Mental Health

NARSAD-Funded Research Identifies How Early Trauma Changes the Brain and Can Cause PTSD

NARSAD-Funded Research Identifies How Early Trauma Changes the Brain and Can Cause PTSD

A PET image of the anterior cingulate, a region of the brain that is involved in emotion controls. The brighter colors in the “Healthy Controls” image (left)indicate more activity points to a higher number of 1b receptors than in the PTSD (middle) and PTSD+MDD (right) groups.

NARSAD-Funded Research Identifies How Early Trauma Changes the Brain and Can Cause PTSD

Alexander Neumeister, M.D., NARSAD 2007 Independent Investigator, leads largest PET study on PTSD

A PET image of the anterior cingulate, a region of the brain that is involved in emotion controls. The brighter colors in the “Healthy Controls” image (left)indicate more activity points to a higher number of 1b receptors than in the PTSD (middle) and PTSD+MDD (right) groups.

 Dr. Alexander Neumeister, Department of Psychiatry, Mount Sinai School of Medicine, tracks the response of stress on the serotonin system in the brain and discovers that people who experience trauma early in life have a lower number of serotonin 1B receptors than healthy controls. Dr. Neumeister representsa generation of researchers that brings together biology and psychology to identify underlying causes and improve treatments of brain and behavior disorders. With a NARSAD Independent Investigator grant in addition to a Merit award from the Department of Veterans Affairs (VA), a grant from the VA Center on PTSD and two grants from National Institutes of Health, Dr. Neumeister undertook the largest Positron Emission Tomography (PET) study to date of individuals with PTSD to understand how stress affects their brains.

PET brain imaging technology allowed Dr. Neumeister and his team to take two-hour movies of how the brain works. Of specific interest to Dr. Neumeister and his team are serotonin type-1B receptors. These receptors influence various biological and neurological processes, such as aggression, anxiety, cognition, memory and mood. Dr. Neumeister’s study included 96 participants – 49 individuals with PTSD, 20 individuals exposed to early trauma without PTSD and 27 healthy “controls” (participants not traumatized). Of the patients experiencing trauma, each lived through their first trauma at 15.

A main finding of Dr. Neumeister’s study was that the serotonin system is involved in stress response and people who experience trauma earlier in life have a lower number of 1B receptors than healthy controls. Additionally, the earlier someone is traumatized, their PTSD symptoms are more severe and there is a greater occurrence of PTSD being accompanied by another disorder like major depression. This is the first time a neurobiological correlation in brain function and behavioral alterations in PTSD has been made, proof that the brains of people with PTSD work differently.

“Some people think, ‘What does PTSD have to do with the brain?’” Dr. Neumeister said. “This study shows that the trauma people experience affects the brain.” His team shows that the trauma itself and not the symptoms are related to neurobiological messages.

Dr. Neumeister’s goal is ultimately to identify pathological processes and find targets for treatments. The efficacy of the only class of drugs – SSRIs (selective serotonin reuptake inhibitors) – approved for treating PTSD is limited, Dr. Neumeister explained.

Discovering the Brain’s Role in Resiliency and Susceptibility to Stress

Amelia J. Eisch, Ph.D., NARSAD 2010 Independent Investigator, seeks to understand resiliency in order to find ways to prevent and treat stress-related illnesses like PTSD

NARSAD Independent Investigator Dr. Amelia J. Eisch at the University of Texas Southwestern Medical Center at Dallas seeks to explain why some individuals exposed to extreme stress are more susceptible to developing major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), and more resilient individuals exposed to similar levels of stress are not.

She and her team have discovered that weeks after experiencing a stressful event, mice that were more susceptible to stress exhibited enhanced neurogenesis – the birth of new neurons in the brain. Specifically, the neurons that these animals produced after a stressful event survived longer than new brain cells produced by mice that were more resilient to the stress.

While much research has explored how stress influences neurogenesis, little work has been done on the long-lasting effects of stress on neurogenesis after the stress is over. Also, no research has explored whether stress leads to long-lasting adaptations in adult hippocampal neurogenesis that directly affects behavior.

The hippocampus, a brain region critical for memory, is exquisitely responsive to stressful experiences, making it an excellent target for explorations into the neurobiology of resilience. Interestingly, new brain cells are generated in the hippocampus throughout life. Scientists have discovered that this “adult hippocampal neurogenesis” is decreased by stressful experiences, stimulated by antidepressant therapeutics like running, and may contribute to hippocampal functions. Such connections have led researchers to further explore the contribution of adult neurogenesis to mood regulation and even the response to antidepressant treatment.

