Posts Tagged ‘mental illness’

A pair of new studies links childhood cat ownership and infection with the parasite Toxoplasma gondii (T. gondii) with later onset schizophrenia and other mental illness. Researchers published their findings in the online Schizophrenia Research and Acta Psychiatrica Scandinavica.

In the Schizophrenia Research study, investigators compared two previous studies that suggested childhood cat ownership could be a possible risk factor for schizophrenia or another serious mental illness with a third, even earlier survey on mental health to see if the finding could be replicated.

“The results were the same,” researchers reported, “suggesting that cat ownership in childhood is significantly more common in families in which the child later becomes seriously mentally ill.”

If accurate, the researchers expect the culprit to be infection with T. gondii, a parasite commonly carried by cats. At this point, though, they are urging others to conduct further studies to clarify the apparent link between cat ownership and schizophrenia.

The Acta Psychiatrica Scandinavica study was a meta-analysis of 50 previously published studies to investigate the prevalence of t. gondii infection in people diagnosed with psychiatric disorders compared with healthy controls.

In cases of schizophrenia, researchers said evidence of an association with T. gondii was “overwhelming,” CBS News reported. Specifically, people infected with T. gondii were nearly twice as likely to be diagnosed with schizophrenia as people never infected with the parasite, according to the report.

The meta-analysis also suggested associations between T. gondii infection and bipolar disorder, obsessive-compulsive disorder, and addiction. No association, however, was found for major depression.

—Jolynn Tumolo

References

1. Fuller Torrey E, Simmons W, Yolken RH. Is childhood cat ownership a risk factor for schizophrenia later in life? Schizophrenia Research. 2015 April 18. [Epub ahead of print].

2. Sutterland AL, Fond G, Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatrica Scandinavica. 2015 April 15. [Epub ahead of print].

http://www.psychcongress.com/article/studies-link-cat-ownership-schizophrenia-other-mental-illness

by Bahar Golipour

What is the earliest memory you have?

Most people can’t remember anything that happened to them or around them in their toddlerhood. The phenomenon, called childhood amnesia, has long puzzled scientists. Some have debated that we forget because the young brain hasn’t fully developed the ability to store memories. Others argue it is because the fast-growing brain is rewiring itself so much that it overwrites what it’s already registered.

New research that appears in Nature Neuroscience this week suggests that those memories are not forgotten. The study shows that when juvenile rats have an experience during this infantile amnesia period, the memory of that experience is not lost. Instead, it is stored as a “latent memory trace” for a long time. If something later reminds them of the original experience, the memory trace reemerges as a full blown, long-lasting memory.

Taking a (rather huge) leap from rats to humans, this could explain how early life experiences that you don’t remember still shape your personality; how growing up in a rich environment makes you a smarter person and how early trauma puts you at higher risk for mental health problems later on.

Scientists don’t know whether we can access those memories. But the new study shows childhood amnesia coincides with a critical time for the brain ― specifically the hippocampus, a seahorse-shaped brain structure crucial for memory and learning. Childhood amnesia corresponds to the time that your brain matures and new experiences fuel the growth of the hippocampus.

In humans, this period occurs before pre-school, likely between the ages 2 and 4. During this time, a child’s brain needs adequate stimulation (mostly from healthy social interactions) so it can better develop the ability to learn.

And not getting enough healthy mental activation during this period may impede the development of a brain’s learning and memory centers in a way that it cannot be compensated later.

“What our findings tell us is that children’s brains need to get enough and healthy activation even before they enter pre-school,” said study leader Cristina Alberini, a professor at New York University’s Center for Neural Science. “Without this, the neurological system runs the risk of not properly developing learning and memory functions.”

The findings may illustrate one mechanism that could in part explain scientific research that shows poverty can shrink children’s brains.

Extensive research spanning decades has shown that low socioeconomic status is linked to problems with cognitive abilities, higher risk for mental health issues and poorer performance in school. In recent years, psychologists and neuroscientists have found that the brain’s anatomy may look different in poor children. Poverty is also linked to smaller brain surface area and smaller volume of the white matter connecting brain areas, as well as smaller hippocampus. And a 2015 study found that the differences in brain development explain up to 20 percent of academic performance gap between children from high- and low-income families.

Critical Periods

For the brain, the first few years of life set the stage for the rest of life.

Even though the nervous system keeps some of its ability to rewire throughout life, several biochemical events that shape its core structure happen only at certain times. During these critical periods of the developmental stages, the brain is acutely sensitive to new sights, sounds, experiences and external stimulation.

Critical periods are best studied in the visual system. In the 1960s, scientists David Hubel and Torsten Wiesel showed that if they close one eye of a kitten from birth for just for a few months, its brain never learns to see properly. The neurons in the visual areas of the brain would lose their ability respond to the deprived eye. Adult cats treated the same way don’t show this effect, which demonstrates the importance of critical periods in brain development for proper functioning. This finding was part of the pioneering work that earned Hubel and Wiesel the 1981 Nobel Prize in Physiology or Medicine.

