Sarah Paul @spaul1124
Clinical Psych PhD student @BRAINLab_WUSTL. Cross-disorder, alcohol involvement, polygenic risk | NIH F31 Fellow. She/her. @[email protected] St Louis, MO Joined July 2011-
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Excited to share that this manuscript has now been published @NatMentHealth! nature.com/articles/s4422…
PREPRINT ALERT! We conducted a PheWAS testing associations between latent psychopathology polygenic scores (PRS) and >1,200 phenotypes in ABCD! Thanks to @karcher_dr, Ryan Bogdan, @BarchDbarch, @e_covey_johnson, @AlexanderHatoum, @SMCColbert, @GorelikAaron, @David_Baranger (1/8)
Washington University in St. Louis NIMH T32 Postdoctoral Fellowship in Developmental Neuroscience and Child Psychopathology – Positions Open Starting 7/1/25! #BlackInNeuro
@David_Baranger @MedicalCollege Congratulations, David!! I love the lab name!
@e_covey_johnson @FABBS @BehaviorGenetic Congratulations, Emma!! You’re on a roll!!
Wonderful and thought-provoking symposium chaired by @e_covey_johnson today at #BGA2024 on the impacts of population dynamics, large biobank biases, and autozygosity on psychiatric traits and how we understand them!
@aidangcw @Cassie_Boness @KMKing_Psych @DrAndreaHoward @AndreaWycoff @jonas_dora_ @KatieWitkiewitz The theory that folks use alcohol to regulate/reduce/cope with negative affect does not seem to be borne out in EMA data! @KatieWitkiewitz distinguished between mood and one's reactivity to their mood - possibly the latter is more important?? Really fantastic set of talks!
@MaddyFrumkin @dartmouth @dartmouthCTBH Congratulations, Maddy!!!
Would love to chat with anyone interested in these topics and/or who has any questions or comments about the paper.
2) Some retrospective reporting of sx onsets (used first report to minimize bias). 3) Typical timing of psychopathology onset influences interpretation. 4) Couldn't evaluate subthreshold symptoms longitudinally, which would be ideal for testing predisposition vs. consequence.
Images with alt-text, in order:
I do want to mention a few of the *seven* limitations we discussed: 1) Only 3 PGS could be used for African ancestry, so our European ancestry-specific findings may contribute further to disparities in how research findings are applicable (or not) to different populations.
Tweeting is hard. I'm cheating & quoting our last sentence: "...partial support for the notion that behavioral stage-based addiction phenotypes, as operationalized here, may not only reflect putative alcohol-related behavioral consequences but also developmental risk for AUD."
One of the most interesting findings, in my view, is that when we looked mild, moderate, and severe AUD onsets, we saw that SAD symptoms and suicidal ideation were associated future severe (not mild or moderate) AUD:
The only PGS association that survived multiple testing correction was between problematic alcohol use PGS in European ancestry and increased hazards for the onset of suicidal ideation.
Alcohol initiation and AUD diagnoses were both associated with increase hazards of a major depressive episode and suicidal ideation, and initiation was also linked with higher hazards of future conduct disorder symptoms.
Externalizing (ADHD hyperactive, ODD, conduct sxs) was linked with increased hazards for all alcohol transitions, while neither internalizing sxs nor EF showed prospective links with alcohol outcomes. (Not shown, alcohol milestones were also not associated with EF trajectories.)
Data came from the COGA Prospective Study (n=3681, wave 1 ages 12-21) and mixed effects proportional hazards models to test associations b/w alcohol milestones & hazards of sx onsets (& vice versa), and b/w PGS and alcohol & sx onsets. See methods for fun nitty gritty details!
We also test associations between polygenic scores (PGS) for these/related phenotypes in both African and European ancestry and phenotypic expression, to further probe the role of predisposition in accounting for these relationships.
In this paper, we examine bidirectional associations between a) psychopathology with broadly impulsive (e.g., conduct disorder) and negative affect (e.g., MDD, SAD) qualities, as well as measures of EF, and b) transitions in alcohol use (first: use, intoxication, AUD sx, AUD dx).
This cycle may lead to preoccupation with and impaired ability to moderate use, as prefrontal control of reward- and affect-related circuits diminishes (reduced executive function [EF] and regulatory capacity).
Aidan Wright @aidangcw
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