In this study, when Dr. Eisch and her team prevented neurogenesis in both stress-susceptible and resilient mice, the animals previously susceptible to stress became more resilient, highlighting the direct correlation between neurogenesis and behavior traits. In mice exposed to a prolonged stressful psychosocial experience called social defeat, without the prevention of neurogenesis, susceptible mice displayed behavioral and physiological indices reminiscent of MDD and PTSD and avoided an aggressor mouse in a social environment, while resilient mice did not.

“This work shows that there is a period of time during which it may be possible to alter memories relevant to a social situation by manipulating adult-generated neurons in the brain,” Dr. Eisch said. “Understanding the neurobiological underpinnings of this variable response to stress has enormous potential to enhance our comprehension, treatment and even prevention of stress-related disorders like MDD and PTSD.”


A Person with Mental Illness, not a Mentally Ill Person

Donna Morrissey invests in brain and behavior research hoping for development of better diagnostic tools for people, like her son, living with mental illness

The misdiagnosis of Donna Morrissey’s son, Michael, mobilized her as an advocate for mental health research.

At 22, Michael started to experience auditory hallucinations and was feeling increasingly threatened, Morrissey said. One day he heard a hostile voice while alone at work and called his mother. Donna and Michael went to the emergency room and Michael was admitted to the hospital.

Based on his symptoms and his father’s history of treatment for schizophrenia, Michael was diagnosed with schizophrenia and began treatment. Morrissey noted that the diagnosis of her ex-husband’s illness was “assumed” – doctors were hesitant to diagnose him with schizophrenia because he didn’t fully fit the profile, but they didn’t know how else to respond to his symptoms. She believes doctors initially responded to Michael’s symptoms by basing their diagnosis primarily on his father’s history.

Following a month of treatment, with no improvement and with his symptoms getting worse, Michael went back to his outpatient psychiatrist and said he didn’t think schizophrenia was the correct diagnosis. Michael soon had another episode where he was in crisis, his mother said, which resulted in another trip to the emergency room. This time, a new team of physicians evaluated Michael and came to the conclusion that he was more likely suffering from post-traumatic stress disorder (PTSD).

With this new diagnosis and a different course of treatment, “the results were amazing,” Morrissey said. “It struck me then that the diagnosis process is faulty. What quantitative result or test leads to a diagnosis? The more researchers can identify and develop the right criteria to distinguish one mental illness from another, the more defined and effective a treatment can be.”

Added to the weight of the diagnosis was the fact that Michael did not have health insurance at the time.

“It’s very frustrating when someone you care about is struggling with something and there’s nothing you can do,” Morrissey said. But Donna Morrissey was far from inactive. Her son’s struggle with PTSD and his looming medical bills prompted her to host a benefit concert.

Michael’s PTSD also sent Morrissey to the Internet where she found NARSAD. “NARSAD was one of the only organizations speaking of mental illness in positive and hopeful terms,” Morrissey said. “I thought, ‘Finally, somebody gets it!’ These are solvable problems, not a diagnosis that says, ‘Close the book on your life.’”

Morrissey’s Benefit Concert for Mental Health donates proceeds from the event to NARSAD to support the mental health research she believes is so important. “As I watched everything Michael was going through I decided this was what needed more support – researchers digging to find better diagnostic tools to improve people’s lives,” Morrissey said. “Another benefit to better diagnostic tools will be to improve the response of health care professionals to people’s symptoms.”

Michael’s PTSD finds its roots in childhood trauma. From elementary school through high school, Michael was bullied by his peers. Michael’s mother wasn’t aware of the full extent of the bullying. “The problem with bullying is that there is pressure to not tell people about what’s going on,” Morrissey observed. “One of the first things children hear when they begin school is to not be a tattle-tale. And if you don’t want to make the situation worse, you won’t say anything.”

Michael’s behaviors in school were different from his classmates’ because Michael is partially deaf, is dyslexic and has other nonverbal learning disabilities, Morrissey said. “He did not fit in with the cultural norm. Children who were more aggressive recognized, and took advantage of, his more passive personality.” Michael became a target and so began years of name calling, pushes and shoves, violent physical threats, and ongoing fear for his safety.

The trauma from years of bullying added to the normal pressures Michael faced in life, and led to his development of PTSD, which is now successfully treated with therapy and medication. “Michael is doing well,” his mother said. “He works full time and is engaged to be married. He is trying to turn his negative experience with bullying into a positive one and is thinking about how he can share his experience with children and schools.”

“I’m very proud of him and his resiliency to move beyond his challenges and not let those define him,” Morrissey said. “He’s a person with mental illness, not a mentally ill person.”

The third annual Benefit Concert for Mental Health will be held May 13, 2011 at Daylesford Abbey in Paoli, Pennsylvania.

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