Traumatic stress changes brains of boys, girls differently
Researchers have discovered that traumatic stress has a very different effect on girls than on boys. Specific differences in a certain - insula - brain area can be identified on scans.
Boys and girls react very differently to post-traumatic stress disorder (PTSD).
Researchers at Stanford University in the USA found structural differences in the brains of boys and girls with PTSD. The results were recently published in the journal Depression and Anxiety.
Children without trauma are the same
The researchers made an MRI scan of a total of 59 test subjects aged 9 to 17 years. 30 of these test subjects exhibited symptoms of trauma as a result of different experiences, while this was not the case with the 29 people in the control group.
All children and young people had a similar IQ.
There was no difference between the brains of boys and girls without trauma. But that was different with the kids who had experience a traumatic event.
Brain part shrinks in girls
Adolescent girls with PTSD appear to undergo accelerated maturation in a region of the brain that integrates emotions and actions.
The differences were seen in the insula brain area. This area is involved in traumatic experience.
The differences were seen in the insula brain area. This area is involved in the processing of emotions and in empathy.
The boys with PTSD had a larger insula - both in terms of mass and area - than boys in the control group. In girls with PTSD, the insula was smaller than that of girls without trauma.
Different treatments needed
Because the researchers have only studied the scans, they cannot yet say whether the difference affects, for example, the processing of emotions and empathy.
But according to research leader Megan Klabunde, the results may indicate that boys and girls show completely different trauma symptoms and may therefore benefit from a different treatment.
Source: Standord Childrens health
"Enough misery drives you crazy"
However, our understanding of the relationship between trauma and psychosis can still be considered as starting as a comparison, despite the evidence to provide a clear link between negative childhood experiences and psychotic symptoms (1-3). Moreover, only relatively recently have clinical interventions focused on the trauma and its consequences for people presenting with psychosis. This may be partly due to a historical focus on biological explanations for the development of psychotic disorders, but also to the perceived fear of clinicians to "open Pandora's Box" by talking to people with psychotic symptoms about their traumatic experiences and for fear of a stabilization risk and exacerbation of their symptoms (4). The prevalence of PTSD in people diagnosed with psychotic disorder is estimated at 30% compared to 7.8% in the general population (5), although this is underestimated because there is concern that trauma and PTSD are not reported and not be recognized at
persons with a serious mental illness (6). The relationship between psychosis and trauma is complex and multi-factorial with various suggested pathways. These include (1) psychosis due to childhood adversity (3), (2) trauma due to psychotic symptoms or involuntary treatment experiences (7, 8), (3) psychosis as a dimension of PTSD due to trauma (9) ), 10), and (4) PTSD and retraumatization as stressors that can aggravate the course of a psychotic disorder (11). In addition to the impact of trauma on the development of psychosis and PTSD, there are indications that traumatic experiences influence the content of psychotic symptoms, including hallucinations and delusions (2, 12). However, the mechanisms involved in these trajectories from trauma to psychosis and PTSD are not fully understood and various models have been made to make this link explicit.
Source: Frontiers in Psychiatry
Neuroimaging of child abuse: a critical assessment
Child abuse is a stressor that can lead to the development of behavioral problems and affect brain structure and function. This review summarizes the current evidence for the effects of child abuse on behavior, cognition and the brain in adults and children. Neuropsychological studies suggest a link between child abuse and IQ deficiencies, memory, working memory, attention, response inhibition and emotion discrimination. Structural neuroimaging studies provide evidence of brain volume, gray and white matter deficits in different regions, most prominently the dorsolateral and ventromedial prefrontal cortex
discussed, most notably the lack of control for comorbid psychiatric disorders, which makes it difficult to disentangle which of the aforementioned effects are due to abuse, the associated psychiatric disorders or a combination or interaction between the two. In general, the better controlled studies that show a direct correlation between child abuse and brain measurements suggest that the most notable deficits associated with early child abuse are in the function and structure of lateral and ventromedial frontal limbic brain areas and networks that conduct and affect to mediate
Emotions and the brain
The researchers discovered that the thickness of the myelin coating of a significant proportion of the nerve fibers was reduced only in the brains of those who had suffered from child abuse. They also found underlying molecular alterations that selectively affect the cells that are responsible for myelin generation and maintenance.
Finally, they found increases in the diameters of some of the largest axons among only this group and they speculate that together, these changes may alter functional coupling between the cingulate cortex and subcortical structures such as the amygdala and nucleus accumbens areas of the brain linked respectively to emotional regulation and to reward and
satisfaction) and contribute to altered emotional processing in people who have been abused during childhood.
The researchers conclude that adversity in early life may lastingly disrupt a range of neural functions in the anterior cingulate cortex. And while they don’t yet know where in the brain and when during development, and how, at a molecular level these effects are sufficient to have an impact on the regulation of emotions and attachment, they are now planning to explore this in further research.
The research appears in the American Journal of Psychiatry
Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [18F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs. healthy control (HCs) subjects. In an independent sample of human postmortem tissue, we investigated
expression of proteins that have a functional relationship with mGluR5 and glucocorticoids in PTSD. We observed significantly higher cortical mGluR5 availability in PTSD in vivo and positive correlations between mGluR5 availability and avoidance symptoms. In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD. Results of this study provide insight into molecular mechanisms underlying PTSD and suggest that mGluR5 may be a promising target for mechanism-based treatments aimed at mitigating this disorder.
