2015 Research Highlights by NARSAD Grantees

Top Research Discoveries Made in 2013 by NARSAD Grantees

2015 NARSAD Grant-Funded Breakthrough
Vince D. Calhoun, Ph.D.
The Mind Research Network
2004 NARSAD
Young Investigator Grant

Vince D. Calhoun, Ph.D.

Basic Research: Addiction
Long-Term Effects of Marijuana on the Brain**

Studies of the long-term effects of marijuana on the brain have provided an inconsistent picture, in part due to variations in research methods. In a study using a wide range of brain-scanning methods to characterize brain alterations associated with chronic marijuana use in 48 marijuana users and 62 matched control subjects, Dr. Calhoun and colleagues found changes in gray matter volume and potential functional abnormalities in grey matter as well in connections within the brain’s white matter. Specifically, they found that chronic exposure to marijuana reduces gray matter volume in the orbitofrontal cortex; increases structural and functional connectivity; and leads to neural alterations that are affected by the age of onset and duration of use. All in all, these findings suggest that chronic marijuana use results in complex neuroadaptive processes. Future studies will be needed to determine whether these changes revert back to normal following prolonged abstinence.
Journal: Proceedings of the National Academy of Sciences, November 25, 2014

Tobias Gerhard, Ph.D.
Rutgers University
2010 NARSAD
Young Investigator Grant


*Team included:
Davangere P. Devanand, M.D.,
1997 Independent Investigator,
1987 Young Investigator and
Mark Olfson, M.D., M.P.H.,
2005 Distinguished Investigator

 

Tobias Gerhard, Ph.D.

Basic Research/Treatment: Bipolar Disorder
Lithium Linked to Lower Incidence of Dementia in Older People with Bipolar Disorder

Analyzing data from 40,000+ adults with bipolar disorder, the team* found that regular treatment with lithium correlated with lowered risk of dementia in patients over 50. For those who took lithium more than 300 days during the year prior to taking part in the study, dementia developed over the study period of three years less frequently than for those who took the drug less frequently or not at all during the same period. Using lithium sporadically or intermittently did not affect the incidence of dementia, nor did treatment with anticonvulsants, no matter how often they were used. Patients with bipolar disorder are thought to be more likely to develop dementia than people without the disorder. The new study contributes to the evidence that consistent treatment with lithium—and not anticonvulsants— may reduce this risk.
Journal: British Journal of Psychiatry, January 22, 2015

J. John Mann, M.D.
Columbia University
Scientific Council Member
2008 NARSAD
Distinguished Investigator Grant


*Team included:
David A. Brent, M.D.,
2001 Distinguished Investigator
John G. Keilp, Ph.D.,
1998 and 1996 Young Investigator and
Nadine M. Melhem, Ph.D.,
2013 and 2004
Young Investigator

 

J. John Mann, M.D.

Prevention/Diagnosis: Suicidal Behavior
Parent’s History of Suicide Attempts Helps Predict Suicide Attempts In Children

After six years of following 701 children of 334 people diagnosed with a mood disorder, Dr. Mann’s team* concluded that three long-term risk factors are most useful in predicting suicide attempts: a family history of suicide attempts, a family history of mood disorders, and a personal history of impulsive aggression. It’s important that such families focus on early detection and treatment of mood disorders and aggressive-impulsive traits, the team advised. Having a parent who had attempted suicide made it nearly five times more likely that one of their children would make an attempt.
Journal: JAMA Psychiatry, February 2015

Helen Lavretsky, M.D.
University of Southern California
2010 NARSAD
Distinguished Investigator Grant

Helen Lavretsky, M.D.

Next-Generation Treatments: Depression (Geriatric)
Combined Drug Treatment Improved Results in Geriatric Depression**

Dr. Lavretsky and her team reported results of the first comprehensive and well-controlled trial to find out if the drug methylphenidate (Ritalin) can enhance clinical and cognitive outcomes in patients with geriatric depression. Combination treatment over 16 weeks with citalopram (Celexa) and methylphenidate did in fact result in higher remission rates (62% vs. 42%) and shorter time to remission than treatment with citalopram alone. The rate of side effects was the same in both treatment modes. Citalopram treatment appeared to be beneficial for cognition, although augmentation with methylphenidate did not offer additional benefits. However, participants treated with methylphenidate demonstrated improvement in their global cognitive performance score. Improvements were also noted in clinical reports of “wellbeing” in the group that received combined treatment.
Journal: American Journal of Psychiatry, February 13, 2015

Mark H. Rapaport, M.D.
Emory University School
of Medicine

1999 NARSAD
Independent Investigator Grant

Andrew A. Nierenberg, M.D.
Massachusetts
General Hospital

Scientific Council Member
Foundation 2013 Colvin Prizewinner and
2003 NARSAD
Distinguished Investigator Grant
2000 NARSAD
Independent Investigator Grant

David Mischoulon, M.D., Ph.D.
Massachusetts
General Hospital

2000, 1998 NARSAD
Young Investigator Grant

Mark H. Rapaport, M.D., Andrew A.<br />
Nierenberg, M.D., David Mischoulon,<br />
M.D., Ph.D.

