Posts Tagged ‘mental health’

by David N. Osser, MD

Current estimates are that 4% to 5% of the population is at risk for a disorder on the bipolar spectrum. Among the patients in the so-called soft portion of that spectrum are those with a disturbance of temperament in the direction of hypomania.

The concept of temperament is a product of German nosological research from a century ago starting with Kraepelin. In the US, the concept has been championed by Hagop Akiskal, MD and his colleagues. Akiskal is now the editor emeritus of the Journal of Affective Disorders. The notion of depressive temperament has been incorporated into DSM-5 nosology in the form of “persistent depressive disorder” (previously called dysthymia). The other pole was called hyperthymia by the Germans. DSM committees have considered adding hyperthymia but have not done so. The research base on it is still, to many, unconvincing. However, it seems that in clinical practice one encounters individuals who have chronic low-grade hypomanic symptoms—high energy, need for less sleep than others, chronic optimism, chronic risk taking. These individuals can be prone to major depressions and can become severely suicidal.

Akiskal and colleagues have been describing these patients for almost 40 years. Their research criteria for hyperthymic temperament include onset before age 21, habitual sleep of less than 6 hours even on weekends, excessive use of denial, and traits (described originally by Schneider et al) that include being overoptimistic, self-assured, grandiose, overtalkative, warm and people-seeking, uninhibited, promiscuous, and meddlesome (1). Neurobiological studies have suggested the individuals have dopaminergic dysregulation (2),

Treatment issues have focused on what medications to use when hyperthymic individuals become depressed. The studies have all been uncontrolled. However, it seems that antidepressants are ineffective for these depressions and often trigger a mixed state or frank mania at times. Mood stabilizers and medications effective for bipolar depression may be more appropriate for the depressions in these patients.Usually their sunny temperament itself doesn’t require treatment and may, in fact, foster excellent productivity and creativity during much of their lifespan.

Disclosures:
Dr Osser is a Consulting Psychiatrist, US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, MA.

References:
1. Akiskal HS, Mallya G. Criteria for the “soft” bipolar spectrum: treatment implications. Psychopharmacol Bull. 1987;23:68-73.

2. Rihmer Z, Akiskal KK, Rihmer A, Akiskal HS. Current research on affective temperaments. Curr Opin Psychiatry. 2010;23:12-18.

by Bruce Jancin

The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

https://www.the-hospitalist.org/hospitalist/article/207875/depression/statins-may-do-double-duty-antidepressants?channel=51329

by Lisa Rapaport

Kids who have more supportive experiences with family, friends, and people in their school and community may be less likely to have psychological or relationship troubles in adulthood, a new study suggests.

Adverse childhood experiences (ACEs) like abuse, neglect, violence, and parental absence have long been linked to lasting negative effects on physical and mental health, researchers note in JAMA Pediatrics. But less is known about whether positive experiences make it easier for kids to cope, or what happens with children whose lives have mix of negative and positive experiences

For the current study, researchers surveyed 6,118 adults about how often in childhood they felt able to talk to family and friends about feelings; felt their family stood by them during difficult times; enjoyed participating in community traditions; felt a sense of belonging in high school; felt supported by friends; had at least two nonparent adults who took an interest in them; and felt safe and protected by an adult in their home.

Overall, adults who reported six to seven of these positive childhood experiences were 72% less likely to have depression or at least 14 poor mental health days each month than adults who reported no more than two positive childhood experiences. Even three to five positive experiences were tied to a 50% lower likelihood of depression or poor mental health than two or fewer.

These associations held true even when respondents reported multiple adverse childhood experiences.

“The absence of the types of positive childhood experiences we assessed in our study is very stressful for a child,” said lead study author Christina Bethell of the Bloomberg School of Public Health at Johns Hopkins University in Baltimore.

“Without positive nurturance, children’s stress hormones can get stuck on high and this impacts how their brain develops in ways that can make it hard for them to experience safety, relaxation and to become open, curious and learn to have positive relationships with others,” Bethell said by email.

The association between positive life experiences and better adult mental health and relationships persisted even among people who experienced ACEs during childhood.

