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Principal Investigator: Chella Kamarajan
Organization: SUNY DOWNSTATE MEDICAL CENTER
Fiscal Year: 2024
Award: $507,544
Funding agency: National Institute on Alcohol Abuse and Alcoholism
This COGA (Collaborative Study on the Genetics of Alcoholism) spinoff application aims to understand
structural/functional features in key brain networks (Default Mode Network (DMN), Executive Control Network
(ECN), Reward/Salience Network (RSN)) underlying the critical transition from regular drinking to DSM-5
Alcohol Use Disorder (AUD) in young adult offspring from enriched COGA families, by combining newly
ascertained structural, diffusion and functional (s/d/fMRI), Neuropsychological (NPsych) and Electrophysiological
(EPhys) data together with existing multimodal longitudinal data (85% with 3+ assessments). The well-
characterized, genetically informative COGA sample with many offspring from families densely affected with AUD
at higher risk to develop AUD will be moving through the understudied age of young adulthood/early midlife (20's,
30's), when most longitudinal AUD development studies end and when our data predicts that a substantial portion
from high density families will transition from regular alcohol use to AUD. This proposal will target 150 young
adults (mean age 26) from the COGA study who are current regular drinkers (1/month+ for >6 months, but do
not currently meet criteria for DSM-5 AUD), and will follow them longitudinally with a multimodal approach to
compare those who transition to DSM-5 AUD and those who do not. We will add s/d/fMRI measures that are not
part of the COGA protocol, to provide anatomical specificity to complement current and existing NPsych and
EPhys longitudinal data during resting state, and three analogous cognitive/affective tasks [response inhibition
(Go/NoGo), reward processing (monetary gambling task), and affect modulation (cognitive/affective Stroop)].
Combining machine learning methods, advanced nonparametric, linear mixed methods, survival model, and joint
models of longitudinal data and survival data, we will: (Aim 1) identify features in specific neural circuits (DMN,
ECN, RSN) during resting state and during cognitive/affective tasks in young adults who transition from regular
drinking to AUD diagnosis from those who do not; (Aim 2) study the effects of drinking behaviors (e.g. age,
pattern, duration of alcohol use) on the s/d/fMRI, EPhys, and NPsych features in specific neural circuits
associated with the transition to AUD identified in Aim 1; and (Aim 3) determine the role of polygenic risk as
measured by polygenic risk score (PRS) derived from alcohol use- and brain-related GWAS, other risk/protective
factors [i.e., sex, race/ethnicity, family history, comorbid substance use (nicotine, cannabis), and psychiatric
disorders (depression), COVID-related traumatic stress] on neural circuits and their developmental trajectories
associated with transitions to AUD identified in Aims 1 and 2. The strength of our diverse, genetically informative,
enriched high-risk sample of young adults, longitudinal multimodal measures, and novel integrative analyses
will elucidate vulnerabilities and reciprocal relationships among neural circuits, genomic and other
risk/protectives factors in the transition to AUD during the 20s and 30s, with utility in prevention and treatment
initiatives.
