Posts Tagged ‘mental health’

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How and why human-unique characteristics such as highly social behavior, languages and complex culture have evolved is a long-standing question. A research team led by Tohoku University in Japan has revealed the evolution of a gene related to such human-unique psychiatric traits.

PhD candidate Daiki Sato and Professor Masakado Kawata have discovered SLC18A1 (VMAT1), which encodes vesicular monoamine transporter 1, as one of the genes evolved through natural selection in the human lineage. VMAT1 is mainly involved in the transport of neurochemicals, such as serotonin and dopamine in the body, and its malfunction leads to various psychiatric disorders. VMAT1 has variants consisting of two different amino acids, threonine (136Thr) and isoleucine (136Ile), at site 136.

Several studies have shown that these variants are associated with psychiatric disorders, including schizophrenia, bipolar disorder, anxiety, and neuroticism (a personality trait). It has been known that individuals with 136Thr tend to be more anxious and more depressed and have higher neuroticism scores. They showed that other mammals have 136Asn at this site but 136Thr had been favored over 136Asn during human evolution. Moreover, the 136Ile variant had originated nearly at the Out-of-Africa migration, and then, both 136Thr and 136Ile variants have been positively maintained by natural selection in non-African populations.

The study by Sato and Kawata indicates that natural selection has possibly shaped our psychiatric traits and maintained its diversity. The results provide two important implications for human psychiatric evolution. First, through positive selection, the evolution from Asn to Thr at site 136 on SLC18A1 was favored by natural selection during the evolution from ancestral primates to humans, although individuals with 136Thr are more anxious and have more depressed minds.

Second, they showed that the two variants of 136Thr and 136Ile have been maintained by natural selection using several population genetic methods. Any form of natural selection that maintains genetic diversity within populations is called “balancing selection”. Individual differences in psychiatric traits can be observed in any human population, and some personality traits are also found in non-human primates. This suggests the possibility that a part of genetic diversity associated with personality traits and/or psychiatric disorders are maintained by balancing selection, although such selective pressure is often weak and difficult to detect.

https://neurosciencenews.com/personality-psychiatry-genetics-9820/

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The NIHR and King’s College London are calling for 40,000 people diagnosed with depression or anxiety to enrol online for the Genetic Links to Anxiety and Depression (GLAD) Study and join the NIHR Mental Health Bioresource.

Researchers hope to establish the largest ever database of volunteers who can be called up to take part in research exploring the genetic factors behind the two most common mental health conditions – anxiety and depression.

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The GLAD study will make important strides towards better understanding of these disorders and provide a pool of potential participants for future studies, reducing the time-consuming process of recruiting patients for research.

Research has shown 30-40% of the risk for both depression and anxiety is genetic and 60-70% due to environmental factors. Only by having a large, diverse group of people available for studies will researchers be able to determine how genetic and environmental triggers interact to cause anxiety and depression.

Leader of the GLAD study and the NIHR Mental Health BioResource, Dr Gerome Breen of King’s College London, said: “It’s a really exciting time to become involved in mental health research, particularly genetic research which has made incredible strides in recent years – we have so far identified 46 genetic links for depression and anxiety.

“By recruiting 40,000 volunteers willing to be re-contacted for research, the GLAD Study will take us further than ever before. It will allow researchers to solve the big unanswered questions, address how genes and environment act together and help develop new treatment options.”

The GLAD Study, a collaboration between the NIHR BioResource and King’s College London, has been designed to be particularly accessible, with a view to motivating more people to take part in mental health research.

Research psychologist and study lead Professor Thalia Eley, King’s College London, said: “We want to hear from all different backgrounds, cultures, ethnic groups and genders, and we are especially keen to hear from young adults. By including people from all parts of the population, what we learn will be relevant to everyone. This is a unique opportunity to participate in pioneering medical science.”

https://www.nihr.ac.uk/news/nihr-launches-largest-ever-study-of-genetic-links-to-depression-and-anxiety/9201

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The 51-year-old University of Cape Town researcher had been suffering from depression, and his death has prompted reflection on being a black academic in South Africa.

Bongani Mayosi, a prominent cardiologist and dean of the Faculty of Health Sciences at the University of Cape Town in South Africa, died of suicide on July 27. He was 51.