In the new study in rats, the team shows that a similar critical period may be happening to the hippocampus.

Alberini and her colleagues took a close look at what exactly happens in the brain of rats in their first 17 days of life (equivalent to the first three years of a human’s life). They created a memory for the rodents of a negative experience: every time the animals entered a specific corner of their cage, they received a mildly painful shock to their foot. Young rats, like kids, aren’t great at remembering things that happened to them during their infantile amnesia. So although they avoided that corner right after the shock, they returned to it only a day later. In contrast, a group of older rats retained the memory and avoided this place for a long time.

However, the younger rats, had actually kept a trace of the memory. A reminder (such as another foot shock in another corner) was enough to resurrect the memory and make the animals avoid the first corner of the cage.

Researchers found a cascade of biochemical events in the young rats’ brains that are typically seen in developmental critical periods.

“We were excited to see the same type of mechanism in the hippocampus,” Alberini told The Huffington Post.

The Learning Brain And Its Mysteries

Just like the kittens’ brain needed light from the eyes to learn to see, the hippocampus may need novel experiences to learn to form memories.

“Early in life, while the brain cannot efficiently form long-term memories, it is ‘learning’ how to do so, making it possible to establish the abilities to memorize long-term,” Alberini said. “However, the brain needs stimulation through learning so that it can get in the practice of memory formation―without these experiences, the ability of the neurological system to learn will be impaired.”

This does not mean that you should put your kids in pre-pre-school, Alberini told HuffPost. Rather, it highlights the importance of healthy social interaction, especially with parents, and growing up in an environment rich in stimulation. Most kids in developed countries are already benefiting from this, she said.

But what does this all mean for children who grow up exposed to low levels of environmental stimulation, something more likely in poor families? Does it explain why poverty is linked to smaller brains? Alberini thinks many other factors likely contribute to the link between poverty and brain. But it is possible, she said, that low stimulation during the development of the hippocampus, too, plays a part.

Psychologist Seth Pollak of University of Wisconsin at Madison who has found children raised in poverty show differences in hippocampal development agrees.

Pollak believes the findings of the new study represent “an extremely plausible link between early childhood adversity and later problems.”

“We must always be cautious about generalizing studies of rodents to understanding human children,” Pollas added. “But the nonhuman animal studies, such as this one, provide testable hypotheses about specific mechanisms underlying human behavior.”

Although the link between poverty and cognitive performance has been repeatedly seen in numerous studies, scientists don’t have a good handle on how exactly many related factors unfold inside the developing brain, said Elizabeth Sowell, a researcher from the Children’s Hospital Los Angeles. Studies like this one provide “a lot of food for thought,” she added.

http://www.huffingtonpost.com.au/2016/07/24/the-things-you-dont-remember-shape-who-you-are/

by Tori Rodriguez, MA, LPC

Although there was a consistent reduction in US suicide rates from 1986 through 1999, the trend appears to have reversed during the most recent investigation period. A new report from the Centers for Disease Control and Prevention (1) reveals that suicide rates increased by 24% from 1999 to 2014, with the greatest increase observed in the latter half of that period.

The increase occurred among males and females in all age groups from 10-74. While rates for males still exceed those for females, the gap began to narrow during the most recent period. Among females, the rate increase was almost triple that of males: 45% vs 16%.

While the highest suicide rate was observed among men aged 75 and older, there was a reduction of 8% in this group from the previous report. There was a 43% increase among males in the 45-64 age group, making it the group with the greatest rate increase and the second-highest suicide rate among males. The second highest increase (37%) occurred among males aged 10–14, although this group had the lowest rate among all of the age groups.

As with males, the suicide rate also decreased among females in the 75 and over group, by 11%. The steepest increase (200%) occurred among females aged 10-14, though the actual number of suicides in this age group was relatively small (150 in 2014). The females with the highest suicide rates comprised the 45-64 age group, which had the second greatest increase (63%) since the previous period. For females in the age groups of 15-24, 25-44, and 65-74, rate increases ranged from 31% to 53%.

The most common cause of suicide in females was poisoning, which accounted for 34.1% of cases, while the use of firearms accounted for more than half of male suicides (55.4%). Cases involving some form of suffocation–including hanging and strangulation–increased among both males and females.

Though the report does not provide possible explanations for these trends, other recent findings offer clues about a host of variables that could be influencing rates in the middle age brackets in particular, with especially strong support for economic issues as a potential influence. A study published in 2015 in the American Journal of Preventive Medicine, for example, found that economic and legal problems disproportionately affected adults aged 40-64 who had committed suicide (2). Research reported in 2014 showed a robust link between suicide rates and unemployment rates in adults in middle-aged adults but not other age groups, and according to a 2011 CDC study, suicide rates increased during periods of economic recession and declined during economic growth among people aged 25-64 years (3,4).

A co-author of the 2014 and 2015 studies, Julie A. Phillips, PhD, of the Institute for Health, Health Care Policy and Aging Research at Rutgers University, has received a grant from the American Foundation of Suicide to investigate the numerous variables that could be influencing the trend in middle-aged adults.

