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Wen YT, Lien KP, Lai JCY, Chen SJ. Influence of tobacco smoking and alcohol drinking on anxiety in sample of 30 836 individuals in Taiwan Biobank. BJPsych Open 2025; 11:e78. [PMID: 40165523 PMCID: PMC12052577 DOI: 10.1192/bjo.2025.24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 01/12/2025] [Accepted: 02/02/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Anxiety disorders are among the most common mental disorders worldwide, and most previous studies have focused solely on alcohol drinking or tobacco smoking as risk factors for anxiety. AIM This study investigated the associations of alcohol drinking and tobacco smoking with anxiety. METHOD The data of 30 836 individuals in the Taiwan Biobank were retrieved and analysed in our study. To investigate the associations of tobacco and alcohol use with anxiety, we analysed Patient Health Questionnaire 4 (specifically scores for the first two questions assessing generalised anxiety disorder) results of the included participants and data on their tobacco and alcohol use, and other covariates. RESULTS Participants who used only tobacco and those using both tobacco and alcohol were more likely to experience anxiety than were those who did not use tobacco or alcohol. Among men, the use of alcohol and/or tobacco was associated with a significantly higher risk of anxiety. Among women, the use of both alcohol and tobacco was associated with a significantly higher risk of anxiety. Older age was associated with a lower risk of anxiety. CONCLUSIONS Tobacco and alcohol use significantly influence the risk of anxiety, particularly in men, and older age also influences this risk. The associations of anxiety with tobacco and alcohol use in women may change because of the increasing prevalence of their use among women in Taiwan in recent years.
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Affiliation(s)
- Ya-Ting Wen
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
- Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kuan-Po Lien
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
- Department of Surgery, Cathay General Hospital, Taipei, Taiwan
| | - Jerry Cheng-Yen Lai
- Department of Medical Research, Taitung MacKay Memorial Hospital, Taitung, Taiwan
- Master Programme in Biomedicine, National Taitung University, Taitung, Taiwan
| | - Shaw-Ji Chen
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
- Master Programme in Biomedicine, National Taitung University, Taitung, Taiwan
- Department of Psychiatry, Taitung MacKay Memorial Hospital, Taitung, Taiwan
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El Mostafi H, Elhessni A, Doumar H, Touil T, Mesfioui A. Behavioral and Amygdala Biochemical Damage Induced by Alternating Mild Stress and Ethanol Intoxication in Adolescent Rats: Reversal by Argan Oil Treatment? Int J Mol Sci 2024; 25:10529. [PMID: 39408860 PMCID: PMC11476757 DOI: 10.3390/ijms251910529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 09/19/2024] [Accepted: 09/22/2024] [Indexed: 10/20/2024] Open
Abstract
Adolescence is a critical period when the effects of ethanol and stress exposure are particularly pronounced. Argan oil (AO), a natural vegetable oil known for its diverse pharmacological benefits, was investigated for its potential to mitigate addictive-like behaviors and brain damage induced by adolescent intermittent ethanol intoxication (IEI) and unpredictable mild stress (UMS). From P30 to P43, IEI rats received a daily ip ethanol (3 g/kg) on a two-day on/two-day off schedule. On alternate days, the rats were submitted to UMS protocol. Next, a two-bottle free access paradigm was performed over 10 weeks to assess intermittent 20% ethanol voluntary consumption. During the same period, the rats were gavaged daily with AO (15 mL/kg). Our results show that IEI/UMS significantly increased voluntary alcohol consumption (from 3.9 g/kg/24 h to 5.8 g/kg/24 h) and exacerbated withdrawal signs and relapse-like drinking in adulthood. Although AO treatment slightly reduced ethanol intake, it notably alleviated withdrawal signs during abstinence and relapse-like drinking in adulthood. AO's effects were associated with its modulation of the HPA axis (elevated serum corticosterone), restoration of amygdala oxidative balance, BDNF levels, and attenuation of neurodegeneration. These findings suggest that AO's neuroprotective properties could offer a potential therapeutic avenue for reducing ethanol/stress-induced brain damage and addiction. Further research is needed to explore its mechanisms and therapeutic potential in alcohol use disorders.
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Affiliation(s)
- Hicham El Mostafi
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14 000, Morocco; (A.E.); (H.D.); (A.M.)
| | - Aboubaker Elhessni
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14 000, Morocco; (A.E.); (H.D.); (A.M.)
| | - Hanane Doumar
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14 000, Morocco; (A.E.); (H.D.); (A.M.)
| | - Tarik Touil
- Higher Institute of Nursing and Health Professions of Rabat, Rabat 4502, Morocco;
| | - Abdelhalem Mesfioui
- Laboratory of Biology and Health, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14 000, Morocco; (A.E.); (H.D.); (A.M.)
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3
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Gnatowski ER, Jurmain JL, Dozmorov MG, Wolstenholme JT, Miles MF. Ninein, a candidate gene for ethanol anxiolysis, shows complex exon-specific expression and alternative splicing differences between C57BL/6J and DBA/2J mice. Front Genet 2024; 15:1455616. [PMID: 39323865 PMCID: PMC11422218 DOI: 10.3389/fgene.2024.1455616] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 08/29/2024] [Indexed: 09/27/2024] Open
Abstract
Ethanol's anxiolytic actions contribute to increased consumption and the development of Alcohol Use Disorder (AUD). Our laboratory previously identified genetic loci contributing to the anxiolytic-like properties of ethanol in BXD recombinant inbred mice, derived from C57BL/6J (B6) and DBA/2J (D2) progenitor strains. That work identified Ninein (Nin) as a candidate gene underlying ethanol's acute anxiolytic-like properties in BXD mice. Nin has a complex exonic content with known alternative splicing events that alter cellular distribution of the NIN protein. We hypothesize that strain-specific differences in Nin alternative splicing contribute to changes in Nin gene expression and B6/D2 strain differences in ethanol anxiolysis. Using quantitative reverse-transcriptase PCR to target specific Nin splice variants, we identified isoform-specific exon expression differences between B6 and D2 mice in prefrontal cortex, nucleus accumbens and amygdala. We extended this analysis using deep RNA sequencing in B6 and D2 nucleus accumbens samples and found that total Nin expression was significantly higher in D2 mice. Furthermore, exon utilization and alternative splicing analyses identified eight differentially utilized exons and significant exon-skipping events between the strains, including three novel splicing events in the 3' end of the Nin gene that were specific to the D2 strain. Additionally, we document multiple single nucleotide polymorphisms in D2 Nin exons that are predicted to have deleterious effects on protein function. Our studies provide the first in-depth analysis of Nin alternative splicing in brain and identify a potential genetic mechanism altering Nin expression and function between B6 and D2 mice, thus possibly contributing to differences in the anxiolytic-like properties of ethanol between these strains. This work adds novel information to our understanding of genetic differences modulating ethanol actions on anxiety that may contribute to the risk for alcohol use disorder.
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Affiliation(s)
- E. R. Gnatowski
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, United States
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, United States
| | - J. L. Jurmain
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, United States
| | - M. G. Dozmorov
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, United States
- Department of Biostatistics, Virginia Commonwealth University, Richmond, United States
| | - J. T. Wolstenholme
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, United States
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, United States
| | - M. F. Miles
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, United States
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, United States
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Asefi MB, Heidari A, Hajikarim-Hamedani A, Mousavi Z, Ashabi G, Sadat-Shirazi MS, Zarrindast MR. Preconception ethanol exposure changes anxiety, depressive and checking-like behavior and alter the expression levels of MAO-B in male offspring. Neurotoxicol Teratol 2024; 104:107367. [PMID: 38866258 DOI: 10.1016/j.ntt.2024.107367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 05/18/2024] [Accepted: 06/08/2024] [Indexed: 06/14/2024]
Abstract
Alcohol use, which alters the epigenome, increases the probability that it could affect subsequent generations, even if they were never directly exposed to ethanol or even in utero. We explored the effects of parental ethanol exposure before conception on behavioral changes in the offspring. Considering the role of Monoamine oxidase-B (MAO-B) in dopamine turnover in the prefrontal cortex (PFC) and its influence on behavior, and taking into account that ethanol exposure could alter MAO-B, we assessed the protein levels in the offspring. Male and female rats were exposed to ethanol for 30 days and then allowed ten days of abstinence. Afterward, they were mated with either control or ethanol-exposed rats. The F1 and F2 male offspring underwent tests to assess behavioral changes. Additionally, the levels of MAO-B in the PFC were evaluated. Results revealed that in the F1, anxiety increased only in the bi-parental ethanol-exposed male offspring in the elevated plus maze test (p < 0.05), while depressive-like behavior rose only in maternal and bi-parental ethanol-exposed offspring (p < 0.01). However, compulsive-like behavior increased in all ethanol-exposed offspring (p < 0.01). No significant phenotypic changes were observed in the F2. The levels of MAO-B in the PFC increased in the maternal (p < 0.05) and bi-parental ethanol-exposed offspring (p < 0.01). Our study demonstrates that parental ethanol exposure, even in the days preceding mating, adversely affects behaviors and induces molecular changes in the brain. Given these findings, it becomes imperative to monitor children exposed to parental (especially maternal) ethanol for the prevention of mental disorders.
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Affiliation(s)
- Mohammad Basir Asefi
- Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.
| | - Amirhossein Heidari
- Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | | | - Zahra Mousavi
- Department of Pharmacology-Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Iran
| | - Ghorbangol Ashabi
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad-Reza Zarrindast
- Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Gottlieb S, van der Vaart A, Hassan A, Bledsoe D, Morgan A, O'Rourke B, Rogers WD, Wolstenholme JT, Miles MF. A selective GSK3β inhibitor, tideglusib, decreases intermittent access and binge ethanol self-administration in C57BL/6J mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.13.593949. [PMID: 38798478 PMCID: PMC11118361 DOI: 10.1101/2024.05.13.593949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
Abstract
Over 10% of the US population over 12 years old meets criteria for Alcohol Use Disorder (AUD), yet few effective, long-term treatments are currently available. Glycogen synthase kinase 3 beta (GSK3β) has been implicated in ethanol behaviors and poses as a potential therapeutic target in the treatment of AUD. Here we investigate the role of tideglusib, a selective GSK3β inhibitor, in ethanol consumption and other behaviors. We have shown tideglusib decreases ethanol consumption in both a model of daily, progressive ethanol intake (two-bottle choice, intermittent ethanol access) and binge-like drinking behavior (drinking-in-the-dark) without effecting water intake. Further, we have shown tideglusib to have no effect on ethanol pharmacokinetics, taste preference, or anxiety-like behavior, though there was a transient increase in total locomotion following treatment. Additionally, we assessed liver health following treatment via serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and showed no effect on aminotransferase levels though there was a decrease in alkaline phosphatase. RNA sequencing studies revealed a role of GSK3β inhibition via tideglusib on the canonical Wnt signaling pathway, suggesting tideglusib may carry out its effects on ethanol consumption through effects on β-catenin binding to the transcription factors TCF3 and LEF1. The data presented here further implicate GSK3β in alcohol consumption and support the use of tideglusib as a potential therapeutic in the treatment of AUD.