New PTSD study identifies potential path to treatment
A study of post-traumatic stress disorder (PTSD) — conducted by the VA National Center for PTSD (NCPTSD), National PTSD Brain Bank, and Yale University — has identified a new potential mechanism contributing to the biology of the disorder that may be targeted by future treatments.
Among combat veterans, PTSD is a common and disabling condition that is associated with high suicide risk, and in some cases it is difficult to treat effectively. Patients — civilians with significant trauma history and veterans with combat-related or civilian trauma history — are commonly treated with a combination of psychological therapy and medications aimed at alleviating diverse symptoms, such as hyper-arousal and depression.
PET images indicating higher mGluR5 receptor availability in an individual with PTSD vs. a healthy comparison participant.
At present, there are two medications approved by the FDA for the treatment of PTSD symptoms, but the limited effectiveness of these medications results in patients being treated frequently with multiple medications that are not specifically approved for PTSD, note the researchers.
“We really need to examine what is happening at a molecular level so we can start developing novel efficacious therapies,” said Sophie Holmes, postdoctoral research associate in the Yale Department of Psychiatry and lead author of the study published in the Proceedings of the U.S. National Academy of Sciences.
The study, led by NCPTSD and Yale psychologist and PET imager Irina Esterlis, is the first to implicate a specific alteration in
brain glutamate signaling in PTSD. Glutamate is a chemical messenger of brain signals, and alterations in glutamate levels in PTSD were described previously. The new study reports that positron emission tomography (PET) scans show increased levels of a subtype of glutamate receptor in the brain, metabotropic glutamate receptor-5 (mGluR5), in patients with PTSD. In animals, overstimulation of mGluR5 is associated with fear and stress-related behaviors; drugs that reduce mGluR5 function may reduce these symptoms. Thus, the current study may have implications for the treatment of PTSD, said the researchers.This study also provided potential insights into how the increases in mGluR5 might arise. A novel and important feature of this study, according to the researchers, is that it is the first to link brain chemistry findings in patients with PTSD, as measured through PET scans, to detailed molecular analyses of brain changes in PTSD that can only be conducted in brain tissue that has been donated by veterans or their families for research purposes. The analyses, conducted in the laboratory of Yale neuroscientist Ronald Duman, found a clue at the level of gene expression, or the conversion of DNA to RNA. Messenger RNA (mRNA) levels of mGluR5 were not increased, but mRNA levels that code for the Shank1 protein were increased. Shank1 “activates” mGluR5 by linking them to the cell surface. The PET scans may have detected higher mGluR5 availability at the cell surface in PTSD.
“This study is one of the first examples to highlight the importance of the new National PTSD Brain Bank in enabling us to study the biology of PTSD at a deeper level. We have a long way to go to understand the complex neurobiology of PTSD, but these new research approaches should have a significant impact on the field”, said Esterlis.
Source: Yale News
A new theory about what really happens in PTSD brains
Building on research from the past, U-M scientists propose a uniform way to explain many of the symptoms and much of the neurobiology of PTSD.
Military dog tags
For decades, neuroscientists and doctors have tried to explain why only a few people are vulnerable to post-traumatic stress disorder and why they experience so many symptoms and disability.
Experts in the field now agree that PTSS indeed comes from very real, physical processes in the brain - and not from some psychological weakness.
But there is no clear consensus about what exactly these changed processes are.
In a perspective article published in Neuron, a few professors from the University of Michigan Medical School - who have studied many PTSD for years - say that people with PTSD seem to suffer from disturbed context processing. Context processing is a central brain function that allows people and animals to recognize that a particular stimulus may require different responses depending on the context. It is what enables us to get an appropriate emotional or physical response to every encounter we have.
The professors hope to stimulate interest in the theory and invite others in the field to test it.
A story of two lions
A simple example, they write, is recognizing that a mountain lion seen in a zoo does not require the same fear-of-flight response as when it is unexpectedly encountered in the wild.
For someone with PTSD, a stimulus associated with the trauma they have experienced previously - such as a loud sound or a certain smell - causes an anxiety reaction, even if the context is safe. That is why they react even when the hard sound of the front door was slammed and no gunshot, or the smell comes from the dinner that is accidentally burned on the fire and not from a fire.
Context processing includes the hippocampus of the brain and the connections with two other regions, the prefrontal cortex and the amygdala.
Research has shown that the activity in these areas of the brain is disrupted in PTSD patients. The U-M team believes that their theory can unite extensive evidence by showing how a disruption in this circuit can disrupt the processing of the context and explain most of the symptoms and a large part of the PTSD biology.
"We hope to create some order in all information collected on PTSD from studies of human patients and animal models of the disorder," says Israel Liberzon, MD, professor of psychiatry at UM and a researcher at the VA Ann Arbor Healthcare System, who also treats veterans with PTSD.
"We hope to create a testable hypothesis that is not as common in mental health research as it should, and if this hypothesis is true, we may be able to unravel some of the underlying pathophysiological processes and offer better treatments."
Israel Liberzon, MD professor of psychiatry who treats veterans with PTSD
"If this hypothesis comes true, we might be able to unravel some of the underlying pathophysiological processes and offer better treatments."
