NIMH » Accelerating Science to Advance Early Interventions for Schizophrenia


It unfolds gradually. Grades may start to slip; friendships melt away. You notice new and unusual behaviors, fragmented and circuitous sentences. You wonder what happened to the bright, engaging child you once knew. After a while, you realize—something is really different here. You ask for help and your family doctor sends you to a specialist or an emergency room, and maybe you hear a word you hadn’t really thought of before: schizophrenia.

Schizophrenia is a serious mental illness, affecting multiple facets of the lives of those who bear its burden. Impaired cognition, altered social functioning, and symptoms of psychosis—including disordered thoughts, auditory hallucinations, and paranoid delusions—are all characteristic features of schizophrenia. Untreated, these symptoms can become disabling, impairing one’s ability to learn, work, and participate in family and community life. The good news is that effective treatments are available. A combination of medication, cognitive and behavioral therapies, school and job support, and family education and support can help many, particularly if these interventions are started early in the course of the illness.

Given the importance of early intervention, NIMH-funded research has focused on understanding how schizophrenia emerges in teenagers and young adults. This work has shown that many young people who receive a schizophrenia diagnosis experienced a prolonged period of functional decline before they were diagnosed. Individuals in this clinical high risk (CHR) group face significant challenges. But collectively, this group also offers researchers unique insight into the factors that predict a person’s clinical trajectory. For example, the NIMH-funded North American Prodrome Longitudinal Study has developed a tool that uses clinical and cognitive evaluations to estimate psychosis risk for individuals identified as being at CHR. Getting these folks into treatment programs early may help reduce the impact of the illness and maximize their chances of recovery.

Even with early evidence-based treatment, many individuals with schizophrenia will experience significant, life-altering disability. While modestly effective for psychotic symptoms such as hallucinations or delusions, current pharmacologic treatments often leave the social and cognitive symptoms of schizophrenia untouched. Truly novel advances that transform the lives of those with schizophrenia have proved challenging to discover and develop.

It is now clear that achieving these advances requires a truly novel research effort, one that engages the entire mental health community—scientists, clinicians, pharmaceutical companies, regulators, advocates, and those with lived experience. That is why NIMH, in concert with the Foundation for the National Institutes of Health (FNIH) and public and private partners, just launched the Accelerating Medicines Partnership (AMP) Schizophrenia initiative, part of the broader AMP program managed by FNIH.

AMP Schizophrenia represents the first foray of AMP into research on mental illnesses, and it builds on successful AMP endeavors focused on Alzheimer’s disease, autoimmune disorders, diabetes, and Parkinson’s disease. AMP Schizophrenia partners comprise non-profit organizations, including the American Psychiatric Association Foundation, National Alliance on Mental Illness, One Mind, and Wellcome; pharmaceutical companies, including Boehringer Ingelheim, Janssen, and Otsuka; and federal agencies, including the U.S. Food and Drug Administration, European Medicines Agency, and NIH.

AMP Schizophrenia seeks to capitalize on these partnerships to develop novel treatment approaches that will make a meaningful difference in the lives of individuals identified as being at CHR. It seeks to build on the promise that detection and intervention before psychosis develops could attenuate, postpone, or even prevent the transition to psychosis, and improve individuals’ clinical and functional outcomes. AMP Schizophrenia will develop measures that further define the early stages of risk and predict the likelihood of progression to psychosis and other outcomes. Such tools will enable clinical trials to test new pharmacologic interventions that probe the biological mechanisms leading to the CHR state, aim to treat symptom domains in addition to psychosis, and seek to prevent the onset of schizophrenia.

Getting AMP Schizophrenia off the ground was no easy feat. It has required ongoing support from FNIH, the intense efforts of no fewer than three NIMH Directors (my predecessors, Tom Insel, M.D., and Steve Hyman, M.D., began the process some time ago), a strong push from the National Alliance on Mental Illness, and vigorous engagement from our other partners to bring it to fruition.

The initial effort of AMP Schizophrenia will support a network of academic and community-based research sites to study a large cohort of individuals identified as being at CHR. The lead investigators of this CHR research network include Scott Woods, M.D., at Yale University; Carrie Bearden, Ph.D., at the University of California, Los Angeles; John Kane, M.D., at Northwell Health and Hofstra University; and Barnaby Nelson, Ph.D., and Patrick McGorry, M.D., Ph.D., at Orygen and Melbourne University. Together, these researchers will be recruiting more than 1,000 individuals at CHR across 42 clinical sites, collecting a variety of clinical, behavioral, and biomarker data to understand and predict outcomes.