“In the last two years he has battled with depression and on that day [Friday] took the desperate decision to end his life,” his family said in a statement at the time, News24 reports. “We are still struggling to come to terms with this devastating loss.”

Born in 1967, Mayosi grew up under apartheid in the Transkei region of South Africa. Homeschooled by his mother as a child, he later studied medicine at the University of KwaZulu-Natal, incorporating a year of research to qualify for a BMedSci degree. In 1998, he won a fellowship to join the PhD program in the department of cardiovascular medicine at the University of Oxford.

Upon returning to South Africa a few years later, Bongani worked on a number of projects, including searching for the genetic mutations underpinning arrhythmogenic cardiomyopathy to identifying risk factors involved in cardiovascular disease. In 2006, at 38 years old, he became the first black person to chair the Department of Medicine at the University of Cape Town (UCT).

His career over the next decade would be marked by several awards recognizing his contributions to cardiology. In 2007, he was named one of the top 25 “influential leaders in healthcare in South Africa,” and, two years later, received the Order of Mapungubwe, South Africa’s highest honor. In 2017, he was elected to the US National Academy of Medicine.

Becoming dean in 2016, Mayosi was responsible for handling part of the university’s response to a tumultuous period of student unrest across the country. In a letter published on News24, the university’s vice chancellor Mamokgethi Phakeng writes that during that period, Mayosi’s “office was occupied for about two weeks in 2016. He had to manage pressure coming from many different directions, including from staff and students.” Over the next two years, Mayosi suffered from depression and took time off from his position; he resigned twice, but was persuaded to change his mind.

Mayosi’s death has led colleagues to examine the external forces that might have contributed to his desperation. In early August, Johannesburg’s City Press and other outlets reported that UCT had instigated an inquiry into the circumstances surrounding Mayosi’s death following calls from concerned colleagues and the university’s Black Academic Caucus. In a statement on Facebook on August 2, the Caucus wrote that “it is hard for us to exclude the UCT working environment from the tragic death of our colleague, and indeed others, including students.” Many researchers and activists also highlighted challenges Mayosi faced as a black academic in South Africa.

Matshidiso Moeti, the African regional director for the World Health Organization—where Mayosi had chaired the African Advisory Committee on Health Research & Development—was one of many health officials and researchers to send condolences after news of Mayosi’s death. “We will always cherish him for his diligence and immense contribution to the development of the WHO strategy for strengthening the use of evidence, information and research for policy-making in the African Region,” she wrote.

Cardiologists Hugh Watkins of the University of Oxford and Ntobeko Ntusi of UCT write in a memorial published yesterday (September 11) in Circulation that “one of the most striking impressions from his funeral, attended by thousands of mourners who remembered him with awe and love, was the abundant evidence of his commitment to bring others with him, nurture talent, and provide the sorts of opportunity from which he had benefited. . . . We speak for many in saying that we are in awe of what Bongani achieved.”

https://www.the-scientist.com/news-opinion/celebrated-cardiologist-bongani-mayosi-dies-64787?utm_campaign=TS_DAILY%20NEWSLETTER_2018&utm_source=hs_email&utm_medium=email&utm_content=65896990&_hsenc=p2ANqtz-_Xn_C3066EAlU479N7jk9yk0YpvAneSzSm7Ae9hwdounQSXC6y1NB1SlSwEHpKfuJXV3J_nz64REq0mTIGy6GuyMPE0Q&_hsmi=65896990

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A 3-D rendering of the serotonin system in the left hemisphere of the mouse brain reveals two groups of serotonin neurons in the dorsal raphe that project to either cortical regions (blue) or subcortical regions (green) while rarely crossing into the other’s domain.

As Liqun Luo was writing his introductory textbook on neuroscience in 2012, he found himself in a quandary. He needed to include a section about a vital system in the brain controlled by the chemical messenger serotonin, which has been implicated in everything from mood to movement regulation. But the research was still far from clear on what effect serotonin has on the mammalian brain.

“Scientists were reporting divergent findings,” said Luo, who is the Ann and Bill Swindells Professor in the School of Humanities and Sciences at Stanford University. “Some found that serotonin promotes pleasure. Another group said that it increases anxiety while suppressing locomotion, while others argued the opposite.”