Additionally, a randomized controlled trial published in 2016 in PLoS Medicine found promising results with a brief, low-cost treatment designed to address the main risk factor for suicide: previous attempts (5).

An approach called the Attempted Suicide Short Intervention Program (ASSIP) was shown to reduce subsequent attempts by 80% among patients admitted to the emergency department after a suicide attempt.

If you or someone you know is experiencing suicidal thoughts, contact the National Suicide Prevention Line at 1-800-273-TALK (8255) and visit online at http://www.suicidepreventionlifeline.org.

References

1. Curtin SC, Warner M, Hedegaard H. Increase in suicide in the United States, 1999–2014. NCHS data brief, no 241. 2016; Hyattsville, MD: National Center for Health Statistics.

2. Hempstead KA, Phillips JA. Rising suicide among adults aged 40-64 years: the role of job and financial circumstances. Am J Prev Med. 2015; 48(5):491-500.

3. Phillips JA, Nugent CN. Suicide and the Great Recession of 2007-2009: the role of economic factors in the 50 U.S. states. Social Science & Medicine. 2014; 116:22-31.

4. Luo F, Florence CS, Quispe-Agnoli M, et al. Impact of business cycles on US suicide rates, 1928-2007. Am J Public Health. 2011; 101(6):1139-46.

5. Gysin-Maillart A, Schwab S, Soravia L, Megert M, Michel K. A novel brief therapy for patients who attempt suicide: A 24-months follow-up randomized controlled study of the Attempted Suicide Short Intervention Program (ASSIP). PLoS Medicine. 2016; 13(3): e1001968.

http://www.psychiatryadvisor.com/suicide-and-self-harm/increase-in-suicide-rates-in-united-states-cdc/article/492762/?DCMP=EMC-PA_Update_RD&cpn=psych_md,psych_all&hmSubId=&hmEmail=5JIkN8Id_eWz7RlW__D9F5p_RUD7HzdI0&NID=1710903786&dl=0&spMailingID=14943637&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=820858811&spReportId=ODIwODU4ODExS0


Relatively small increases in air pollution were associated with a significant increase in treated psychiatric problems, the research showed.

by Damian Carrington

A major new study has linked air pollution to increased mental illness in children, even at low levels of pollution.

The new research found that relatively small increases in air pollution were associated with a significant increase in treated psychiatric problems. It is the first study to establish the link but is consistent with a growing body of evidence that air pollution can affect mental and cognitive health and that children are particularly vulnerable to poor air quality.

The research, published in the peer-reviewed journal BMJ Open, examined the pollution exposure of more than 500,000 under-18s in Sweden and compared this with records of medicines prescribed for mental illnesses, ranging from sedatives to anti-psychotics.

“The results can mean that a lower concentration of air pollution, first and foremost from traffic, may reduce psychiatric disorders in children and adolescents,” said Anna Oudin, at Umeå University, who led the study. “I would be worried myself if I lived in an area with high air pollution.”

Prof Frank Kelly, at King’s College London, said the research was important. “This builds on existing evidence that children are particularly sensitive to poor air quality probably because their lifestyles increase the dose of air pollution they are exposed too – ie they are more active – and that developing organs may be more vulnerable until they fully mature.”

Air pollution in the UK is above legal limits in many cities and estimated to cause 40,000 early deaths a year, though this only includes illnesses such as lung disease, heart attacks and strokes.

The EU and WHO limit for nitrogen dioxide (NO2) is 40mcg/m3 (micrograms per cubic metre), but levels can reach many times that in polluted cities like London. The researchers found that a 10mcg/m3 increase in NO2 corresponded to a 9% increase in mental illness in the children. For the same increase in tiny particulate matter (PM2.5 and PM10), the increase was 4%.

One striking aspect of the new research is that Sweden has low levels of air pollution, but the researchers still saw the link even below levels of 15mcg/m3. “Sweden is not a country that suffers from very bad air quality, said Kelly. “This suggests that other countries and cities have an even bigger challenge, as they will have to make significant improvements to their air quality so that it is even cleaner than Sweden’s.”

It is not possible to say from this study what would happen to rates of mental illness at higher levels of air pollution, but Oudin said they could rise: “In all the air pollution studies I have been involved in, the effects seem to be linear.”

This type of research cannot prove a causal link between the air pollution and increases in mental illness, but there is a plausible mechanism. “We know air pollution can get into bodies and brains and cause inflammation,” said Oudin. Animal studies indicate that inflammation is associated with a range of psychiatric disorders.

There have also been several earlier studies that found associations between air pollution and autism spectrum disorders and learning and development in children. “This study adds to evidence that air pollution may have detrimental effects on the brains of children and adolescents,” the Swedish researchers said.

In May, the Guardian revealed an unpublished air pollution report that demonstrated that 433 schools in London are located in areas that exceed EU limits for NO2 pollution and that four-fifths of those are in deprived areas. In May, a WHO report concluded that air pollution was rising at an “alarming rate” in the world’s cities, while a report in September found 3 million people a year suffer early deaths around the world from air pollution.

