Predicting risk for Alcohol Use Disorder using longitudinal data with multimodal biomarkers and family history: a machine learning study.

Predictive models have succeeded in distinguishing between individuals with Alcohol use Disorder (AUD) and controls. However, predictive models identifying who is prone to develop AUD and the biomarkers indicating a predisposition to AUD are still unclear. Our sample (n = 656) included offspring and non-offspring of European American (EA) and African American (AA) ancestry from the Collaborative Study of the Genetics of Alcoholism (COGA) who were recruited as early as age 12 and were unaffected at first assessment and reassessed years later as AUD (DSM-5) (n = 328) or unaffected (n = 328). Machine learning analysis was performed for 220 EEG measures, 149 alcohol-related single nucleotide polymorphisms (SNPs) from a recent large Genome-wide Association Study (GWAS) of alcohol use/misuse and two family history (mother DSM-5 AUD and father DSM-5 AUD) features using supervised, Linear Support Vector Machine (SVM) classifier to test which features assessed before developing AUD predict those who go on to develop AUD. Age, gender, and ancestry stratified analyses were performed. Results indicate significant and higher accuracy rates for the AA compared with the EA prediction models and a higher model accuracy trend among females compared with males for both ancestries. Combined EEG and SNP features model outperformed models based on only EEG features or only SNP features for both EA and AA samples. This multidimensional superiority was confirmed in a follow-up analysis in the AA age groups (12-15, 16-19, 20-30) and EA age group (16-19). In both ancestry samples, the youngest age group achieved higher accuracy score than the two other older age groups. Maternal AUD increased the model's accuracy in both ancestries' samples. Several discriminative EEG measures and SNPs features were identified, including lower posterior gamma, higher slow wave connectivity (delta, theta, alpha), higher frontal gamma ratio, higher beta correlation in the parietal area, and 5 SNPs: rs4780836, rs2605140, rs11690265, rs692854, and rs13380649. Results highlight the significance of sampling uniformity followed by stratified (e.g., ancestry, gender, developmental period) analysis, and wider selection of features, to generate better prediction scores allowing a more accurate estimation of AUD development

Early Sexual Trauma Exposure and Neural Response Inhibition in Adolescence and Young Adults: Trajectories of Frontal Theta Oscillations During a Go/No-Go Task

Objective Trauma, particularly when experienced early in life, can alter neurophysiologic and behavioral development, thereby increasing risk for substance use disorders and related psychopathology. However, few studies have empirically examined trauma using well-characterized developmental samples that are followed longitudinally. Method The association of assaultive, non-assaultive, and sexual assaultive experiences before 10 years of age with developmental trajectories of brain function during response inhibition was examined by measuring electrophysiologic theta and delta oscillations during no-go and go conditions in an equal probability go/no-go task. Data were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort, composed of offspring from high-risk and comparison families who were 12 to 22 years old at enrollment, with follow-ups at 2-year intervals since 2004. In addition, other important predictors of neurophysiologic functioning (eg, substance use, impulsivity, and parental alcohol use disorders) were investigated. Moreover, associations of neurophysiologic functioning with alcohol and cannabis use disorder symptom counts and externalizing and internalizing psychopathology were examined. Results Individuals exposed to sexual assaultive trauma before 10 years of age had slower rates of change in developmental trajectories of no-go frontal theta during response inhibition. Importantly, effects remained significant after accounting for exposure to other traumatic exposures, such as parental history of alcohol use disorder and participants’ substance use, but not measures of impulsivity. Further, slower rates of change in no-go frontal theta adolescent and young adult development were associated with increased risk for alcohol use disorder symptoms and internalizing psychopathology, but not for cannabis use disorder symptoms or externalizing psychopathology. Conclusion Childhood sexual assault is associated with atypical frontal neurophysiologic development during response inhibition. This could reflect alterations in frontal lobe development, synaptic pruning, and/or cortical maturation involving neural circuits for inhibitory control. These same areas could be associated with increased risk for young adult alcohol use disorder symptoms and internalizing psychopathology. These findings support the hypothesis that changes in neurocognitive development related to early sexual trauma exposure could increase the risk for mental health and substance use problems in young adulthood

Density and Dichotomous Family History Measures of Alcohol Use Disorder as Predictors of Behavioral and Neural Phenotypes: A Comparative Study Across Gender and Race/Ethnicity

