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  1. Article: Multi-ancestry Whole-exome Sequencing Study of Alcohol Use Disorder in Two Cohorts.

    Wang, Lu / Kranzler, Henry R / Gelernter, Joel / Zhou, Hang

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. There has been substantial progress in identifying genetic variants underlying AUD. However, there are few whole-exome sequencing (WES) studies of AUD. We analyzed WES of 4, ... ...

    Abstract Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. There has been substantial progress in identifying genetic variants underlying AUD. However, there are few whole-exome sequencing (WES) studies of AUD. We analyzed WES of 4,530 samples from the Yale-Penn cohort and 469,835 samples from the UK Biobank (UKB). After quality control, 1,420 AUD cases and 619 controls of European ancestry (EUR) and 1,142 cases and 608 controls of African ancestry (AFR) from Yale-Penn were retained for subsequent analyses. WES data from 415,617 EUR samples (12,861 cases), 6,142 AFR samples (130 cases) and 4,607 South Asian (SAS) samples (130 cases) from UKB were also analyzed. Single-variant association analysis identified the well-known functional variant rs1229984 in
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.05.24305412
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Genetic and non-genetic predictors of risk for opioid dependence.

    Na, Peter J / Deak, Joseph D / Kranzler, Henry R / Pietrzak, Robert H / Gelernter, Joel

    Psychological medicine

    2024  , Page(s) 1–8

    Abstract: Background: Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating ... ...

    Abstract Background: Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating polygenic risk for opioid use disorder (OUD).
    Methods: Data from 1958 European ancestry adults who participated in the Yale-Penn 3 study were analyzed. Polygenic risk scores (PRS) were based on a large-scale multi-trait analysis of genome-wide association studies (MTAG) of OUD.
    Results: A total of 420 (21.1%) individuals had a lifetime diagnosis of OD. OUD PRS were positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21-1.66). Household income and education were the strongest correlates of OD. Among individuals with higher OUD PRS, those with higher education level had lower odds of OD (OR 0.92, 95% CI 0.85-0.98); and those with posttraumatic stress disorder (PTSD) were more likely to have OD relative to those without PTSD (OR 1.56, 95% CI 1.04-2.35).
    Conclusions: Results suggest an interplay between genetics and psychosocial environment in contributing to OD risk. While PRS alone do not yet have useful clinical predictive utility, psychosocial factors may help enhance prediction. These findings could inform more targeted clinical and policy interventions to help address this public health crisis.
    Language English
    Publishing date 2024-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 217420-0
    ISSN 1469-8978 ; 0033-2917
    ISSN (online) 1469-8978
    ISSN 0033-2917
    DOI 10.1017/S0033291723003732
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book: Dual diagnosis and psychiatric treatment

    Kranzler, Henry R.

    substance abuse and comorbid disorders

    (Medical psychiatry ; 27)

    2004  

    Author's details ed. by Henry R. Kranzler
    Series title Medical psychiatry ; 27
    Collection
    Keywords Diagnosis, Dual (Psychiatry) ; Mental Disorders / therapy ; Mental Disorders / complications ; Substance-Related Disorders / therapy ; Substance-Related Disorders / complications
    Language English
    Size IX, 573 S. : graph. Darst.
    Edition 2. ed.
    Publisher Dekker
    Publishing place New York u.a.
    Publishing country United States
    Document type Book
    Old title 1. Aufl. u.d.T. Dual diagnosis and treatment
    HBZ-ID HT013966610
    ISBN 0-8247-5042-X ; 978-0-8247-5042-8
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2004 A 2294 order for loan Magazin

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  4. Article: Novel digital approaches to the assessment of problematic opioid use.

    Freda, Philip J / Kranzler, Henry R / Moore, Jason H

    BioData mining

    2022  Volume 15, Issue 1, Page(s) 14

    Abstract: The opioid epidemic continues to contribute to loss of life through overdose and significant social and economic burdens. Many individuals who develop problematic opioid use (POU) do so after being exposed to prescribed opioid analgesics. Therefore, it ... ...

    Abstract The opioid epidemic continues to contribute to loss of life through overdose and significant social and economic burdens. Many individuals who develop problematic opioid use (POU) do so after being exposed to prescribed opioid analgesics. Therefore, it is important to accurately identify and classify risk factors for POU. In this review, we discuss the etiology of POU and highlight novel approaches to identifying its risk factors. These approaches include the application of polygenic risk scores (PRS) and diverse machine learning (ML) algorithms used in tandem with data from electronic health records (EHR), clinical notes, patient demographics, and digital footprints. The implementation and synergy of these types of data and approaches can greatly assist in reducing the incidence of POU and opioid-related mortality by increasing the knowledge base of patient-related risk factors, which can help to improve prescribing practices for opioid analgesics.
    Language English
    Publishing date 2022-07-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2438773-3
    ISSN 1756-0381
    ISSN 1756-0381
    DOI 10.1186/s13040-022-00301-1
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  5. Article ; Online: Corrigendum to "Examining a brief measure and observed cutoff scores to identify reward and relief drinking profiles: Psychometric properties and pharmacotherapy response" [Drug Alcohol Depend. 232 (2022) 109257].