The new Swedish paper concludes: “The severe impact of child and adolescent mental health problems on society, together with the plausible and preventable association of exposure to air pollution, deserves special attention.”

by Erin Zaleski

A young French woman broadcast her last moments in a haunting livestream video.

More than 1,000 people are believed to have watched the young woman kill herself.

They watched her calmly discuss her decision to die, just as they watched her slip on her sneakers before heading to a nearby station and throwing herself in front of an oncoming suburban RER C train.

No one watching was able to approach the platform, or yell for her to stop, or to do anything else that may have prevented her from carrying out her desperate act, because no one could. The hundreds of people who witnessed her last moments watched the drama unfold behind their phone screens.

At the Egly train station south of Paris on Tuesday, a French teenager broadcast her suicide on Periscope, a smartphone app that allows users to stream live videos. The video has reportedly been removed from Periscope, but footage of the minutes leading up to her death has been posted on YouTube.

While suicide, and even public suicide, is nothing new, the age of social media makes such acts of despair accessible in a way they have never been previously. Indeed, Tuesday’s tragedy near Paris is not the first time a young person has broadcast a suicide on social media. In 2010, a 21-year-old Swedish man hanged himself on a live webcam broadcast. And a young woman in Shanghai documented the events leading up to her suicide on Instagram in 2014, uploading a series of disturbing images, including one in which her legs are dangling out of the window of a high-rise apartment.

“I will haunt you day and night after I’m dead,” she reportedly posted on the photo-sharing app in a message to her ex-boyfriend before jumping to her death.

In its guidelines, Periscope, which is owned by Twitter, prohibits what it deems “explicitly graphic content or media that is intended to incite violent, illegal or dangerous activities.” However, with some 10 million active users, monitoring every account 24/7 would be daunting, if not impossible.

“Why do you say you love me, you don’t even know me?” asks the pretty young woman seated on a red couch in her apartment and facing the camera. She is pale with long brown hair and piercings, one in her left nostril and two just beneath her lower lip. A prospective suitor has messaged her, but she calmly and firmly rebuffs his advances.

“Yes, I am single, but I am not looking for that. Really.”

She rolls a cigarette before continuing.

“What is about to happen is very shocking, so those who are underage should leave.”

She takes a long drag and continues to field questions from users. She tells them that she is 19 and works at a retirement home. Her determined, unemotional demeanor is a bit unsettling to watch. As is the way she calmly answers questions, sometimes even cracking a smile or unleashing a soft giggle.

“Why are you asking me who I am?” she asks with a chuckle before taking another drag. “I am no one.”

At one point she stops speaking and continues to smoke while scrolling through messages other Periscope users are sending her—mostly lame pick-up lines and other typical online inanities. Footage of her final act has been replaced with a black screen, but the faint voices of emergency personnel can be heard on the audio track, and messages from fellow users shift from playful banter to disbelief to concern.

“Stop messing around,” one of them reads.

“Where did she go? Call the cops!” reads another.

Indeed, it was a fellow Periscope user who alerted emergency services, but by the time they arrived at the station yesterday afternoon it was too late. French police have reportedly launched an investigation into her death.

Before she died, the young French woman reportedly claimed to be a victim of a sexual assault and named her alleged attacker. Whether it was the trauma of rape or another reason that drove her to violently end her life is not known. More unnerving is her decision to broadcast her death to hundreds of strangers. It’s not clear whether it’s a cry for help, since in the video she refuses to divulge any personal details, including her name and location. Had she wanted to feel less alone? Was she seeking empathy? Or in today’s digital world, where we joke that an event never really happened unless it’s posted, tweeted, or streamed, was she merely seeking to document, and thus, validate, the last moments of her life?

“What I want to make clear is that I am not doing this for the hype, but to send a message, to open minds,” she explains in the video.

The precise nature of the message she was hoping to send may never be understood. Instead, we are left a troubling glimpse of a young woman in pain, whom no one could help in time.

http://www.thedailybeast.com/articles/2016/05/11/french-teen-periscopes-her-suicide.html

An immersive virtual reality therapy could help people with depression to be less critical and more compassionate towards themselves, reducing depressive symptoms, finds a new study from UCL (University College London) and ICREA-University of Barcelona.

The therapy, previously tested by healthy volunteers, was used by 15 depression patients aged 23-61. Nine reported reduced depressive symptoms a month after the therapy, of whom four experienced a clinically significant drop in depression severity. The study is published in the British Journal of Psychiatry Open and was funded by the Medical Research Council.

Patients in the study wore a virtual reality headset to see from the perspective of a life-size ‘avatar’ or virtual body. Seeing this virtual body in a mirror moving in the same way as their own body typically produces the illusion that this is their own body. This is called ’embodiment’.

While embodied in an adult avatar, participants were trained to express compassion towards a distressed virtual child. As they talked to the child it appeared to gradually stop crying and respond positively to the compassion. After a few minutes the patients were embodied in the virtual child and saw the adult avatar deliver their own compassionate words and gestures to them. This brief 8-minute scenario was repeated three times at weekly intervals, and patients were followed up a month later.

