Bipolar4LifeSupport

Depression is almost twice as common, and poor quality of life almost five times as common, in people with bipolar disorder who have elevated or low levels of the stress hormone cortisol in the blood. Researchers at Umeå University, Sweden, report this in a study published in the journal PLOS ONE.

“In bipolar depression the stress system is often activated, which means that the affected individuals have elevated cortisol levels in the blood. We have now been able to show that both over- and underactivity in the stress system, with corresponding elevated or reduced cortisol levels, can impair mental health in terms of depression and poor quality of life in these patients,” says Martin Maripuu, a PhD student at the Department of Clinical Sciences, Psychiatry Unit Umeå University and physician at the psychiatric clinic, Ostersund Hospital.

Bipolar disorder is a lifelong disease that causes recurrent episodes of both mania and depression. Stress is a known trigger for these episodes, and depression and mania also adds to the accumulated stress load.

One of the body’s main stress systems is the HPA axis. This system regulates the production and level of the vital stress hormone cortisol. Cortisol is a hormone that everyone needs in everyday life in order to cope with various stressful situations, such as pain, illness and stress at work.

Stress causes overactivity in the stress system, resulting in elevated levels of cortisol. If the stress continues in the long-term, it is believed to cause an underactivity in the stress system, which results in low cortisol levels.

Previous studies have shown that the stress system is often overactive in patients with bipolar depression. To investigate the relationship between cortisol levels and depression among these patients, the researchers at Umeå University conducted a study with 145 patients who had bipolar disorder, as well as 145 people in a control group. The researchers measured cortisol levels in the participants, both under normal conditions and after the participants had completed a so-called dexamethasone suppression test, which is sensitive to early abnormalities in the stress system.

The results of the study show that more than half of the patients with bipolar disorder who had elevated or low levels of cortisol in the blood, also had depression. Depression was additionally almost twice as common in those who had high cortisol levels and in those who had low cortisol levels, compared with those who had normal levels of the hormone in the blood. Prevalence of low quality of life was six times more common in the group with low cortisol levels and nearly five times more common among those with high cortisol levels, compared with those who exhibited normal activity in the stress system.

The study also shows that people who had low cortisol levels, on average, have had their disease longer than those with high cortisol levels, which could suggest that chronic stress in bipolar disorder can lead to an “exhaustion” of the stress system with reduced cortisol levels as a result. The researchers also believe that the low cortisol levels, once developed, can contribute to a more chronic, manifested state of the disorder.

“These are important results that in the future could contribute to a more personally tailored medical treatment of bipolar disorder. The results may also ultimately lead to the development of new drugs that work by normalizing the stress system and cortisol levels,” says Martin Maripuu.

Scientists at Yerkes National Primate Research Center, Emory University have identified a drug that appears to make memories of fearsome events less durable in mice.

The finding may accelerate the development of treatments for preventing PTSD (post-traumatic stress disorder). The drug, called osanetant, targets a distinct group of brain cells in a region of the brain that controls the formation and consolidation of fear memories.

The results were published in the journal Neuron.

“Potentially, drugs that act on this group of cells could be used to block fear memory consolidation shortly after exposure to a trauma, which would aid in preventing PTSD,” says Kerry Ressler, MD, PhD, professor of psychiatry and behavioral sciences at Emory University School of Medicine and Yerkes National Primate Research Center. “PTSD is unique among psychiatric disorders in that we know when it starts – at the time of the trauma. Finding ways to prevent its development in the first place – in the emergency department or the battlefield – is an important and exciting avenue of research in this area.”

The first author of the paper is postdoctoral fellow Raül Andero Galí, PhD. Ressler and Andero were sifting through a list of many genes that are activated in the brains of mice after they learn to become afraid of a sound, because the sound is paired with a mild electric shock. The researchers were probing for changes in the central amygdala, a region of the brain known to regulate fear learning.

Out of thousands of genes they examined, their “top gene” was Tachykinin 2 or Tac2. The Tac2 gene was turned on more strongly during fear learning in mice that were previously exposed to a model of traumatic stress.