Background: Family history (FH) is an important risk factor for the development of alcohol use disorder (AUD). A variety of dichotomous and density measures of FH have been used to predict alcohol outcomes; yet, a systematic comparison of these FH measures is lacking. We compared 4 density and 4 commonly used dichotomous FH measures and examined variations by gender and race/ethnicity in their associations with age of onset of regular drinking, parietal P3 amplitude to visual target, and likelihood of developing AUD. Methods: Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were utilized to compute the density and dichotomous measures. Only subjects and their family members with DSM-5 AUD diagnostic information obtained through direct interviews using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) were included in the study. Area under receiver operating characteristic curves were used to compare the diagnostic accuracy of FH measures at classifying DSM-5 AUD diagnosis. Logistic and linear regression models were used to examine associations of FH measures with alcohol outcomes. Results: Density measures had greater diagnostic accuracy at classifying AUD diagnosis, whereas dichotomous measures presented diagnostic accuracy closer to random chance. Both dichotomous and density measures were significantly associated with likelihood of AUD, early onset of regular drinking, and low parietal P3 amplitude, but density measures presented consistently more robust associations. Further, variations in these associations were observed such that among males (vs. females) and Whites (vs. Blacks), associations of alcohol outcomes with density (vs. dichotomous) measures were greater in magnitude. Conclusions: Density (vs. dichotomous) measures seem to present more robust associations with alcohol outcomes. However, associations of dichotomous and density FH measures with different alcohol outcomes (behavioral vs. neural) varied across gender and race/ethnicity. These findings have great applicability for alcohol research examining FH of AUD

Binge and High-Intensity Drinking – Associations with Intravenous Alcohol Self-Administration and Underlying Risk Factors

Some styles of alcohol consumption are riskier than others. How the level and rate of alcohol exposure contribute to the increased risk of alcohol use disorder is unclear, but likely depends on the alcohol concentration time course. We hypothesized that the brain is sensitive to the alcohol concentration rate of change and that people at greater risk would self-administer faster. We developed a novel intravenous alcohol self-administration paradigm to allow participants direct and reproducible control over how quickly their breath alcohol concentration changes. We used drinking intensity and the density of biological family history of alcohol dependence as proxies for risk. Thirty-five alcohol drinking participants aged 21-28 years provided analytical data from a single, intravenous alcohol self-administration session using our computer-assisted alcohol infusion system rate control paradigm. A shorter time to reach 80 mg/dl was associated with increasing multiples of the binge drinking definition (p = 0.004), which was in turn related to higher density of family history of alcoholism (FHD, p = 0.04). Rate-dependent changes in subjective response (intoxication and stimulation) were also associated with FHD (each p = 0.001). Subsequently, given the limited sample size and FHD range, associations between multiples of the binge drinking definition and FHD were replicated and extended in analyses of the Collaborative Study on the Genetics of Alcoholism database. The rate control paradigm models binge and high-intensity drinking in the laboratory and provides a novel way to examine the relationship between the pharmacokinetics and pharmacodynamics of alcohol and potentially the risk for the development of alcohol use disorders

Predicting alcohol use disorder remission: a longitudinal multimodal multi-featured machine learning approach

Predictive models for recovering from alcohol use disorder (AUD) and identifying related predisposition biomarkers can have a tremendous impact on addiction treatment outcomes and cost reduction. Our sample (N = 1376) included individuals of European (EA) and African (AA) ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA) who were initially assessed as having AUD (DSM-5) and reassessed years later as either having AUD or in remission. To predict this difference in AUD recovery status, we analyzed the initial data using multimodal, multi-features machine learning applications including EEG source-level functional brain connectivity, Polygenic Risk Scores (PRS), medications, and demographic information. Sex and ancestry age-matched stratified analyses were performed with supervised linear Support Vector Machine application and were calculated twice, once when the ancestry was defined by self-report and once defined by genetic data. Multifeatured prediction models achieved higher accuracy scores than models based on a single domain and higher scores in male models when the ancestry was based on genetic data. The AA male group model with PRS, EEG functional connectivity, marital and employment status features achieved the highest accuracy of 86.04%. Several discriminative features were identified, including collections of PRS related to neuroticism, depression, aggression, years of education, and alcohol consumption phenotypes. Other discriminated features included being married, employed, medication, lower default mode network and fusiform connectivity, and higher insula connectivity. Results highlight the importance of increasing genetic homogeneity of analyzed groups, identifying sex, and ancestry-specific features to increase prediction scores revealing biomarkers related to AUD remission

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Social-Cognitive Dynamics Enable Flexible Adaptation to Environments: Evidence from Social Decision-Making, Self-Regulation, and Adult-Attachment Research

