Method Enables 3-D Analysis of Fine Structure and Connections – NIH-funded Study
A breakthrough method, called CLARITY, developed by National Institutes of Health-funded researchers, opens the intact postmortem brain to chemical, genetic and optical analyses that previously could only be performed using thin slices of tissue. By replacing fat that normally holds the brain’s working components in place with a clear gel, they made its normally opaque and impenetrable tissue see-through and permeable. This made it possible to image an intact mouse brain in high resolution down to the level of cells and molecules. The technique was even used successfully to study a human brain.
“CLARITY has the potential to unmask fine details of brains from people with brain disorders without losing larger-scale circuit perspective.”
The physicist and mathematician Freeman Dyson once noted, “New directions in science are launched by new tools much more often than by new concepts.” This week marks the publication of a new tool that may alter the way we look at the brain. Karl Deisseroth and his colleagues at Stanford University have developed a method they call CLARITY. Yes, CLARITY is an acronym, for Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel.
By replacing the brain’s fat with a clear gel, CLARITY turns the opaque and impenetrable brain into a transparent and permeable structure. Most important, the hydrogel holds the brain’s anatomy intact. And because the hydrogel is permeable, the brain can be stained to localize proteins, neurotransmitters, and genes at a high resolution (see images below). Unlike other recent breakthroughs in neuroanatomy, this one can be used in human brains.
This technique is only for post-mortem tissue. And it measures structure not function. But I predict this new tool will revolutionize neuropathology, opening a new era for studying the neural basis of mental disorders. Indeed, in this initial report Deisseroth and his colleagues describe findings from a brain of someone who had died with autism 6 years earlier. With CLARITY they detected an unusual pattern of bridging connections from a particular class of inhibitory cells in this brain. Of course, this finding from a single brain needs to be replicated. The beauty of CLARITY is that other brains can now be tested, even tissue that has been stored for years.
by Thomas Insel, NIMH
A new study showed that a weight-loss intervention can help overweight and obese people with serious mental illnesses—such as schizophrenia, bipolar disorder and major depression—lose significant weight and keep it off.
More than 80% of people with serious mental illnesses are overweight or obese—a major factor that helps lead to a death rate 3 times that of the overall population. Factors that contribute to obesity include unhealthy eating habits and lack of physical activity. Medications to help control mental illness symptoms can increase appetite and encourage weight gain. Adding to these challenges, people with serious mental illnesses may have impairments in memory and mental processes that make it more difficult for them to learn and adopt new weight loss behaviors such as counting calories.
To address the problem, researchers led by Dr. Gail L. Daumit at Johns Hopkins University tested the effectiveness of an 18-month behavioral weight-loss program tailored for adults with serious mental illnesses. The findings demonstrate that overweight and obese adults with serious mental illness can adopt healthy habits while in an outpatient psychiatric rehabilitation program. “We’re showing that serious mentally ill patients can make successful, sustained changes with proper interventions,” Daumit says. The researchers now hope to expand the program.
–National Institutes of Health (NIH)
Behavioral health providers agree that following detention or arrest, the best place for many people with mental illness or addictions is in community treatment, not in jail or prison. Not only is it good public policy from a health perspective, but it saves money for the counties and states, since treatment in the community is far less costly than incarceration.
Most people who end up in jail who have mental illness are not dangerous and have not committed any violent crime, said Polzin. Two of every three people with a mental illness who end up in jail “are there because they have decompensated in some way, become a nuisance, trespassed, done this or that which is not socially acceptable,” said Polzin. “They commit a minor misdemeanor offense, and then they sit in jail because they are not able to post bond.”
Those with a mental illness who are fortunate enough to have benefits such as Medicaid or SSI find those benefits are suspended or terminated by federal law when they enter incarceration, even before trial when they are presumed innocent. Thus, he explains, the costs for any mental health treatment they receive – as well as the jail costs – become ‘100-percent county costs,’ he said, noting that in most cases, counties run the most of the nation’s jails. He called the costs of such treatment “a huge burden for counties.”
by Alison Knopf, Behavioral Healthcare
Today at the White House, President Obama unveiled the “BRAIN” Initiative—a bold new research effort to revolutionize our understanding of the human mind and uncover new ways to treat, prevent, and cure brain disorders like Alzheimer’s, schizophrenia, autism, epilepsy, and traumatic brain injury.
The BRAIN Initiative — short for Brain Research through Advancing Innovative Neurotechnologies — builds on the President’s State of the Union call for historic investments in research and development to fuel the innovation, job creation, and economic growth that together create a thriving middle class.
The Initiative promises to accelerate the invention of new technologies that will help researchers produce real-time pictures of complex neural circuits and visualize the rapidfire interactions of cells that occur at the speed of thought. Such cutting-edge capabilities, applied to both simple and complex systems, will open new doors to understanding how brain function is linked to human behavior and learning, and the mechanisms of brain disease.
by Francis Collins and Arati Prabhakar
Currently, there are 11 first-generation antipsychotics (FGA) and 10 second-generation antipsychotics (SGA) available to treat patients with schizophrenia. Clinicians tend to favor SGAs; 75 percent of patients with schizophrenia were prescribed an SGA in 2003. Despite these preferences, there is controversy over the comparative benefits and disadvantages of FGAs and SGAs. A recent review of studies showed few differences of clinical importance between FGAs and SGAs. A total of 263 publications representing 114 primary studies were identified from the literature for inclusion in the analysis. Of these, 110 were randomized clinical trials. A total of 22 drug comparisons were included. All studies were published between 1974 and 2012.