“The Tac2 gene is robustly activated after fear learning and belongs to a pathway that can be specifically blocked with a drug,” Ressler says. “It was interesting that Tac2 is highly expressed in one particular part of the amygdala, but with low or no expression in other brain areas related to the formation of fear memories. Also, we found that the cells that express Tac2 are distinct from those other investigators had previously identified as being involved in fear expression.”

Tac2 is part of a family of messengers in the nervous system known as tachykinins. Drugs that block a product encoded by Tac2’s relative, Tac1, are antiemetics, often prescribed when someone is receiving chemotherapy for cancer.

Osanetant, which blocks the action of Tac2, has been tested in previous clinical studies for schizophrenia and was safe but not effective in addressing that disorder. It has not been tested in humans for PTSD prevention.

“Osanetant is a safe and well-tolerated drug in humans and could be potentially used to prevent PTSD when given shortly after trauma, although more research is needed,” Andero says.

Under the influence of osanetant, mice could still learn to become afraid of a sound paired with a shock, but the mice did not freeze as much in response to the sound a day later, even if the drug was given an hour after training.

“Our goal is to specifically impair emotional memories related to a traumatic event instead of all memories associated with it. Thus, the trauma and its circumstances are remembered but the consolidation of fear memories is impaired, which could decrease the likelihood of developing fear-related disorders,” Andero says.

For children, stress can go a long way. A little bit provides a platform for learning, adapting and coping. But a lot of it – chronic, toxic stress like poverty, neglect and physical abuse – can have lasting negative impacts.

A team of University of Wisconsin-Madison researchers recently showed these kinds of stressors, experienced in early life, might be changing the parts of developing children’s brains responsible for learning, memory and the processing of stress and emotion. These changes may be tied to negative impacts on behavior, health, employment and even the choice of romantic partners later in life.

The study, published in the journal Biological Psychiatry, could be important for public policy leaders, economists and epidemiologists, among others, says study lead author and recent UW Ph.D. graduate Jamie Hanson.

“We haven’t really understood why things that happen when you’re 2, 3, 4 years old stay with you and have a lasting impact,” says Seth Pollak, co-leader of the study and UW-Madison professor of psychology.

Brain Stress
Different forms of early life stress, such as child maltreatment or poverty, impacted the size of two important brain regions: the hippocampus (shown in red) and amygdala (shown in green), according to new University of Wisconsin-Madison research. Children who experienced such stress had small amygdalae and hippocampai, which was related to behavioral problems in these same individuals.
Credit: Image courtesy of Jamie Hanson and Seth Pollak

Yet, early life stress has been tied before to depression, anxiety, heart disease, cancer, and a lack of educational and employment success, says Pollak, who is also director of the UW Waisman Center’s Child Emotion Research Laboratory.

“Given how costly these early stressful experiences are for society … unless we understand what part of the brain is affected, we won’t be able to tailor something to do about it,” he says.

For the study, the team recruited 128 children around age 12 who had experienced either physical abuse, neglect early in life or came from low socioeconomic status households.

Researchers conducted extensive interviews with the children and their caregivers, documenting behavioral problems and their cumulative life stress. They also took images of the children’s brains, focusing on the hippocampus and amygdala, which are involved in emotion and stress processing. They were compared to similar children from middle-class households who had not been maltreated.

Hanson and the team outlined by hand each child’s hippocampus and amygdala and calculated their volumes. Both structures are very small, especially in children (the word amygdala is Greek for almond, reflecting its size and shape in adults), and Hanson and Pollak say the automated software measurements from other studies may be prone to error.

Indeed, their hand measurements found that children who experienced any of the three types of early life stress had smaller amygdalas than children who had not. Children from low socioeconomic status households and children who had been physically abused also had smaller hippocampal volumes. Putting the same images through automated software showed no effects.

Behavioral problems and increased cumulative life stress were also linked to smaller hippocampus and amygdala volumes.

Why early life stress may lead to smaller brain structures is unknown, says Hanson, now a postdoctoral researcher at Duke University’s Laboratory for Neuro Genetics, but a smaller hippocampus is a demonstrated risk factor for negative outcomes. The amygdala is much less understood and future work will focus on the significance of these volume changes.

“For me, it’s an important reminder that as a society we need to attend to the types of experiences children are having,” Pollak says. “We are shaping the people these individuals will become.”