A data processing, analysis, and coordination center, led by Martha Shenton, Ph.D., at Brigham and Women’s Hospital and Harvard University, and Rene Kahn, M.D., Ph.D., at the Icahn School of Medicine at Mount Sinai, will integrate and analyze CHR biomarker and clinical data generated by the CHR research network and existing CHR-related datasets, in collaboration with the AMP Schizophrenia partners and research network lead investigators. Data from AMP Schizophrenia will be available to the research community for additional analyses via the NIMH Data Archive.

That is just the first phase. In the second phase of the initiative, researchers will use the findings from the CHR cohort to form specific, testable hypotheses about key brain mechanisms underlying the early stages of schizophrenia. The aim is to draw on academic and pharmaceutical industry partners’ expertise to design clinical trials that target these brain mechanisms. With guidance from the nonprofit partners, these trials will also address the specific needs of individuals at CHR, focusing not only on reducing or preventing future illness but also on improving well-being and maximizing recovery in the moment.

We’re very excited about this major step forward. AMP Schizophrenia marks a major public-private partnership for psychiatry—and a major new endeavor aimed squarely at helping reduce the impact of serious mental illnesses. Thanks to all the partners and hard-working people at FNIH and NIMH who helped us get this off the ground, the future looks a little brighter for early intervention in schizophrenia.

References

Cannon, T. D., Changhong, Y., Addington, J., Bearden, C. E., Cadenhead, K. S., Cornblatt, B. A., Heinssen, R., Jeffries, C. D., Mathalon, D. H., McGlashan, T. H., Perkins, D. O., Seidman, L. J., Tsuang, M. T., Walker, E. F., Woods, S. W., & Kattan, M. W. (2016). An individualized risk calculator for research in prodromal psychosis. The American Journal of Psychiatry, 173(10), 980-988. doi: 10.1176/appi.ajp.2016.15070890



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Accelerating water dissociation in bipolar membranes and for electrocatalysis


Easing water apart

Traditional setups for splitting water into hydrogen and oxygen operate either in acid or in base. A bipolar membrane can potentially enhance efficiency by bridging acidic hydrogen evolution to basic oxygen evolution. Oener et al. undertook a systematic study of how catalysts paired with such a membrane might accelerate the preliminary step of water dissociation into protons and hydroxide ions. Using insights from this study for optimal catalyst integration, they were able to substantially lower the overpotential of a bipolar membrane electrolyzer.

Science, this issue p. 1099

Abstract

Catalyzing water dissociation (WD) into protons and hydroxide ions is important both for fabricating bipolar membranes (BPMs) that can couple different pH environments into a single electrochemical device and for accelerating electrocatalytic reactions that consume protons in neutral to alkaline media. We designed a BPM electrolyzer to quantitatively measure WD kinetics and show that, for metal nanoparticles, WD activity correlates with alkaline hydrogen evolution reaction activity. By combining metal-oxide WD catalysts that are efficient near the acidic proton-exchange layer with those efficient near the alkaline hydroxide-exchange layer, we demonstrate a BPM driving WD with overpotentials of <10 mV at 20 mA·cm−2 and pure water BPM electrolyzers that operate with an alkaline anode and acidic cathode at 500 mA·cm−2 with a total electrolysis voltage of ~2.2 V.



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WHO warns coronavirus pandemic is accelerating


WHO warns coronavirus pandemic is accelerating

The World Health Organisation has warned the coronavirus pandemic is entering a new phase.

In a new single day record, more than 150,000 new cases were reported.

The majority were recorded in The Americas, accounting for about half of the new cases.

Large outbreaks are also occurring in the Middle East and South Asia.

The WHO said it was concerned about the health and safety of people living in refugee camps and countries emerging from lockdown.

More than eight million infections have been recorded since the outbreak began.



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COVID-19 pandemic is accelerating, WHO chief warns


“Many people are understandably fed up with being at home (and) countries are understandably eager to open up their societies.” But Tedros warned that measures like social distancing, mask wearing and hand-washing were still critical.

More than 8.53 million people have been reported infected by the novel coronavirus globally and 453,834​ have died, a Reuters tally shows.

WHO emergencies expert Mike Ryan drew attention to the situation in Brazil, where he said there had been 1230 additional COVID-19 deaths in the previous 24 hours.

About 12 per cent of infections in Brazil involved healthcare workers, he added, praising their bravery. Brazil has the world’s worst outbreak outside the US, with 978,142 confirmed cases and 47,748 deaths.