    Votaw, Victoria R / Mann, Karl / Kranzler, Henry R / Roos, Corey R / Nakovics, Helmut / Witkiewitz, Katie

    Drug and alcohol dependence

    2024  Volume 255, Page(s) 111095

    Language English
    Publishing date 2024-01-18
    Publishing country Ireland
    Document type Published Erratum
    ZDB-ID 519918-9
    ISSN 1879-0046 ; 0376-8716
    ISSN (online) 1879-0046
    ISSN 0376-8716
    DOI 10.1016/j.drugalcdep.2024.111095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  6. Article: Effects of topiramate therapy on serum bicarbonate concentration in a sample of 10,279 veterans.

    Naps, Michelle S / Leong, Shirley H / Hartwell, Emily E / Rentsch, Christopher T / Kranzler, Henry R

    Alcohol (Hanover, York County, Pa.)

    2023  Volume 47, Issue 3, Page(s) 438–447

    Abstract: Background: Topiramate, which is increasingly being used to treat alcohol use disorder (AUD), is commonly associated with reduced serum bicarbonate concentrations. However, estimates of the prevalence and magnitude of this effect are from small samples ... ...

    Abstract Background: Topiramate, which is increasingly being used to treat alcohol use disorder (AUD), is commonly associated with reduced serum bicarbonate concentrations. However, estimates of the prevalence and magnitude of this effect are from small samples and do not address whether topiramate's effects on acid-base balance differ in the presence of an AUD or by topiramate dosage.
    Methods: Veterans Health Administration electronic health record (EHR) data were used to identify patients with a minimum of 180 days of topiramate prescription for any indication and a propensity score-matched control group. We differentiated patients into two subgroups based on the presence of a diagnosis of AUD in the EHR. Baseline alcohol consumption was determined using Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores in the EHR. Analysis also included a three-level measure representing mean daily dosage. The topiramate-associated changes in serum bicarbonate concentration were estimated in difference-in-differences linear regression models. A serum bicarbonate concentration <17 mEq/L was considered to represent possible clinically significant metabolic acidosis.
    Results: The cohort comprised 4287 topiramate-treated patients and 5992 propensity score-matched controls with a mean follow-up period of 417 days. The mean topiramate-associated reductions in serum bicarbonate concentration were <2 mEq/L in the low (≤88.75), medium (>88.75 and ≤141.70), and high (>141.70) mg/day dosage tertiles, irrespective of AUD history. Concentrations <17 mEq/L occurred in 1.1% of topiramate-treated patients and 0.3% of controls and were not associated with alcohol consumption or an AUD diagnosis.
    Conclusions: The excess prevalence of metabolic acidosis associated with topiramate treatment does not differ with dosage, alcohol consumption, or the presence of an AUD. Baseline and periodic serum bicarbonate concentration measurements are recommended during topiramate therapy. Patients prescribed topiramate should be educated about the symptoms of metabolic acidosis and urged to report their occurrence promptly to a healthcare provider.
    MeSH term(s) Humans ; Topiramate ; Bicarbonates ; Alcoholism ; Veterans ; Acidosis/chemically induced ; Acidosis/diagnosis ; Acidosis/epidemiology
    Chemical Substances Topiramate (0H73WJJ391) ; Bicarbonates
    Language English
    Publishing date 2023-02-21
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    DOI 10.1111/acer.15011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The phenomics and genetics of addictive and affective comorbidity in opioid use disorder.

    Freda, Philip J / Moore, Jason H / Kranzler, Henry R

    Drug and alcohol dependence

    2021  Volume 221, Page(s) 108602

    Abstract: Opioid use disorder (OUD) creates significant public health and economic burdens worldwide. Therefore, understanding the risk factors that lead to the development of OUD is fundamental to reducing both its prevalence and its impact. Significant sources ... ...

    Abstract Opioid use disorder (OUD) creates significant public health and economic burdens worldwide. Therefore, understanding the risk factors that lead to the development of OUD is fundamental to reducing both its prevalence and its impact. Significant sources of OUD risk include co-occurring lifetime and current diagnoses of both psychiatric disorders, primarily mood disorders, and other substance use disorders, and unique and shared genetic factors. Although there appears to be pleiotropy between OUD and both mood and substance use disorders, this aspect of OUD risk is poorly understood. In this review, we describe the prevalence and clinical significance of addictive and affective comorbidities as risk factors for OUD development as a basis for rational opioid prescribing and OUD treatment and to improve efforts to prevent the disorder. We also review the genetic variants that have been associated with OUD and other addictive and affective disorders to highlight targets for future study and risk assessment protocols.
    MeSH term(s) Analgesics, Opioid/therapeutic use ; Behavior, Addictive ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Mood Disorders/epidemiology ; Mood Disorders/genetics ; Opioid-Related Disorders/drug therapy ; Opioid-Related Disorders/genetics ; Phenomics ; Practice Patterns, Physicians' ; Prevalence ; Risk Factors
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2021-02-22
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 519918-9
    ISSN 1879-0046 ; 0376-8716
    ISSN (online) 1879-0046
    ISSN 0376-8716
    DOI 10.1016/j.drugalcdep.2021.108602
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1310: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    ab Jg. 2022: Lesesaal (EG)