But the findings, Hanson and Pollak say, are just markers for neurobiological change; a display of the robustness of the human brain, the flexibility of human biology. They aren’t a crystal ball to be used to see the future.

“Just because it’s in the brain doesn’t mean it’s destiny,” says Hanson.

In 2011, the United States Military repealed its “don’t ask, don’t tell” policy that prevented gay and lesbian service members from disclosing their sexual orientation. Current estimates indicate that more than 1 million veterans identify as lesbian, gay or bisexual (LGB). Now, a University of Missouri researcher says these service members and veterans often are marginalized and may benefit from mental health professionals, including social workers, who are informed about the needs of individuals who identify as LGB.

“Identifying as LGB and serving in the military can provide a distinct set of experiences and challenges for individuals,” said Michael Pelts, a doctoral student at the School of Social Work in the MU College of Human Environmental Sciences. “Within the U.S., identifying as a service member or veteran can marginalize individuals. This is also true for people who identify as LGB. The impact may be compounding. For example, suicide has a high occurrence rate among veterans and even more so among veterans who identify as LGB.”

Pelts said studies show that the majority of LGB service members and veterans who seek mental health care services do so outside of Veterans Affairs.

“Social workers in the public and private sectors make up the largest group of mental health service providers to veterans and their families,” Pelts said. “It is likely that social workers will continue to see current and new generations of veterans struggling with their sexual identity and with the impact of internal and societal stigmas related to identifying as LGB. Therefore, mental health professionals need to be equipped to care for members of this population.”

Social workers and other mental health providers should challenge their cultural assumptions when treating clients who are veterans or service members, Pelts said.

“It’s not ethically sound practice to assume that all service members and veterans are heterosexual,” Pelts said. “Assuming individuals are heterosexual can compound stress for LGB individuals and make them less likely to share information, which can make it more difficult for health professionals and mental health providers to provide adequate care.”

Pelts said health providers should adopt practices to be more inclusive to veterans who identify as LGB. Part of increasing inclusivity includes simple changes such as modifying medical history forms and in-take documents. By using more inclusive terminology, individuals who identify as LGB may feel less alienated, Pelts said.

“It is essential for mental health professionals to create culturally competent practice approaches,” Pelts said. “Social workers have a tremendous opportunity, if not ethical responsibility, to be leaders in the provision of mental health services for LGB service members, veterans and their families.”

Pelts recently wrote, “Veterans Mental Health: Implication for Services With Gay Men and Lesbians Who Have Served,” which was published in Social Work in Mental Health.

A new register-based study from Karolinska Institutet in Sweden shows that drug therapy for ADHD does not entail an increased risk of suicide attempts or suicide, as was previously feared. The results are published in the British Medical Journal (BMJ).

“Our work in several ways shows that most likely there is no link between treatment with ADHD drugs and an increased risk of suicide attempts or suicide. The results rather indicate that ADHD drugs may have a protective effect,” says Henrik Larsson, researcher at the Department of Medical Epidemiology and Biostatistics, who headed the study.

Earlier research has indicated that ADHD drug treatment would increase the occurrence of suicidal thoughts. However, these studies have been small scale and/or the methods used have been limited, which make the results uncertain. To gain clarity in this matter, researchers at Karolinska Institutet have now used national patient registers to identify all patients in Sweden diagnosed with ADHD between 1960 and 1996; a total of 37,936 individuals. These people were then followed over the period 2006-2009, in terms of drug treatment and events that could be linked to suicide attempts and suicide.

Among other things, the study compared the rate of suicidal behaviors while the patients were receiving ADHD medication, as compared with the rate for the same patients while not receiving medication. Using this design the researchers were able to determine that there was no evidence to support that ADHD drug therapy would increase the risk of suicide attempts/suicide. One strong point of the study now being published is that all the individuals were compared to themselves, as this allowed the researchers to take into account the differences between those taking the drugs and those who do not.

“Many epidemiological studies on the risks related to drugs fail to adjust for the differences between individuals who take the drugs and those who do not. This is a critical limitation given that the individuals on medication are usually more severely ill than the others,” says Henrik Larsson.