Tag Archive for: schizophrenia

Adelaide Robb

Changing the game in pediatric psychopharmacology

Adelaide Robb

“I realized adequate treatment in youth can prevent many of the harmful outcomes in adults who were never treated properly for their symptoms,” says Adelaide Robb, M.D.

Over three decades ago, Adelaide Robb, M.D., sat in her office with a clear goal in mind: follow a career in adult psychiatry. Her patients displayed all sorts of symptoms: generalized anxiety, depression, bipolar disorder, autism, schizophrenia.

“In the early 1990s, my patients would tell me other doctors didn’t believe in their children having bipolar disorder,” she says.

These adult patients had been sick for 5, 10 and even 15 years but had not been diagnosed or treated properly. Eventually, they started bringing their children with them, who also had similar symptoms.

“I realized adequate treatment in youth can prevent many of the harmful outcomes in adults who were never treated properly for their symptoms,” Dr. Robb says.

She soon came to another realization: there was a massive gap in the health care world – pediatric psychopharmacology. She felt the need to bridge this gap and help children, motivating her to change the course of her career. Since joining Children’s National Hospital in 1994, she’s been an unstoppable force in the pediatric psychopharmacology world, quickly changing the rules of the game.

The big picture

Pediatricians in the United States continue to grapple with a mental health crisis that was exacerbated by the COVID-19 pandemic and declared a national emergency in 2021.

Mental health plays a key role in a child’s mental, emotional and behavioral well-being. It affects the way they think, feel and act while also impacting how they handle stress, relate to their peers and make choices.

According to the Centers for Disease Control and Prevention, attention deficit hyperactivity disorder (ADHD), anxiety, behavior problems and depression are the most commonly diagnosed mental health disorders in children. While available treatments vary, over the years, data has proven how medications can play a role in improving most mental health conditions.

Children’s National leads the way

For decades, Dr. Robb has led research focused on pediatric psychopharmacology with more than 80 clinical trials. Children’s National is one of only a few sites nationwide to participate in federally funded mental health clinical trials. Major trials she has led include:

  • Lexapro for major depression in youth
  • Prozac for obsessive compulsive disorder
  • Abilify for pediatric bipolar and schizophrenia
  • Latuda for pediatric bipolar depression
  • Concerta for ADHD

Dr. Robb also co-chaired the American Academy of Child and Adolescent Psychiatry’s Pediatric Psychopharmacology Initiative Committee for more than 8 years. She has also been active for more than 15 years in the American Academy of Pediatrics Committee on drugs (pharmacology).

“Since its inception in the ‘90s, pediatric psychopharmacology has changed in two major ways: First, we started to do regular testing of new medications in children and not just adults. Second, there’s been congressional and FDA mandates for testing of all medications that can be used in kids,” says Dr. Robb. “It’s no longer a guessing game – we have an evidence-based approach to children with mental illness using psychopharmacology.”

Currently, Dr. Robb is the principal investigator on several open clinical trials at Children’s National, including a study that compares the effectiveness of treating a parent with ADHD medication plus behavioral parent training (BPT) versus BPT alone on their child’s ADHD related symptoms.

Moving the field forward

Earlier this year, Dr. Robb moderated a panel on mental health and precision genomics which touched on what we know about depression, anxiety and other disorders and the future of pediatric behavioral health care.

“The goal is to give people with depression and other mental health illnesses the opportunity to go to school and function, whether they have depression, ADHD or any other disorder. This can make a huge difference in someone’s life,” Dr. Robb says.

Children’s National is uniquely positioned with a dedicated pharmacokinetic clinical team – which has greatly aided its ADHD and Learning Differences Program and most recent Addictions Program.

“We changed how ADHD was treated because our patients had early access to new trialed drugs,” says Dr. Robb. “This makes a big difference and gives children the opportunity to have better control of their symptoms so they’re paying attention and learning in school.”

Read more about our advances in Behavioral Health.

Dr. Anna Penn uses a microscope

New model mimics persistent interneuron loss seen in prematurity

Dr. Anna Penn uses a microscope

Children’s research-clinicians created a novel preclinical model that mimics the persistent interneuron loss seen in preterm human infants, identifying interneuron subtypes that could become future therapeutic targets to prevent or lessen neurodevelopmental risks.

Research-clinicians at Children’s National Health System have created a novel preclinical model that mimics the persistent interneuron loss seen in preterm human infants, identifying interneuron subtypes that could become future therapeutic targets to prevent or lessen neurodevelopmental risks, the team reports Jan. 31, 2019, in eNeuro. The open access journal for Society for Neuroscience recognized the team’s paper as its “featured” article.

In the prefrontal cortex (PFC) of infants born preterm, there are decreased somatostatin and calbindin interneurons seen in upper cortical layers in infants who survived for a few months after preterm birth. This neuronal damage was mimicked in an experimental model of preterm brain injury in the PFC, but only when the newborn experimental models had first experienced a combination of prenatal maternal immune activation and postnatal chronic sublethal hypoxia. Neither neuronal insult on its own produced the pattern of interneuron loss in the upper cortical layers observed in humans, the research team finds.

“These combined insults lead to long-term neurobehavioral deficits that mimic what we see in human infants who are born extremely preterm,” says Anna Penn, M.D., Ph.D., a neonatologist in the Division of Neonatology and the Fetal Medicine Institute and a developmental neuroscientist at Children’s National Health System, and senior study author. “Future success in preventing neuronal damage in newborns relies on having accurate experimental models of preterm brain injury and well-defined outcome measures that can be examined in young infants and experimental models of the same developmental stage.”

According to the Centers for Disease Control and Prevention 1 in 10 infants is born preterm, before the 37th week of pregnancy. Many of these preterm births result from infection or inflammation in utero. After delivery, many infants experience other health challenges, like respiratory failure. These multi-hits can exacerbate brain damage.

Prematurity is associated with significantly increased risk of neurobehavioral pathologies, including autism spectrum disorder and schizophrenia. In both psychiatric disorders, the prefrontal cortex inhibitory circuit is disrupted due to alterations of gamma-aminobutyric acid (GABA) interneurons in a brain region involved in working memory and social cognition.

Cortical interneurons are created and migrate late in pregnancy and early infancy. That timing leaves them particularly vulnerable to insults, such as preterm birth.

In order to investigate the effects of perinatal insults on GABAergic interneuron development, the Children’s research team, led by Helene Lacaille, Ph.D., in Dr. Penn’s laboratory, subjected the new preterm encephalopathy experimental model to a battery of neurobehavioral tests, including working memory, cognitive flexibility and social cognition.

“This translational study, which examined the prefrontal cortex in age-matched term and preterm babies supports our hypothesis that specific cellular alterations seen in preterm encephalopathy can be linked with a heightened risk of children experiencing neuropsychiatric disorders later in life,” Dr. Penn adds. “Specific interneuron subtypes may provide specific therapeutic targets for medicines that hold the promise of preventing or lessening these neurodevelopmental risks.”

In addition to Dr. Penn and Lead Author Lacaille, Children’s co-authors include Claire-Marie Vacher; Dana Bakalar, Jiaqi J. O’Reilly and Jacquelyn Salzbank, all of Children’s Center for Neuroscience Research.

Financial support for research described in this post was provided by the National Institutes of Health under award R01HD092593, District of Columbia Intellectual Developmental Disabilities Research Center under award U54HD090257, Cerebral Palsy Alliance Research Foundation, Children’s National Board of Visitors, Children’s Research Institute and Fetal Medicine Institute.