Ketamine reverses neural changes underlying depression-related behaviors in mice

Researchers have identified ketamine-induced brain-related changes that are responsible for maintaining the remission of behaviors related to depression in mice — findings that may help researchers develop interventions that promote lasting remission of depression in humans. The study, funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, appears in the journal Science.

Major depression is one of the most common mental disorders in the United States, with approximately 17.3 million adults experienced a major depressive episode in 2017. However, many of the neural changes underlying the transitions between active depression, remission, and depression re-occurrence remain unknown. Ketamine, a fast-acting antidepressant which relieves depressive symptoms in hours instead of weeks or longer, provides an opportunity for researchers to investigate the short- and long-term biological changes underlying these transitions.

“Ketamine is a potentially transformative treatment for depression, but one of the major challenges associated with this drug is sustaining recovery after the initial treatment,” said study author Conor Liston, M.D., Ph.D., of Weill Cornell Medicine, New York City.

Full story at Science Daily

NIH Study Shows Many Preteens Screen Positive for Suicide Risk During ER Visits

A research team found nearly one-third of youth ages 10 to 12 years screened positive for suicide risk in emergency department settings. As part of a larger study on youth suicide risk screening in emergency departments, researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, and collaborators sought to explore how frequently preteen youth ages 10 to 12 screened positive for suicide risk. Notably, 7 percent of the preteens who screened positive for suicide risk were seeking help for physical – not psychiatric – concerns. The study appears online March 11 in Hospital Pediatrics.

“Typically, suicidal thoughts and behaviors are seen in older teens. It was troubling to see that so many preteens screened positive for suicide risk, and we were alarmed to find that many of them had acted on their suicidal thoughts in the past,” said Lisa Horowitz, Ph.D., M.P.H., a clinical scientist in the NIMH Division of Intramural Research Programs (DIRP) and an author on the paper. “This study shows that children as young as 10 who show up in the emergency department may be thinking about suicide, and that screening all preteens — regardless of their presenting symptoms — may save lives. Otherwise, they may pass through our medical systems undetected.”

Full story at NIMH

Neuromelanin-Sensitive MRI Identified as a Potential Biomarker for Psychosis

Researchers have shown that a type of magnetic resonance imaging — called neuromelanin-sensitive MRI (NM-MRI) — is a potential biomarker for psychosis. NM-MRI signal was found to be a marker of dopamine function in people with schizophrenia and an indicator of the severity of psychotic symptoms in people with this mental illness. The study, funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, appears in the Proceedings of the National Academy of Science.

“Disturbances affecting the neurotransmitter dopamine are associated with a host of mental and neurological disorders, such as schizophrenia and Parkinson’s disease,” said Joshua A. Gordon, M.D., Ph.D., director of NIMH. “Because of the role dopamine plays in these disorders, the ability to measure dopamine activity is critical for furthering our understanding of these disorders, including how to best diagnose and treat them.”

Neuromelanin is a dark pigment created within dopamine neurons of the midbrain — particularly in the substantia nigra, a brain area that plays a role in reward and movement. Neuromelanin accumulates over the lifespan and is only cleared away from cells following cell death, as occurs in neurodegenerative disorders such as Parkinson’s disease. Researchers have found that NM-MRI signal is lower in the substantia nigra of people with Parkinson’s disease, reflecting the cell death that occurs in these patients.

Full story at NIMH

Mega Docking Library Poised to Speed Drug Discovery

Researchers have launched an ultra-large virtual docking library expected to grow to more than 1 billion molecules by next year. It will expand by 1000-fold the number of such “make-on-demand” compounds readily available to scientists for chemical biology and drug discovery. The larger the library, the better its odds of weeding out inactive “decoy” molecules that could otherwise lead researchers down blind alleys. The project is funded by the National Institutes of Health.

“To improve medications for mental illnesses, we need to screen huge numbers of potentially therapeutic molecules,” explained Joshua A. Gordon, M.D., Ph.D., director of NIH’s National Institute of Mental Health (NIMH), which co-funded the research. “Unbiased computational modeling allows us to do this in a computer, vastly expediting the process of discovering new treatments. It enables researchers to virtually “see” a molecule docking with its receptor protein – like a ship in its harbor berth or a key in its lock – and predict its pharmacological properties, based on how the molecular structures are predicted to interact. Only those relatively few candidate molecules that best match the target profile on the computer need to be physically made and tested in a wet lab.”