Next-Generation Therapy: Depression
Omega-3 Relieves Depression Symptoms in People With Bodily Inflammation

Research demonstrated that certain fatty acids, including omega-3, can reduce symptoms of depression in people with high levels of inflammation in their body. The study focused on omega-3 fatty acids. People with major depressive disorder were given one of two types of omega-3s, called EPA and DHA. People with high inflammation showed a greater reduction in depressive symptoms if taking EPA, relative to people taking placebos. People without elevated inflammation responded less to EPA than either DHA or placebo. The different effects may stem from EPA’s stimulation of anti-inflammatory chemicals in the body—chemicals that DHA does not stimulate.
Journal: Molecular Psychiatry, March 24, 2015

Cynthia S. Weickert, Ph.D.
University of New South
Wales, Australia

2004 NARSAD
Independent Investigator Grant
2001, 1999 NARSAD
Young Investigator Grant


*Team included:
Rhoshel K. Lenroot, M.D.,
2003 Young Investigator
Ans Vercammen, Ph.D.,
2010 Young Investigator
Jayashri Kulkarni, MBBS, MPM, FRANZCP, Ph.D.,
2000
Independent Investigator and
her husband and first author
Thomas W. Weickert, Ph.D.

 

Cynthia S. Weickert,<br />
Ph.D.

Next-Generation Therapy: Schizophrenia
Estrogen Drug Improves Cognition in Schizophrenia Patients

Dr. Weickert’s team* discovered the estrogen-related drug raloxifene can help improve some cognitive problems in schizophrenia that are hard to treat with existing drugs. Estrogen is a protector of nerve cells in the brain. The team found estrogen receptors are altered in some people with schizophrenia, blunting their ability to respond to the hormone’s beneficial effects. Raloxifene, used to treat osteoporosis in women, stimulates estrogen receptors and can help overcome a blunted estrogen response. Examining the responses of 98 patients, both male and female, the team found those taking 20 mg of oral raloxifene daily for six weeks in addition to their usual antipsychotic had improved scores on memory and attention tests, compared to those taking placebo plus antispychotic. The drug didn’t reduce the severity of schizophrenia symptoms compared with placebo, but it did reduce the number of symptoms experienced overall, and its effects continued after withdrawal of the drug.
Journal: Molecular Psychiatry, May 18, 2015

Patrick F. Sullivan, M.D., FRANZCP
University of North Carolina
School of Medicine and the
Karolinska Institute

Foundation 2014 Lieber Prizewinner and
2010 NARSAD
Distinguished Investigator Grant

Dorret I. Boomsma, Ph.D.
VU University Amsterdam
Netherlands

2011 NARSAD
Distinguished Investigator Grant

Patrick F. Sullivan,<br />
M.D., FRANZCP, Dorret I. Boomsma,<br />
Ph.D.

Basic Research: Depression/MDD
Gene Expression Analysis Points Toward Pathways Involved in Major Depression

An international team identified 119 genes whose activity differs significantly in people with major depressive disorder. Whether stemming from inherited genetic factors and/or environmental influences, these gene expression changes help point scientists toward biological pathways likely to be involved in the disorder. Many of the 119 genes whose activity differed in depression were related to immune system function. The study also pointed to 19 genes whose expression was more likely to have returned to normal if an individual had recovered from an earlier depression.
Journal: Molecular Psychiatry, May 26, 2015

Sohee Park, Ph.D.
Vanderbilt University
2012 NARSAD
Distinguished Investigator Grant
2004 NARSAD
Independent Investigator Grant
1996, 1991 NARSAD
Young Investigator Grant

Sohee Park, Ph.D.