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Bao SL, Olarewaju G, Wang L, Sang J, Zhu J, Lachowsky NJ, Lal A, Ablona A, Ho D, Baharuddin F, Villa L, Lambert S, Dulai J, Moore DM. Ethno-racial variations in mental health symptoms among sexually-active gay, bisexual, and other men who have sex with men in Vancouver, Canada: a longitudinal analysis. BMC Public Health 2024; 24:282. [PMID: 38267930 PMCID: PMC10807146 DOI: 10.1186/s12889-024-17743-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 01/11/2024] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Minority stress from racism and heterosexism may uniquely interact to impact the mental health of racialized sexual minorities. We examined variations in anxiety and depressive symptoms by reported by ethno-racial identity among gay, bisexual, and other men who have sex with men (gbMSM) in Vancouver, Canada. METHODS We recruited gbMSM aged ≥ 16 years from February 2012 to February 2015 using respondent-driven sampling (RDS). Participants completed computer assisted self-interviews (CASI) at enrollment and every 6 months until February 2017. We examined factors associated with moderate/severe anxiety and depression scores (> 10) on the Hospital Anxiety and Depression Scale (HADS) and differences in key explanatory variables including sociodemographic, psychosocial, and substance use factors. We used multivariable mixed effects models to assess whether moderate/severe scores were associated with ethno-racial identity across all visits. RESULTS After RDS-adjustment, of 774 participants, 79.9% of participants identified as gay. 68.6% identified as white, 9.2% as Asian, 9.8% as Indigenous, 7.3% as Latin American, and 5.1% as other ethno-racial identities. Participants contributed a median of 6 follow-up visits (Q1-Q3: 4-7). In the multivariable analysis, Asian participants had decreased odds of moderate/severe anxiety scores compared to white participants (aOR = 0.39; 95% CI: 0.18-0.86), and Latin American participants had decreased odds of moderate/severe depression scores compared to both white (aOR = 0.17; 95% CI: 0.08-0.36) and Asian (aOR = 0.07; 95% CI: 0.02-0.20) participants. CONCLUSION Asian and Latino gbMSM reported decreased mental health symptoms compared to white participants. Asian and Latino gbMSM in Vancouver appear to manage multiple minority stressors without adversely affecting their mental health.
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Affiliation(s)
- Seraph L Bao
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Gbolahan Olarewaju
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Lu Wang
- BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6T 1Y6, Canada
| | - Jordan Sang
- BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6T 1Y6, Canada
| | - Julia Zhu
- BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6T 1Y6, Canada
| | - Nathan J Lachowsky
- BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6T 1Y6, Canada
- University of Victoria, Victoria, BC, Canada
| | - Allan Lal
- BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6T 1Y6, Canada
| | - Aidan Ablona
- Momentum Health Study People of Colour Advisory Board, Vancouver, BC, Canada
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Darren Ho
- Momentum Health Study People of Colour Advisory Board, Vancouver, BC, Canada
- Community Based Research Centre, Vancouver, BC, Canada
| | - Fahmy Baharuddin
- Momentum Health Study People of Colour Advisory Board, Vancouver, BC, Canada
- Living Positive Resource Centre, Kelowna, BC, Canada
| | - Lorenz Villa
- Momentum Health Study People of Colour Advisory Board, Vancouver, BC, Canada
| | - Sandy Lambert
- Momentum Health Study People of Colour Advisory Board, Vancouver, BC, Canada
| | - Joshun Dulai
- Momentum Health Study People of Colour Advisory Board, Vancouver, BC, Canada
| | - David M Moore
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
- BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6T 1Y6, Canada.
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Yang G, King SG, Lin HM, Goldstein RZ. Emotional Expression on Social Media Support Forums for Substance Cessation: Observational Study of Text-Based Reddit Posts. J Med Internet Res 2023; 25:e45267. [PMID: 37467010 PMCID: PMC10398365 DOI: 10.2196/45267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 05/02/2023] [Accepted: 06/09/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND Substance use disorder is characterized by distinct cognitive processes involved in emotion regulation as well as unique emotional experiences related to the relapsing cycle of drug use and recovery. Web-based communities and the posts they generate represent an unprecedented resource for studying subjective emotional experiences, capturing population types and sizes not typically available in the laboratory. Here, we mined text data from Reddit, a social media website that hosts discussions from pseudonymous users on specific topic forums, including forums for individuals who are trying to abstain from using drugs, to explore the putative specificity of the emotional experience of substance cessation. OBJECTIVE An important motivation for this study was to investigate transdiagnostic clues that could ultimately be used for mental health outreach. Specifically, we aimed to characterize the emotions associated with cessation of 3 major substances and compare them to emotional experiences reported in nonsubstance cessation posts, including on forums related to psychiatric conditions of high comorbidity with addiction. METHODS Raw text from 2 million posts made, respectively, in the fall of 2020 (discovery data set) and fall of 2019 (replication data set) were obtained from 394 forums hosted by Reddit through the application programming interface. We quantified emotion word frequencies in 3 substance cessation forums for alcohol, nicotine, and cannabis topic categories and performed comparisons with general forums. Emotion word frequencies were classified into distinct categories and represented as a multidimensional emotion vector for each forum. We further quantified the degree of emotional resemblance between different forums by computing cosine similarity on these vectorized representations. For substance cessation posts with self-reported time since last use, we explored changes in the use of emotion words as a function of abstinence duration. RESULTS Compared to posts from general forums, substance cessation posts showed more expressions of anxiety, disgust, pride, and gratitude words. "Anxiety" emotion words were attenuated for abstinence durations >100 days compared to shorter durations (t12=3.08, 2-tailed; P=.001). The cosine similarity analysis identified an emotion profile preferentially expressed in the cessation posts across substances, with lesser but still prominent similarities to posts about social anxiety and attention-deficit/hyperactivity disorder. These results were replicated in the 2019 (pre-COVID-19) data and were distinct from control analyses using nonemotion words. CONCLUSIONS We identified a unique subjective experience phenotype of emotions associated with the cessation of 3 major substances, replicable across 2 time periods, with changes as a function of abstinence duration. Although to a lesser extent, this phenotype also quantifiably resembled the emotion phenomenology of other relevant subjective experiences (social anxiety and attention-deficit/hyperactivity disorder). Taken together, these transdiagnostic results suggest a novel approach for the future identification of at-risk populations, allowing for the development and deployment of specific and timely interventions.
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Affiliation(s)
- Genevieve Yang
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
| | - Sarah G King
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
| | - Hung-Mo Lin
- Department of Anesthesiology, Yale School of Medicine, Yale University, New Haven, CT, United States
- Yale Center for Analytical Sciences, Yale School of Public Health, Yale University, New Haven, CT, United States
| | - Rita Z Goldstein
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
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Anker JJ, Thuras P, Shuai R, Hogarth L, Kushner MG. Evidence for an alcohol-related "harm paradox" in individuals with internalizing disorders: Test and replication in two independent community samples. Alcohol Clin Exp Res 2023; 47:713-723. [PMID: 37115410 PMCID: PMC10416809 DOI: 10.1111/acer.15036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/05/2023] [Accepted: 02/06/2023] [Indexed: 04/29/2023]
Abstract
BACKGROUND Internalizing (anxiety and mood) disorders (INTD) commonly co-occur (are "comorbid") with alcohol use disorder (AUD). The literature suggests that excessive alcohol use aimed at coping with INTD symptoms is, at best, a partial explanation for the high comorbidity rates observed. We hypothesized that individuals with INTD experience greater susceptibility to developing AUD symptoms due to the partially shared neurobiological dysfunctions underlying both conditions. We probe this hypothesis by testing the prediction that, after accounting for the volume of alcohol intake, individuals with INTD experience higher levels of alcohol-related symptoms. METHODS Data from the National Epidemiological Survey on Alcohol-Related Conditions (NESARC) Wave 3 were used for the primary analyses, and NESARC Wave 1 data were used for independent replication analyses. Individuals who reported any alcohol use in the prior year were categorized as: (1) never having had an INTD diagnosis ("INTD-Never"); (2) having a remitted INTD diagnosis only ("INTD-Remitted"); or (3) having current INTD diagnosis ("INTD-Current"). Between-group contrasts of alcohol-related symptoms controlled for total alcohol intake (past year), drinking pattern (e.g., binging) and variables previously shown to mark exaggerated AUD symptoms relative to drinking amount (e.g., SES, gender, and family history). RESULTS With all covariates in the model, individuals in the INTD-Current group and the INTD-Remitted group reported significantly greater alcohol-related symptoms than those in the INTD-Never group but did not themselves differ in level of alcohol-related symptoms. These results were replicated in the NESARC 1 dataset. CONCLUSIONS Individuals with INTD experience more alcohol-related symptoms than those who drink at the same level. While considering other explanations, we argue that this "harm paradox" is best explained by the view that INTD confers a neurobiologically mediated susceptibility to the development of AUD symptoms.