“People who struggle with anxiety and depression can be excessively self-critical when things go wrong in their lives,” explains study lead Professor Chris Brewin (UCL Clinical, Educational & Health Psychology). “In this study, by comforting the child and then hearing their own words back, patients are indirectly giving themselves compassion. The aim was to teach patients to be more compassionate towards themselves and less self-critical, and we saw promising results. A month after the study, several patients described how their experience had changed their response to real-life situations in which they would previously have been self-critical.”

The study offers a promising proof-of-concept, but as a small trial without a control group it cannot show whether the intervention is responsible for the clinical improvement in patients.

“We now hope to develop the technique further to conduct a larger controlled trial, so that we can confidently determine any clinical benefit,” says co-author Professor Mel Slater (ICREA-University of Barcelona and UCL Computer Science). “If a substantial benefit is seen, then this therapy could have huge potential. The recent marketing of low-cost home virtual reality systems means that methods such as this could potentially be part of every home and be used on a widespread basis.”

Publication: Embodying self-compassion within virtual reality and its effects on patients with depression. Falconer, CJ et al. British Journal of Psychiatry Open (February, 2016)

An international team of researchers has linked specific symptoms of schizophrenia with various anatomical characteristics in the brain, according to research published in NeuroImage.

By analyzing the brain’s anatomy with magnetic resonance imaging (MRI), researchers from the University of Granada, Washington University in St. Louis, and the University of South Florida have demonstrated the existence of distinctive subgroups among patients with schizophrenia who suffer from different symptoms.

These findings could herald a significant step forward in diagnosing and treating schizophrenia.

To perform the study, the researchers conducted the MRI technique “diffusion tensor imaging” on 36 healthy participants and 47 schizophrenic participants.

The researchers found that tests on schizophrenic participants revealed various abnormalities in parts of the corpus callosum, a bundle of neural fibers that connects the left and right cerebral hemispheres and is essential for effective interhemispheric communication.

Different anomalies in the corpus callosum were associated with different symptoms in the schizophrenic participants. An anomaly in one part of the brain structure was associated with strange and disorganized behavior; another anomaly was associated with disorganized thought and speech, as well as negative symptoms such as a lack of emotion; and other anomalies were associated with hallucinations.

In 2014, this same research group proved that schizophrenia is not a single illness. The team demonstrated the existence of 8 genetically distinct disorders, each with its own symptoms. Igor Zwir, PhD, and Javier Arnedo from the University of Granada’s Department of Computer Technology and Artificial Intelligence found that different sets of genes were strongly linked with different clinical symptoms.

“The current study provides further evidence that schizophrenia is a heterogeneous group of disorders, as opposed to a single illness, as was previously thought to be case,” Dr Zwir said in a statement.

While current treatments for schizophrenia tend to be generic regardless of the symptoms exhibited by each patient, the researchers believe that in the future, analyzing how specific gene networks are linked to various brain features and specific symptoms will help develop treatments that are adapted to each patient’s individual disorder.

To conduct the analysis of the gene groups and brain scans, the researchers developed a new, complex analysis of the relationships between different types of data and recommendations regarding new data. The system is similar to that used by companies such as Netflix to determine what movies they want to broadcast.

“To conduct the research, we did not begin by studying individuals who had certain schizophrenic symptoms in order to determine whether they had the corresponding brain anomalies,” said Dr Zwir in a statement. “Instead, we first analyzed the data, and that’s how we discovered these patterns. This type of information, combined with data on the genetics of schizophrenia, will someday be of vital importance in helping doctors treat the disorders in a more precise and effective way.”

Reference
Arnedo J, Mamah D, Baranger DA, et al. Decomposition of brain diffusion imaging data uncovers latent schizophrenias with distinct patterns of white matter anisotropy. NeuroImage. 2015; doi:10.1016/j.neuroimage.2015.06.083.

http://www.psychiatryadvisor.com/schizophrenia-and-psychoses/types-subgroups-schizophrenia-linked-various-different-brain-anomalies-corpus-callosum/article/470226/?DCMP=EMC-PA_Update_rd&cpn=psych_md&hmSubId=&hmEmail=5JIkN8Id_eWz7RlW__D9F5p_RUD7HzdI0&NID=&dl=0&spMailingID=13630678&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=720090900&spReportId=NzIwMDkwOTAwS0

With the pressure for a certain body type prevalent in the media, eating disorders are on the rise. But these diseases are not completely socially driven; researchers have uncovered important genetic and biological components as well and are now beginning to tease out the genes and pathways responsible for eating disorder predisposition and pathology.

As we enter the holiday season, shoppers will once again rush into crowded department stores searching for the perfect gift. They will be jostled and bumped, yet for the most part, remain cheerful because of the crisp air, lights, decorations, and the sound of Karen Carpenter’s contralto voice ringing out familiar carols.