Israel Liberzon, M.D.
A unifying theory of PTSD
Liberzon and his colleague, James Abelson, M.D., Ph.D., describe models of PTSD that have emerged in recent years and provide evidence for each. The problem, they say, is that not enough the different symptoms are explained, nor all the complex neurobiological changes that are observed in patients with PTSD and in animal models of this condition.
The first model, abnormal learning from fear, is rooted in the amygdala - the 'fight-or-flight' center of the brain - that focuses on responses to threats or safe environments. This model arose from working on anxiety conditioning, fear extinguishing and anxiety generalization.
The second, exaggerated detection of threats, is rooted in the brain areas that find out which signals from the environment are 'salient', or important to pay attention to and respond to. This model focuses on vigilance and disproportionate responses to perceived threats.
The third, with regard to the executive function and regulation of emotions, is mainly rooted in the prefrontal cortex - the center of the brain to control and plan emotions or to switch between tasks.
By focusing only on the evidence that supports one of these theories, researchers can "search under the streetlight", says Liberzon. "But if we look at everything in the light of the disruption of context processing, we can explain why different teams have seen different things, they do not exclude each other."
The most important thing, says Liberzon, is that "context is not only information about your environment, but also evokes the right emotion and memories for the context in which you find yourself".
The "detached" feeling
A shortage in context processing can lead people with PTSD to feel 'unloved' of the world around them, unable to shape their answers to fit into their current context. Instead, their brain would impose an internalized context - one that always expects danger - in every situation.
This type of deficiency, which arises in the brain through a combination of genetics and life experiences, can in the first place create vulnerability to PTSD, they say. After trauma, it would generate symptoms of hypervigilance, insomnia, intrusive thoughts and dreams, and inappropriate emotional and physical outbursts.
Liberzon and Abelson say that testing the context processing theory will increase the understanding of PTSD, even if all its details are not verified. They hope that the PTSD community will help them in the pursuit of the necessary research, in PTSD patients and in animal models. They place specific ideas in the Neuron paper to encourage this and start such research themselves.
The U-M / VA team are currently recruiting people with PTSD - veterans or not - for brain imaging studies and other tests. Interested parties can call 734-232-0190.
In the meantime, they note that there are a growing number of therapeutic tools that can help patients with PTSD, such as cognitive behavior therapy, training in the field of mindfulness and pharmacological approaches. These can help by anchoring PTSD patients in their current environment and can be more effective as researchers learn how to specifically strengthen the processing capacities in the brain.
Source: M Health Lab
How traumatic memories remain hidden in the brain and how they can be found
By Marla Paul on August 17, 2015
3d Illustration of a nerve cell on a colored background with light effects
A new study has shown for the first time that the neurotransmitter pathways that enable stressful memories of anxiety become consciously inaccessible.
Some stressful experiences - such as chronic abuse of children - are so overwhelming and traumatic that the memories hide like a shadow in the brain.
In the beginning, hidden memories that cannot be consciously evoked can protect the individual from the emotional pain of remembering the event. But ultimately, those suppressed memories can cause debilitating psychological problems such as anxiety, depression, post-traumatic stress disorder, or dissociative disorders.
A process known as state-dependent learning is supposed to contribute to the formation of memories that are inaccessible to normal consciousness. Thus, memories formed in a certain mood, excitement or drug-induced state are best recalled when the brain is back in that state.
In a new study with mice, researchers from Northwestern Medicine have for the first time discovered the mechanism by which state-dependent learning deliberately makes stress-sensitive memories inaccessible.
"The findings show that there are multiple routes to storage of anxious memories and we have found an important one for anxiety-related memories," said lead researcher Jelena Radulovic, MD, PhD, Dunbar Professor in Bipolar Disease in Psychiatry and Behavioral Sciences and Pharmacology. "This could eventually lead to new treatments for patients with psychiatric disorders who require conscious access to their traumatic memories if they want to recover."
It is difficult for therapists to help these patients, Dr. Radulovic said, because the patients themselves cannot remember their traumatic experiences that are causing their symptoms.
The best way to access the memories in this system is to bring the brain back to the same state of consciousness as when the memory was coded, according to the study published in Nature Neuroscience.
The radio frequencies of the brain change
Two amino acids, glutamate and GABA, are the yin and yang of the brain, drive the emotional tides and check whether nerve cells are excited or inhibited (calm). The system is balanced under normal circumstances. But if we are hyper-aroused and vigilant, glutamate thrusts. Glutamate is also the primary chemical that stores memories in our neuronal networks in a way that they are easy to remember.
GABA, on the other hand, calms us and helps us sleep and blocks the action of irritable glutamate. The most used sedative drug, benzodiazepine, activates GABA receptors in our brains.
A new study has shown for the first time that the neurotransmitter pathways that enable stressful memories of anxiety become consciously inaccessible.
There are two types of GABA receptors. One type, synaptic GABA receptors, works in combination with glutamate receptors to balance brain excitation in response to external events such as stress.