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Affiliation(s)
- Justin J. Anker
- Department of Psychiatry and Behavioral Sciences, University of Minnesota – Minneapolis, Minneapolis, Minnesota, USA
| | - Paul Thuras
- Minneapolis VA Medical Center, Minneapolis, Minneapolis, Minnesota, USA
| | | | - Lee Hogarth
- School of Psychology, University of Exeter, Exeter, UK
| | - Matt G. Kushner
- Department of Psychiatry and Behavioral Sciences, University of Minnesota – Minneapolis, Minneapolis, Minnesota, USA
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Patel P, Ali H, Inayat F, Pamarthy R, Giammarino A, Ilyas F, Smith-Martinez LA, Satapathy SK. Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations: A ten-year United States study. World J Hepatol 2023; 15:289-302. [PMID: 36926245 PMCID: PMC10011900 DOI: 10.4254/wjh.v15.i2.289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/01/2023] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Chronic liver disease is associated with various neuropsychiatric conditions. There are currently no large studies assessing and comparing the prevalence of psychiatric illnesses based on patient profiles and the etiology of cirrhosis. AIM To examine the trends of hospitalizations among psychiatric conditions in cirrhosis. METHODS We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis. The outcomes included the prevalence, trends, and associations of psychiatric diagnoses in these hospitalizations. Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized. RESULTS The prevalence of generalized anxiety disorder (GAD) in liver cirrhosis hospitalizations increased from 0.17% in 2009 to 0.92% in 2019 (P < 0.001). The prevalence of depression increased from 7% in 2009 to 12% in 2019 (P < 0.001). Attention deficit hyperactivity disorder (ADHD) prevalence increased from 0.06% to 0.24%. The prevalence of schizophrenia increased from 0.59% to 0.87% (P < 0.001). Schizoaffective disorder prevalence increased from 0.10% to 0.35% (P < 0.001). Post-traumatic stress disorder (PTSD) prevalence displayed increasing trends from 0.36% in 2009 to 0.93% in 2019 (P < 0.001). The prevalence of suicidal ideation increased from 0.23% to 0.56% in 2019. Cirrhosis related to alcoholic liver disease [adjusted odds ratios (aOR) 1.18, 95%CI 1.08-1.29, P < 0.001] and non-alcoholic fatty liver disease (NAFLD) (aOR 1.14, 95%CI 1.01-1.28, P = 0.025) was associated with depression more than other causes. Alcohol- and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders. Females had a higher association with GAD (aOR 2.56, 95%CI 2.14-3.06, P < 0.001), depression (aOR 1.78, 95%CI 1.71-1.84, P < 0.001), bipolar disorder (aOR 1.64, 95%CI 1.52-1.77, P < 0.001] and chronic fatigue (aOR 2.31, 95%CI 1.31-4.07, P < 0.001) when compared to males. Blacks, Hispanics, and Asian/Native Americans had a significantly lower association with GAD, depression, bipolar disorder, PTSD, and ADHD when compared to the white race. CONCLUSION The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade. Females had a higher association with psychiatric disorders compared to males. Blacks, Hispanics, and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.
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Affiliation(s)
- Pratik Patel
- Department of Gastroenterology, Mather Hospital and Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, United States
| | - Hassam Ali
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States.
| | - Faisal Inayat
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore 54550, Punjab, Pakistan
| | - Rahul Pamarthy
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Alexa Giammarino
- Department of Internal Medicine, North Shore University Hospital and Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, United States
| | - Fariha Ilyas
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Lucia Angela Smith-Martinez
- Department of Psychiatry, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Sanjaya K Satapathy
- Department of Hepatology, North Shore University Hospital and Hofstra University Zucker School of Medicine, Manhasset, NY 11030, United States
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McCabe CJ, Brumback T, Brown SA, Meruelo AD. Assessing cross-lagged associations between depression, anxiety, and binge drinking in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. Drug Alcohol Depend 2023; 243:109761. [PMID: 36621201 PMCID: PMC10122417 DOI: 10.1016/j.drugalcdep.2022.109761] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 12/01/2022] [Accepted: 12/24/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Between 20 % and 30 % of teens suffer from depression or anxiety before reaching adulthood, and up to half also use or misuse alcohol. Although theories suggest bidirectional links between harmful alcohol use (e.g., binge drinking) and internalizing symptoms (i.e., depression and anxiety), empirical evidence to-date has been mixed. Systematic reviews have attributed mixed findings to limitations in study design, such as the utilization of between-person analyses and the focus on unidirectional effects. The goal of this study was to address these limitations by assessing bidirectional within-person associations between internalizing symptoms and binge drinking over the course of 5 years in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) sample, a large cohort recruited at ages 12-21 and followed annually on substance use and psychiatric functioning. METHODS We used latent curve models with structured residuals to examine within-person lagged associations between depression, anxiety, and past month counts of binge drinking using NCANDA data (N = 831). Analyses were supplemented with post-hoc power simulations. RESULTS We found marginal evidence linking binge drinking with subsequent depression symptoms one year later among females. We found no evidence that depression or anxiety predicted subsequent binge drinking despite sufficient power. CONCLUSIONS Social and cognitive consequences of binge drinking may predict later depression symptoms in adolescence and young adulthood for young women, though there was little evidence favoring self-medication models for binge drinking. We note several moderating variables and common factor mechanisms that may better explain this link.
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Anxiety Screening among the General Population of Latvia and Associated Factors. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58091163. [PMID: 36143841 PMCID: PMC9505088 DOI: 10.3390/medicina58091163] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 01/23/2023]
Abstract
Background and Objectives: The aim of this study was to determine the point prevalence of at least mild anxiety symptoms and symptoms of generalized anxiety disorder in the Latvian general population, and to analyze the associated factors. Materials and Methods: A computer-assisted face-to-face survey was conducted in 2019−2020 with a multistage stratified probability sample of the Latvian general adult population (n = 2687). Anxiety was assessed using the 7-item Generalized Anxiety Disorder (GAD-7) scale; a score of ≥5 was defined as indicating the presence of mild symptoms of anxiety, and a score of ≥10 as the cutoff for identifying cases of generalized anxiety disorder. The Patient Health Questionnaire 9 (PHQ-9) and MINI International Neuropsychiatric Interview (M.I.N.I.) modules were used for assessing comorbid conditions. Multinomial logistic regression was conducted. Results: The point prevalence of mild anxiety symptoms was 10.9%. The point prevalence of generalized anxiety disorder symptoms was 3.9%. Higher odds of mild anxiety symptoms were detected in respondents of a young age (vs. 65 y.o. and older, aOR 3.1, p < 0.001), unmarried respondents (vs. married/cohabiting, aOR 1.5, p = 0.02), those living in the capital city (aOR 1.6, p = 0.008) or rural areas (aOR 1.5, p = 0.03) (vs. other towns), respondents with poor self-rated health (vs. good, aOR 2.6, p < 0.001), and diagnosed alcohol use disorder (aOR 1.9, p < 0.001), suicidal behavior (aOR 2.4, p < 0.001), and symptoms of depression (aOR 6.4, p < 0.001) (vs. no such conditions). As for symptoms of generalized anxiety disorder, female sex (vs. males, aOR 2.5, p = 0.003), age below 44 years (vs. 65+, aOR 6.2, p = 0.002), average self-rated health (vs. good, aOR 2.6, p = 0.005), and poor self-rated health (vs. good, aOR 5.3, p < 0.001), together with comorbid suicidal behavior (aOR 6.1, p < 0.001) and symptoms of depression (aOR 43.4, p < 0.001) (vs. no such conditions), increased the odds. Conclusions: Young age, poor self-rated health, and comorbid symptoms of depression and suicidal behavior were significant factors associated with symptoms of both mild anxiety and generalized anxiety disorder. Being unmarried, living in the capital city or rural areas, and alcohol use disorder were associated with mild anxiety symptoms alone. Female sex was associated with generalized anxiety disorder symptoms alone.
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12
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Kovács I, Gál BI, Horváth Z, Demeter I, Rózsa S, Janka Z, Urbán R, Demetrovics Z, Andó B. Externalizing personality characteristics define clinically relevant subgroups of alcohol use disorder. PLoS One 2022; 17:e0265577. [PMID: 35303035 PMCID: PMC8932598 DOI: 10.1371/journal.pone.0265577] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 03/03/2022] [Indexed: 11/19/2022] Open
Abstract
AIMS Higher levels of externalizing characteristics, i.e. impulsivity, novelty seeking and aggression, could contribute to the development, progression and severity of alcohol use disorder (AUD). The present study aims to explore whether these externalizing characteristics together have a potential group-forming role in AUD using latent profile analysis (LPA). METHODS Externalizing characteristics of 102 AUD patients were analyzed using LPA to explore the group-forming role of externalizing symptoms; groups were compared in terms of demographic and alcohol-related variables, indices of psychopathological, depressive and anxiety symptom severity. RESULTS LPA revealed and supported a two-group model based on externalizing symptoms. The group with higher levels of externalizing symptoms showed significantly elevated levels of alcohol-related and anxio-depressive symptoms. CONCLUSIONS Externalizing characteristics converge and have a group-forming role in chronic AUD, and are associated with a more severe form of AUD. By making the diagnostic category less heterogeneous, these different subtypes within AUD may provide aid in tailoring treatments to patients' specific needs.
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Affiliation(s)
- Ildikó Kovács
- Department of Psychiatry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- * E-mail: (IK); (BA)
| | - Bernadett I. Gál
- Department of Psychiatry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Zsolt Horváth
- Doctoral School of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Ildikó Demeter
- Department of Psychiatry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Sándor Rózsa
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States of America
- Institute of Psychology, Károli Gáspár University of the Reformed Church in Hungary, Budapest, Hungary
| | - Zoltán Janka
- Department of Psychiatry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Róbert Urbán
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Zsolt Demetrovics
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
- Centre of Excellence in Responsible Gaming, University of Gibraltar, Gibraltar, Gibraltar
| | - Bálint Andó
- Department of Psychiatry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- * E-mail: (IK); (BA)
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13
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Stoychev K, Dilkov D, Naghavi E, Kamburova Z. Genetic Basis of Dual Diagnosis: A Review of Genome-Wide Association Studies (GWAS) Focusing on Patients with Mood or Anxiety Disorders and Co-Occurring Alcohol-Use Disorders. Diagnostics (Basel) 2021; 11:1055. [PMID: 34201295 PMCID: PMC8228390 DOI: 10.3390/diagnostics11061055] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 01/02/2023] Open
Abstract
(1) Background: Comorbidity between Alcohol Use Disorders (AUD), mood, and anxiety disorders represents a significant health burden, yet its neurobiological underpinnings are elusive. The current paper reviews all genome-wide association studies conducted in the past ten years, sampling patients with AUD and co-occurring mood or anxiety disorder(s). (2) Methods: In keeping with PRISMA guidelines, we searched EMBASE, Medline/PUBMED, and PsycINFO databases (January 2010 to December 2020), including references of enrolled studies. Study selection was based on predefined criteria and data underwent a multistep revision process. (3) Results: 15 studies were included. Some of them explored dual diagnoses phenotypes directly while others employed correlational analysis based on polygenic risk score approach. Their results support the significant overlap of genetic factors involved in AUDs and mood and anxiety disorders. Comorbidity risk seems to be conveyed by genes engaged in neuronal development, connectivity, and signaling although the precise neuronal pathways and mechanisms remain unclear. (4) Conclusion: given that genes associated with complex traits including comorbid clinical presentations are of small effect, and individually responsible for a very low proportion of the total variance, larger samples consisting of multiple refined comorbid combinations and confirmed by re-sequencing approaches will be necessary to disentangle the genetic architecture of dual diagnosis.