Compared to participants who reported no more than two positive childhood experiences, people who experienced six to seven positive childhood experiences were also more than three times more likely to report that as adults, they “always” got the social and emotional support they needed.

When people had no more than two positive childhood experiences, only about one-third reported always getting the social and emotional support they needed – even when they didn’t have a history of ACEs.

The study doesn’t prove that positive childhood experiences impact adult mental health or relationships.

“In fact, people with poor mental health might be less likely to view their childhood experiences as positive,” said Dr. Rebecca Dudovitz, a researcher at the David Geffen School of Medicine at the University of California Los Angeles.

“It might actually be that adults with depression remember their childhood differently than adults without depression,” Dudovitz, who wasn’t involved in the study, said by email.

Parents may not be able to prevent adverse childhood experiences, but they can help kids become resilient, said Dr. Angelica Robles, a developmental-behavioral pediatrician at Novant Health in Charlotte, North Carolina, who wasn’t involved in the study.

“Parents can accomplish this by simply talking about feelings with their children, standing by their children during difficult times, and showing interest in their daily lives,” Robles said by email. “The child will then feel safe, and it is in this sense of security in the face of stress that the child learns to flourish.”

https://www.reuters.com/article/us-health-childhood/positive-childhood-experiences-tied-to-better-adult-mental-health-idUSKCN1VU2CP

An ambitious research project aims to assess the state of mental-health resources and support for graduate students. The 22-month initiative is a joint venture of the Council of Graduate Schools (CGS) in Washington DC and the Jed Foundation, a non-profit organization in New York City that focuses on the mental health of young adults. The initiative will explore current schemes and programmes centred on student wellness at CGS member universities in the United States and Canada, and provide recommendations for future approaches to promote mental and emotional well-being in students.

“We want to create a road map for moving forward,” says Suzanne Ortega, CGS president and the principal investigator of the project, called Supporting Mental Health and Wellness of Graduate Students. “We’ll be offering advice about policies and resources that will help students in crisis while also creating an environment where graduate students can thrive.”

The project, supported by nearly US$280,000 in grants from the Alfred P. Sloan Foundation and the Andrew W. Mellon Foundation, will gather input through surveys of administrators at CGS’s 500 or so member institutions across the world, along with focus groups that will probably involve students as well as those advocating on behalf of students. A key part of the conversation will take place at a workshop for students, administrators and mental-health specialists that is tentatively scheduled for October next year in Washington DC. An initial report of findings and recommendations for policies is scheduled to be published in December next year.

Unmet needs

The pressure, competition and stress experienced by graduate students puts them at high risk for mental-health issues, Ortega says. Precise estimates of the prevalence of anxiety and depression in this population remain elusive, she notes, and graduate students need and deserve thoughtful, evidence-based support. “We’re convinced by the need,” she says. “We know that a significant minority of graduate students have clinical symptoms of distress.”

Nance Roy, the Jed Foundation’s chief clinical officer, says that few effective mental-health programmes aimed at graduate students are currently offered at academic institutions. The Jed Foundation assisted universities in developing guidelines that will help to address undergraduate mental health, but Roy points out that graduate students have different needs and life situations that could require tailored approaches. For example, graduate students might find it especially difficult to take time off when they’re feeling overwhelmed. “They may not be able to just step away from a research project,” she says. “We want to promote people taking time off if they need it.”

Roy is also concerned about mentorship, a crucial aspect of graduate training that doesn’t always receive much scrutiny. “That relationship needs a tremendous amount of attention,” she says.

Ortega and other investigators have identified some innovative approaches that deserve a closer look. Boston University in Massachusetts, for example, instituted a holiday policy this year that ensures two weeks, or ten working days, of paid holiday every year for PhD students on annual stipends. “The idea is that this will foster work–life balance, which is a big part of student wellness,” says Ortega.

Another is the Mental Health Bill of Rights and Responsibilities that was adopted by the graduate education department at Vanderbilt University in Nashville, Tennessee, in February. The document states that, among other things, any student who seeks mental-health treatment through the university will be assigned a care coordinator who can help them to navigate the system and connect with resources.