The other population, extra-synaptic GABA receptors, are independent agents. They ignore the peppy glutamate. Instead, their work is internally focused, adjusting brain waves and mental states according to the levels of internal chemicals such as GABA, sex hormones, and micro-RNAs. Extra-synaptic GABA receptors change the state of the brain to make us excited, sleepy, alert, numb, drunk or even psychotic. Northwestern scientists, however, discovered another important role; these receptors also help to encode and then store memories of a frightening event, hidden from consciousness.
"The brain functions in different states, just like a radio works on AM and FM frequency bands," Dr. said. Radulovic. "It seems like the brain is normally tuned to FM stations to access memories, but needs to be tuned to AM stations to open unconscious memories. If a traumatic event occurs when these extra-synaptic GABA receptors are activated , the memory of this event cannot be accessed unless these receptors are reactivated, essentially tuning the brain to the AM stations. "
Recall stressful memories from mice
In the experiment, scientists injected the hippocampus of mice with gaboxadol, a drug that stimulates extra-synaptic GABA receptors. "It's like we're making them a little drunk, just enough to change their brain status," Dr. said. Radulovic.
The mice were then put in a box and given a short, mild electric shock. When the mice were returned to the same box the next day, they moved freely and were not afraid, indicating that they did not remember the previous shock in the room. However, when scientists put the mice back on the drug and put them back in the box, she froze, anxiously anticipating another shock.
"This determines when the mice were returned to the same brain state as by the drug, they remembered the stressful experience of shock," said Dr. Radulovic.
The experiment demonstrated when the extra-synaptic GABA receptors were activated with the drug
Source: M Northwestern medicine
Study reveals areas of the brain affected by PTSD
Researchers from the Boston University School of Medicine (BUSM) and the VA Boston Healthcare System are one step closer to understanding the specific nature of changes in the brain associated with Posttraumatic Stress Disorder (PTSD).
The findings, which appear in the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, can lead to a better diagnosis and treatment of the condition.
PTSD is a psychiatric disorder that follows a traumatic event and is characterized by flashing (or re-experiencing trauma), avoiding thoughts / feelings associated with the trauma and hyperarousal or hypervigilance. It has been known for some time that persons suffering from PTSD have abnormalities in the structure and function of the brain, but more recently it has become clear that PTSD is also associated with changes in how brain regions communicate with each other. In particular, PTSD has been associated with disruptions in the communication of a network of brain regions involved in internally directed forms of mental activity, such as during spontaneous thinking.
Led by evidence that this network can be divided into different parts with specialized functions, Danielle R. Miller, PhD and her colleagues have studied communication within this network of brain regions in more detail.
Sixty-nine recurring war veterans with PTSD and 44 veterans with a history of trauma but without PTSD underwent functional Magnetic Resonance Imaging (fMRI) of the brain to measure brain activity through blood flow. The researchers discovered that disruptions of the aforementioned network in veterans with PTSD specifically influenced communication between brain areas involved in memory.
In addition, they found that the less these areas of the brain communicated with each other, the more people with PTSD exhibited avoidance symptoms, such as avoiding trauma-related thoughts or feelings, avoiding trauma memories, avoiding trauma situations, or inability to think, remember certain aspects of the trauma.
"This study emphasizes that disturbances in communication between brain areas involved in memory may be an important mechanism in PTSD. Although this study was not a treatment study, our research suggests that treatments aimed at improving this communication may improve PTSD symptoms," Miller explained.
Miller believes that every step towards identifying mechanisms that contribute to PTSD is important and crucial for improved care for people suffering from the condition.
Source: Bosten University Medical Center
Mechanism behind EMDR therapy clarified
11 May 2017 - Making eye movements suppresses a brain area that stores memories. A therapy based on eye movements (EMDR) can help to forget stressful events. This is the conclusion of researcher Linda de Voogd of Radboudumc. She will be promoting her research on the recall and forgetting of stressful events on 11 May.
We often remember stressful or emotional events much better than everyday events. These memories are sometimes so strong that they develop into post-traumatic stress disorder (PTSD). Earlier research showed that Eye Movement Desensitization and Reprocessing (EMDR) therapy reduced memories of stressful events, but the mechanism of action remained unclear. De Voogd has now clarified that.
How eye movements forget stressful events
Consider stressful events better
Eye Movement Desensitization and Reprocessing (EMDR) therapy is a treatment in which you make simple eye movements and at the same time evoke the unpleasant memories. This therapy is regularly used in people with PTSD. To find out how traumatic memories can develop, De Voogd first investigated why stressful
events are better remembered than neutral events. De Voogd: "In healthy subjects, changes in the brain in the period after a stressful event play a major role in remembering the events. In this period, the brain plays the memories again and thus they are stored better.
"Forgotten by eye movements"
To intervene in this process of replay, De Voogd looked at whether making eye movements can reduce the memory. The Guardian compared the brain activity during the making of eye movements with the brain activity at rest. She discovered that when you make eye movements, a specific area of the brain involved in storing memories, the amygdala, is suppressed. "The suppression of this area makes us forget the memories that are recalled. The eye movements attract your full attention, so you can no longer pay attention to the memory, "says the Guardian.