Humans adapt and optimize behavior in their interaction with the environment and their functioning is socially interdependent and richly contextualized. In four papers, spanning different areas of study (social decision-making, self-regulation, adult-attachment), I examined how social-cognitive dynamics enable flexible adaptation to the environment. In Paper 1, across two studies, I show that social category cues (i.e., partner-attractiveness) can color interpersonal judgments about unknown others. But, despite the persisting effect of such cues, participants showed evidence of learning partner-utility information and overtime made choices that maximized profits. In Paper 2, I examined intraindividual variability in delaying of gratification (DG), across four studies. Multilevel analyses revealed that ~25% of the variability (Studies 1-3) in perceived success at DG was attributable to inter-individual variability. But, much of the variability (~75%, Studies 1-3) was attributable to intra-individual variability. I showed that individuals’ personal construals, like active pursuit of and value of delayed rewards (e.g., being healthy) and whether DG is perceived as easy/difficult, explained intra-individual variability in success at DG. Therefore, beyond the nominal/objective situation, an individual’s subjective construals of the situation allow for examining when and why individuals delay or not. In Paper 3, across two studies, I show that merely sharing an experience/context can affect impression formation. In Study 1, when the participant was socially excluded along with another player (i.e., co-excluded), we found that the co-excluded was evaluated more positively compared to the excluders. In Study 2, I show that the positivity towards the co-excluded is not merely a contrast effect of increased negativity towards the excluders or a reconnection effect following exclusion. Therefore, not just perceiver or target related characteristics drive impressions but the encountered context also can affect them. Lastly, in Paper 4 the malleability of attachment security/insecurity in response to partner-responsiveness was examined. In two studies, implicitly pairing smiling (i.e., accepting; Study 1 and 2) versus disgust (i.e., rejecting; Study 2) faces with distressing (vs. neutral) stimuli primed the processing speed for words signaling general secure attachment (Study 1) or partner evaluative words that signal security (vs. insecurity; Study 2). Specifically, accepting faces, during distress led to strong association with secure attachment and partner evaluative words but rejecting faces during distress led to association with insecure partner evaluative words. Thus, as evidenced by the aforementioned studies, social-cognitive dynamics do enable flexible adaptation to interactions and changes in one’s environment

Social-Cognitive Dynamics Enable Flexible Adaptation to Environments: Evidence from Social Decision-Making, Self-Regulation, and Adult-Attachment Research

Humans adapt and optimize behavior in their interaction with the environment and their functioning is socially interdependent and richly contextualized. In four papers, spanning different areas of study (social decision-making, self-regulation, adult-attachment), I examined how social-cognitive dynamics enable flexible adaptation to the environment. In Paper 1, across two studies, I show that social category cues (i.e., partner-attractiveness) can color interpersonal judgments about unknown others. But, despite the persisting effect of such cues, participants showed evidence of learning partner-utility information and overtime made choices that maximized profits. In Paper 2, I examined intraindividual variability in delaying of gratification (DG), across four studies. Multilevel analyses revealed that ~25% of the variability (Studies 1-3) in perceived success at DG was attributable to inter-individual variability. But, much of the variability (~75%, Studies 1-3) was attributable to intra-individual variability. I showed that individuals’ personal construals, like active pursuit of and value of delayed rewards (e.g., being healthy) and whether DG is perceived as easy/difficult, explained intra-individual variability in success at DG. Therefore, beyond the nominal/objective situation, an individual’s subjective construals of the situation allow for examining when and why individuals delay or not. In Paper 3, across two studies, I show that merely sharing an experience/context can affect impression formation. In Study 1, when the participant was socially excluded along with another player (i.e., co-excluded), we found that the co-excluded was evaluated more positively compared to the excluders. In Study 2, I show that the positivity towards the co-excluded is not merely a contrast effect of increased negativity towards the excluders or a reconnection effect following exclusion. Therefore, not just perceiver or target related characteristics drive impressions but the encountered context also can affect them. Lastly, in Paper 4 the malleability of attachment security/insecurity in response to partner-responsiveness was examined. In two studies, implicitly pairing smiling (i.e., accepting; Study 1 and 2) versus disgust (i.e., rejecting; Study 2) faces with distressing (vs. neutral) stimuli primed the processing speed for words signaling general secure attachment (Study 1) or partner evaluative words that signal security (vs. insecurity; Study 2). Specifically, accepting faces, during distress led to strong association with secure attachment and partner evaluative words but rejecting faces during distress led to association with insecure partner evaluative words. Thus, as evidenced by the aforementioned studies, social-cognitive dynamics do enable flexible adaptation to interactions and changes in one’s environment.2020-08-2