While Carpenter is mainly remembered for her musical talents, unfortunately, she is also known for introducing the world to anorexia nervosa (AN), a severe life-threatening mental illness characterized by altered body image and stringent eating patterns that claimed her life just before her 33rd birthday in 1983.

Even though eating disorders (ED) carry one of the highest mortality rates of any mental illness, many researchers and clinicians still view them as socially reinforced behaviors and diagnose them based on criteria such as “inability to maintain body weight,” “undue influence of body weight or shape on self-evaluation,” and “denial of the seriousness of low body weight” (1). This way of thinking was prevalent when Michael Lutter, then an MD/PhD student at the University of Texas Southwestern Medical Center, began his psychiatry residency in an eating disorders unit. “I just remember the intense fear of eating that many patients exhibited and thought that it had to be biologically driven,” he said.

Lutter carried this impression with him when he established his own research laboratory at the University of Iowa. Although clear evidence supports the idea that EDs are biologically driven—they predominantly affect women and significantly alter energy homeostasis—a lack of well-defined animal models combined with the view that they are mainly behavioral abnormalities have hindered studies of the neurobiology of EDs. Still, Lutter is determined to find the biological roots of the disease and tease out the relationship between the psychiatric illness and metabolic disturbance using biochemistry, neuroscience, and human genetics approaches.

We’ve Only Just Begun

Like many diseases, EDs result from complex interactions between genes and environmental risk factors. They tend to run in families, but of course, for many family members, genetics and environment are similar enough that teasing apart the influences of nature and nurture is not easy. Researchers estimate that 50-80% of the predisposition for developing an ED is genetic, but preliminary genome-wide analyses and candidate gene studies failed to identify specific genes that contribute to the risk.

According to Lutter, finding ED study participants can be difficult. “People are either reluctant to participate, or they don’t see that they have a problem,” he reported. Set on finding the genetic underpinnings of EDs, his team began recruiting volunteers and found 2 families, 1 with 20 members, 10 of whom had an ED and another with 5 out of 8 members affected. Rather than doing large-scale linkage and association studies, the team decided to characterize rare single-gene mutations in these families, which led them to identify mutations in the first two genes, estrogen-related receptor α (ESRRA) and histone deacetylase 4 (HDAC4), that clearly associated with ED predisposition in 2013 (1).

“We have larger genetic studies on-going, including the collection of more families. We just happened to publish these two families first because we were able to collect enough individuals and because there is a biological connection between the two genes that we identified,” Lutter explained.

ESRRA appears to be a transcription factor upregulated by exercise and calorie restriction that plays a role in energy balance and metabolism. HDAC4, on the other hand, is a well-described histone deacteylase that has previously been implicated in locomotor activity, body weight homeostasis, and neuronal plasticity.

Using immunoprecipitation, the researchers found that ESRRA interacts with HDAC4, in both the wild type and mutant forms, and transcription assays showed that HDAC4 represses ESRRA activity. When Lutter’s team repeated the transcription assays using mutant forms of the proteins, they found that the ESRRA mutation seen in one family significantly reduced the induction of target gene transcription compared to wild type, and that the mutation in HDAC4 found in the other family increased transcriptional repression for ESRRA target genes.

“ESRRA is a well known regulator of mitochondrial function, and there is an emerging view that mitochondria in the synapse are critical for neurotransmission,” Lutter said. “We are working on identifying target pathways now.”

Bless the Beasts and the Children

Finding genes associated with EDs provides the groundwork for molecular studies, but EDs cannot be completely explained by the actions of altered transcription factors. Individuals suffering these disorders often experience intense anxiety, intrusive thoughts, hyperactivity, and poor coping strategies that lead to rigid and ritualized behaviors and severe crippling perfectionism. They are less aware of their emotions and often try to avoid emotion altogether. To study these complex behaviors, researchers need animal models.

Until recently, scientists relied on mice with access to a running wheel and restricted access to food. Under these conditions, the animals quickly increase their locomotor activity and reduce eating, frequently resulting in death. While some characteristics of EDs—excessive exercise and avoiding food—can be studied in these mice, the model doesn’t allow researchers to explore how the disease actually develops. However, Lutter’s team has now introduced a promising new model (3).

Based on their previous success with identifying the involvement of ESRRA and HDAC4 in EDs, the researchers wondered if mice lacking ESRRA might make suitable models for studies on ED development. To find out, they first performed immunohistochemistry to understand more about the potential cognitive role of ESRRA.

“ESRRA is not expressed very abundantly in areas of the brain typically implicated in the regulation of food intake, which surprised us,” Lutter said. “It is expressed in many cortical regions that have been implicated in the etiology of EDs by brain imaging like the prefrontal cortex, orbitofrontal cortex, and insula. We think that it probably affects the activity of neurons that modulate food intake instead of directly affecting a core feeding circuit.”

With these data, the team next tried providing only 60% of the normal daily calories to their mice for 10 days and looked again at ESRRA expression. Interestingly, ESRRA levels increased significantly when the mice were insufficiently fed, indicating that the protein might be involved in the response to energy balance.