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Affiliation(s)
- Kaloyan Stoychev
- Department of Psychiatry, Medical University Pleven, 5800 Pleven, Bulgaria
| | - Dancho Dilkov
- Department of Psychiatry, Military Medical Academy Sofia, 1606 Sofia, Bulgaria;
| | | | - Zornitsa Kamburova
- Department of Medical Genetics, Medical University Pleven, 5800 Pleven, Bulgaria;
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14
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Kagan ER, Frank HE, Knepley MJ, Kendall PC. Beyond 16 Sessions: Extending Manualized Treatment of Anxious Youth. JOURNAL OF CHILD AND FAMILY STUDIES 2021; 30:493-501. [PMID: 34335000 PMCID: PMC8317605 DOI: 10.1007/s10826-020-01872-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/23/2020] [Indexed: 06/13/2023]
Abstract
Cognitive behavioral therapy (CBT) is well established as an efficacious treatment for anxious youth, yet a number of youth remain symptomatic after the 10-16 sessions of treatment stipulated by most CBT treatment manuals. While a significant minority do not respond, no study has examined the frequency and impact of additional therapy sessions. This study examined youth receiving outpatient therapy at an anxiety clinic who were offered the option to continue treatment after completing 16 sessions of manual-based CBT. Fifty-nine percent of participants chose to continue treatment, with an average of approximately 20 total sessions across participants. Therapist ratings demonstrated a significant overall improvement between session 16 and the final session. No pre-treatment measure of symptom severity differed between those who extended treatment and those who ended at session 16. Parent-rated anxiety differed between groups at session 16, as did the length of time between the pre-treatment assessment and week 16 assessments. Findings indicate that extending treatment is not uncommon, is typically limited to several additional sessions, and is associated with an increase in treatment gains. Current results suggest that two factors at session 16, parental perceptions of anxiety and time to complete 16 sessions, are influential and may be central to the decision to continue treatment past this point. Clinical implications and future directions are discussed.
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15
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Agabio R, Baldwin DS, Amaro H, Leggio L, Sinclair JMA. The influence of anxiety symptoms on clinical outcomes during baclofen treatment of alcohol use disorder: A systematic review and meta-analysis. Neurosci Biobehav Rev 2021; 125:296-313. [PMID: 33454289 DOI: 10.1016/j.neubiorev.2020.12.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 12/17/2020] [Accepted: 12/27/2020] [Indexed: 12/22/2022]
Abstract
Given the high coexistence of anxiety symptoms in people with alcohol use disorder (AUD), we aimed to determine the influence of anxiety symptoms on outcomes in patients with AUD treated with the GABAB receptor agonist baclofen. A meta-analysis of 13 comparisons (published 2010-2020) including baseline and outcome data on alcohol consumption and anxiety after 12 weeks was undertaken. There were significantly higher rates of abstinent days in patients treated with baclofen compared to placebo (p = 0.004; high certainty evidence); specifically in those with higher baseline anxiety levels (p < 0.00001; high certainty evidence) compared to those with lower baseline anxiety levels (p = 0.20; moderate certainty evidence). The change in anxiety ratings over 12 weeks did not differ between those treated with baclofen or placebo (p = 0.84; moderate certainty evidence). This may be due to different anxiety constructs being measured by scales not validated in this patient group, or that anxiety is not a biobehavioral mechanism by which baclofen may reduce alcohol drinking. Given the prevalence of anxiety symptoms in AUD all these factors warrant further research.
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Affiliation(s)
- Roberta Agabio
- Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
| | - David S Baldwin
- Faculty of Medicine, University of Southampton, Southampton, UK; University Department of Psychiatry and Mental Health, University of Cape Town, South Africa.
| | - Hugo Amaro
- Faculty of Medicine, University of Southampton, Southampton, UK
| | - Lorenzo Leggio
- Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, MD, United States; Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, United States; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, RI, United States; Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Department of Neuroscience, Georgetown University Medical Center, Washington DC, United States.
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16
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Alcohol. Alcohol 2021. [DOI: 10.1016/b978-0-12-816793-9.00001-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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17
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Caputo F, Cibin M, Loche A, De Giorgio R, Zoli G. The recognition and management of protracted alcohol withdrawal may improve and modulate the pharmacological treatment of alcohol use disorder. J Psychopharmacol 2020; 34:1171-1175. [PMID: 32648800 DOI: 10.1177/0269881120936483] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
About 50% of persons with an alcohol use disorder may have symptoms of alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption. Protracted alcohol withdrawal (PAW), an underestimated and not yet clearly defined clinical condition that follows the acute stage of AWS, is characterized by the presence of substance-specific signs and symptoms (i.e. anxiety, irritability, mood instability, insomnia, craving) common to acute AWS, but persisting beyond the generally expected acute AWS time frames. Considering that PAW symptoms are mainly related to the neuro-adaptive changes of gamma-aminobutyric acid (GABA) and N-methyl-d-aspartate (NMDA) systems, naltrexone, nalmefene, and disulfiram may not be able to suppress the symptoms of PAW. After treatment of the acute phase of AWS, a more specifically pharmacological therapy able to suppress PAW symptoms could perhaps be used earlier and may be more helpful in preventing the risk of alcohol relapse, which remains higher during the first months of treatment. In light of this, medications acting on GABA and NMDA neurotransmitter systems to counterbalance the up-regulation of NMDA and the down-regulation of GABA could be employed in combination and started as soon as possible.
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Affiliation(s)
- Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, University of Ferrara, Ferrara, Italy.,Italian Society on Alcohol (SIA), Bologna, Italy
| | - Mauro Cibin
- Italian Society of Substance Abuse (SITD), Dolo (Venezia), Italy
| | | | - Roberto De Giorgio
- Department of Morphology, Surgery, Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - Giorgio Zoli
- Department of Morphology, Surgery, Experimental Medicine, University of Ferrara, Ferrara, Italy
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18
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Dong E, Pandey SC. Prenatal stress induced chromatin remodeling and risk of psychopathology in adulthood. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2020; 156:185-215. [PMID: 33461663 PMCID: PMC7864549 DOI: 10.1016/bs.irn.2020.08.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
New insights into the pathophysiology of psychiatric disorders suggest the existence of a complex interplay between genetics and environment. This notion is supported by evidence suggesting that exposure to stress during pregnancy exerts profound effects on the neurodevelopment and behavior of the offspring and predisposes them to psychiatric disorders later in life. Accumulated evidence suggests that vulnerability to psychiatric disorders may result from permanent negative effects of long-term changes in synaptic plasticity due to altered epigenetic mechanisms (histone modifications and DNA methylation) that lead to condensed chromatin architecture, thereby decreasing the expression of candidate genes during early brain development. In this chapter, we have summarized the literature of clinical studies on psychiatric disorders induced by maternal stress during pregnancy. We also discussed the epigenetic alterations of gene regulations induced by prenatal stress. Because the clinical manifestations of psychiatric disorders are complex, it is obvious that the biological progression of these diseases cannot be studied only in postmortem brains of patients and the use of animal models is required. Therefore, in this chapter, we have introduced a well-established mouse model of prenatal stress (PRS) generated in restrained pregnant dams. The behavioral phenotypes of the offspring (PRS mice) born to the stressed dam and underlying epigenetic changes in key molecules related to synaptic activity were described and highlighted. PRS mice may serve as a useful model for investigating the pathogenesis of psychiatric disorders and may be a useful tool for screening for the potential compounds that may normalize aberrant epigenetic mechanisms induced by prenatal stress.
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Affiliation(s)
- Erbo Dong
- Center for Alcohol Research in Epigenetics, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
| | - Subhash C Pandey
- Center for Alcohol Research in Epigenetics, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States; Jesse Brown VA Medical Center, Chicago, IL, United States
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19
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Rodriguez KM, Smith BL, Caldwell HK. Voluntary alcohol consumption is increased in female, but not male, oxytocin receptor knockout mice. Brain Behav 2020; 10:e01749. [PMID: 32666677 PMCID: PMC7507036 DOI: 10.1002/brb3.1749] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 06/17/2020] [Accepted: 06/19/2020] [Indexed: 01/30/2023] Open
Abstract
INTRODUCTION The oxytocin (Oxt) system, while typically associated with the neural regulation of social behaviors, also plays a role in an individual's vulnerability to develop alcohol use disorders (AUD). In humans, changes to the Oxt system, due to early life experience and/or genetic mutations, are associated with increased vulnerability to AUD. While a considerable amount is known about Oxt's role in AUD in males, less is known or understood, about how Oxt may affect AUD in females, likely due to many clinical and preclinical studies of AUD not directly considering sex as a biological variable. This is unfortunate given that females are more vulnerable to the effects of alcohol and have increased alcohol consumption, as compared to males. Therefore, in the current study we wanted to determine whether genetic disruption of the Oxt receptor (Oxtr), that is, Oxtr knockout (-/-) mice, affected stress-induced alcohol consumption in males and females. We hypothesized that genetic disruption of the Oxtr would result in increased stress-induced alcohol consumption in both males and females compared to wild-type (+/+) controls. Though, we predicted that these disruptions might be greater in female Oxtr -/- mice. METHODS To test this hypothesis, a two-bottle preference test was utilized along with the forced swim test (FST), and pre- and poststress alcohol consumption and preference measured within each sex (males and females were run separately). As a follow-up experiment, a taste preference test, to control for possible genotypic differences in taste, was also performed. RESULTS In males, we found no significant genotypic differences in alcohol consumption or preference. However, in females, we found that genetic disruption of the Oxtr resulted in a greater consumption of alcohol both pre- and poststress compared to controls. CONCLUSION These data suggest that in females, disruptions in Oxt signaling may contribute to increased vulnerability to alcohol-associated addiction.
