com). Meditation has also been shown to reduce high activity levels in the amygdala (the brain’s emotional centre) experienced in PTSD sufferers as anxiety, stress and phobias.

Sources used in this article:

http://www.ptsdalliance.org

http://intellihub.com

http://digitaljournal.com

http://www.thedoctorwillseeyounow.com

Magic Mushrooms Repair Brain Damage From Extreme Trauma.


A new study by The University of South Florida has found that low doses of the active ingredient in magic mushrooms repairs brain damage caused by extreme trauma, offering renewed hope to millions of sufferers of PTSD (Post-Traumatic Stress Disorder).

The study confirms previous research by Imperial College London, that psilocybin, a naturally occurring compound present in “shrooms”, stimulates new brain cell growth and erases frightening memories. Mice conditioned to fear electric shock when hearing a noise associated with the shock “simply lost their fear”, says Dr. Juan Sanchez-Ramos, who co-authored the study. A low dose of psilocybin led them to overcome “fear conditioning” and the freeze response associated with it faster than the group of mice on Ketanserin (a drug that counteracts the receptor that binds psilocybin in the brain) and a control group on saline.

shroomery
An estimated 5 percent of Americans – more than 13 million people – have PTSD at any given time, according to the PTSD Alliance. The condition more often associated with combat veterans, is twice as likely to develop in women because they tend to experience interpersonal violence (such as domestic violence, rape and abuse) more often than men.

PTSD is not just psychological

Common symptoms, such as hyper-vigilance, memory fragmentation, flashbacks, dissociation, nightmares and fight or flight responses to ‘triggers’, are generally thought to be psychological and therefore treatable by learning to change thought processes. But new research suggests that they may in fact be the result of long term physiological mutations to the brain.

In the South Florida University study, the mice treated with low doses of psilocybin grew healthy new brain cells and their overactive medial prefrontal cortex regions (common in PTSD sufferers) were restored to normal functionality.

Further independent studies (http://www.thedoctorwillseeyounow.com ) have shown that the hippocampus part of the brain is damaged by extreme stress and that this is specific to PTSD and not associated with anxiety or panic disorders.

Dr. Sanchez-Ramos acknowledged that there was no way of knowing whether the mice in the experiment experienced altered states of consciousness or hallucinations – commonly experienced with magic mushrooms, but he believed the doses were too low to cause psychoactive effects.