Certain medication can also suppress the amygdala, but now it appears that simple eye movements can do the same. De Voogd hopes that clarifying the mechanism of action behind EMDR therapy will lead to more acceptance. "Until now it was known that the therapy works, but not yet how. Now that the mechanism of action is known, this will probably offer new opportunities to improve therapy. "
Trauma, psychosis, PTSD and the use of EMDR
- D.P.G VAN DEN BERG
- B.M. VAN DER VLEUGEL
- A.B.P. STARING
The interactions between trauma, psychosis and PTSD are complex. There is a large mutual influence, cohesion and overlap, making it sometimes difficult to distinguish from each other. It is clear that bad life experiences may play an important role in the genesis of psychosis. By traumatic experiences that underlie hearing the voices or to negative conclusions about the person (e.g. "I'm vulnerable) or others (e.g.," others cannot be trusted "), complaints reduction can be achieved. A follow-up with regular CBT for psychosis is almost always necessary. In addition, a considerable part of the patients with psychoses have the burden of post-traumatic stress symptoms. We recommend treating these patients with treatment-focused CBT and EMDR, especially when the patient asks for it. When diagnosing PTSD there arises a problem: the A criterion. A prerequisite for diagnosing PTSD is that the physical integrity of the person is threatened , or that he has seen it up close to one another. He also had to be overwhelmed by feelings of fear, horror and helplessness. There may also be a PTSD if the situation was not really threatening, but was only perceived as such? We think so. Designated psychotherapeutic treatment, or CGT EMDR. There are many
reasons why practitioners do not ask about trauma in the history of patients with psychoses (for an overview, Read et al., 2007, p. 104). One of the most important is the fact that many practitioners wrongly fear the consequences of discussing trauma. In addition, many clinicians doubt the veracity of the memories from patients with psychoses. But while distortions occur, patients with schizophrenia turn out to be reliable in the trauma which they report. They tend to more likely even to under- than over-reporting of traumata (Goodman et al., 1999;. Meyer et al, 1996). And although it is known that patients are not inclined to start from themselves about traumas, they do expect that social worker asked them about it. Most patients (and lay) see traumatic life experiences, namely as the main cause of psychoses (Read, Rudegeair, & Farrelly, 2006). It is for that reason alone useful to talk during treatment about trauma.
We hope that you will after reading this article you are somewhat aware of the major role that bad life experiences can have in the lives of people with psychoses, that you think sooner about PTSD in patients with psychoses and you take a step faster toward treatment of such complaints with the Directive EMDR
Journal of Neuroscience: Cortisol further considered
30-09-2016 NIJMEGEN - After a stressful event the cortisol level in the body rises. It was always assumed that this hormone contributes to the stress response. Now a study by brain researchers at Radboud University Nijmegen shows that cortisol suppresses sensitivity to stress. When stressed, the amygdala, the emotional alarm in the brain, becomes extra active and ensures that all sorts of substances are released that bring the body to a state of preparedness.
Cortisol is one of the substances that increases during such a reaction and is therefore always used as a 'stress indicator'. Now the research shows that this hormone works just to rest the body and the brain after exposure to stress. Very important, because the body does not stop being constantly alert. If the recovery fails, there is a risk of PTSD and depression.
For the study, 72 male subjects were given cortisol either a few hours before they entered the fMRI scanner, or shortly before they received a placebo.
In the scanner they were shown faces whose expression changed from neutral to scared or cheerful. It is known that this evokes an emotional reaction in the brain. Compared to the placebo group, the group that received cortisol shortly before showed a greatly reduced response of the amygdala to both emotions. The group that received cortisol longer in advance showed a normal reaction to the negative emotions, but still a reduced response to the positive emotions. The body is thus the first to restore the sensitivity to 'danger'. From a survival perspective, this is easily explained: the amygdala can then respond to a new threat.
The study is published in the Journal of Neuroscience.
Time to leave the bio-bio-bio model of psychosis: Exploring the epigenetic and psychological mechanisms that lead to psychotic symptoms due to potentially negative events in life
John Read, Richard P. Bentall and Roar Fosse
For decades, mental health care and research have been dominated by a rather simplistic, reductionist focus on biological phenomena, with minimal consideration of the social context in which genes and brains inevitably work. This 'medical model' ideology, enthusiastically supported by the pharmaceutical industry, has been particularly powerful in the field of psychoses, where it has led to an unjustified and harmful pessimism about recovery. Failure to find convincing evidence of a genetic predisposition to psychosis in general or schizophrenia in particular, can be understood in terms of recently developed knowledge about how
epigenetic processes gene transcription is switched on and off via mechanisms that are strongly influenced by individual social-environmental experiences. In order to understand the emerging evidence of the relationship between unwanted childhood events and subsequent psychosis, it is necessary to integrate this epigenetic, especially those where the stress control functions of the HPA axis, with research into the psychological mechanisms that can lead to specific types of childhood trauma to specific types of psychotic experiences. The implications for research, mental health care and primary prevention are profound.
