2018 Leading Research Achievements

We are pleased to present you with the Top Advancements & Breakthroughs by Foundation Grantees, Prizewinners and Scientific Council members in 2018. They are presented in the order of their publication in scientific journals.

A Rapid Form of Brain Stimulation for Treatment-Resistant Depression

Next-Generation Therapies, New Technologies: Depression

• Daniel M. Blumberger, M.D., Centre for Addiction and Mental Health, University of Toronto; 2010 BBRF Young Investigator 

A new form of transcranial magnetic stimulation, or TMS, has been successfully tested in patients whose depression did not respond to one or more standard treatments. The new TMS technology is called iTBS (intermittent theta burst stimulation). It can safely and painlessly deliver stimulation to brain areas affected by depression in only 3 minutes—delivering benefits to patients that researchers report are just as effective as standard, 37-minute TMS treatments. Like standard TMS, iTBS enabled half of patients to achieve at least a 50 percent reduction in symptoms, and one-third to achieve full remission. Read more.

Journal: The Lancet, April 28, 2018

Largest-Ever Cortical Imaging Study of OCD Patients Offers Clues to Causes

Basic Research: Obsessive-Compulsive Disorder (OCD)

• Odile A. van den Heuvel, M.D., Ph.D., VU University Medical Center in Amsterdam, Netherlands; 2009 BBRF Young Investigator

A study has provided new clues about which parts of the brain are disrupted in people with obsessive-compulsive disorder. By comparing brain scans of 1,905 people with OCD with those of 1,760 unaffected people, researchers noted a thinning in the parietal lobe, a part of the cortex involved in attention, planning, and response inhibition. This might contribute to patients’ recurring thoughts and repetitive behaviors. The thinning was noted in both adolescent and adult patients. Read more.

Journal: American Journal of Psychiatry, May 1, 2018

Pregnancy Complications Provide Opportunity for Schizophrenia Risk Genes to Harm the Fetus

Basic Research: Schizophrenia, Autism, Childhood disorders

• Daniel R. Weinberger, M.D., Lieber Institute for Brain Development; BBRF Scientific Council; 2000, 1990 Distinguished Investigator; 1993 Lieber Prize

Researchers have discovered that some of the most significant gene variants associated with schizophrenia affect pathways sensitive to pre-birth events influencing the response of the placenta to stress. The findings suggest the placenta is the link between schizophrenia risk genes and potentially harmful external stresses, including complications during pregnancy or birth. In an analysis that included nearly 3,000 individuals, including 2,038 with schizophrenia, researchers found that early-life complications amplify a person’s inherited risk for schizophrenia more than 10-fold, and tend to affect a male fetus more than a female fetus. Read more.

Journal: Nature Medicine, May 28, 2018

A Revealing Genetic Comparison of Schizophrenia and Bipolar Disorder

Basic Research: Schizophrenia, Bipolar Disorder

• Douglas M. Ruderfer, Ph.D., Vanderbilt University; 2015 BBRF Young Investigator

Schizophrenia and bipolar disorder are distinct diagnoses yet they have symptoms that overlap. They also share some of their underlying genetics, and now a study in which over 100,000 genomes were analyzed has enabled scientists to show 114 locations in the genome implicating pathways shared between the two illnesses, and four genome regions that contribute to differences in their biology. One implication of the research is that it may become possible to say, based on an individual’s genetic risk score for each illness, whether or not they are likely to have certain symptoms. Another implication is that we may be able to determine the genetic signature not just for risk of an illness, like schizophrenia, "but also for key symptom dimensions like psychosis or mania," which cut across diagnostic boundaries. Read more.

Journal: Cell, June 14, 2018

Machine-learning Helped Identify Newly Diagnosed Schizophrenia and Predicted Treatment Response

Diagnostic Tools/Early Intervention: Schizophrenia, Psychosis

• Bo Cao, Ph.D., University of Alberta; 2016 Young Investigator 

By teaching computers to analyze specific yet very subtle features in brain scans—a method called machine learning—researchers were able to identify schizophrenia in 78 percent of a group of newly diagnosed patients. They could further predict, with 82 percent accuracy, which patients would respond to treatment with the antipsychotic medicine risperidone. It is an important step toward finding reliable biomarkers to assist in diagnosing schizophrenia and even to predict it before symptoms appear. Read more.

Journal: Molecular Psychiatry, June 19, 2018

Interactive Parent-Child Therapy Reduced Depression Symptoms in Very Young Children

Next-Generation Therapies: Depression, Childhood disorders

• Joan L. Luby, M.D., Washington University School of Medicine; BBRF Scientific Council; 2008, 2004 Independent Investigator; 2004 Klerman Prize; 1999 Young Investigator

Young children diagnosed with depression can benefit from an interactive form of therapy involving a parent, according to a clinical trial which evaluated the effects on depressed children between the ages of 3 and 7. Those in the treatment group participated in 20 therapy sessions over 18 weeks, in which therapists guided parents to better help their children recognize and regulate their emotions. Children who received the therapy had significantly lower rates of depression and less severe symptoms than those in the group that did not receive the therapy, while their parents also experienced a reduction in their own depression symptoms and in stress. This suggests that earlier identification and intervention offers a key pathway for more effective treatment. Read more.

