Browsing by Author "Tillman, Rebecca"

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    Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users
    (Oxford University Press, 2023) Johnson, Emma C.; Colbert, Sarah M. C.; Jeffries, Paul W.; Tillman, Rebecca; Bigdeli, Tim B.; Karcher, Nicole R.; Chan, Grace; Kuperman, Samuel; Meyers, Jacquelyn L.; Nurnberger, John I.; Plawecki, Martin H.; Degenhardt, Louisa; Martin, Nicholas G.; Kamarajan, Chella; Schuckit, Marc A.; Murray, Robin M.; Dick, Danielle M.; Edenberg, Howard J.; D'Souza, Deepak Cyril; Di Forti, Marta; Porjesz, Bernice; Nelson, Elliot C.; Agrawal, Arpana; Medical and Molecular Genetics, School of Medicine
    Background and hypothesis: Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs. Study design: We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African ancestry; 42% female; 74% meeting lifetime criteria for an AUD). Study results: Cannabis use disorder (CUD) was prevalent in this analytic sample (70%), with 40% classified as mild, 25% as moderate, and 35% as severe. Polygenic risk for schizophrenia was positively associated with cannabis-related paranoia, feeling depressed or anhedonia, social withdrawal, and cognitive difficulties, even when controlling for duration of daily cannabis use, CUD, and age at first cannabis use. The schizophrenia PRS was most robustly associated with cannabis-related cognitive difficulties (β = 0.22, SE = 0.04, P = 5.2e-7). In an independent replication sample (N = 1446), associations between the schizophrenia PRS and cannabis-related experiences were in the expected direction and not statistically different in magnitude from those in the COGA sample. Conclusions: Among individuals who regularly use cannabis, genetic liability for schizophrenia-even in those without clinical features-may increase the likelihood of reporting unusual experiences related to cannabis use.
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    Associations between Suicidal Thoughts and Behaviors and Genetic Liability for Cognitive Performance, Depression, and Risk-Taking in a High-Risk Sample
    (Karger, 2021) Johnson, Emma C.; Aliev, Fazil; Meyers, Jacquelyn L.; Salvatore, Jessica E.; Tillman, Rebecca; Chang, Yoonhoo; Docherty, Anna R.; Bogdan, Ryan; Acion, Laura; Chan, Grace; Chorlian, David B.; Kamarajan, Chella; Kuperman, Samuel; Pandey, Ashwini; Plawecki, Martin H.; Schuckit, Marc; Tischfield, Jay; Edenberg, Howard J.; Bucholz, Kathleen K.; Nurnberger, John I.; Porjesz, Bernice; Hesselbrock, Victor; Dick, Danielle M.; Kramer, John R.; Agrawal, Arpana; Psychiatry, School of Medicine
    Background: Suicidal thoughts and behaviors (STBs) and nonsuicidal self-injury (NSSI) behaviors are moderately heritable and may reflect an underlying predisposition to depression, impulsivity, and cognitive vulnerabilities to varying degrees. Objectives: We aimed to estimate the degrees of association between genetic liability to depression, impulsivity, and cognitive performance and STBs and NSSI in a high-risk sample. Methods: We used data on 7,482 individuals of European ancestry and 3,359 individuals of African ancestry from the Collaborative Study on the Genetics of Alcoholism to examine the links between polygenic scores (PGSs) for depression, impulsivity/risk-taking, and cognitive performance with 3 self-reported indices of STBs (suicidal ideation, persistent suicidal ideation defined as ideation occurring on at least 7 consecutive days, and suicide attempt) and with NSSI. Results: The PGS for depression was significantly associated with all 4 primary self-harm measures, explaining 0.6-2.5% of the variance. The PGS for risk-taking behaviors was also associated with all 4 self-harm behaviors in baseline models, but was no longer associated after controlling for a lifetime measure of DSM-IV alcohol dependence and abuse symptom counts. Polygenic predisposition for cognitive performance was negatively associated with suicide attempts (q = 3.8e-4) but was not significantly associated with suicidal ideation nor NSSI. We did not find any significant associations in the African ancestry subset, likely due to smaller sample sizes. Conclusions: Our results encourage the study of STB as transdiagnostic outcomes that show genetic overlap with a range of risk factors.