Mark Wallace, a neuroscientist and dean of the Vanderbilt University Graduate School, says that the bill of rights was a product of many discussions between graduate students and university leaders. “This approach ensures that everyone has a role to play in tackling mental-health issues on our campus, whether they be students, faculty or staff,” he says.

Covering new ground

Ortega says that the CGS initiative is the first of its kind in the United States and Canada. She and other investigators were partly inspired by other mental-health schemes, including the UK Council For Graduate Education’s first International Conference on the Mental Health & Wellbeing of Postgraduate Researchers, which took place in May (and was supported by Nature Research).

The CGS will co-host a global summit, Cultural Contexts of Health and Well-Being in Graduate Education, at the University of Manchester, UK, on 1–3 September. “There’s a growing recognition of these issues in Europe,” Ortega says.

Ortega and Roy hope that their project will inspire universities around the United States to take a closer look at at what they’re doing — or not doing — to promote the mental health of graduate students. The results should also lay the foundation for a future of better support for graduate students, including more scientifically rigorous studies of issues that this group faces, Ortega says.

“Graduate-student mental health and well-being has become one of the hottest topics that our graduate dean members want to see addressed,” Ortega says. “Clearly, we have a lot of work to do in the next 22 months.”

https://www.nature.com/articles/d41586-019-02584-7?utm_source=Nature+Briefing&utm_campaign=0a58fd4efb-briefing-dy-20190902&utm_medium=email&utm_term=0_c9dfd39373-0a58fd4efb-44039353

Within four hours of a traumatic experience, certain physiological markers—namely, sweating—are higher in people who go on to develop posttraumatic stress disorder (PTSD), according to a new study by a researcher at Case Western Reserve University and other institutions.

Around 90% of people who experience a traumatic event do not develop PTSD, according to existing data and research, making the medical community eager for better insights into the 10% who do—and for how to best treat these patients.

The study, conducted at Atlanta’s Grady Memorial Hospital, found that micro perspirations—detected non-invasively by a mobile device in an emergency department—can be plugged into a new mathematical model developed by the researchers to help predict who may be more at risk for developing PTSD.

The findings are especially important for targeting early treatment efforts and prevention of the disorder, said Alex Rothbaum, a pre-doctoral researcher in the Department of Psychological Sciences in the College of Arts and Sciences at Case Western Reserve.

“With PTSD, there is a need for more reliable and immediate patient information, especially in situations where research suggests people may underreport their own symptoms, such as with men, and those who live in violent neighborhoods or are on active duty,” said Rothbaum, a co-author of the study, which was published in the journal Chronic Stress.

“While skin is always secreting sweat, our method can discern meaningful, actionable information from perspirations too small for the naked eye to see,” he added.

The measurement differs from traditional practices to diagnose PTSD, which look for psychological differences in patients based on self-reported data and clusters of symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (often referred to as the DSM) published by the American Psychiatric Association.

“Eventually, this finding may help contribute to changes in how we diagnose and treat PTSD, pointing us toward which patients would do better in therapy, with medication, or a combination of the two—or no treatment at all,” said Rothbaum.

New testing device: less expensive, more accessible
Researchers hope the PTSD test can become available and standard in emergency departments, aided by the recent development of a practical and inexpensive device that can plug into common tablets and can measure “skin conductance response”—a measure of sweating.

Before, such tests could only be conducted on a large stand-alone machine costing upwards of $10,000. While the new device lacks the sensitivity of its more expensive counterpart, the readings it provides can be used to determine who should continue with additional testing and who is not at risk for developing PTSD.

The study—which included nearly 100 patients—was prompted, in part, by recent research showing the ineffectiveness of current methods practiced with patients immediately after traumas, known as critical incident stress debriefing and psychological debriefing.

Both the new method and model created by researchers will need to be further validated by a larger study underway with a National Institutes of Health grant.

The research
The study was co-authored with researchers at Emory University School of Medicine: Rebecca Hinrichs, Sanne J. H. van Rooij, Jennifer Stevens, Jessica Maples-Keller and Barbara O. Rothbaum; Vasiliki Michopoulos of Emory and Yerkes National Primate Research Center; Katharina Schultebraucks and Isaac Galatzer-Levy of New York University School of Medicine; Sterling Winters of Wayne State University; Tanja Jovanovic of Emory and Wayne State; and Kerry J. Ressler of Emory and Harvard/ McLean Hospital.

