Benjamin Xu, Ph.D., Division of Neuroscience and Behavior

Purpose

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) seeks to continue the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), a nation-wide consortium of five research project sites to study the impact of alcohol drinking on brain structure and function during adolescence and into early adulthood.

Background

Adolescent or underage drinking is a serious public health issue because it affects the developing brain with concomitant effects on behavior and cognitive abilities. Recent statistics from the National Survey on Drug and Alcohol Use showing that by age 15 about 35% of adolescents have had at least one drink with the percentage increasing to around 65% by age 18. Nearly 90% of the alcohol that is consumed by adolescents is in the dangerous form of binge drinking, that is, consuming many drinks (about 5 or more drinks for male, and 4 or more drinks for female) in a short time period that brings the blood alcohol concentration to, at least, the legal intoxication level (BAC = 0.08 percent).

NIAAA recognized that alcohol drinking during adolescence could produce profound and enduring adverse consequences on brain and cognitive development with potential lasting impact throughout the life span. In 2012, the NIAAA, with support from NIMH, NICHD and NIDA, funded the nation-wide research consortium, the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), to investigate adolescent brain and behavior development in a cross-sectional longitudinal study with a particular emphasis on the effects of drinking alcohol during adolescence and into early adulthood. The NCANDA consortium used an accelerated cross-sectional longitudinal design with the enrollment age starting at 12-21. Within the first five-year funding period, NCANDA established a coordinated enrollment, testing, and data archiving infrastructure, and enrolled a unique cohort of 831 participants. The NCANDA consortium was subsequently renewed in 2017 to follow the cohort of 831 enrolled participants (age 15-25) into early adulthood. As the second funding period continues, data are emerging showing changes in developmental trajectories of both brain structures and functions as well as sex differences in relation to adolescent alcohol use.

The NCANDA consortium consists of an overall Administrative Resource core, a central Data Analysis Resource core, and five research projects sites where the participants are enrolled with a common study protocol. The studies supported by the NCANDA consortium included multi-modality behavioral, neurocognitive, neurobiological, and brain imaging measures with an accelerated longitudinal and demographically representative sampling design. The NCANDA consortium has successfully retained over 94% (N = 785) of the participants since the initial enrollment and a projected cohort of participants spanning from age 19 to 30 by the end of the currently funded project period (June 2022). Through these efforts, NCANDA has collected a unique set of data on adolescent substance use history and neuro-maturational trajectories that can be applied to identify psychobiological vulnerabilities that may elevate risks for alcohol use disorder (AUD) and other adverse life outcomes as well as targeted intervention during the development of adolescence and early adulthood.

Scope/Research Objective

The objective of this consortium is to support research addressing the knowledge gap(s) related to the following questions:

• What are the effects of both long and shorter-term adolescent alcohol exposure on the developing human brain?
• What is the effect of timing, dose, and duration of alcohol exposure on brain development?
• To what extent do these effects resolve or persist?
• How to factor key covariates into alcohol's effects on the brain development?
• How to identify early neural, cognitive, and affective markers that may predict alcohol misuse and onset or worsening of mental illness during adolescence and into adulthood?

Achievements

NCANDA achievements are reflected in the following areas:

Demographically Representative Sample

• NCANDA enrolled a total of 831 participants demographically representative of diverse racial and ethnic backgrounds and with a retention rate of > 94%. This unique cohort of participants allows in-depth study of developmental changes, predictors, and brain function associated with adolescent alcohol use.

Data Reproducibility and Sharing

• Developed methods and techniques in neuroimaging data harmonization across multiple research sites and MRI scanner types to provide consistent data quality for data sharing both within the consortium and with the scientific public.
• Created data sharing resources and archives, and released longitudinal data (e.g., structural and functional MRI, neuropsychological assessments, and clinical and demographic information) for use by investigators within and outside NCANDA.

Research Tool and techniques development

• Developed integrated techniques combining NCANDA mobile apps (mNCANDA) with a wearable device (FitBit) for repeated online data collection for Ecological Momentary Assessments (EMA);
• Initiated the development and testing of a novel non-invasive wearable nano-biosensing system for real-time measurements of alcohol oxidase concentration from interstitial fluid (ISF) with Bluetooth technology.

