2019 Leading Research Achievements

We are pleased to present you with the 2019 Leading Research Achievements by BBRF Grantees, Prizewinners & Scientific Council Members. They are presented in the order of their publication in scientific journals.

Adding Guanfacine Boosted Benefits of Cognitive Remediation Therapy in a Schizophrenia Spectrum Disorder

Next-Generation Therapies: Schizophrenia

• Margaret M. McClure, Ph.D., Icahn School of Medicine at Mount Sinai; 2013 BBRF Young Investigator

Adding the FDA-approved drug guanfacine to a validated therapy program to treat cognitive deficits led to even better results for individuals with a schizophrenia spectrum disorder. This was demonstrated in a study of 28 patients with schizotypal personality disorder. Like others across the schizophrenia spectrum, these patients had cognitive impairments affecting verbal and spatial memory, attention, abstract reasoning, and verbal fluency. Those receiving guanfacine in addition to cognitive remediation plus social skills training showed significantly greater improvement in reasoning, problem-solving, functional skills, and in some cases, social skills, compared with patients who received only cognitive remediation therapy plus social skills training. Read more.

American Journal of Psychiatry, April 2019

Higher Maternal Choline Levels in Pregnancy Had Protective Role in Infant Brain Development

Diagnostic Tools/Early Intervention: Schizophrenia, Psychosis, ADHD

• Robert R. Freedman, M.D., University of Colorado Denver School of Medicine; BBRF Scientific Council, 2015 Lieber Prize, 2006 and 1999 BBRF Distinguished Investigator
• M. Camille Hoffman, M.D., University of Colorado Denver School of Medicine; 2015 Baer Prize

A study of 132 pregnancies found that children born to mothers who had infections during the first 16 post-conception weeks performed better in two key postnatal measures of healthy brain function when their mothers had higher levels of choline—an essential nutrient—during pregnancy, compared with children whose mothers had lower choline levels. A deficiency of choline, affecting up to half of pregnant women, appears to impair the development of inhibitory circuitry around the time of birth, possibly contributing to pathology seen in schizophrenia, psychosis, attention-deficit and other disorders. This research supports the case for choline supplementation during pregnancy. Read more.

Journal of Pediatrics, May 2019

Over-sensitivity to Sound, Smell, Touch, or Taste in Preschoolers Predicted Higher Risk for Anxiety at Age 6

Diagnostic Tools/Early Intervention: Anxiety

• Kimberly L. H. Carpenter, Ph.D., Duke University School of Medicine; 2015 BBRF Young Investigator

Researchers reported that sensory over-sensitivity in children of preschool age (2 to 5) is a risk factor for subsequent anxiety disorder, and can predict the appearance of anxiety symptoms at age 6. The intensity of anxiety symptoms, in turn, was found to correspond with the seriousness of concurrent behavioral issues such as irritability, picky eating, and sleep problems. Fifty-two percent of preschool children in the study with at least one sensory sensitivity went on to meet criteria for anxiety disorder at school age. These included physical contact with other people or fabrics and clothes tags; food textures; visual experience such as bright lights; auditory experiences such as loud or high-pitched noises; olfactory experiences; tastes; and sensations of motion. Read more.

Journal of Abnormal Child Psychology, June 2019

Study Finds Lithium Has Advantages Over Other Mood Stabilizers in Youths with Bipolar Disorder

Next-Generation Therapies: Bipolar Disorder

• Boris Birmaher, M.D., University of Pittsburgh School of Medicine; 2013 Colvin Prize

The drug lithium is widely regarded as a first-line treatment for adults with bipolar disorder. Its suitability for younger patients has now been demonstrated. Taking advantage of a 15-year study that has followed 413 youths with bipolar disorder recruited at ages 7 to 17, researchers compared outcomes in 340 of the youths. These participants had over 2,600 follow-ups: 886 were in participants being maintained on lithium, while 1,752 were in participants taking other medications. Lithium use was associated with fewer suicide attempts, fewer depression symptoms, better psychosocial function, and less parent-reported aggression, the team found. Read more.

Journal of the American Academy of Child & Adolescent Psychiatry, July 2019

Large Genome Study Suggests Anorexia Nervosa is a Metabolic Disorder as Well as a Psychiatric One

Basic Research: Eating Disorders

• Cynthia Bulik, Ph.D., University of North Carolina, Chapel Hill and Karolinska Institute, Sweden; 2017 BBRF Distinguished Investigator

The largest genetic study to date of anorexia nervosa, involving nearly 17,000 patients and over 55,000 controls, has identified eight areas in the human genome where DNA variations contribute to risk for the illness. More important, potentially: the research extends our understanding of this psychiatric illness by showing that genetic factors that influence metabolism, and specifically body mass index (BMI), also contribute to its origins. Thus, processes in the body that normally regulate metabolism, including weight regulation, may be malfunctioning in anorexia nervosa patients, underlying some of the weight and feeding symptoms previously explained as psychological. Read more.