Fast forward six years, and Luo’s team thinks it has reconciled those earlier confounding results. Using neuroanatomical methods that they invented, his group showed that the serotonin system is actually composed of at least two, and likely more, parallel subsystems that work in concert to affect the brain in different, and sometimes opposing, ways. For instance, one subsystem promotes anxiety, whereas the other promotes active coping in the face of challenges.

“The field’s understanding of the serotonin system was like the story of the blind men touching the elephant,” Luo said. “Scientists were discovering distinct functions of serotonin in the brain and attributing them to a monolithic serotonin system, which at least partly accounts for the controversy about what serotonin actually does. This study allows us to see different parts of the elephant at the same time.”

The findings, published online on August 23 in the journal Cell, could have implications for the treatment of depression and anxiety, which involves prescribing drugs such as Prozac that target the serotonin system – so-called SSRIs (selective serotonin reuptake inhibitors). However, these drugs often trigger a host of side effects, some of which are so intolerable that patients stop taking them.

“If we can target the relevant pathways of the serotonin system individually, then we may be able to eliminate the unwanted side effects and treat only the disorder,” said study first author Jing Ren, a postdoctoral fellow in Luo’s lab.

Organized projections of neurons

The Stanford scientists focused on a region of the brainstem known as the dorsal raphe, which contains the largest single concentration in the mammalian brain of neurons that all transmit signals by releasing serotonin (about 9,000).

The nerve fibers, or axons, of these dorsal raphe neurons send out a sprawling network of connections to many critical forebrain areas that carry out a host of functions, including thinking, memory, and the regulation of moods and bodily functions. By injecting viruses that infect serotonin axons in these regions, Ren and her colleagues were able to trace the connections back to their origin neurons in the dorsal raphe.

This allowed them to create a visual map of projections between the dense concentration of serotonin-releasing neurons in the brainstem to the various regions of the forebrain that they influence. The map revealed two distinct groups of serotonin-releasing neurons in the dorsal raphe, which connected to cortical and subcortical regions in the brain.

“Serotonin neurons in the dorsal raphe project to a bunch of places throughout the brain, but those bunches of places are organized,” Luo said. “That wasn’t known before.”

Two parts of the elephant

In a series of behavioral tests, the scientists also showed that serotonin neurons from the two groups can respond differently to stimuli. For example, neurons in both groups fired in response to mice receiving rewards like sips of sugar water but they showed opposite responses to punishments like mild foot shocks.

“We now understand why some scientists thought serotonin neurons are activated by punishment, while others thought it was inhibited by punishment. Both are correct – it just depends on which subtype you’re looking at,” Luo said.

What’s more, the group found that the serotonin neurons themselves were more complex than originally thought. Rather than just transmitting messages with serotonin, the cortical-projecting neurons also released a chemical messenger called glutamate – making them one of the few known examples of neurons in the brain that release two different chemicals.

“It raises the question of whether we should even be calling these serotonin neurons because neurons are named after the neurotransmitters they release,” Ren said.

Taken together, these findings indicate that the brain’s serotonin system is not made up of a homogenous population of neurons but rather many subpopulations acting in concert. Luo’s team has identified two groups, but there could be many others.

In fact, Robert Malenka, a professor and associate chair of psychiatry and behavioral sciences at Stanford’s School of Medicine, and his team recently discovered a group of serotonin neurons in the dorsal raphe that project to the nucleus accumbens, the part of the brain that promotes social behaviors.

“The two groups that we found don’t send axons to the nucleus accumbens, so this is clearly a third group,” Luo said. “We identified two parts of the elephant, but there are more parts to discover.”

https://medicalxpress.com/news/2018-08-brain-serotonin.html

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For what is thought to be the largest study of its kind, the researchers analyzed brain scans of 31,227 people aged 9 months–105 years.

In a paper that now features in the Journal of Alzheimer’s Disease, they describe how they identified “patterns of aging” from the brain scans.

These were done using single photon emission computed tomography (SPECT) and came from people with psychiatric conditions such as attention deficit hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder. They were all attending a psychiatric clinic that was based at several locations.

Each participant underwent two SPECT brain scans — one during a resting state, and another during completion of “a concentration task” — giving a total of 62,454 scans.

The scientists found that they could predict a person’s age from the pattern of blood flow in their brain.