The research was supported by the National Institute of Mental Health and a Brain and Behavior Research Foundation NARSAD Independent Investigator Award.

Sweating is a clue into who develops PTSD—and who doesn’t


A mouse exploring one of the custom hologram generators used in the experiments at Stanford. By stimulating particular neurons, scientists were able to make engineered mice see visual patterns that weren’t there.

By Carl Zimmer

In a laboratory at the Stanford University School of Medicine, the mice are seeing things. And it’s not because they’ve been given drugs.

With new laser technology, scientists have triggered specific hallucinations in mice by switching on a few neurons with beams of light. The researchers reported the results on Thursday in the journal Science.

The technique promises to provide clues to how the billions of neurons in the brain make sense of the environment. Eventually the research also may lead to new treatments for psychological disorders, including uncontrollable hallucinations.

“This is spectacular — this is the dream,” said Lindsey Glickfeld, a neuroscientist at Duke University, who was not involved in the new study.

In the early 2000s, Dr. Karl Deisseroth, a psychiatrist and neuroscientist at Stanford, and other scientists engineered neurons in the brains of living mouse mice to switch on when exposed to a flash of light. The technique is known as optogenetics.

In the first wave of these experiments, researchers used light to learn how various types of neurons worked. But Dr. Deisseroth wanted to be able to pick out any individual cell in the brain and turn it on and off with light.

So he and his colleagues designed a new device: Instead of just bathing a mouse’s brain in light, it allowed the researchers to deliver tiny beams of red light that could strike dozens of individual brain neurons at once.

To try out this new system, Dr. Deisseroth and his colleagues focused on the brain’s perception of the visual world. When light enters the eyes — of a mouse or a human — it triggers nerve endings in the retina that send electrical impulses to the rear of the brain.

There, in a region called the visual cortex, neurons quickly detect edges and other patterns, which the brain then assembles into a picture of reality.

The scientists inserted two genes into neurons in the visual cortices of mice. One gene made the neurons sensitive to the red laser light. The other caused neurons to produce a green flash when turned on, letting the researchers track their activity in response to stimuli.

The engineered mice were shown pictures on a monitor. Some were of vertical stripes, others of horizontal stripes. Sometimes the stripes were bright, sometimes fuzzy. The researchers trained the mice to lick a pipe only if they saw vertical stripes. If they performed the test correctly, they were rewarded with a drop of water.

As the mice were shown images, thousands of neurons in their visual cortices flashed green. One population of cells switched on in response to vertical stripes; other neurons flipped on when the mice were shown horizontal ones.

The researchers picked a few dozen neurons from each group to target. They again showed the stripes to the mice, and this time they also fired light at the neurons from the corresponding group. Switching on the correct neurons helped the mice do better at recognizing stripes.

Then the researchers turned off the monitor, leaving the mice in darkness. Now the scientists switched on the neurons for horizontal and vertical stripes, without anything for the rodents to see. The mice responded by licking the pipe, as if they were actually seeing vertical stripes.

Anne Churchland, a neuroscientist at Cold Spring Harbor Laboratory who was not involved in the study, cautioned that this kind of experiment can’t reveal much about a mouse’s inner experience.

“It’s not like a creature can tell you, ‘Oh, wow, I saw a horizontal bar,’” she said.

Dr. Churchland said that it would take more research to better understand why the mice behaved as they did in response to the flashes of red light. Did they see the horizontal stripes more clearly, or were they less distracted by misleading signals?

One of the most remarkable results from the study came about when Dr. Deisseroth and his colleagues narrowed their beams of red light to fewer and fewer neurons. They kept getting the mice to lick the pipe as if they were seeing the vertical stripes.

In the end, the scientists found they could trigger the hallucinations by stimulating as few as two neurons. Thousands of other neurons in the visual cortex would follow the lead of those two cells, flashing green as they became active.