Lutter now believes that upregulation of ESRRA helps organisms adapt to calorie restriction, an effect possibly not happening in those with ESRRA or HDAC4 mutations. “This makes sense for the clinical situation where most individuals will be doing fine until they are challenged by something like a diet or heavy exercise for a sporting event. Once they start losing weight, they don’t adapt their behaviors to increase calorie intake and rapidly spiral into a cycle of greater and greater weight loss.”

When Lutter’s team obtained mice lacking ESRRA, they found that these animals were 15% smaller than their wild type littermates and put forth less effort to obtain food both when fed restricted calorie diets and when they had free access to food. These phenotypes were more pronounced in female mice than male mice, likely due to the role of estrogen signaling. Loss of ESRRA increased grooming behavior, obsessive marble burying, and made mice slower to abandon an escape hole after its relocation, indicating behavioral rigidity. And the mice demonstrated impaired social functioning and reduced locomotion.

Some people with AN exercise extensively, but this isn’t seen in all cases. “I would say it is controversial whether or not hyperactivity is due to a genetic predisposition (trait), secondary to starvations (state), or simply a ritual that develops to counter the anxiety of weight related obsessions. Our data would suggest that it is not due to genetic predisposition,” Lutter explained. “But I would caution against over-interpretation of mouse behavior. The locomotor activity of mice is very different from people and it’s not clear that you can directly translate the results.”

For All We Know

Going forward, Lutter’s group plans to drill down into the behavioral phenotypes seen in their ESRRA null mice. They are currently deleting ESRRA from different neuronal cell types to pair individual neurons with the behaviors they mediate in the hope of working out the neural circuits involved in ED development and pathology.

In addition, the team has created a mouse line carrying one of the HDAC4 mutations previously identified in their genetic study. So far, this mouse “has interesting parallels to the ESRRA-null mouse line,” Lutter reported.

The team continues to recruit volunteers for larger-scale genetic studies. Eventually, they plan to perform RNA-seq to identify the targets of ESRRA and HDAC4 and look into their roles in mitochondrial biogenesis in neurons. Lutter suspects that this process is a key target of ESRRA and could shed light on the cognitive differences, such as altered body image, seen in EDs. In the end, a better understanding of the cells and pathways involved with EDs could create new treatment options, reduce suffering, and maybe even avoid the premature loss of talented individuals to the effects of these disorders.

References

1. Lutter M, Croghan AE, Cui H. Escaping the Golden Cage: Animal Models of Eating Disorders in the Post-Diagnostic and Statistical Manual Era. Biol Psychiatry. 2015 Feb 12.

2. Cui H, Moore J, Ashimi SS, Mason BL, Drawbridge JN, Han S, Hing B, Matthews A, McAdams CJ, Darbro BW, Pieper AA, Waller DA, Xing C, Lutter M. Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. J Clin Invest. 2013 Nov;123(11):4706-13.

3. Cui H, Lu Y, Khan MZ, Anderson RM, McDaniel L, Wilson HE, Yin TC, Radley JJ, Pieper AA, Lutter M. Behavioral disturbances in estrogen-related receptor alpha-null mice. Cell Rep. 2015 Apr 21;11(3):344-50.

http://www.biotechniques.com/news/Exploring-the-Biology-of-Eating-Disorders/biotechniques-361522.html

An automated speech analysis program correctly differentiated between at-risk young people who developed psychosis over a two-and-a-half year period and those who did not. In a proof-of-principle study, researchers at Columbia University Medical Center, New York State Psychiatric Institute, and the IBM T. J. Watson Research Center found that the computerized analysis provided a more accurate classification than clinical ratings. The study, “Automated Analysis of Free Speech Predicts Psychosis Onset in High-Risk Youths,” was recently published in NPJ-Schizophrenia.

About one percent of the population between the age of 14 and 27 is considered to be at clinical high risk (CHR) for psychosis. CHR individuals have symptoms such as unusual or tangential thinking, perceptual changes, and suspiciousness. About 20% will go on to experience a full-blown psychotic episode. Identifying who falls in that 20% category before psychosis occurs has been an elusive goal. Early identification could lead to intervention and support that could delay, mitigate or even prevent the onset of serious mental illness.
Speech provides a unique window into the mind, giving important clues about what people are thinking and feeling. Participants in the study took part in an open-ended, narrative interview in which they described their subjective experiences. These interviews were transcribed and then analyzed by computer for patterns of speech, including semantics (meaning) and syntax (structure).

The analysis established each patient’s semantic coherence (how well he or she stayed on topic), and syntactic structure, such as phrase length and use of determiner words that link the phrases. A clinical psychiatrist may intuitively recognize these signs of disorganized thoughts in a traditional interview, but a machine can augment what is heard by precisely measuring the variables. The participants were then followed for two and a half years.
The speech features that predicted psychosis onset included breaks in the flow of meaning from one sentence to the next, and speech that was characterized by shorter phrases with less elaboration. The speech classifier tool developed in this study to mechanically sort these specific, symptom-related features is striking for achieving 100% accuracy. The computer analysis correctly differentiated between the five individuals who later experienced a psychotic episode and the 29 who did not. These results suggest that this method may be able to identify thought disorder in its earliest, most subtle form, years before the onset of psychosis. Thought disorder is a key component of schizophrenia, but quantifying it has proved difficult.