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Affiliation(s)
- Karla M Rodriguez
- School of Biomedical Sciences and the Brain Health Research Institute, Kent State University, Kent, OH, USA.,Laboratory of Neuroendocrinology and Behavior, Department of Biological Sciences, Kent State University, Kent, OH, USA
| | - Brittany L Smith
- Laboratory of Neuroendocrinology and Behavior, Department of Biological Sciences, Kent State University, Kent, OH, USA.,Department of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA
| | - Heather K Caldwell
- School of Biomedical Sciences and the Brain Health Research Institute, Kent State University, Kent, OH, USA.,Laboratory of Neuroendocrinology and Behavior, Department of Biological Sciences, Kent State University, Kent, OH, USA
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20
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Garey L, Olofsson H, Garza T, Rogers AH, Kauffman BY, Zvolensky MJ. Directional Effects of Anxiety and Depressive Disorders with Substance Use: a Review of Recent Prospective Research. CURRENT ADDICTION REPORTS 2020. [DOI: 10.1007/s40429-020-00321-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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21
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Bezerra-Karounis MA, Krahe TE, Maisonnette S, Landeira-Fernandez J. Alcohol intake in Carioca High- and Low-conditioned Freezing rats. Pharmacol Biochem Behav 2020; 197:173019. [PMID: 32827503 DOI: 10.1016/j.pbb.2020.173019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 08/15/2020] [Accepted: 08/17/2020] [Indexed: 11/28/2022]
Abstract
Evidence from clinical and epidemiological studies point towards an association between generalized anxiety disorder (GAD) and alcohol abuse. In the present study we investigated whether a similar relationship could be observed in an animal model of GAD. Specifically, we evaluated the alcohol intake of Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively). Sex differences in alcohol drinking behavior were also studied. Male and female rats from randomized crossbreeding populations served as controls (CTL). Free- and forced-choice protocols were used to measure alcohol consumption, and quinine and saccharin were used as taste control solutions. Our results indicate that CHF rats consumed more alcohol than CLF and CTL ones in both the free-choice (6 and 10% concentrations) and the forced-choice (10% concentration) conditions. CHF female rats exhibited the highest amount of alcohol intake in the forced-choice condition. CHF females also consumed more quinine than CHF male rats. Finally, CHF rats exhibited lower saccharin consumption compared to CLF and CTL animals. Altogether, these results support the hypothesis that there is a positive relationship between anxiety and alcohol intake, and provide further evidence for the use of CHF rats as a model of GAD.
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Affiliation(s)
| | - Thomas E Krahe
- Department of Psychology, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Silvia Maisonnette
- Department of Psychology, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - J Landeira-Fernandez
- Department of Psychology, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, Brazil.
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22
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Lau CI, Liu MN, Chen WH, Walsh V, Wang SJ. Clinical and biobehavioral perspectives: Is medication overuse headache a behavior of dependence? PROGRESS IN BRAIN RESEARCH 2020; 255:371-402. [PMID: 33008514 DOI: 10.1016/bs.pbr.2020.05.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 04/28/2020] [Accepted: 05/01/2020] [Indexed: 02/08/2023]
Abstract
Medication overuse headache (MOH), previously known as analgesic abuse headache or medication misuse headaches, is a common form of chronic headache disorder that has a detrimental impact on health and society. Although it has been widely accepted that overusing abortive medications is paradoxically the cause of MOH and drug discontinuation is the treatment of choice, ongoing debates exist as to whether drug consumption per se is the cause or consequence of headache chronification. Certain features in MOH such as their compulsive drug-seeking behavior, withdrawal headaches and high relapse rates share similarities with drug dependence, suggesting that there might be common underlying biological and psychobehavioral mechanisms. In this regard, this article will discuss the updated evidence and current debates on the possible biobehavioral overlap between MOH and drug dependence. To begin with, we will discuss whether MOH has characteristics of substance dependence based on standard psychiatry diagnostic criteria and other widely used dependence scales. Recent epidemiological studies underscoring common psychiatric comorbidities between the two disorders will also be presented. Although both demonstrate seemingly distinct personality traits, recent studies revealed similar decision-making impairment from a cognitive perspective, indicating the presence of a maladaptive reward system in both disorders. In addition, emerging imaging studies also support this notion by showing reversible morphological and functional brain changes related to the mesocorticolimbic reward circuitry in MOH, with a strong resemblance to those in addiction. Finally, an increased familial risk for drug dependence and genetic association with dopaminergic and drug dependence molecular pathways in MOH also support a possible link between MOH and addiction. Understanding the role of dependence in MOH will have a great impact on disease management as this will provide the missing piece of the puzzle in current therapeutic strategies.
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Affiliation(s)
- Chi Ieong Lau
- Dementia Center, Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Applied Cognitive Neuroscience Group, Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan; College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; University Hospital, Taipa, Macau
| | - Mu-N Liu
- Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, Memory and Aging Centre, University of California, San Francisco, CA, United States
| | - Wei-Hung Chen
- Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Vincent Walsh
- Applied Cognitive Neuroscience Group, Institute of Cognitive Neuroscience, University College London, London, United Kingdom
| | - Shuu-Jiun Wang
- Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Brain Research Center and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
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23
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Che Q, Yang P, Gao H, Liu M, Zhang J, Cai T. Application of the Chinese Version of the BIS/BAS Scales in Participants With a Substance Use Disorder: An Analysis of Psychometric Properties and Comparison With Community Residents. Front Psychol 2020; 11:912. [PMID: 32457687 PMCID: PMC7225352 DOI: 10.3389/fpsyg.2020.00912] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 04/14/2020] [Indexed: 11/22/2022] Open
Abstract
Carver and White developed the Behavioral Inhibition/Behavioral Activation Scales (the BIS/BAS Scales) based on Reinforcement Sensitivity Theory proposed by Gray. Subsequent studies proposed that substance abuse was closely related to Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS). However, researches on the psychometric properties of the BIS/BAS scales in clinical samples are scarce. The present study was conducted to analyze the applicability of the BIS/BAS scales in a sample suffering from a substance use disorder (SUD) and undergoing treatment in compulsory detoxification institutions (n = 1117). Meanwhile, 822 community residents were selected for comparison. Confirmatory factor analysis was carried out to examine the construct validity and the results showed that the five-factor model was the best fit for people with a substance use disorder' data. Besides, Cronbach's alpha coefficient for the total scale was 0.808, indicating the satisfactory internal consistency reliability. Analysis of the correlation coefficient of the questionnaire with the corresponding personality traits showed that BAS was more associated with the impulsive trait. Surprisingly, participants with a substance use disorder showed more insensitivity for the reward dimension compared with that of community residents and the result of comparison between two samples supported joint subsystems hypothesis. Generally, the BIS/BAS scales showed good reliability and validity. These findings provide more direct evidence on the personality traits of people with a substance use disorder and should form the basis for further research.
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Affiliation(s)
- Qingqing Che
- Medical Psychological Center, Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute, Central South University, Changsha, China
- National Clinical Research Center for Mental Disorders, Changsha, China
| | - Peiwen Yang
- Medical Psychological Center, Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute, Central South University, Changsha, China
- National Clinical Research Center for Mental Disorders, Changsha, China
| | - Huiyuan Gao
- Medical Psychological Center, Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute, Central South University, Changsha, China
- National Clinical Research Center for Mental Disorders, Changsha, China
| | - Meizhu Liu
- Medical Psychological Center, Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute, Central South University, Changsha, China
- National Clinical Research Center for Mental Disorders, Changsha, China
| | - Jun Zhang
- Hunan Judicial Police Vocational College, Changsha, China
| | - Taisheng Cai
- Medical Psychological Center, Second Xiangya Hospital, Central South University, Changsha, China
- Medical Psychological Institute, Central South University, Changsha, China
- National Clinical Research Center for Mental Disorders, Changsha, China
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Demoulin S, Nguyen N, Chevallereau T, Fontesse S, Bastart J, Stinglhamber F, Maurage P. Examining the role of fundamental psychological needs in the development of metadehumanization: A multi-population approach. BRITISH JOURNAL OF SOCIAL PSYCHOLOGY 2020; 60:196-221. [PMID: 32346901 DOI: 10.1111/bjso.12380] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 02/11/2020] [Indexed: 11/28/2022]
Abstract
In the present paper, we investigate dehumanization processes from a victim perspective. We propose that dehumanization experiences, that is metadehumanization, arise from people's feelings that their fundamental human needs are thwarted and that such experiences influence their emotions, self-esteem, and coping strategies. Our model is put at test in three contexts involving different types of dehumanization victims: Women (Study 1a, N = 349), patients with severe alcohol use disorder (Study 1b, N = 120), and employees in organizations (Study 1c, N = 347). Our integrated model of metadehumanization, which considers both its antecedents and consequences, proved stable across contexts and populations and therefore helps building bridges between different psychological disciplines in which dehumanization occurs.
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Affiliation(s)
| | - Nathan Nguyen
- Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | | | | | | | | | - Pierre Maurage
- Université Catholique de Louvain, Louvain-la-Neuve, Belgium
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Elevation of Transient Receptor Potential Vanilloid 1 Function in the Lateral Habenula Mediates Aversive Behaviors in Alcohol-withdrawn Rats. Anesthesiology 2020; 130:592-608. [PMID: 30676422 DOI: 10.1097/aln.0000000000002615] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
WHAT WE ALREADY KNOW ABOUT THIS TOPIC Chronic alcohol use and withdrawal leads to increased pain perception, anxiety, and depression. These aberrant behaviors are accompanied by increased excitatory glutamatergic transmission to, and activity of, the lateral habenula neurons.Vanilloid type 1, or TRPV1, channels are expressed in the habenula and they facilitate glutamatergic transmission. Whether TRPV1 channel plays a role in habenula hyperactivity is not clear. WHAT THIS ARTICLE TELLS US THAT IS NEW Glutamatergic transmission in the lateral habenula was inhibited by TRPV1 channel antagonists. In vivo, local administration of TRPV1 antagonists into the lateral habenula attenuated hyperalgesia, anxiety, and relapse-like drinking in rats who chronically consumed alcohol.The data suggest that enhanced TRPV1 channel function during withdrawal may contribute to aberrant behavior that promotes relapse alcohol consumption. BACKGROUND Recent rat studies indicate that alcohol withdrawal can trigger a negative emotional state including anxiety- and depression-like behaviors and hyperalgesia, as well as elevated glutamatergic transmission and activity in lateral habenula neurons. TRPV1, a vanilloid receptor expressed in the habenula, is involved in pain, alcohol dependence, and glutamatergic transmission. The authors therefore hypothesized that TRPV1 contributes to the changes in both the behavioral phenotypes and the habenula activity in alcohol-withdrawn rats. METHODS Adult male Long-Evans rats (n = 110 and 280 for electrophysiology and behaviors, respectively), randomly assigned into the alcohol and water (Naïve) groups, were trained to consume either alcohol or water-only using an intermittent-access procedure. Slice electrophysiology was used to measure spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons. The primary outcome was the change in alcohol-related behaviors and lateral habenula activity induced by pharmacologic manipulation of TRPV1 activity. RESULTS The basal frequency of spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons in alcohol-withdrawn rats was significantly increased. The TRPV1 antagonist capsazepine (10 µM) induced a stronger inhibition on spontaneous excitatory postsynaptic currents (mean ± SD; by 26.1 ± 27.9% [n = 11] vs. 6.7 ± 18.6% [n = 17], P = 0.027) and firing (by 23.4 ± 17.6% [n = 9] vs. 11.9 ± 16.3% [n = 12], P = 0.025) in Withdrawn rats than Naive rats. By contrast, the TRPV1 agonist capsaicin (3 μM) produced a weaker potentiation in Withdrawn than Naïve rats (spontaneous excitatory postsynaptic currents: by 203.6 ± 124.7% [n = 20] vs. 415.2 ± 424.3% [n = 15], P < 0.001; firing: 38.1 ± 14.7% [n = 11] vs. 73.9 ± 41.9% [n = 11], P < 0.001). Conversely, capsaicin's actions in Naïve but not in Withdrawn rats were significantly attenuated by the pretreatment of TRPV1 endogenous agonist N-Oleoyldopamine. In Withdrawn rats, intra-habenula infusion of TRPV1 antagonists attenuated hyperalgesia and anxiety-like behaviors, decreased alcohol consumption upon resuming drinking, and elicited a conditioned place preference. CONCLUSIONS Enhanced TRPV1 function may contribute to increased glutamatergic transmission and activity of lateral habenula neurons, resulting in the aberrant behaviors during ethanol withdrawal.