Overall, there was low or insufficient strength of evidence from the studies. Wide variation existed in the ways symptoms were measured. In addition, there were only a small number of studies for specific drug comparisons. Nevertheless, the researchers were able to draw some conclusions. First, when it came to treating core illness symptoms, few differences of clinical importance were observed between FGAs and SGAs and those differences depended on the measure used for the symptoms. The FGA haloperidol appeared to be better than the SGA olanzapine for improving positive symptoms, such as hallucinations, delusions, and thought and movement disorders. However, the level of evidence was stronger for SGAs when it came to treating negative symptoms, such as flat affect and the lack of pleasure in everyday life. In this case, olanzapine was better than haloperidol.
Although the strength of evidence was low regarding medication-associated side effects, there was a higher incidence of developing the metabolic syndrome with olanzapine than for haloperidol. A higher incidence of tardive dyskinesia (repetitive and involuntary movements) was found for the FGA chlorpromazine than for the SGA clozapine. No differences in mortality were found for chlorpromazine versus clozapine or haloperidol versus the SGA aripiprazole.
–Agency for Healthcare Research and Quality
Research suggests that targeted stimulation of the brain’s prefrontal cortex is a promising treatment for addiction.
Could drug addiction treatment of the future be as simple as an on/off switch in the brain? A study in rats has found that stimulating a key part of the brain reduces compulsive cocaine-seeking and suggests the possibility of changing addictive behavior generally. The study, published in Nature, was conducted by scientists at the Intramural Research Program of the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the University of California, San Francisco.
“This exciting study offers a new direction of research for the treatment of cocaine and possibly other addictions,” said NIDA Director Dr. Nora D. Volkow. “We already knew, mainly from human brain imaging studies, that deficits in the prefrontal cortex are involved in drug addiction. Now that we have learned how fundamental these deficits are, we feel more confident than ever about the therapeutic promise of targeting that part of the brain.”
Compulsive drug-taking, despite negative health and social consequences, has been the most difficult challenge in human drug addiction. NIDA researchers used an animal model of cocaine addiction, in which some rats exhibited addictive behavior by pushing levers to get cocaine even when followed by a mild electric shock to the foot. Other rats did not exhibit addictive responses.
–National Institutes of Health (NIH)
The mental health effects associated with prolonged solitary confinement demand close consideration and should influence any future policy on use of the practice in U.S. prisons.
Anthony Graves, an exonerated former death-row inmate, spent the majority of his 18 years at a Texas prison in solitary confinement.
“I lived under the rules of a system that is literally driving men out of their minds,” said Graves in describing the inhumane conditions of serving time in a small cell without access to human interaction or proper medical care. “No one can begin to imagine the psychological effects isolation has on another human being.”
According to recent estimates from the Web-based advocacy project Solitary Watch, approximately 82,000 inmates are currently segregated in federal and state prison systems in the United States. And a 2010 study published by the American Academy of Psychiatry and the Law (AAPL) concluded that segregation over prolonged periods of time has the capacity to induce harmful psychological effects such as anxiety, anger, cognitive disturbance, perceptual distortion, obsessive thoughts, paranoia, and psychosis.
The AAPL study also estimated that between 8 percent and 19 percent of current U.S. prisoners suffer from psychiatric disorders, with an additional 15 percent to 20 percent of prisoners requiring some form of psychiatric intervention during incarceration. These individuals, according to AAPL’s findings, often require costly psychiatric hospitalization or crisis-intervention services, and face a heightened risk of suicide.
by Jonathan Wolfe, Psychiatric News
Shining a light on particular cells in the prefrontal cortex can reduce cocaine addiction in rats, according to a study published April 3 in Nature. The senior scientist was Antonello Bonci, M.D., scientific director of the National Institute on Drug Abuse (NIDA). “Our results can be immediately translated to clinical research settings with humans, and we are planning clinical trials to stimulate this brain region using noninvasive methods,” Bonci reported in a press statement. “By targeting a specific portion of the prefrontal cortex, our hope is to reduce compulsive cocaine-seeking and craving in patients.”
“This exciting study offers a new direction in research for the treatment of cocaine and possibly other addictions,” added NIDA Director Nora Volkow, M.D. “We already knew, mainly from human brain imaging studies, that deficits in the prefrontal cortex are involved in drug addiction. Now that we have learned how fundamental these deficits are, we feel more confident than ever about the therapeutic promise of targeting that part of the brain.”
–Psychiatric News Alert
Up to twelve chromosome regions may harbor genes for keeping the brain in good working order, reports a new study by Brain & Behavior Research Foundation NARSAD Grantee David Braff, M.D., and his research team. Because problems with certain jobs done by the brain, such as remembering information, have been linked to schizophrenia, pinpointing the genes that help those jobs get done well may be a backdoor route to finding genes that contribute to the disorder.
Problems with certain brain functions, including those related to attention, memory, verbal learning and the ability to suppress a movement were sometimes associated with certain stretches of DNA (molecules that contain heredity encoding information) along the chromosomes. For example, a person’s ability to suppress an eye movement was associated with a region of chromosome 3.
by David Braff, M.D.