For the field of schizophrenia research, and for psychiatry more broadly, this opens the possibility that new technology can aid in prognosis and diagnosis of severe mental disorders, and track treatment response. Automated speech analysis is inexpensive, portable, fast, and non-invasive. It has the potential to be a powerful tool that can complement clinical interviews and ratings.

Further research with a second, larger group of at-risk individuals is needed to see if this automated capacity to predict psychosis onset is both robust and reliable. Automated speech analysis used in conjunction with neuroimaging may also be useful in reaching a better understanding of early thought disorder, and the paths to develop treatments for it.

http://medicalxpress.com/news/2015-08-psychosis-automated-speech-analysis.html

Schizophrenia is associated with structural and functional alterations of the visual system, including specific structural changes in the eye. Tracking such changes may provide new measures of risk for, and progression of the disease, according to a literature review published online in the journal Schizophrenia Research: Cognition, authored by researchers at New York Eye and Ear Infirmary of Mount Sinai and Rutgers University.

Individuals with schizophrenia have trouble with social interactions and in recognizing what is real. Past research has suggested that, in schizophrenia, abnormalities in the way the brain processes visual information contribute to these problems by making it harder to track moving objects, perceive depth, draw contrast between light and dark or different colors, organize visual elements into shapes, and recognize facial expressions. Surprisingly though, there has been very little prior work investigating whether differences in the retina or other eye structures contribute to these disturbances.

“Our analysis of many studies suggests that measuring retinal changes may help doctors in the future to adjust schizophrenia treatment for each patient,” said study co-author Richard B. Rosen, MD, Director of Ophthalmology Research, New York Eye and Ear Infirmary of Mount Sinai, and Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai. “More studies are needed to drive the understanding of the contribution of retinal and other ocular pathology to disturbances seen in these patients, and our results will help guide future research.”

The link between vision problems and schizophrenia is well established, with as many as 62 percent of adult patients with schizophrenia experience visual distortions involving form, motion, or color. One past study found that poorer visual acuity at four years of age predicted a diagnosis of schizophrenia in adulthood, and another that children who later develop schizophrenia have elevated rates of strabismus, or misalignment of the eyes, compared to the general population.

Dr. Rosen and Steven M. Silverstein, PhD, Director of the Division of Schizophrenia Research at Rutgers University Behavioral Health Care, were the lead authors of the analysis, which examined the results of approximately 170 existing studies and grouped the findings into multiple categories, including changes in the retina vs. other parts of the eye, and changes related to dopamine vs. other neurotransmitters, key brain chemicals associated with the disease.

The newly published review found multiple, replicated, indicators of eye abnormalities in schizophrenia. One of these involves widening of small blood vessels in the eyes of schizophrenia patients, and in young people at high risk for the disorder, perhaps caused by chronic low oxygen supply to the brain. This could explain several key vision changes and serve as a marker of disease risk and worsening. Also important in this regard was thinning of the retinal nerve fiber layer in schizophrenia, which is known to be related to the onset of hallucinations and visual acuity problems in patients with Parkinson’s disease. In addition, abnormal electrical responses by retinal cells exposed to light (as measured by electroretinography) suggest cellular-level differences in the eyes of schizophrenia patients, and may represents a third useful measure of disease progression, according to the authors.

In addition, the review highlighted the potentially detrimental effects of dopamine receptor-blocking medications on visual function in schizophrenia (secondary to their retinal effects), and the need for further research on effects of excessive retinal glutamate on visual disturbances in the disorder.

Interestingly, the analysis found that there are no reports of people with schizophrenia who were born blind, suggesting that congenital blindness may completely or partially protect against the development of schizophrenia. Because congenitally blind people tend to have cognitive abilities in certain domains (e.g., attention) that are superior to those of healthy individuals, understanding brain re-organization after blindness may have implications for designing cognitive remediation interventions for people with schizophrenia.

“The retina develops from the same tissue as the brain,” said Dr. Rosen. “Thus retinal changes may parallel or mirror the integrity of brain structure and function. When present in children, these changes may suggest an increased risk for schizophrenia in later life. Additional research is needed to clarify these relationships, with the goals of better predicting emergence of schizophrenia, and of predicting relapse and treatment response and people diagnosed with the condition.”

Dr. Silverstein points out that, to date, vision has been understudied in schizophrenia, and studies of the retina and other ocular structures in the disorder are in their infancy. However, he added, “because it is much faster and less expensive to obtain data on retinal structure and function, compared to brain structure and function, measures of retinal and ocular structure and function may have an important role in both future research studies and the routine clinical care of people with schizophrenia.”

http://www.eurekalert.org/pub_releases/2015-08/tmsh-rcm081715.php