Journal: American Journal of Psychiatry, June 20, 2018

Esketamine Reduced Suicidal Thoughts Within Hours of Treatment

Next-Generation Therapies: Suicide, Depression

• Carla M. Canuso, M.D., Johnson & Johnson/Janssen R&D; 1998 Young Investigator

The experimental drug esketamine rapidly reduced thoughts of suicide and symptoms of depression in a small clinical trial involving 68 patients. The benefits of esketamine, like the closely related drug ketamine, were greatest within hours of treatment. By the end of the 4-week trial and 8-week follow-up (during which all patients continued taking their prior medications) those who had received a placebo rather than esketamine achieved similar reductions in depression and suicidal thoughts as did the esketamine group. This suggests esketamine could be valuable for managing severe depression and reducing suicide risk until traditional antidepressants can take effect. Read more.

Journal: American Journal of Psychiatry, July 1, 2018

Adult-Born Neurons Can Protect Against Chronic Stress

Basic Research: Anxiety, Depression

• René Hen, Ph.D., Columbia University; BBRF Scientific Council; 2009, 2003 Distinguished Investigator; 1998 Independent Investigator

The birth of new neurons in the adult brain appears to be important for resilience to chronic stress. The discovery, made in mice, suggests that adult-born cells in the hippocampus—a part of the brain that regulates mood—rein in the activity of stress-responsive cells. This, in turn, reduces stress-induced anxiety. The findings suggest these newly born cells may be important for protecting against prevalent stress-related disorders such as depression and anxiety. They raise the prospect that manipulating neuronal activity in a section of the hippocampus might be a way to protect against stress-related psychiatric disorders. Read more.

Journal: Nature, July 5, 2018

Rapid, Intensive Outpatient Treatment Reduced Vets’ PTSD Symptoms Within Weeks

Next-Generation Therapies: Post-Traumatic Stress Disorder (PTSD)

• Alyson Kay Zalta, Ph.D., University of California, Irvine; 2016 Young Investigator 

Three weeks of intensive outpatient treatment significantly reduces the symptoms of post-traumatic stress disorder (PTSD) in veterans. The short course of treatment enabled 91 percent of trial participants to stay with the program to its end, an important factor in its success. Residential treatment programs typically last 6 to 12 weeks, a period that can be disruptive to work and family life. The new 3-week outpatient program involved daily trauma-focused psychotherapy called Cognitive Processing Therapy, and mindfulness-based resiliency training, which teaches patients to focus on the present moment to reduce stress and improve tolerance to trauma-related stimuli. Depression symptoms declined steadily throughout the program, and PTSD symptoms began to decline after the first week, and reduced more quickly as the therapy continued. Read more.

Journal: BMC Psychiatry, July 27, 2018

Researchers Train Computers to Identify a Biological Signature of Bipolar Disorder

Diagnostic Tools/Early Intervention: Bipolar Disorder

• Tomas Hajek, M.D., Ph.D., Dalhousie University; 2015 Independent Investigator; 2007 Young Investigator 

A large international team has used machine-learning methods to identify diagnostic markers of bipolar disorder. After assembling over 3,000 brain scans of bipolar disorder patients and controls from multiple sites, researchers tested whether computers could train themselves to reliably distinguish patients from controls. The encouraging results provide a proof-of-concept for a brain-imaging signature of bipolar disorder to identify the illness in individuals. The team’s aim is differential diagnosis—being able to distinguish between different psychiatric disorders with similar manifestations. Read more.

Journal: Molecular Psychiatry, August 31, 2018

Folic Acid-Fortified Foods During Pregnancy May Lower Child’s Psychosis Risk After Birth

Diagnostic Tools/Early Intervention: Psychosis, Schizophrenia, Autism, Developmental Disorders

• Joshua L. Roffman, M.D., M.M.Sc., Harvard Medical School/Massachusetts General Hospital; 2014 Independent Investigator; 2007 Young Investigator

Researchers used MRI scans to compare the brains of more than 1,200 children and adolescents born before, at the time of, and following a 1996 government order directing food producers to supplement grain products with folic acid. Deficiencies of this basic nutrient can cause birth defects including neural tube defects. The research showed that children who were not exposed to folic acid during the fetal period displayed earlier cortical thinning, which is associated with higher psychosis risk. Those born after fortification was mandated had the longest delays in thinning and thus the lowest relative risk. Read more. 

Journal: JAMA Psychiatry, September 1, 2018

Computer-Delivered Cognitive Training Significantly Helped Schizophrenia Patients in Rehab Setting

Next-Generation Therapies: Schizophrenia

• Gregory A. Light, Ph.D., University of California, San Diego; 2014 Baer Prize; 2013 Independent Investigator; 2006, 2003 Young Investigator

Researchers have shown that a form of therapy called targeted cognitive training (TCT) can help individuals with schizophrenia who have suffered from severe symptoms and required stabilization on high medication dosages for many years. Patients received 3-5 hours of TCT training per week, delivered via laptop computers, with tasks focusing on a variety of auditory processes. Deficits in auditory perception and verbal learning have been traced to the brain’s auditory processing system. “TCT produced significant improvements in auditory perception and verbal learning,” the team reported. Patients also experienced a “significant reduction in auditory hallucinations.” Read more.

Journal: Schizophrenia Research, December 1, 2018