Next-Generation Therapy: Schizophrenia
Non-Invasive Stimulation Reworks Brain Waves, Improves Cognition

Dr. Park’s team discovered that transcranial direct current stimulation (tDCS), a non-invasive, affordable and portable way to stimulate the brain, can help induce normal neural activity and make thought processes more flexible in people with schizophrenia. The method, which stimulates the brain at low current via electrodes placed on the scalp, is a drug-free and safe way of treating debilitating cognitive problems in schizophrenia, for which antipsychotics are not completely effective. After a 20-minute treatment, key brain waves were observed in patients to “normalize” by showing greater synchrony, in this way more resembling patterns seen in healthy controls.
Journal: Proceedings of the National Academy of Sciences, June 29, 2015

Marc G. Caron, Ph.D.
Duke University
Scientific Council Member
Foundation 2013 Lieber Prizewinner
2005 NARSAD
Distinguished Investigator Grant

Marc G. Caron, Ph.D.

Basic Research: Schizophrenia
New Compounds Show Promise in Treating Schizophrenia Symptoms

Two new small-molecule drugs tested in mice alleviated some symptoms of schizophrenia-like behaviors, including movement abnormalities, social avoidance, and cognitive performance. Current antipsychotic drugs bind to and block one specific communication pathway through dopamine D2 receptors on nerve cells, but the receptors are involved in other signaling pathways. The team found that drugs called UNC9975 and UNC9994 influence the beta-arrestin communication pathway and reduced hyperactive movements, improved memory for novel stimuli, and made the test mice more social. The work shows that hitting other pathways in schizophrenia has the potential to treat symptoms in more individualized, fine-tuned ways.
Journal: Neuropsychopharmacology, July 1, 2015

Kerry J. Ressler, M.D., Ph.D.
McLean Hospital, Harvard
Medical School

Scientific Council Member
2005, 2002 NARSAD
Young Investigator Grant

Kerry J. Ressler, M.D.,<br />
Ph.D.

Next-Generation Therapy: Anxiety, Post-Traumatic Stress Disorder
Drug Helps Mice Respond Normally to Fear After Traumatic Experience

Dr. Ressler and colleagues demonstrated that treatment with the corticosteroid drug dexamethasone can help mice overcome a preconditioned trauma-related fear response. They trained a group of mice using sounds and mild electrical shocks to learn and then to inhibit a specific fear. Animals that had experienced a traumatic event before the fear training were more likely to inhibit or extinguish the fear if they were given a low dose of dexamethasone four hours beforehand to suppress the internal stress response. The fear was also more likely to remain extinguished 24 hours later in those same animals, suggesting the potential of this approach in development of new therapeutics to treat PTSD and anxiety.
Journal: Neuropsychopharmacology, July 15, 2015

Flora M. Vaccarino, M.D., Ph.D.
Johns Hopkins University
2011 NARSAD
Distinguished Investigator Grant
2003, 2000, 1993, 1990 NARSAD
Young Investigator Grant


*Team included:
Gianfilippo Coppola, Ph.D.,
2013 Young Investigator

 

Flora M. Vaccarino,<br />
M.D., Ph.D.

Next-Generation Technology/Basic Research: Autism
Watching Patient-Derived Brain Cells Take Shape in the Lab Reveals Autism Defect

By reprogramming skin cells sampled from autistic people to grow into brain-like clusters of cells called organoids, Dr. Vaccarino and colleagues* uncovered a developmental flaw that seems to skew the balance of excitatory and inhibitory neurons in the brain. The findings suggest that overproduction of certain cell types during early development could lead to faulty brain wiring in people who later display symptoms of autism and ASD. The team correlated overactivity of a gene called FOXG1 to overproliferation of neurons; in organoids in which this gene was blocked, key developmental defects did not appear, pointing to FOXG1 activity as a potential diagnostic marker and treatment target in autism.
Journal: Cell, July 16, 2015

Patrick McGorry, M.D., Ph.D., FRCP, FRANZCP
University of Melbourne,
Australia

Foundation 2015 Lieber Prizewinner
1998 NARSAD
Distinguished Investigator Grant

Patrick McGorry, M.D.,<br />
Ph.D., FRCP, FRANZCP

Next-Generation Treatments: Psychosis, Schizophrenia, Bipolar Disorder
Omega-3 Supplements Linked to Reduced Risk of Developing Psychosis**

Dr. McGorry, along with study leader Dr. G. Paul Amminger and colleagues, found that a 12-week course of omega-3 polyunsaturated fatty acid (PUFA) supplements reduced the risk years later that young adults would develop schizophrenia or other psychiatric illnesses such as major depression or bipolar disorder. The team’s prior study showed benefits extending up to a year after a 12-week treatment course. The new study looked at the longer-term impact of the supplements among 81 people aged 13 to 25 with early symptoms of psychosis. After following the patients for an average of 6.7 years after treatment, four of 41 patients (9.8%) who received the omega-3 PUFAs had at some point developed a psychotic disorder, compared to 16 of 40 (40%) of those who received placebos. It’s not clear exactly how omega-3 PUFA affects the development of psychosis. It has been postulated to reduce inflammation in the brain and aid the growth of new neurons.
Journal: Nature Communications, August 11, 2015