A suspected coronavirus patient is taken to an ambulance in Mexico City on Friday.

A suspected coronavirus patient is taken to an ambulance in Mexico City on Friday.Credit:Getty Images

‘Difficult journey’ to vaccine

With many nations easing restrictions but fearful of a second wave of infections, Ryan urged a gradual and scientific approach.

“Exiting lockdowns must be done carefully, in a step-wise manner, and must be driven by the data,” he said. “If you don’t know where it is, the chances are the virus will surprise you.”

Ryan said the resurgence of new clusters did not necessarily mean a second wave, while “second peaks” were also possible in one wave. The emergencies expert praised Germany, China and South Korea for their handling of the pandemic.

With trials under way around the world to find medicines and a vaccine for COVID-19, WHO officials warned that large-scale testing would be needed with side-effects carefully monitored.

“Although it is not impossible to find a vaccine … it’s going to be a very difficult journey,” Tedros said.

Virus was in wastewater in northern Italy before Christmas

A study by Italy’s National Institute of Health has found that the new coronavirus was in circulation in wastewater in the northern cities of Milan and Turin in December 2019, at least two months before the virus was confirmed to have spread locally in the population.

The study, released on Thursday, was based on 40 water samples collected as part of regular checks from sewage treatment plants in northern Italy from October 2019 to February 2020. It showed the virus that causes COVID-19 in December 18 samples from Milan and Turin, while earlier samples were negative.

“This research can contribute to understanding the beginning of the circulation of the virus in Italy,” the institute said in a statement.

The research has so far not linked any confirmed cases to the virus’ earlier presence, but researchers have proposed using the system to monitor the presence of the new coronavirus in water systems in a bid to help identify any possible new outbreaks.

A pilot monitoring system will launch next month in tourist destinations, in preparation for wider monitoring ahead of a possible new spike in contagion next autumn, the institute said.

New cases remain stable in China

New coronavirus cases remained stable in China’s capital on Friday, a day after a public health official declared Beijing’s latest outbreak under control.

Beijing recorded 25 new cases, up by just four from Thursday, out of a total of 32 cases reported nationwide.

Beijing has confirmed 183 new cases over the past week, but an official of the Chinese Centre for Disease Control and Prevention said on Thursday that the daily numbers should begin to decline soon. Wu Zunyou said such outbreaks were inevitable, although this one was larger than expected because it spread from Beijing’s main wholesale market.

Classes in the city have been suspended and opening-up plans for everything from sports events to art exhibitions are on hold.

A worker disinfects a site where Beijing residents are being tested for COVID-19.

A worker disinfects a site where Beijing residents are being tested for COVID-19.Credit:Getty Images

China’s latest virus outbreak likely came from Europe

The WHO confirmed on Friday that the UN agency received genetic sequences from China involving Beijing’s recent coronavirus outbreak and said it appeared the virus was exported from Europe.

Michael Ryan noted that “strains and viruses have moved around the world” throughout the virus pandemic and said the fact that a virus from Europe sparked China’s latest outbreak did not mean the virus originated there.

“What it’s saying most likely is that the disease was probably imported from outside Beijing at some point,” Ryan said, adding that “establishing when that happened and how long the chain of transmission is, is important.” He said that many coronavirus strains spreading in New York could also be linked to Europe.

Ryan said that analysis of the genetic sequences China provided so far suggests that the virus spread from other people – and does not suggest that it jumped to humans from animals.

After the new coronavirus was first detected in the Chinese city of Wuhan in late December, officials hypothesised that it likely jumped into people from animals at a wildlife market, although the species responsible has never been identified.

“This coronavirus (in China’s latest outbreak) looks very much like it’s of human origin,” Ryan said, calling for a detailed investigation to determine how the imported cases sparked such a large cluster.

Virus spreads in South Korea

The coronavirus continues to spread in South Korea, particularly in the densely populated Seoul metropolitan region, which is home to half the country’s 51 million people.

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The Korea Centre for Disease Control and Prevention reported 49 new cases for the nation on Friday, with 26 of them in Seoul and the nearby port city of Incheon. South Korea has had a total of 12,306 infections, including 280 deaths.

Officials have been reporting around 30 to 50 new cases a day since late May, inspiring second guessing on whether officials were too quick to ease social distancing guidelines in April after the country’s first wave of infections waned.

Hundreds of cases in the Seoul area have been linked to leisure and religious activities and low-income workers who can’t afford to stay home.

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