Brain circulation varied over lifespan
They observed that blood flow varied from childhood into older age throughout the lifespan. They also saw that brain aging was more visible in scans of men and those with schizophrenia, anxiety, bipolar disorder, and ADHD.

Brain aging was also more strongly associated with use of cannabis and alcohol.

“Based on one of the largest brain imaging studies ever done,” says lead study author Dr. Daniel G. Amen, a psychiatrist and founder of Amen Clinics in Costa Mesa, CA, “we can now track common disorders and behaviors that prematurely age the brain.”

He suggests that improving the treatment of these disorders could “slow or even halt the process of brain aging.”

https://www.medicalnewstoday.com/articles/322852.php

Many people think of psychedelics as relics from the hippie generation or something taken by ravers and music festival-goers, but they may one day be used to treat disorders ranging from social anxiety to depression, according to research presented at the annual convention of the American Psychological Association.

“Combined with psychotherapy, some psychedelic drugs like MDMA, psilocybin and ayahuasca may improve symptoms of anxiety, depression and post-traumatic stress disorder,” said Cristina L. Magalhaes, PhD, of Alliant International University Los Angeles, and co-chair of a symposium on psychedelics and psychotherapy. “More research and discussion are needed to understand the possible benefits of these drugs, and psychologists can help navigate the clinical, ethical and cultural issues related to their use.”

Hallucinogens have been studied in the U.S. for their potential healing benefits since the discovery of LSD in the 1940s. However, research has mostly stalled since psychedelics were outlawed in the late 1960s.

A shift may be coming soon though, as MDMA, commonly known as ecstasy, is beginning its third and final phase of clinical trials in an effort to win Food and Drug Administration approval for treatment of post-traumatic stress disorder, said Adam Snider, MA, of Alliant International University Los Angeles, and co-chair of the symposium.

Findings from one study presented at the symposium suggested that symptoms of social anxiety in autistic adults may be treatable with a combination of psychotherapy and MDMA. Twelve autistic adults with moderate to severe social anxiety were given two treatments of pure MDMA plus ongoing therapy and showed significant and long-lasting reductions in their symptoms, the research found.

“Social anxiety is prevalent in autistic adults and few treatment options have been shown to be effective,” said Alicia Danforth, PhD, of the Los Angeles Biomedical Research Institute at the HarborUCLA Medical Center, who conducted the study. “The positive effects of using MDMA and therapy lasted months, or even years, for most of the research volunteers.”

Research discussed also explored how LSD, psilocybin (known colloquially as “magic mushrooms”) and ayahuasca (a brew used by indigenous people of the Amazon for spiritual ceremonies) may benefit people with anxiety, depression and eating disorders.

Adele Lafrance, PhD, of Laurentian University, highlighted a study of 159 participants who reported on their past use of hallucinogens, level of spirituality and relationship with their emotions.

Using hallucinogens was related to greater levels of spirituality, which led to improved emotional stability and fewer symptoms of anxiety, depression and disordered eating, the study found.

“This study reinforces the need for the psychological field to consider a larger role for spirituality in the context of mainstream treatment because spiritual growth and a connection to something greater than the self can be fostered,” said Lafrance.

Other research presented suggested that ayahuasca may help alleviate depression and addiction, as well as assist people in coping with trauma.

“We found that ayahuasca also fostered an increase in generosity, spiritual connection and altruism,” said Clancy Cavnar, PhD, with Núcleo de Estudos Interdisciplinares sobre Psicoativos.

For people suffering from life-threatening cancer, psilocybin may provide significant and lasting decreases in anxiety and distress.

When combined with psychotherapy, psilocybin helped a study’s 13 participants grapple with loss and existential distress. It also helped the participants reconcile their feelings about death as nearly all participants reported that they developed a new understanding of dying, according to Gabby Agin-Liebes, BA, of Palo Alto University, who conducted the research.

“Participants made spiritual or religious interpretations of their experience and the psilocybin treatment helped facilitate a reconnection to life, greater mindfulness and presence, and gave them more confidence when faced with cancer recurrence,” said Agin-Liebes.

Presenters throughout the symposium discussed the need for more research to fully understand the implications of using psychedelics as an adjunct to psychotherapy as well as the ethical and legal issues that need to be considered.