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  8. Book: Dual diagnosis and treatment

    Kranzler, Henry R.

    substance abuse and comorbid medical and psychiatric disorders

    (Medical psychiatry ; 8)

    1998  

    Author's details ed. by Henry R. Kranzler
    Series title Medical psychiatry ; 8
    Collection
    Keywords Diagnosis, Dual (Psychiatry) ; Mental Disorders / therapy ; Mental Disorders / complications ; Substance-Related Disorders / therapy ; Substance-Related Disorders / complications ; Drogenabhängigkeit ; Sekundärkrankheit
    Subject Folgekrankheit ; Erworbener Defekt ; Sekundärerkrankung ; Folgeerkrankung ; Zweiterkrankung ; Begleitkrankheit ; Komorbidität ; Begleiterkrankung ; Conduct disorder ; Comorbid disorder ; Drogensucht ; Drogen ; Toxikomanie ; Substanzabhängigkeit
    Language English
    Size XIII, 584 S. :graph. Darst.
    Edition 1. print.
    Publisher Dekker
    Publishing place New York u.a.
    Publishing country United States
    Document type Book
    New title 2. Aufl. u.d.T. Dual diagnosis and psychiatric treatment
    HBZ-ID HT008267324
    ISBN 0-8247-9895-3 ; 978-0-8247-9895-6
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    1998 A 2192 order for loan Magazin

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  9. Article: A Multivariate Genome-Wide Association Study Reveals Neural Correlates and Common Biological Mechanisms of Psychopathology Spectra.

    Davis, Christal / Khan, Yousef / Toikumo, Sylvanus / Jinwala, Zeal / Boomsma, D / Levey, Daniel / Gelernter, Joel / Kember, Rachel / Kranzler, Henry

    Research square

    2024  

    Abstract: There is considerable comorbidity across externalizing and internalizing behavior dimensions of psychopathology. We applied genomic structural equation modeling (gSEM) to genome-wide association study (GWAS) summary statistics to evaluate the factor ... ...

    Abstract There is considerable comorbidity across externalizing and internalizing behavior dimensions of psychopathology. We applied genomic structural equation modeling (gSEM) to genome-wide association study (GWAS) summary statistics to evaluate the factor structure of externalizing and internalizing psychopathology across 16 traits and disorders among European-ancestry individuals (n's = 16,400 to 1,074,629). We conducted GWAS on factors derived from well-fitting models. Downstream analyses served to identify biological mechanisms, explore drug repurposing targets, estimate genetic overlap between the externalizing and internalizing spectra, and evaluate causal effects of psychopathology liability on physical health. Both a correlated factors model, comprising two factors of externalizing and internalizing risk, and a higher-order single-factor model of genetic effects contributing to both spectra demonstrated acceptable t. GWAS identified 409 lead single nucleotide polymorphisms (SNPs) associated with externalizing and 85 lead SNPs associated with internalizing, while the second-order GWAS identified 256 lead SNPs contributing to broad psychopathology risk. In bivariate causal mixture models, nearly all externalizing and internalizing causal variants overlapped, despite a genetic correlation of only 0.37 (SE = 0.02) between them. Externalizing genes showed cell-type specific expression in GABAergic, cortical, and hippocampal neurons, and internalizing genes were associated with reduced subcallosal cortical volume, providing insight into the neurobiological underpinnings of psychopathology. Genetic liability for externalizing, internalizing, and broad psychopathology exerted causal effects on pain, general health, cardiovascular diseases, and chronic illnesses. These findings underscore the complex genetic architecture of psychopathology, identify potential biological pathways for the externalizing and internalizing spectra, and highlight the physical health burden of psychiatric comorbidity.
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-4228593/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Identifying and Reducing Bias in Genome-Wide Association Studies of Alcohol-Related Traits.

    Kranzler, Henry R / Zhou, Hang / Kember, Rachel L

    The American journal of psychiatry

    2021  Volume 179, Issue 1, Page(s) 14–16

    MeSH term(s) Alcoholism/genetics ; Behavior, Addictive ; Genome-Wide Association Study ; Humans ; Phenotype
    Language English
    Publishing date 2021-12-28
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 280045-7
    ISSN 1535-7228 ; 0002-953X
    ISSN (online) 1535-7228
    ISSN 0002-953X
    DOI 10.1176/appi.ajp.2021.21111107
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    Ui I Zs.30: Show issues Location:
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