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Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons. eNeuro 2020; 7:ENEURO.0132-19.2019. [PMID: 31548367 PMCID: PMC7070451 DOI: 10.1523/eneuro.0132-19.2019] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/12/2019] [Accepted: 08/23/2019] [Indexed: 11/25/2022] Open
Abstract
The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can drive innate, anxiety-related behaviors, but it is unclear whether reciprocal projections from the mPFC to BLA have similar roles. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC (dmPFC) and ventral mPFC (vmPFC) medial prefrontal cortical terminals in the BLA. We exposed adult male Sprague Dawley rats to chronic intermittent ethanol (CIE) using vapor chambers, measured anxiety-like behavior on the elevated zero maze, and used electrophysiology to record glutamatergic and GABAergic responses in BLA principal neurons. We found that withdrawal from a 7 d CIE exposure produced opposing effects at dmPFC (increased glutamate release) and vmPFC (decreased glutamate release) terminals in the BLA. Chemogenetic inhibition of dmPFC terminals in the BLA attenuated the increased anxiety-like behavior we observed during withdrawal. These data demonstrate that chronic ethanol exposure and withdrawal strengthen the synaptic connections between the dmPFC and BLA but weakens the vmPFC–BLA pathway. Moreover, facilitation of the dmPFC–BLA pathway during withdrawal contributes to anxiety-like behavior. Given the opposing roles of dmPFC–BLA and vmPFC–BLA pathways in fear conditioning, our results suggest that chronic ethanol exposure simultaneously facilitates circuits involved in the acquisition of and diminishes circuits involved with the extinction of withdrawal-related aversive behaviors.
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Bates ME, Mun EY, Buckman JF, Vaschillo E, Vaschillo B, Lehrer P, Udo T, Lesnewich LM. Getting to the Heart of Low Sensitivity to Alcohol: Context Moderates Low Cardiovascular Response to Alcohol in Persons With a Family History of Alcohol Use Disorder. Alcohol Clin Exp Res 2020; 44:589-599. [PMID: 31984514 PMCID: PMC7079052 DOI: 10.1111/acer.14293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Accepted: 01/16/2020] [Indexed: 01/16/2023]
Abstract
Background Low sensitivity to alcohol in persons with a family history of alcoholism (FH+), compared to those without (FH−), contributes to risk for alcohol use disorder (AUD). However, sensitivity of FH+ cardiovascular response to alcohol is not well understood. This gap is significant because cardiovascular processes contribute to emotional regulation and stress response problems theorized to be central to the development and persistence of AUD. This study compared changes in heart rate (HR) and HR variability (HRV) between FH groups after consuming alcohol and control beverages and examined how these changes were moderated by emotional and alcohol‐related contexts. Methods Young adults (N = 165) with FH+ (n = 110) or FH− (n = 55) each completed 2 sessions, separated by 1 week. They received one of 3 different beverages (alcohol, placebo, and told‐no‐alcohol) in each session. Electrocardiogram data were recorded during pre–beverage consumption and post–beverage consumption baselines, and then during 4 picture cue tasks (neutral, positive, negative, and alcohol‐related). Generalized estimating equations were used to examine differences in cardiovascular reactivity (changes in HR and HRV power at ~ 0.1 Hz) across FH groups, beverage conditions, and picture cue tasks. Results A significant beverage condition × cue task × FH interaction effect on HRV was observed. The FH+ group, compared to the FH− group, showed (a) significantly less HRV suppression in specific cue contexts following alcohol, (b) a mixed pattern of more and less HRV suppression across cue contexts following placebo, and (c) a similar HRV reactivity pattern in the told‐no‐alcohol condition across cue tasks. For HR, there were no significant effects involving FH. Conclusions Diminished cardiovascular sensitivity to oral alcohol in FH+ persons varied within a given drinking episode depending on emotional and alcohol‐related features of the context, suggesting that environmental characteristics play a role in the expression of low sensitivity to alcohol among FH+ individuals.
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Affiliation(s)
- Marsha E Bates
- From the, Division of Life Sciences, (MEB, JFB, EV, BV), Department of Kinesiology and Health, School of Arts and Sciences, Rutgers University - New Brunswick, New Brunswick, New Jersey.,Center of Alcohol and Substance Use Studies, (MEB, JFB, EV, BV, LML), Graduate School of Applied and Professional Psychology, Rutgers University - New Brunswick, Piscataway, New Jersey
| | - Eun-Young Mun
- Department of Health Behavior and Health Systems, (E-YM), School of Public Health, University of North Texas Health Science Center, Fort Worth, Texas
| | - Jennifer F Buckman
- From the, Division of Life Sciences, (MEB, JFB, EV, BV), Department of Kinesiology and Health, School of Arts and Sciences, Rutgers University - New Brunswick, New Brunswick, New Jersey.,Center of Alcohol and Substance Use Studies, (MEB, JFB, EV, BV, LML), Graduate School of Applied and Professional Psychology, Rutgers University - New Brunswick, Piscataway, New Jersey
| | - Evgeny Vaschillo
- From the, Division of Life Sciences, (MEB, JFB, EV, BV), Department of Kinesiology and Health, School of Arts and Sciences, Rutgers University - New Brunswick, New Brunswick, New Jersey.,Center of Alcohol and Substance Use Studies, (MEB, JFB, EV, BV, LML), Graduate School of Applied and Professional Psychology, Rutgers University - New Brunswick, Piscataway, New Jersey
| | - Bronya Vaschillo
- From the, Division of Life Sciences, (MEB, JFB, EV, BV), Department of Kinesiology and Health, School of Arts and Sciences, Rutgers University - New Brunswick, New Brunswick, New Jersey.,Center of Alcohol and Substance Use Studies, (MEB, JFB, EV, BV, LML), Graduate School of Applied and Professional Psychology, Rutgers University - New Brunswick, Piscataway, New Jersey
| | - Paul Lehrer
- Department of Psychiatry, (PL), Robert Wood Johnson Medical School, Rutgers University - New Brunswick, Piscataway, New Jersey
| | - Tomoko Udo
- Department of Health Policy, Management, and Behavior, (TU), School of Public Health, University at Albany- SUNY, Rensselaer, New York
| | - Laura M Lesnewich
- Center of Alcohol and Substance Use Studies, (MEB, JFB, EV, BV, LML), Graduate School of Applied and Professional Psychology, Rutgers University - New Brunswick, Piscataway, New Jersey.,Department of Psychology, (LML), School of Arts and Sciences, Rutgers University - New Brunswick, Piscataway, New Jersey
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An Analysis of the Child Behavior Checklist Anxiety Problems Scale's Predictive Capabilities. JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT 2019; 41:249-256. [PMID: 31666760 DOI: 10.1007/s10862-019-09722-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The Child Behavior Checklist (CBCL) is widely used to assess behavioral and emotional problems in youth. The CBCL Diagnostic and Statistical Manual (DSM)-Oriented Anxiety Problems subscale (CBCL-AP) was developed for the identification of DSM-IV anxiety disorders. Using data from 298 youth aged 6- to 18, the CBCL-AP scale was examined to determine its ability to differentially predict, via Receiver Operating Characteristics (ROC) analysis, the presence of (a) generalized anxiety disorder (GAD), (b) separation anxiety disorder (SAD), (c) specific phobia (SPPH), or (d) the presence of any of these disorders. Independent Evaluators (IEs) administered the Anxiety Disorders Interview Schedule for Children (ADIS-C/P) to determine the presence of an anxiety disorder. The ability of the CBCL-AP to predict to anxiety disorders was compared to the ability of the CBCL Anxious/Depressed (CBCL-A/D) scale and the seven empirically derived CBCL syndrome subscales and five DSM-Oriented subscales to predict anxiety disorder diagnoses. Results revealed that CBCL-AP scores significantly predicted all diagnoses. CBCL-A/D scores significantly predicted SAD (AUC = 0.67), GAD (AUC = 0.69), and the presence of any of the three disorders (AUC = 0.72), but not the presence of SPPH (AUC = 0.52). Although the CBCL-AP scale may not be a substitute for extensive diagnostics, it has demonstrated utility as an instrument for assessing anxiety and can serve to identify anxious youth in need of mental health services.