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    Characterization of Service Use for Alcohol Problems Across Generations and Sex in Adults With Alcohol Use Disorder
    (Wiley, 2020-03) Bourdon, Jessica L.; Tillman, Rebecca; Francis, Meredith W.; Dick, Danielle M.; Stephenson, Mallory; Kamarajan, Chella; Edenberg, Howard J.; Kramer, John; Kuperman, Samuel; Bucholz, Kathleen K.; McCutcheon, Vivia V.; Biochemistry and Molecular Biology, School of Medicine
    Background: There are gaps in the literature on service use (help-seeking and treatment utilization) for alcohol problems among those with alcohol use disorder (AUD). First, policy changes and cultural shifts (e.g., insurance) related to AUD have occurred over the last few decades, making it important to study generational differences. Second, multiple studies have found that females receive fewer services than males, and exploring whether these sex differences persist across generations can inform public health and research endeavors. The current study examined service use for alcohol problems among individuals with AUD. The aims were as follows: (i) to describe service use for alcohol problems; (ii) to assess generational differences (silent [b. 1928 to 1945], boomer [b. 1946 to 1964], generation X [b. 1965 to 1980], millennial [b. 1981 to 1996]) in help-seeking and treatment utilization; and (iii) to examine sex differences across generations. Methods: Data were from affected family members of probands who participated in the Collaborative Study on the Genetics of Alcoholism (N = 4,405). First, frequencies for service use variables were calculated across generations. Pearson chi-square and ANOVA were used to test for differences in rates and types of service use across generations, taking familial clustering into account. Next, Cox survival modeling was used to assess associations of generation and sex with time to first help-seeking and first treatment for AUD, and time from first onset of AUD to first help-seeking and first treatment. Interactions between generation and sex were tested within each Cox regression. Results: Significant hazards were found in all 4 transitions. Overall, younger generations used services earlier than older generations, which translated into higher likelihoods of these behaviors. Regardless of generation, younger females were less likely to use services than males. Conclusions: There are generational and sex differences in service use for alcohol problems among individuals with AUD. Policy and clinical implications are discussed.
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    Exploring the relationship between polygenic risk for cannabis use, peer cannabis use, and the longitudinal course of cannabis involvement
    (Wiley, 2019-04) Johnson, Emma C.; Tillman, Rebecca; Aliev, Fazil; Meyers, Jacquelyn L.; Salvatore, Jessica E.; Anokhin, Andrey P.; Dick, Danielle M.; Edenberg, Howard J.; Kramer, John; Kuperman, Samuel; McCutcheon, Vivia V.; Nurnberger, John I., Jr.; Porjesz, Bernice; Schuckit, Marc; Tischfield, Jay; Bucholz, Kathleen K.; Agrawal, Arpana; Biochemistry and Molecular Biology, School of Medicine
    Background and aims: Few studies have explored how polygenic propensity to cannabis use unfolds across development, and no studies have yet examined this question in the context of environmental contributions such as peer cannabis use. Outlining the factors that contribute to progression from cannabis initiation to problem use over time may ultimately provide insights into mechanisms for targeted interventions. We sought to examine the relationships between polygenic liability for cannabis use, cannabis use trajectories across ages 12–30, and perceived peer cannabis use at ages 12–17. Design: Mixed effect logistic and linear regressions were used to examine associations between polygenic risk scores, cannabis use trajectory membership, and perceived peer cannabis use. Setting: USA Participants: From the Collaborative Study on the Genetics of Alcoholism (COGA) study, a cohort of 1,167 individuals aged 12–26 years at their baseline (i.e., first) interview. Measurements: Key measurements included lifetime cannabis use (yes/no), frequency of past 12-month cannabis use, maximum lifetime frequency of cannabis use, cannabis use disorder (using DSM-5 criteria), and perceived peer cannabis use. Polygenic risk scores (PRS) were created using summary statistics from a large (N = 162,082) genome-wide association study (GWAS) of cannabis use. Three trajectories reflecting no/low (n=844), moderate (n=137) and high (n=186) use were identified. PRS were significantly associated with trajectory membership (p=0.002 – 0.006, maximum conditional R2 = 0.014, ORs = 1.40 – 1.49). Individuals who reported that most/all of their best friends used cannabis had significantly higher PRS than those who reported that none of their friends were users (OR = 1.35, 95% C.I. = [1.04, 1.75], p = 0.023). Perceived peer use itself explained up to 11.3% of the variance in trajectory class membership (OR: 1.50 – 4.65). When peer cannabis use and the cannabis use PRS were entered into the model simultaneously, both the PRS and peer use continued to be significantly associated with class membership (p < 0.01). Conclusions: Genetic propensity to cannabis use derived from heterogeneous samples appears to correlate with longitudinal increases in cannabis use frequency in young adults.