Source: Epidemiology and Psychiatric Sciences
Psychosis, trauma en trauma related psychopathology m. van gerven, o. van der hart, e.r.s. nijenhuis, t. kuipers
Systematic clinical or scientific research show that many psychotic patients report trauma and trauma-related psychopathology. Solely because traumatic experiences could adversely affect the course of the psychosis, it is appropriate to identify and treating them equally in psychoses as in other psychiatric disorders. It must be noted that, in the scarce empirical research in relations between psychosis, trauma and trauma-related psychopathology, trauma is not clearly defined and possible links between psychosis and emotional neglect have not yet been studied. Furthermore there is insufficient use of of structured interviews and the validity of the reported trauma is not determined. Nor there had been done research what the influence is of the severity, duration and age at onset of these experiences. Experiencing a psychosis is often a very stressful experience that can lead to post-traumatic stress disorder. So it is worth considering to add a serious harm to the mental integrity of the stressorcriterium A of PTSD in the next version of the DSM. Psychotic symptoms are often difficult to distinguish from post-traumatic stress
Prof Onno van de Hart
symptoms and dissociative symptoms, resulting in diagnostic confusion and probably inadequate treatment. The use of a structured interview to identify PTSD and dissociative disorders, however, appears to be a important contribution in differential diagnosis. In further research one should examine how to make a difference between positive symptoms of psychosis and dissociative symptoms. There are indications that the overlap between psychotic and dissociative symptoms is particularly strong in patients who report child abuse by relatives. Empirical research should reveal whether this interdependence of symptoms warrants a separate diagnostic category 'reactive dissociative psychosis.'
The impact of psychological trauma more than PTSD alone?
Ruud A. Jongedijk Working on a concept
The last word about PTSD as a diagnostic category will not be said for the time being, not even after the establishment of the DSM-V. How should a practitioner in practice continue? The important thing is to realize that a DSM diagnosis is not a real diagnosis. It's a format, an often arbitrary combination of symptoms, which says nothing about the individual client. For a treatment indication a DSM classification is inadequate. For diagnostics, it is important to take a good anamnesis and be aware of the dangers of the DSM system (Jongedijk 001). In any case, it is important in making a anamnesis to make not a quick DSM-classification. Usually the diagnosis is top-down in practice. In other words, one 'finds' some symptoms, or a trauma, and goes from there continue searching for the other symptoms, which are necessary in order to make the diagnosis. Symptoms that do not fit are being set aside. The use of impairment-specific diagnostic questionnaires are top down diagnostics. Especially with traumatized clients one quickly is moving towards the diagnosis of PTSD,
whereas this is not always the case. Here occurs a bias, which is a side effect of the PTSD concept (Rosen et al 2008) and in general of the DSM system. The impact of psychological trauma: more than PTSD alone?
In short, with top-down diagnosis one is rapidly working towards a specific diagnosis as PTSD where many symptoms of being overlooked. Therefore, in accordance with good diagnostic principles, the diagnosis should not be top-down but should be taken place bottom-up A good examination of all complaints of the client should take place and only then classify and diagnose all possible diagnostic capabilities, justify the complaints of the client (McHugh and Treisman 2007). Diagnosis has implications for the treatment process. And evidence-based treatment is highly dependent on - evidence based - diagnostics, which should take place bottom-up. This article is adapted from a lecture held at the congress of the Dutch Association for Psychological Trauma, November 28, 2007.
Chronic stress changes the dendritic morphology in the medial prefrontal cortex of the rat.
Cook SC1, Wellman CL.
Chronic stress produces cognitive disorders accompanied by changes in neural chemistry and morphology. Median prefrontal cortex is a target for glucocorticoids involved in the stress response. We have previously shown that 3 weeks of daily corticosterone injections result in a dendritic reorganization in pyramidal neurons in layer II-III of the medial prefrontal cortex. To determine whether similar morphological changes occur in response to chronic stress, we assessed the effects of daily limiting stress on dendritic morphology in medial prefrontal cortex. Male rats were exposed to 3 hour limiting stress daily for 3 weeks or left untreated except during weighing during this period. On the last day of restriction, the animals were overdosed and
the brains were stained using a Golgi-Cox procedure. Pyramidal neurons in lamina II-III of medial prefrontal cortex were drawn in three dimensions and the morphology of apical and basal arbours was quantified. Sholl analyzes showed a significant change of apical dendrites in stressed animals: in general, the number and length of apical dendritic branches decreased by 18 and 32%, respectively. The reduction of the apical dendritic arbor was limited to distal and higher order branches and may be a reflection of the atrophy of terminal branches: the number and length of the terminal branch were reduced by 19 and 35%. On the other hand, basal dendrites were not affected. This pattern of dendritic reorganization is comparable to that after daily corticosterone injections. This reorganization probably reflects functional changes in the prefrontal cortex and may contribute to stress-induced changes in cognition.
New psychiatric disorder often erroneously seen as schizophrenia
Date of the message: 17 September 2013
Researchers from the UMC St Radboud, the AMC and GGZ organization Pro Persona seem to have discovered a new psychiatric disorder: posttraumatic stress disorder (PTSD) with secondary psychotic features. Patients with this serious disorder are often wrongly diagnosed with schizophrenia, which means that they do not receive proper treatment. Psychotic PTSD has other characteristics and should be treated differently than schizophrenia, according to Mario Braakman in his doctoral thesis on which he will be awarded a PhD on 18 September.
One in a hundred people goes around with the diagnosis of schizophrenia. This number hardly differs per country and has been remarkably stable for years. In this group of patients there are quite a few people with post-traumatic stress disorder (PTSD) with secondary psychotic characteristics instead of schizophrenia, according to the above-mentioned researchers. But this diagnosis is often missed by doctors and psychiatrists because they mistakenly judge the symptoms as schizophrenia. How many patients are involved is still unclear, but estimates go to ten percent.