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Pucci M, Micioni Di Bonaventura MV, Wille-Bille A, Fernández MS, Maccarrone M, Pautassi RM, Cifani C, D’Addario C. Environmental stressors and alcoholism development: Focus on molecular targets and their epigenetic regulation. Neurosci Biobehav Rev 2019; 106:165-181. [DOI: 10.1016/j.neubiorev.2018.07.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 06/13/2018] [Accepted: 07/09/2018] [Indexed: 01/17/2023]
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Dyer ML, Easey KE, Heron J, Hickman M, Munafò MR. Associations of child and adolescent anxiety with later alcohol use and disorders: a systematic review and meta-analysis of prospective cohort studies. Addiction 2019; 114:968-982. [PMID: 30891835 PMCID: PMC6563455 DOI: 10.1111/add.14575] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 12/12/2018] [Accepted: 01/30/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Despite a wealth of literature, the relationship between anxiety and alcohol use remains unclear. We examined whether (a) child and adolescent anxiety is positively or negatively associated with later alcohol use and disorders and (b) study characteristics explain inconsistencies in findings. DESIGN AND SETTING We conducted a systematic review of 51 prospective cohort studies from 11 countries. Three studies contributed to a meta-analysis. We searched PubMed, Scopus, Web of Science and PsycINFO databases, and studies were included if they met the following criteria: English language publication, human participants, anxiety exposure (predictor variable) in childhood or adolescence and alcohol outcome at least 6 months later. PARTICIPANTS Study sample sizes ranged from 110 to 11 157 participants. Anxiety exposure ages ranged from 3 to 24 years, and alcohol outcome ages ranged from 11 to 42 years. MEASUREMENTS Ninety-seven associations across 51 studies were categorized by anxiety exposure (generalized anxiety disorder, internalizing disorders, miscellaneous anxiety, obsessive compulsive disorder, panic disorder, separation anxiety disorder, social anxiety disorder and specific phobias) and alcohol use outcome (drinking frequency/quantity, binge drinking and alcohol use disorders). FINDINGS The narrative synthesis revealed some evidence for a positive association between anxiety and later alcohol use disorders. Associations of anxiety with later drinking frequency/quantity and binge drinking were inconsistent. Type and developmental period of anxiety, follow-up duration, sample size and confounders considered did not appear to explain the discrepant findings. The meta-analysis also showed no clear evidence of a relationship between generalized anxiety disorder and later alcohol use disorder (odds ratio = 0.94, 95% confidence interval = 0.47-1.87). CONCLUSIONS Evidence to date is suggestive, but far from conclusive of a positive association between anxiety during childhood and adolescence and subsequent alcohol use disorder.
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Affiliation(s)
- Maddy L Dyer
- UK Centre for Tobacco and Alcohol Studies, School of Psychological Science, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK
| | - Kayleigh E Easey
- UK Centre for Tobacco and Alcohol Studies, School of Psychological Science, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK
| | - Jon Heron
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK
| | - Matthew Hickman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK
| | - Marcus R Munafò
- UK Centre for Tobacco and Alcohol Studies, School of Psychological Science, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK
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31
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De Ternay J, Naassila M, Nourredine M, Louvet A, Bailly F, Sescousse G, Maurage P, Cottencin O, Carrieri PM, Rolland B. Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain. Front Pharmacol 2019; 10:627. [PMID: 31214036 PMCID: PMC6554654 DOI: 10.3389/fphar.2019.00627] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 05/15/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Cannabidiol (CBD) is a natural component of cannabis that possesses a widespread and complex immunomodulatory, antioxidant, anxiolytic, and antiepileptic properties. Much experimental data suggest that CBD could be used for various purposes in alcohol use disorder (AUD) and alcohol-related damage on the brain and the liver. Aim: To provide a rationale for using CBD to treat human subjects with AUD, based on the findings of experimental studies. Methods: Narrative review of studies pertaining to the assessment of CBD efficiency on drinking reduction, or on the improvement of any aspect of alcohol-related toxicity in AUD. Results: Experimental studies find that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity. Moreover, CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and by inducing death of activated hepatic stellate cells. Finally, CBD reduces alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties. Conclusions: CBD could directly reduce alcohol drinking in subjects with AUD. Any other applications warrant human trials in this population. By reducing alcohol-related steatosis processes in the liver, and alcohol-related brain damage, CBD could improve both hepatic and neurocognitive outcomes in subjects with AUD, regardless of the individual's drinking trajectory. This might pave the way for testing new harm reduction approaches in AUD, in order to protect the organs of subjects with an ongoing AUD.
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Affiliation(s)
- Julia De Ternay
- Service Universitaire d’Addictologie de Lyon (SUAL), Bron, France
| | - Mickaël Naassila
- Université de Picardie Jules Verne, Centre Universitaire de Recherche en Santé, INSERM UMR 1247, Groupe de Recherche sur l’Alcool & les Pharmacodépendances, Amiens, France
| | | | - Alexandre Louvet
- Service des maladies de l’appareil digestif, CHU Lille, Universitéde Lille and INSERM U995, Lille, France
| | - François Bailly
- Service d’Addictologie et d’Hépatologie, GHN, HCL, Lyon, France
| | - Guillaume Sescousse
- Université de Lyon, UCBL, Centre de Recherche en Neurosciences de Lyon (CRNL), Inserm U1028, CNRS UMR5292, PSYR2, Bron, France
| | - Pierre Maurage
- Laboratory for Experimental Psychopathology (LEP), Psychological Science Research Institute, Université catholique de Louvain, Louvain-la-Neuve, Belgium
| | - Olivier Cottencin
- CHU de Lille, Université Lille, service d’addictologie, CNRS, UMR 9193, SCALab, équipe psyCHIC, Lille, France
| | - Patrizia Maria Carrieri
- INSERM, UMR_S 912, Sciences Economiques & Sociales de la Santé et Traitement de l’Information Médicale (SESSTIM), Marseille, France
| | - Benjamin Rolland
- Service Universitaire d’Addictologie de Lyon (SUAL), Bron, France
- Université de Lyon, UCBL, Centre de Recherche en Neurosciences de Lyon (CRNL), Inserm U1028, CNRS UMR5292, PSYR2, Bron, France
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Domi A, Stopponi S, Domi E, Ciccocioppo R, Cannella N. Sub-dimensions of Alcohol Use Disorder in Alcohol Preferring and Non-preferring Rats, a Comparative Study. Front Behav Neurosci 2019; 13:3. [PMID: 30760988 PMCID: PMC6364792 DOI: 10.3389/fnbeh.2019.00003] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 01/07/2019] [Indexed: 12/17/2022] Open
Abstract
Recent animal models of alcohol use disorder (AUD) are centered in capturing individual vulnerability differences in disease progression. Here, we used genetically selected Marchigian Sardinian alcohol-preferring (msP) and Wistars rats to apply a multidimensional model of AUD adapted from a previously described DSM-IV/DSM-5 multisymptomatic cocaine addiction model. As proof of concept, we hypothesized that msP rats, genetically selected for excessive drinking, would be more prone to develop dependence-like behavior compared to Wistars. Before exposure of animals to alcohol, we monitored basal anxiety in the elevated plus maze (EPM). Animals were then trained in prolonged operant alcohol self-administration, consisting of 30-min daily sessions for 60 days in total. Each session consisted of two 10-min periods of alcohol reinforcement separated by 10-min interval of non-reinforcement. Following training, we applied three criteria of individual vulnerability for AUD: (1) persistence of lever pressing for alcohol when it was not available; (2) motivation for alcohol in a progressive ratio (PR) schedule of reinforcement; and (3) resistance to punishment when alcohol delivery was anticipated by a foot-shock (0.3 mA). We obtained four groups corresponding to the number of criteria met (0–3 crit). Rats in the 0crit and 1crit groups were characterized as resilient, whereas rats in the 2crit and 3crit groups were characterized as prone to develop a dependent-like phenotype. As predicted, the 2–3crit groups were enriched with msP rats while the 0–1crit groups were enriched in Wistar rats. In further analysis, we calculated the global addiction score (GAS) per subject by the sum of the normalized score (z-score) of each criterion. Results showed GAS was highly correlated with animal distribution within the 3 criteria. Specifically, GAS was negative in the 0–1crit groups, and positive in the 2–3crit groups. A positive correlation between basal anxiety and quantity of alcohol intake was detected in msP rats but not Wistars. In conclusion, we demonstrated that the 0/3criteria model is a suitable approach to study individual differences in AUD and that msP rats, selected for excessive-alcohol drinking, show a higher propensity to develop AUD compared to non-preferring Wistars.
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Affiliation(s)
- Ana Domi
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Serena Stopponi
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Esi Domi
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Roberto Ciccocioppo
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Nazzareno Cannella
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
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Dong E, Guidotti A, Zhang H, Pandey SC. Prenatal stress leads to chromatin and synaptic remodeling and excessive alcohol intake comorbid with anxiety-like behaviors in adult offspring. Neuropharmacology 2018; 140:76-85. [PMID: 30016666 PMCID: PMC6499375 DOI: 10.1016/j.neuropharm.2018.07.010] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 06/01/2018] [Accepted: 07/07/2018] [Indexed: 12/16/2022]
Abstract
Epidemiologic evidence suggests that individuals during their prenatal development may be especially vulnerable to the effects of environmental factors such as stress that predisposes them to psychiatric disorders including alcohol use disorder (AUD) later in life. Currently, the epigenetic mechanisms of anxiety comorbid with AUD induced by prenatal stress (PRS) remain to be elucidated. Here, we examined anxiety-like and alcohol drinking behaviors in adult offspring of prenatally stressed dam (PRS-mice) using elevated plus maze, light/dark box and two-bottle free-choice paradigm. It was found that PRS-mice exhibit heightened anxiety-like behaviors and increased alcohol intake in adulthood and these behavioral deficits were associated with a significant decrease in dendritic spine density (DSD) in medial prefrontal cortex (mPFC) relative to non-stressed mice (NS mice). To determine the mechanisms by which PRS reduces DSD, we examined the expressions of key genes associated with synaptic plasticity, including activity regulated cytoskeleton associated protein (Arc), spinophilin (Spn), postsynaptic density 95 (Psd95), tropomyosin receptor kinase B (TrkB), protein kinase B (Akt), mammalian target of rapamycin (mTOR) and period 2 (Per2) in mPFC of PRS and NS mice. The mRNA levels of these genes were significantly decreased in PRS mice. Methylated DNA and chromatin immunoprecipitation studies revealed hyper DNA methylation or reduced histone H3K14 acetylation on promoters of above genes suggesting that epigenetic dysregulation may be responsible for the deficits in their expression. Findings from this study suggest that prenatal stress induced abnormal epigenetic mechanisms and synaptic plasticity-related events may be associated with anxiety-like and alcohol drinking behaviors in adulthood.