Publications

• NCANDA has published over 40 peer-reviewed research articles reporting the findings from its longitudinal research projects since its initiation.

Justification

The continuing support of NCANDA will be based on the existing and unique NCANDA cohort of participants (N = 785; current age 18-29) with continuing data collection to capture a full range of the developmental trajectory and age-related changes in alcohol use behavior and its impact on AUD from adolescence into early adulthood (until age 30). Alcohol use and risks for alcohol-related harm are particularly prevalent during adolescence and early adulthood - the critical period of time in human cognitive and brain development. There continues to be significant knowledge and data gaps in understanding the progression and impact of adolescent drinking on the neurobehavioral development from adolescence into early adulthood. The NCANDA consortium has a study protocol that includes structural and functional imaging of the brain along with detailed social, cognitive, behavioral, neuropsychological, and clinical assessments over a decade or longer follow-ups after participants’ enrollment. The NCANDA study provides extensive and unique data sets with detailed information on alcohol use as well as maturation trajectories. In addition, innovative investigative strategies, methods, tools, and research paradigms emerging from the NCANDA consortium provide invaluable empirical and scientific resources and opportunities to researchers in a wide range of fields to generate targeted intervention strategies, predictors, and hypothesis-based research questions pertaining to the etiology and neurobehavioral effects of heavy drinking and AUD in adulthood. The continuing support of NCANDA will further emphasize the inclusion of early-stage and/or new investigators, underrepresented and minority investigators, as well as relevant experts outside the alcohol field.

Grant Mechanism

The NCANDA consortium will consist of an Administrative Resource core (U24), which will provide the scientific leadership, consortium-wide oversight, and coordination, to the whole consortium. The administrative core will be responsible for managing the Scientific Advisory Board and the research Steering Committee. This component must include a detailed description of the leadership succession plan to ensure that a pipeline of leaders will be available when they are needed, in the event that the Consortium Director becomes incapacitated or for some other reasons, not able to continue as leader of the consortium. The Administrative Core must also lay out a plan on how the next generation of scientists from diverse background would be elevated to leadership positions, and a plan for the examination of COVID-19 impact on alcohol use behavior.

The consortium will also include a Data Analysis Resource core (U24) led by the Consortium Coordinator and Principal Investigators that provides service to the individual research projects (U01s). The research projects (U01s) affiliated with the consortium will focus on the common theme and aims of the consortium as describe above.

The cooperative agreement mechanism requires the appointment of an NIH Project Scientist, who will have substantial involvement above and beyond the normal program stewardship of the award. The NIH Project Scientist is a partner within the research team representing the government's interest in the substantive work of the research team with specific responsibilities.

Limited Competition

The continuing support for the NCANDA consortium will be limited to competing renewals of existing research sites supported by the U24 and U01 grant mechanisms as the longitudinal design of the study relies on continuing data collection and follow-up measures on the participants already enrolled at these research sites for almost a decade since its inception. To ensure the continuity of the longitudinal nature of the study design and data collection uniformity, only renewals will be considered in these NOFOs. The decision to limit competition is recommended in consideration of the success of the current awardees as well as, the costs, risks, and logistical difficulties in developing new sites and the longitudinal focus of the studies.

Diversity

The NCANDA consortium is expected to engage a diverse group of scientists in biomedical research, which includes but is not limited to participation of individuals from underrepresented backgrounds (i.e. racial and ethnic minorities, persons with disabilities, or persons from disadvantaged backgrounds), women, early-stage and experienced investigators with a track record of funding, and investigators from various disciplines/departments and specialties. NOT OD 20-031 (Notice of NIH's Interest in Diversity).

The proposed RFAs, which will be open to qualified and eligible applicants, will be reissues of the following:

RFA-AA-17-003, U01 Research Project – Cooperative Agreements

RFA-AA-17-004, U24 Resource-Related Research Projects - Cooperative Agreements

RFA-AA-17-005, U24 Resource-Related Research Projects – Cooperative Agreements