Terms: <Adolescent and Young Adult><Adult Children><Adult Daughters><Adult Offspring><Adult Sons><Affect><Affective><Age><Alcohol Drinking><Alcohol consumption><Ammon Horn><Anatomic Sites><Anatomic structures><Anatomy><Anisotropy><Behavior><Brain><Brain Nervous System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 associated stress><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 induced stress><COVID-19 pandemic><COVID-19 period><COVID-19 predisposition><COVID-19 public health crisis><COVID-19 related stress><COVID-19 stress><COVID-19 susceptibility><COVID-19 vulnerability><COVID-19 years><CV-19><Cannabis><Central Lobe><Clinical Data><Cognitive><Complement><Complement Proteins><Cornu Ammonis><Coronavirus Infectious Disease 2019><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Corpus Striatum><Corpus striatum structure><DSM-5><DSM-V><DSM5><DWI (diffusion weighted imaging)><DWI-MRI><Data><Data Collection><Development><Diagnosis><Diagnostic and Statistical Manual of Mental Disorders, 5th edition><Diagnostic and Statistical Manual of Mental Disorders-V><Differences between sexes><Differs between sexes><Diffusion><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Disease><Disorder><EEG><Electroencephalogram><Electroencephalography><Electrophysiology><Electrophysiology (science)><Emotional><Encephalon><Epidemic><EtOH drinking><EtOH use><Ethnic Origin><Ethnicity><Event-Related Potentials><Exhibits><Family><Family Medical History><Family Medical History Epidemiology><Family history of><Fiber><Functional MRI><Functional Magnetic Resonance Imaging><Functional impairment><GWA study><GWAS><Gambling><Genetic><Genomics><Hippocampus><History><Impairment><Individual><Inferior Frontal Convolution><Inferior frontal gyrus><Insula><Insula of Reil><Island of Reil><Joints><Literature><Machine Learning><Measures><Mental Depression><Mental disorders><Mental health disorders><Methods><Modeling><Neurocognitive><Neurophysiology / Electrophysiology><Neuropsychologies><Neuropsychology><Nicotine><Nucleus Accumbens><Pattern><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Prevention><Prospective Studies><Protocol><Protocols documentation><Psychiatric Disease><Psychiatric Disorder><Race><Races><Recording of previous events><Recovery><Rest><Rewards><Risk><Risk Factors><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 predisposition><SARS-CoV-2 susceptibility><SARS-CoV-2 vulnerability><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sampling><Sampling Studies><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vulnerability><Sex Differences><Sexual differences><Social Environment><Specificity><Striate Body><Striatum><Thick><Thickness><Time><Work><adult youth><age associated effects><age effect><age related effects><ages><aging effect><alcohol ingestion><alcohol initiation><alcohol intake><alcohol product use><alcohol risk><alcohol use><alcohol use disorder><alcohol use initiation><alcoholic beverage consumption><alcoholic drink intake><analytical method><at-risk drinking><binge alcohol consumption><binge drinking><brain volume><career><cingulate cortex><co-morbid><co-morbidity><cognitive task><comorbidity><complementation><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><dMRI><density><depression><developmental><developmental disease><developmental disorder><diffused><diffuses><diffusing><diffusion tensor imaging><diffusions><disease risk><disorder risk><drinking><drinking behavior><drinking initiation><electrophysiological><emerging adulthood><episodic drinking><ethanol consumption><ethanol drinking><ethanol ingestion><ethanol intake><ethanol product use><ethanol use><ethanol use disorder><event related potential><executive control><executive function><fMRI><fMRI/EEG><functional magnetic resonance imaging/electroencephalography><genetic risk for alcoholism><genetic vulnerability to alcoholism><genetics of alcoholism><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genomewide association scan><genomewide association studies><genomewide association study><high risk><high risk drinking><high risk group><high risk individual><high risk people><high risk population><hippocampal><histories><impact of age><influence of age><life span><lifespan><longitudinal imaging><machine based learning><machine learning based method><machine learning method><machine learning methodologies><mental illness><mid life><mid-life><middle age><middle aged><midlife><multi-modal data><multi-modal datasets><multi-modality><multimodal data><multimodal datasets><multimodality><neural><neural adaptation><neural circuit><neural circuitry><neural network><neuro-genomics><neuroadaptation><neurocircuitry><neurogenomics><neuropsychologic><novel><offspring><polygenic risk score><predisposed to Coronavirus disease 2019><prospective><protective factors><psychiatric illness><psychological disorder><racial><racial background><racial origin><resilience><resilient><response><reward processing><risky drinking><serial imaging><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><social climate><social context><social role><socioenvironment><socioenvironmental><stress due to COVID-19><striatal><substance use><substance using><substantia alba><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><synaptic circuit><synaptic circuitry><temporal measurement><temporal resolution><time measurement><trait><traumatic stress><vulnerable to COVID-19><vulnerable to Coronavirus disease 2019><vulnerable to SARS-CoV-2><vulnerable to Severe acute respiratory syndrome coronavirus 2><white matter><whole genome association analysis><whole genome association studies><whole genome association study><young adult><young adulthood>