Full story at NIMH

New Findings Reveal Surprising Role of the Cerebellum in Reward and Social Behaviors

A new study in rodents has shown that the brain’s cerebellum—known to play a role in motor coordination—also helps control the brain’s reward circuitry. Researchers found a direct neural connection from the cerebellum to the ventral tegmental area (VTA) of the brain, which is an area long known to be involved in reward processing and encoding. These findings, published in Science, demonstrate for the first time that the brain’s cerebellum plays a role in controlling reward and social preference behavior, and sheds new light on the brain circuits critical to the affective and social dysfunction seen across multiple psychiatric disorders. The research was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

“This type of research is fundamental to deepening our understanding of how brain circuit activity relates to mental illnesses,” said Joshua A. Gordon, M.D., Ph.D., director of NIMH. “Findings like the ones described in this paper help us learn more about how the brain works, a key first step on the path towards developing new treatments.”

Full story at NIMH

Hyperconnectivity in a brain circuit may predict psychosis

National Institute of Mental Health (NIMH)-funded scientists have discovered a pattern in the way a brain circuit works that may help predict the onset of psychosis. High levels of chatter, or “hyperconnectivity,” in a circuit involving the cerebellum, thalamus, and cortex emerged as a potential “neural signature” in a functional magnetic resonance imaging (fMRI) study by Tyrone Cannon, Ph.D.of Yale University and colleagues.

The degree of hyperconnectivity within this circuit predicted the length of time it took for an individual to convert from a state of risk to full psychosis – hallucinations, delusions, and disorganized thought and behavior. The researchers also found this same pattern of hyperactivity in a separate group of individuals with schizophrenia.

Full story at NIMH

Diversity Training Programs Nurture Research Career

“It had never occurred to me to do a Ph.D. It’s nothing I’d ever thought of. I didn’t know anyone who’s done a science Ph.D.,” noted Frances Johnson just weeks before matriculating in a neuroscience doctoral program at the University of Pittsburgh. She was just completing a summer stint as a trainee in a neuroscience lab at the National Institute of Mental Health (NIMH) Intramural Research Program on the NIH campus in Bethesda, MD.

A U.S. Army veteran and math major at Western Connecticut State University –  who at times paid the bills working as a substitute teacher – Johnson says her interest in understanding the brain was sparked by curiosity about the origins of a friend’s post-traumatic stress disorder (PTSD) symptoms.

“What caused something like that?” she asked herself. “I think everybody has this kind of curiosity. We have people in our lives, we have family members – especially around mental health.”

Full story at NIMH

NIMH Explores the “Next Big Thing” in Mental Health Services Research

What’s the “next big thing” that could help people with mental illnesses get the treatment and services they need? This important question was the theme of the National Institute of Mental Health (NIMH)’s 24th biennial Mental Health Services Research (MHSR 2018) conference held August 1-2, in Rockville, MD.

“This conference brings together mental health researchers and other experts, trainees, consumers, advocates, and mental health care providers to learn about current research findings and discuss new research that might close the gap between what science shows is most effective and what services people actually receive in real-world settings,” explained Michael Freed, Ph.D., EMT-B., a conference co-chair. “We are thrilled that this year the conference had more presentation proposals, more sessions, and more attendees than ever before. There is clearly a lot of interest in this research.”

Health services research is a multidisciplinary scientific field that examines how to improve people’s access to health care providers and services; how to improve the quality, continuity, and equity of the care they receive; how to most efficiently pay for needed health care; and ultimately, how to improve the symptoms and functioning of people with health conditions. The research considers individual and provider preferences and behavior, innovations in technology, and community, organizational, and systems-level factors to understand how to implement effective practices in care-delivery settings.

Full story at NIMH

Understanding the Brain Mechanisms of Irritability in Youth

In an NIMH-funded study, researchers have identified differences in how the brains of irritable youth react to frustration. The findings, published in The American Journal of Psychiatry, could provide new paths for developing treatments for children and adolescents with severe irritability.

Whether it’s having to wake up earlier than usual or being asked to turn off a favorite TV show, all children can become irritable sometimes. However, some children are more irritable than others, with an increased tendency to experience anger and frustration in comparison with their peers. Children who have severe, chronic irritability can experience significant problems including at home, at school, and with peers. They also tend to have high rates of health care service use, hospitalization, and school suspension and are more likely to develop anxiety and depressive disorders.

Full story at NIMH

A Shorter—but Effective—Treatment for PTSD

First-line treatments for post-traumatic stress disorder (PTSD) often require many treatment sessions and delivery by extensively trained therapists. Now, research supported by the National Institute of Mental Health (NIMH) has shown that a shorter therapy may be just as effective as lengthier first-line treatments. The study appeared in the March 2018 issue of JAMA Psychiatry.

First-line treatments for PTSD consist of psychotherapies that focus on exposure and/or cognitive restructuring. One such therapy is cognitive processing therapy (CPT), which is widely acknowledged as an effective treatment for PTSD. Patients being treated with CPT take part in 12 weekly therapy sessions that are delivered by a highly-trained practitioner. During these sessions, patients learn to recognize and challenge dysfunctional thoughts about their traumatic event, themselves, others, and the world. In addition, patients are given homework to complete between sessions.

Full story at NIMH