Chadi Abdallah, M.D.
Yale University
2015 Klerman Prize
Honorable Mention
2014, 2012 NARSAD
Young Investigator Grant


*Team included:
Sanjay Mathew, M.D.,
2009 Independent Investigator
2006, 2001 Young Investigator
Ramiro Salas, Ph.D.
2012 Young Investigator

 

Chadi Abdallah, M.D.

Next-Generation Diagnostic/ Treatment: Depression/MDD
Size of Brain Structure May Predict Effectiveness of Ketamine

People with severe depression often have smaller- than-normal hippocampi—twin brain structures involved in memory and learning. Such people often respond poorly to traditional antidepressants. Dr. Abdallah and colleagues* used MRI scans to assess the size of the hippocampus in 13 patients with major depression, and then gave each patient a single dose of ketamine. For 10 individuals, symptoms of depression were reduced within 24 hours. Those who responded best were those with the smallest hippocampi on the brain’s left side. For scientists who hope to use ketamine to treat treatment-resistant depression, it’s another important piece in the puzzle of understanding which patients might benefit the most.
Journal: Journal of Pyschopharmacology, August 13, 2015

Avshalom Caspi, Ph.D.
Duke University
Foundation 2010 Ruane Prizewinner

Terrie E. Moffitt, Ph.D.
Duke University
Foundation 2010 Ruane Prizewinner

Guilherme V. Polanczyk, M.D., Ph.D.
University of São Paulo School
of Medicine, Brazil

2008 NARSAD
Young Investigator Grant

Avshalom Caspi, Ph.D., Terrie E. Moffitt, Ph.D., Guilherme V.<br />
Polanczyk, M.D.,<br />
Ph.D.

Basic Research/Next-Generation Diagnosis: ADHD
Distinguishing Childhood and Adult Forms of ADHD**

New research led to unexpected insights about attention deficit-hyperactivity disorder (ADHD). The team followed a single group of over 1,000 individuals born between 1972 and 1973 in Dunedin, New Zealand, 95 percent of whom were still taking part in the study at age 38. Participants were comprehensively examined at a dozen intervals over the years. During childhood, six percent of the group, mostly boys, were diagnosed with ADHD. But in adulthood, only three percent received an ADHD diagnosis, with males and females affected about equally. The great surprise was that almost none of those with adult ADHD were among the portion of the group that had been diagnosed during childhood. The study raises the possibility that adult ADHD is not a neurodevelopmental disorder that begins in childhood, as is widely believed, but may in fact be a separate condition with other causes.
Journal: American Journal of Psychiatry, October 1, 2015

Nina R. Schooler, Ph.D.
State University of New York
Downstate Medical Center

Scientific Council Member
1998 NARSAD
Distinguished Investigator Grant

Kim T. Mueser, Ph.D.
Boston University
2003 NARSAD
Distinguished Investigator Grant
1989, 1988 NARSAD
Young Investigator Grant


*Team included:
Mary F. Brunette, M.D.,
2000 Young Investigator
Christoph U. Correll, M.D.
2007Young Investigator
Jennifer D. Gottlieb, Ph.D.
2009 Young Investigator
Robert K. Heinssen, Ph.D.
1990 Young Investigator
Delbert G. Robinson, M.D.
2005 Independent Investigator

 

Nina R. Schooler, Ph.D., Kim T. Mueser, Ph.D.

Next-Generation Treatment: Psychosis, Schizophrenia
Hopeful News on Comprehensive Team Treatment of Early Psychosis**

Drs. Schooler, Mueser, and five other recipients* of NARSAD grant awards were members of a team that demonstrated that early intervention and coordinated team care can make a real, positive difference in outcomes for first-episode psychosis patients. Over two years, the team treated 223 patients with a protocol called NAVIGATE, a first-episode intervention stressing low-dose antipsychotic medications; cognitive behavioral therapy to support resiliency and illness self-management skills; family psychoeducation and support; and supported employment and educational opportunities. The better outcomes suggest the importance of early and coordinated intervention after a first psychotic episode.
Journal: American Journal of Psychiatry, October 20, 2015

** New England Journal of Medicine’s Journal Watch Psychiatry Top Stories of 2015