A new study using machine learning has identified brain-based dimensions of mental health disorders, an advance towards much-needed biomarkers to more accurately diagnose and treat patients. A team at Penn Medicine led by Theodore D. Satterthwaite, MD, an assistant professor in the department of Psychiatry, mapped abnormalities in brain networks to four dimensions of psychopathology: mood, psychosis, fear, and disruptive externalizing behavior. The research is published in Nature Communications this week.

Currently, psychiatry relies on patient reporting and physician observations alone for clinical decision making, while other branches of medicine have incorporated biomarkers to aid in diagnosis, determination of prognosis, and selection of treatment for patients. While previous studies using standard clinical diagnostic categories have found evidence for brain abnormalities, the high level of diversity within disorders and comorbidity between disorders has limited how this kind of research may lead to improvements in clinical care.

“Psychiatry is behind the rest of medicine when it comes to diagnosing illness,” said Satterthwaite. “For example, when a patient comes in to see a doctor with most problems, in addition to talking to the patient, the physician will recommend lab tests and imaging studies to help diagnose their condition. Right now, that is not how things work in psychiatry. In most cases, all psychiatric diagnoses rely on just talking to the patient. One of the reasons for this is that we don’t understand how abnormalities in the brain lead to psychiatric symptoms. This research effort aims to link mental health issues and their associated brain network abnormalities to psychiatric symptoms using a data-driven approach.”

To uncover the brain networks associated with psychiatric disorders, the team studied a large sample of adolescents and young adults (999 participants, ages 8 to 22). All participants completed both functional MRI scans and a comprehensive evaluation of psychiatric symptoms as part of the Philadelphia Neurodevelopmental Cohort (PNC), an effort lead by Raquel E. Gur, MD, Ph.D., professor of Psychiatry, Neurology, and Radiology, that was funded by the National Institute of Mental Health. The brain and symptom data were then jointly analyzed using a machine learning method called sparse canonical correlation analysis.

This analysis revealed patterns of changes in brain networks that were strongly related to psychiatric symptoms. In particular, the findings highlighted four distinct dimensions of psychopathology—mood, psychosis, fear, and disruptive behavior—all of which were associated with a distinct pattern of abnormal connectivity across the brain.

The researchers found that each brain-guided dimension contained symptoms from several different clinical diagnostic categories. For example, the mood dimension was comprised of symptoms from three categories, e.g. depression (feeling sad), mania (irritability), and obsessive-compulsive disorder (recurrent thoughts of self-harm). Similarly, the disruptive externalizing behavior dimension was driven primarily by symptoms of both Attention Deficit Hyperactivity Disorder(ADHD) and Oppositional Defiant Disorder (ODD), but also included the irritability item from the depression domain. These findings suggest that when both brain and symptomatic data are taken into consideration, psychiatric symptoms do not neatly fall into established categories. Instead, groups of symptoms emerge from diverse clinical domains to form dimensions that are linked to specific patterns of abnormal connectivity in the brain.

“In addition to these specific brain patterns in each dimension, we also found common brain connectivity abnormalities that are shared across dimensions,” said Cedric Xia, a MD-Ph.D. candidate and the paper’s lead author. “Specifically, a pair of brain networks called default mode network and frontal-parietal network, whose connections usually grow apart during brain development, become abnormally integrated in all dimensions.”

These two brain networks have long intrigued psychiatrists and neuroscientists because of their crucial role in complex mental processes such as self-control, memory, and social interactions. The findings in this study support the theory that many types of psychiatric illness are related to abnormalities of brain development.

The team also examined how psychopathology differed across age and sex. They found that patterns associated with both mood and psychosis became significantly more prominent with age. Additionally, brain connectivity patterns linked to mood and fear were both stronger in female participants than males.

“This study shows that we can start to use the brain to guide our understanding of psychiatric disorders in a way that’s fundamentally different than grouping symptoms into clinical diagnostic categories. By moving away from clinical labels developed decades ago, perhaps we can let the biology speak for itself,” said Satterthwaite. “Our ultimate hope is that understanding the biology of mental illnesses will allow us to develop better treatments for our patients.”

More information: Cedric Huchuan Xia et al, Linked dimensions of psychopathology and connectivity in functional brain networks, Nature Communications (2018). DOI: 10.1038/s41467-018-05317-y

https://medicalxpress.com/news/2018-08-machine-links-dimensions-mental-illness.html