New psychiatric disorder
In the Netherlands too, quite a few patients are diagnosed with PTSD, while insufficient attention has been paid to secondary psychotic characteristics such as delusions and hallucinations. A post-traumatic stress disorder with secondary psychotic characteristics is a serious clinical picture with symptoms other than 'ordinary' PTSD or schizophrenia and should therefore be treated differently, says psychiatrist Mario Braakman, PhD student at the psychiatric department at UMC St Radboud and head instructor psychiatry at Pro Persona in Wolfheze. 'That is why it is important to recognize this new psychiatric disorder.'
Refugees and asylum seekers
Braakman carried out his doctoral research for an important part at Phoenix, a specialized psychiatric clinic of Pro Persona in Wolfheze. 'Psychiatrists sent patients from all over the country to whom they often did not come from, mainly traumatized refugees and asylum seekers. We are the only clinic in the Netherlands that deals with very complex psychiatric disorders. Centrum '45 also does this for complex psychotrauma complaints, but only for people with PTSD. The psychotic patients therefore all come to us. '
Delusions and hallucinations
The investigated refugees and asylum seekers had first developed a post-traumatic stress disorder and then, sooner or later, developed psychotic symptoms - hence the indication PTSD with secondary psychotic characteristics. Their delusions and hallucinations were found
to be very poorly treated with antipsychoticmedication. Neither turned out to be the case. Psychotic PTSD, as he abbreviated the clinical picture, is a new psychiatric diagnosis that requires specific treatment. Psychotic PTSD is a complex and serious disease. The right treatment for this should be studied even better, but Braakman expects a lot of behavioral therapies such as EMDR (Eye Movement Desensitisation and Reprocessing), an intervention technique that is often used in people with post-traumatic stress disorder. In the US, positive results were achieved with exposure therapies, in which people are exposed to the traumatic experience.
Atom bomb in Tokyo
It is especially important that doctors and psychiatrists recognize the symptoms of psychotic PTSD and make the correct diagnosis. According to Braakman, the distinction between schizophrenia and psychotic PTSD is relatively easy to make. There are three important differences. For example, delusions and hallucinations in psychotic PTSD are rarely bizarre in content, as in schizophrenia. "For example, a schizophrenic patient may think that people can walk through a wall, or that an atomic bomb explodes in Tokyo when he pulls his little finger. In psychotic PTSD delusions always have a relationship with the traumatic experience. For example, someone who has been tortured by the KGB sees KGBers standing behind trees. '
Furthermore, patients with schizophrenia or with psychotic PTSD usually have additional psychiatric disorders, but in psychotic PTSD they are three times as high as in schizophrenia. You also rarely see formal thinking disorders in psychotic PTSD, such as schizophrenia. 'Schizophrenic patients often talk incoherently without any form of logic. You can not see that with psychotic PTSD. These three variables can correctly predict in which group a patient falls in ninety percent of the cases. '
How many patients with psychotic PTSD are wrongly diagnosed with schizophrenia has never been properly investigated in the Netherlands, Braakman notes. 'Estimates in the US show that of the' schizophrenic 'patients between ten and fifty percent also have a post-traumatic stress disorder, which is rarely recognized. Some of these patients will not have schizophrenia but psychotic PTSD, but how many there are are also unknown. It is time for this to be investigated. 'Braakman and his colleagues would have liked to see the diagnosis of PTSD with secondary psychotic characteristics included in the DSM-V, the manual for psychological and psychiatric disorders. They also submitted a proposal for this. 'Unfortunately we never heard anything about it again' / press release UMC St Radboud
Factual or artificial? A psycho-biological study of authentic and simulated dissociative identity states.
Reinders AA1, Willemsen AT, Vos HP, de Boer JA, Nijenhuis ER.
Dissociative identity disorder (DID) is a disputed psychiatric disorder. Research results and clinical observations suggest that DID has an authentic mental disorder related to factors such as traumatization and impaired attachment. A competitive view indicates that DID is the result of fantasy affiliation, suggestibility, suggestion, and role play. Below, we examine whether dissociative identity-state-dependent psychobiological characteristics can be induced in DID in highly or low-fantasy-sensitive individuals through informed and motivated role play and suggestion.
METHODOLOGY / PRINCIPLE BINDING:
DID patients, high fantasy sensitive and low fantasy sensitive controls were examined in two different types of identity states (neutral and trauma related) in an autobiographical memory script-driven (neutral or trauma-related) imagery paradigm. The controls were taught to enter the two DID identity states
Twenty-seven subjects participated in the study: 11 patients with DID, 10 high fantasy-sensitive DID simulation controls and 8 low-fantasy sensitive DID-simulating controls. Autonomic and subjective responses were obtained. Differences in psychophysiological and neural activation patterns were found between the DID patients and both high and low fantasy sensitive controls. That is, the identity states in DID were not convincingly assumed by DID to simulate checks. For example, important differences in regional cerebral blood flow and psychophysiological responses for different types of identity states in patients with DID were maintained after control for DID simulation.
Conclusions / IMPORTANCE:
The findings are in conflict with the idea that differences between different types of dissociative identity states in DID can be explained by high fantasy inclination, motivated role statement and suggestion. They point out that DID has no sociocultural (eg iatrogenic) origin.
Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD
Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by intrusive and persistent memories of a psychologically traumatic event that leads to significant functional and social impairment in affected individuals. The molecular bases underlying persistent outcomes of a transient traumatic event have remained elusive for many years, but recent studies in rodents have implicated epigenetic modifications of chromatin structure and DNA methylation as fundamental mechanisms for the induction and stabilization of fear memory. In addition to mediating adaptations to traumatic events that ultimately cause PTSD, epigenetic mechanisms are also involved in establishing individual differences in PTSD risk and resilience by mediating long-lasting effects of
genes and early environment on adult function and behavior. In this review, we discuss the current evidence for epigenetic regulation of PTSD in human studies and in animal models and comment on ways in which these models can be expanded. In addition, we identify key outstanding questions in the study of epigenetic mechanisms of PTSD in the context of rapidly evolving technologies that are constantly updating and adjusting our understanding of epigenetic modifications and their functional roles. Finally, we discuss the potential application of epigenetic approaches in identifying markers of risk and resilience that can be utilized to promote early intervention and develop therapeutic strategies to combat PTSD after symptom onset.
Source: Front Psychiatry
Gene expression and methylation features of MAN2C1 are associated with PTSD
Authors: Uddin, Monica | Galea, Sandro Chang, Shun-Chiao Aiello, Allison E. | Wildman, Derek E. | de los Santos, Regina | Koenen
Affiliations: Department of Epidemiology, University of Michigan School of Health, Ann Arbor, MI, USA Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, USA Departments of society, human development and health and epidemiology, Harvard School of Public Health, Boston, MA, USA and the center for the developing child, Harvard University, Cambridge, MA, USA | Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA
Abstract: As potential regulators of the accessibility and activity of DNA, epigenetic modifications provide a mechanism by which the environment can determine the effects of genes. To date, however, there have been relatively few studies evaluating epigenetic changes related to post-traumatic stress disorder (PTSD). Below we investigate PTSD-associated methylation differences in 33 genes that previously appeared to be different from blood samples derived genetic expression between them with and without PTSD.
On DNA samples obtained in the same way from whole blood of 100 individuals, 23 with and 77 without PTSS life span, we used methylation microarray data to assess whether these 33 candidate genes showed epigenetic signatures that showed the risk or resilience of PTSD. . Logistic regression analyzes were performed to assess the main and interaction effects of the methylation values of candidate genes and the number of potential traumatic events (PTEs), for age and other covariates to be adjusted. The results show that only one candidate gene - MAN2C1} has demonstrated a significant methylation x PTE interaction, so those with both higher MAN2C1 methylation and greater exposure to PTEs have a marked increase in the risk of PTSD lifetime (OR 4.35, 95 % CI: 1.07, 17.77, p = 0.04). These results indicate that MAN2C1 methylation levels adjust the cumulative traumatic burden to the risk of PTSD and suggest that both gene expression and epigenetic changes at specific loci are associated with this condition.
The relevance of epigenetics for PTSD: Implications for the DSM-V
This work was supported by a VA Merit Review Grant (RY), a NIMH Innovation Award RO1 Genetics, Endocrinology and PTSD Risk in the Population (RY), and funding from the Department of Defense (RY). The authors thank Dr. Janine Flory for reading and commenting on this manuscript.
Epigenetic modifications, such as DNA methylation, can occur in response to environmental influences to change the functional expression of genes in a persistent and potentially intergenerational transmittable way. As such, they can explain interindividual variation, as well as the long-term effects of trauma exposure.
Although there are currently no findings suggesting epigenetic changes specific to posttraumatic stress disorder (PTSD) or PTSD risk, many recent observations are compatible with epigenetic explanations. These include recent findings of stress-related gene expression, contributions from the womb of infant biology, the association of PTSD risk in mothers with PTSD and the relevance of childhood in the development of PTSD. The relevance of epigenetic mechanisms for formulations of PTSD for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is described
DNA methylation regulates reward associative learning
Reward-related memories are essential for adaptive behavior and evolutionary fitness, but they are also a core component of maladaptive brain diseases such as addiction. Reward learning requires dopamine neurons in the ventral tegmental area (VTA), which code the relationships between predictive signals and future rewards. Recent evidence suggests that epigenetic mechanisms, including DNA methylation, are essential regulators of neuronal plasticity and experiential behavioral change. However, the role of epigenetic mechanisms in rewarding learning is poorly understood. Here we show that the formation of reward-related associative memories in rats upregulates important plasticity genes in the VTA, which are correlated with memory strength and are associated with gene-specific changes in DNA methylation.
In addition, DNA methylation in the VTA is required for the formation of stimulus-reward associations. These results provide the first evidence that this activity-dependent methylation and demethylation of DNA is an essential substrate for the behavioral and neuronal plasticity driven by reward-related experiences.
Considering the above, I suspect that dendrite formation in memory networks works in the same way, in other words that mythylation of the DNA, produces RNA that ensures dendrite development and thus the formation of a new or adapted memory. It is therefore important to see how medicines can contribute to therapy during processing in traumas. How can we adjust the epigenetic tags - methylation - so that there is more processing and reinforcement of resilience.