Adolescence/Adulthood

A phase III, randomized, double-blind, placebo-controlled, efficacy and safety study of balovaptan in adults with autism spectrum disorder with a 2-year open-label extension

Principal Investigator:

Suma Jacob, MD, PhD (Department of Psychiatry)

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Abstract:

To date, few studies have investigated the effect of pharmacological treatments on the social and communication deficits in ASD, and no agent has received marketing approval for treating these core symptoms. Currently in the US, the only two approved medications for ASD are the atypical antipsychotics risperidone and aripiprazole, which only target irritability associated with ASD, but not core symptoms. In sum, there is no pharmacological treatment available for the social and communication deficits in individuals with ASD, and as a consequence there is a high unmet medical need for effective pharmacological therapies in the treatment of core symptoms in ASD.

The V1a receptor has been shown to modulate key social behaviors in both human and animal studies. Chronic administration of RO5285119 has been shown to normalize the social behavior and cognitive impairments induced in rats by prenatal valproate (VPA) exposure, an animal model that reflects some of the behavioral changes seen in ASD patients. Also, in the CNTNAP2 KO genetic mouse model of autism, V1a antagonism has been shown to rescue social impairment and repetitive behavior. A V1a antagonist may provide a novel and first approach to treat the core social and communication deficits in ASD.

Family Matters

Principal Investigator:

Alicia Kunin-Batson, PdD, LP (Department of Pediatrics), Mike Troy, PhD, LP (Children's MN - Behavioral Health)

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Collaborators:

Jerica Berge, PhD, MPH, LMFT, CRLE (Family Medicine and Community Health), Rachel Hardemann, PhD, MPH (Health Policy and Management)

Abstract:

The experience of discrimination and harassment due to race/ethnicity is a common and significant problem, with past studies suggesting 40-70% of people of color report such experiences. Evidence is accumulating that racism is a cause of health disparities and poor health outcomes in the United States. Most previous studies have focused on the direct experience of racism at the level of the individual and associations with adult health (e.g., hypertension, all-cause mortality).  However, research also suggests that racism-related stress can also be experienced indirectly, through exposure to the prejudice and discrimination experienced by others (e.g., parent to child) and the persistence of social structures which maintain racial discrimination by fostering inequitable systems (e.g., housing, employment). Few studies have examined the impact of parent-reported discrimination and harassment on children’s health and development and even fewer of these have included measures of exposure to structural racism at the community level.

There is an urgent need to learn more about avenues to disrupt the relationship between racism-related stressors and poor health outcomes. This is particularly true in the context of the current sociopolitical climate which many have argued has created a less accepting environment for immigrants and people of color, contributing to further discrimination and harassment and compounding structural inequality already present in many social systems. Drawing from previous empirical and conceptual studies, we propose that racism-related stressors will be related to important health, mental health, and cognitive developmental outcomes, and that children’s HPA-axis regulation is impacted through exposure to racism-related stress and associated with children’s health and wellness. Parenting behaviors and skills may also be impacted by exposure to racism-related stressors and provide potentially malleable intervention targets to impact children’s stress physiology as well as children’s health and development.

Mapping the Human Connectome During Typical Development

Principal Investigator:

Kathleen Thomas, PhD (Institute of Child Development), Essa Yacoub, PhD (Center for Magnetic Resonance Imaging)

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Abstract:

The major technological and analytical advances in adult human brain imaging achieved as part of the Human Connectome Projects (HCP) have allowed unprecedented examination of structural and functional brain connectivity at previously impossible levels of spatial and temporal resolution. While this information has proven crucial to our understanding of normative variation in adult brain connectivity, little is known about the developmental processes through which this variation arises. In this project, we apply the tools and analytical approaches developed by the HCP to understand how structural and functional wiring of the brain develops. This work is conducted through a consortium of five sites (Harvard University, University of California at Los Angeles, University of Minnesota, University of Oxford, Washington University in St. Louis), with extensive complimentary expertise in human brain imaging and neural development and including many of the investigators from the original adult and pilot lifespan HCPs. This group will acquire, analyze, and publicly share approximately 1500 high quality neuroimaging and associated behavioral datasets on healthy children and adolescents from 5–21 years of age. This unique protocol is designed to provide rich, multimodal data on several biological and cognitive constructs that are of critical importance to health and well-being across this age range and allow a wide range of investigators in the community to test a host of crucial hypotheses about brain development and connectivity.

Toddler and Parent Play Study

Principal Investigator:

Megan Gunnar, PhD (Institute of Child Development)

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Collaborators:

Emily Reilly, PhD candidate (Institute of Child Development)

Abstract:

Sensitive caregiving in the first years of life helps children manage their own emotions and arousal, promoting healthy development and a decreased risk of psychopathology-related symptoms later in childhood. This sensitive care can be derailed by parent trauma histories and depression, which is why sensitivity has become a target of many parenting interventions. Still, these interventions are not successful with some parents, challenging researchers to instead focus on the capacities necessary for sensitive responding. Compassion, we argue, is a principal capacity for sensitivity.

Compassion involves both an understanding of another’s distress and the motivation to act on this understanding to help alleviate their distress — abilities necessary to enact a sensitive response to a child. Encouragingly, compassion is malleable and can be induced with loving kindness meditations, which involve sending thoughts of loving kindness to yourself and a series of people. Biological measures, such as respiratory sinus arrhythmia (RSA), can be used to capture compassionate responding because another’s distress activates our physiological arousal. Employing heart rate variability methods provides an opportunity to measure effects of an LKM intervention at the biological level. Intervening to improve sensitivity by targeting compassion with an LKM could provide a cost-effective, efficient, and possibly more successful method for empowering parents to respond sensitively to their child, thereby preventing the development of mental illness in the next generation. However, it is first necessary to ensure the association between compassion and sensitivity.