Nature Genetics, August 2019

Long-term Study Reveals Trajectory of How Bipolar Disorder Emerges in High-Risk Youth

Basic Research: Bipolar Disorder

• Anne Duffy, M.D., F.R.C.P.C., Queen’s University at Kingston, Ontario; 2005, 2003 BBRF Independent Investigator; 2000 Young Investigator

A multi-decade study focusing on children of parents diagnosed with bipolar disorder quantifies the risk—24.5%—that they themselves will develop bipolar illness, and suggests a “progressive sequence” in which the illness typically unfolds between the ages of 12 and 30. The “trajectory” established in the study is expected to help doctors to diagnose bipolar disorder in young people, which is challenging partly because acute symptoms are often not specific to bipolar disorder and often overlap with those of other disorders. The study found that childhood sleep and anxiety disorders are important predictors of emerging bipolar disorder and that progression to a diagnosis was typically heralded by an episode of mania or hypomania and/or a first episode of psychosis following a single episode or recurrent major depression. Read more.

American Journal of Psychiatry, September 2019

Progress in Research on Brain Wave Patterns to Predict Autism Outcomes

Diagnostic Tools/Early Intervention: Autism Spectrum Disorder

• Charles A. Nelson III, Ph.D., Harvard University, Boston Children’s Hospital; 2017 Ruane Prize
• April R. Levin, M.D., Harvard University, Boston Children’s Hospital; 2016 BBRF Young Investigator

Researchers made an important discovery about the relationship between patterns in brain waves—oscillations created by the activity of neurons—and pathology in autism spectrum disorder (ASD) that emerges in the first 3 years of life. They used EEG (electroencephalograms) to measure brain waves in infants beginning 3 months after birth and continuing until a full behavioral assessment at age 3. The infants were born with high risk for ASD, as each had at least one older sibling who had already been diagnosed. In the 30% who went on to an ASD diagnosis at age 3, when outward symptoms are evident, it was clear in retrospect that brain wave differences predicting that outcome were clearest in the first postnatal year. While not yet ready for the clinic, the biomarker is a strong step toward early diagnosis. Read more.

Nature Communications, September 2019

In Mice, and Perhaps People, Gut Organisms Impact the Ability to Extinguish Fear

Basic Research: PTSD, Anxiety

• Conor Liston, M.D., Ph.D., Weill Cornell Medical College; 2013 BBRF Young Investigator

Researchers demonstrated that changes in the microbiome—organisms and viruses living in the gut— can result in an impaired ability to extinguish fear. In experiments with mice raised without gut organisms and others treated with organism-killing antibiotics, the ability to extinguish fear was impaired, compared with mice whose microbiome was not altered. The difference suggested that signals from the microbiome were necessary for optimal extinction of conditioned fear responses. Such extinction comes into play when a stimulus initially feared is found to be of little or no danger. The inability to extinguish such fears can be an important factor in post-traumatic stress disorder and anxiety. Bacteria and viruses in the gut may affect the central nervous system through their production and circulation of metabolites, four of which were identified in this preliminary study. Read more.

Nature, October 2019

Deep-Brain Stimulation Showed Multi-Year Effectiveness in Severely Depressed, Treatment-Resistant Patients

Next-Generation Therapies: Depression

• Helen S. Mayberg, M.D., Icahn School of Medicine at Mount Sinai; BBRF Scientific Council, 2007 Falcone Prize, 2002 BBRF Distinguished Investigator, 1995 Independent Investigator, 1991 Young Investigator

A long-term follow-up study of 28 people whose serious, treatment-resistant major depression was treated surgically with deep-brain stimulation (DBS) found that 21 of the patients experienced a sustained and robust antidepressant response (at least 50% symptom reduction). The follow-up period ranged from 4 to 8 years. Dr. Mayberg, who pioneered DBS, said these results justify continued clinical testing of DBS, since the level of relief it provided to many of the participants over time “is unmatched” by other treatment types in patients with comparably severe treatment resistance. Participants in the study had failed to respond to at least four prior antidepressant treatments, including electroconvulsive therapy (ECT). Read more.

American Journal of Psychiatry, November 2019

Activity in Newly Discovered Brain Circuit Predicted Future Compulsive Drinking in Mice

Basic Research; Diagnostic Tools/Early Intervention: Addiction—Alcohol

• Kay M. Tye, Ph.D., Salk Institute for Biological Studies; BBRF Scientific Council, 2016 Freedman Prize, 2013 BBRF Young Investigator

While nearly every adult has an alcoholic drink at some point, only some develop an alcohol use disorder. This research sought to discover biological differences between adults who do and do not drink compulsively, via experiments in mice, which can accurately model human drinking behaviors. The researchers discovered a circuit in the mouse brain whose functioning appears to provide a mechanistic explanation for compulsive alcohol drinking. The mice sorted themselves into three distinct groups—one with little appetite for alcohol; another that developed a desire to drink regularly but was sensitive to experiencing discomfort because of it; and a third that drank compulsively regardless of any discomfort. The circuit found to drive the behavior was experimentally manipulated, resulting in increased or decreased compulsive drinking in specific individuals. Importantly, the team was able to see, in retrospect, which animals would go on to drink compulsively based on neural circuit activity that occurred the very first time they drank alcohol. Future research will determine if this finding has translational value in people. Read more.

Science, November 2019