Clusters of neurons in the brain may be tuned so that they’re ready to fire at even a slight stimulus, Dr. Deisseroth and his colleagues concluded — like a snowbank poised to become an avalanche.

But it doesn’t take a fancy optogenetic device to make a few neurons fire. Even when they’re not receiving a stimulus, neurons sometimes just fire at random.

That raises a puzzle: If all it takes is two neurons, why are we not hallucinating all the time?

Maybe our brain wiring prevents it, Dr. Deisseroth said. When a neuron randomly fires, others may send signal it to quiet down.

Dr. Glickfeld speculated that attention may be crucial to triggering the avalanche of neuronal action only at the right times. “Attention allows you to ignore a lot of the background activity,” she said.

Dr. Deisseroth hopes to see what other hallucinations he can trigger with light. In other parts of the brain, he might be able to cause mice to perceive more complex images, such as the face of a cat. He might be able to coax neurons to create phantom sounds, or even phantom smells.

As a psychiatrist, Dr. Deisseroth has treated patients who have suffered from visual hallucinations. In his role as a neuroscientist, he’d like to find out more about how individual neurons give rise to these images — and how to stop them.

“Now we know where those cells are, what they look like, what their shape is,” he said. “In future work, we can get to know them in much more detail.”

An international team spearheaded by researchers at McGill University has discovered a biological mechanism that could explain heightened somatic awareness, a condition where patients experience physical discomforts for which there is no physiological explanation.

Patients with heightened somatic awareness often experience unexplained symptoms – headaches, sore joints, nausea, constipation or itchy skin – that cause emotional distress, and are twice as likely to develop chronic pain. The condition is associated with illnesses such as fibromyalgia, rheumatoid arthritis, and temporomandibular disorders, and is thought to be of psychological origin.

“Think of the fairy tale of the princess and the pea,” says Samar Khoury, a postdoctoral fellow at McGill’s Alan Edwards Centre for Research on Pain. “The princess in the story had extreme sensitivity where she could feel a small pea through a pile of 20 mattresses. This is a good analogy of how someone with heightened somatic awareness might feel; they have discomforts caused by a tiny pea that doctors can’t seem to find or see, but it’s very real.”

Thanks to an existing study on genetic association, Samar Khoury and her colleagues might have found the elusive pea capable of explaining somatic awareness.

Their work, recently published in the Annals of Neurology, used data available through the Orofacial Pain: Prospective Evaluation and Risk Assessment cohort and demonstrates that patients who suffer from somatic symptoms share a common genetic variant. The mutation leads to the malfunctioning of an enzyme critical for the production of serotonin, a neurotransmitter with numerous biological functions.

“I am very happy and proud that our work provides a molecular basis for heightened somatic symptoms,” says Luda Diatchenko, lead author of the new study and a professor in McGill’s Faculty of Dentistry. “We believe that this work is very important to patients because we can now provide a biological explanation of their symptoms. It was often believed that there were psychological or psychiatric problems, that the problem was in that patient’s head, but our work shows that these patients have lower levels of serotonin in their blood.”

The results of their study have laid the groundwork for the development of animal models that could be used to better characterize the molecular pathways in heightened somatic awareness. Above all, Diatchenko and Khoury hope their work will pave the way for treatment options.

“The next step for us would be to see if we are able to target serotonin levels in order to alleviate these symptoms,” says Diatchenko, who holds the Canada Excellence Research Chair in Human Pain Genetics.

This work was supported by the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health and the National Institute of Dental and Craniofacial Research.

https://reachmd.com/news/serotonin-linked-to-somatic-awareness-a-condition-long-thought-to-be-imaginary/1628160/?mkt_tok=eyJpIjoiTTJFM05EYzNORFZsTmpZMSIsInQiOiJ6dnNLckNwK0tZSTUwYnlBcmxBZ1dMSGg4ZTlFQ1FUd2xvOVV5bkpRV0hrOXB5aEs4cG95ckRFNDY2aTFCem41MXQxUTk0ZWtuNjdJMkJ5NUNqRTJzVFFKZkE3ZEpMS2xuMGFBZVBnQXM5WFBZVkpRZW1zZzNscmtUTlJIblJYOSJ9