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Affiliation(s)
- Erbo Dong
- Center for Alcohol Research in Epigenetics, Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago IL, 60612, USA.
| | - Alessandro Guidotti
- Center for Alcohol Research in Epigenetics, Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago IL, 60612, USA
| | - Huaibo Zhang
- Center for Alcohol Research in Epigenetics, Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago IL, 60612, USA; Jesse Brown VA Medical Center, Chicago IL, 60612, USA
| | - Subhash C Pandey
- Center for Alcohol Research in Epigenetics, Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago IL, 60612, USA; Jesse Brown VA Medical Center, Chicago IL, 60612, USA
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Lee KM, Coelho MA, Sern KR, Class MA, Bocz MD, Szumlinski KK. Anxiolytic effects of buspirone and MTEP in the Porsolt Forced Swim Test. CHRONIC STRESS 2017; 1. [PMID: 28884167 PMCID: PMC5584874 DOI: 10.1177/2470547017712985] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Traditionally, a reduction in floating behavior or immobility in the Porsolt forced swim
test is employed as a predictor of anti-depressant efficacy. However, over the past
several years, our studies of alcohol withdrawal-induced negative affect consistently
indicate the coincidence of increased anxiety-related behaviors on various behavioral
tests with reduced immobility in the forced swim test. Further, this
behavioral profile correlates with increased mGlu5 protein expression within limbic brain
regions. As the role for mGlu5 in anxiety is well established, we hypothesized that the
reduced immobility exhibited by alcohol-withdrawn mice when tested in the forced swim test
might reflect anxiety, possibly a hyper-reactivity to the acute swim stressor. Herein, we
evaluated whether or not the decreased forced swim test immobility during alcohol
withdrawal responds to systemic treatment with a behaviorally effective dose of the
prototypical anxiolytic, buspirone (5 mg/kg). We also determined the functional relevance
of the withdrawal-induced increase in mGlu5 expression for forced swim test behavior by
comparing the effects of buspirone to a behaviorally effective dose of the mGlu5 negative
allosteric modulator MTEP (3 mg/kg). Adult male C57BL/6J mice were subjected to a 14-day,
multi-bottle, binge-drinking protocol that elicits hyper-anxiety and increases
glutamate-related protein expression during early withdrawal. Control animals received
only water. At 24-h withdrawal, animals from each drinking condition were subdivided into
groups and treated with an intraperitoneal injection of buspirone, MTEP, or vehicle,
30 min prior to the forced swim test. Drug effects on general locomotor activity were also
assessed. As we reported previously, alcohol-withdrawn animals exhibited significantly
reduced immobility in the forced swim test compared to water controls. Both buspirone and
MTEP significantly increased immobility in alcohol-withdrawn animals, with a modest
increase also seen in water controls. No significant group differences were observed for
locomotor activity, indicating that neither anxiolytic was sedating. These results provide
predictive validity for increased swimming/reduced immobility in the forced swim test as a
model of anxiety and provide novel evidence in favor of mGlu5 inhibition as an effective
therapeutic strategy for treating hyper-anxiety during alcohol withdrawal.
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Affiliation(s)
- Kaziya M Lee
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USA, 93106-9660
| | - Michal A Coelho
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USA, 93106-9660
| | - Kimberly R Sern
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USA, 93106-9660
| | - MacKayla A Class
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USA, 93106-9660
| | - Mark D Bocz
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USA, 93106-9660
| | - Karen K Szumlinski
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USA, 93106-9660.,Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA, 93106-9625
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35
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Connolly RD, Noel V, Mezo PG. Self-Evaluation as a Mediating Variable between Substance Abuse and Stress. Int J Ment Health Addict 2017. [DOI: 10.1007/s11469-017-9735-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Bahorik AL, Leibowitz A, Sterling SA, Travis A, Weisner C, Satre DD. The role of hazardous drinking reductions in predicting depression and anxiety symptom improvement among psychiatry patients: A longitudinal study. J Affect Disord 2016; 206:169-173. [PMID: 27475887 PMCID: PMC5077687 DOI: 10.1016/j.jad.2016.07.039] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 07/06/2016] [Accepted: 07/16/2016] [Indexed: 11/25/2022]
Abstract
BACKGROUND Co-occurrence of depression, anxiety, and hazardous drinking is high in clinical samples. Hazardous drinking can worsen depression and anxiety symptoms (and vice versa), yet less is known about whether reductions in hazardous drinking improve symptom outcomes. METHODS Three hundred and seven psychiatry outpatients were interviewed (baseline, 3-, 6-months) for hazardous drinking (drinking over recommended daily limits), depression (PHQ-9), and anxiety (GAD-7) as part of a hazardous drinking intervention trial. Longitudinal growth models tested associations between hazardous drinking and symptoms (and reciprocal effects between symptoms and hazardous drinking), adjusting for treatment effects. RESULTS At baseline, participants had moderate anxiety (M=10.81; SD=10.82) and depressive symptoms (M=13.91; SD=5.58); 60.0% consumed alcohol at hazardous drinking levels. Over 6-months, participants' anxiety (B=-3.03, p<.001) and depressive symptoms (B=-5.39, p<.001) improved. Continued hazardous drinking led to slower anxiety (B=0.09, p=.005) and depressive symptom (B=0.10, p=.004) improvement; reductions in hazardous drinking led to faster anxiety (B=-0.09, p=.010) and depressive (B=-0.10, p=.015) symptom improvement. Neither anxiety (B=0.07, p=.066) nor depressive (B=0.05, p=.071) symptoms were associated with hazardous drinking outcomes. LIMITATIONS Participants were psychiatry outpatients, limiting generalizability. CONCLUSIONS Reducing hazardous drinking can improve depression and anxiety symptoms but continued hazardous use slows recovery for psychiatry patients. Hazardous drinking-focused interventions may be helpful in promoting symptom improvement in clinical populations.
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Affiliation(s)
- Amber L. Bahorik
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, Box 0984, San Francisco, CA 94143, USA,Division of Research, Kaiser Permanente Northern California Region, 2000 Broadway, 3rd Floor, Oakland, CA 94612, USA,Corresponding authot at:Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, Box 0984, San Francisco, CA 94143, USA. (A.L. Bahorik)
| | - Amy Leibowitz
- Division of Research, Kaiser Permanente Northern California Region, 2000 Broadway, 3rd Floor, Oakland, CA 94612, USA
| | - Stacy A. Sterling
- Division of Research, Kaiser Permanente Northern California Region, 2000 Broadway, 3rd Floor, Oakland, CA 94612, USA
| | - Adam Travis
- Kaiser Permanente Southern Alameda Department of Psychiatry, USA
| | - Constance Weisner
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, Box 0984, San Francisco, CA 94143, USA,Division of Research, Kaiser Permanente Northern California Region, 2000 Broadway, 3rd Floor, Oakland, CA 94612, USA
| | - Derek D. Satre
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, Box 0984, San Francisco, CA 94143, USA,Division of Research, Kaiser Permanente Northern California Region, 2000 Broadway, 3rd Floor, Oakland, CA 94612, USA
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Song TM, An JY, Hayman LL, Woo JM, Yom YH. Stress, Depression, and Lifestyle Behaviors in Korean Adults: A Latent Means and Multi-Group Analysis on the Korea Health Panel Data. Behav Med 2016; 42:72-81. [PMID: 25032882 DOI: 10.1080/08964289.2014.943688] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
It has been reported that stress can induce depression, with the patient's age and sex as moderating factors. Associations between depression and lifestyle in Korean adults have not been addressed. This study was designed to examine if the relationships among stress, problem drinking, exercise, and depression differ by age and sex. For this study, the Korea health panel data was utilized, and a structural equation model using AMOS was employed. The major findings were as follows: women were more likely to experience stress and depression than men. Individuals over 40 showed a higher tendency toward stress and depression than those under 40. Age- and sex-specific paths from stress to problem drinking, exercise, and depression were positively inter-correlated; the path from exercise to depression indicated an inverse association. These results indicate the need for evidence-based stress-management programs for the psychological well-being of Korean adults.
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Affiliation(s)
- Tae Min Song
- a Research Center for Psychosocial Health , Korea Institute for Health and Social Affairs
| | - Ji-Young An
- b u-Healthcare Design and Healthcare Service Design Development Program , Design Institute, Inje University
| | - Laura L Hayman
- c College of Nursing and Health Sciences , University of Massachusetts-Boston
| | - Jong-Min Woo
- d Stress Research Institute, Department of Psychiatry, Seoul Paik Hospital , Inje University
| | - Young-Hee Yom
- e Red Cross College of Nursing , Chung-Ang University
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Vedel E, Emmelkamp PMG. Behavioral Couple Therapy in the Treatment of a Female Alcohol-Dependent Patient With Comorbid Depression, Anxiety, and Personality Disorders. Clin Case Stud 2016. [DOI: 10.1177/1534650103259633] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Behavioral Couple Therapy (BCT) has shown to be effective in the treatment of alcohol dependence. However, it is still unclear whether this intervention is effective in severe caseswith comorbid other conditions. The aim of the present study is to illustrate the assessment, case conceptualization, prioritizing of interventions and treatment in a female “treatment resistant” alcohol-dependent patient, with comorbid depression, anxiety, personality disorders, andmarital problems, using a BCT manual. In total, the treatment consisted of 19 sessions, during a 7-month period. Results show BCT to be successful in treating alcohol dependence and to some extent increasing marital satisfaction. At posttreatment the patient did no longer meet criteria for major depressive disorder. At 3-month follow-up she had been abstinent for 51/2 months, with a 2-day lapse, and her depressive disorder was still in full remission. This case demonstrates—even with severe comorbid conditions—that targeting the drinking problem is the treatment of choice. However, we stress the importance of a thorough assessment of other Axis I and II disorders.
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Abstract
Anxiety and depressive disorders are major public health problems, and desirable changes in lifestyle, such as exercise and proper nutrition, can be of great potential for prevention and treatment. There is growing evidence that physically active people are at a reduced risk of developing depression and that exercise interventions are associated with significant benefits for patients with mild to moderate forms of depression as well as in reducing anxiety. These findings have led to the proposal that exercise may serve as an alternative or a supplement to traditional forms of therapy. The prevalence of depression is lower in countries where the consumption of seafood is high, and omega-3 fatty acids seem to be beneficial in the management of mood disorders. Stimulants are often used as forms of self-medication in patients with anxiety or depressive disorders. Although providing short-term relief, they may have long-term adverse effects. This article presents a broad overview of research involving the efficacy of exercise as a means to treat depression and anxiety, as well as related issues regarding dosage and compliance. Research on the influence of nutrition and selected dietary supplements on depression and anxiety also are presented.
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Affiliation(s)
| | - John S. Raglin
- Department of Kinesiology, Indiana University, Bloomington
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40
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Nucleus accumbens lentiviral-mediated gain of function of the oxytocin receptor regulates anxiety- and ethanol-related behaviors in adult mice. Physiol Behav 2016; 164:249-58. [PMID: 27306084 DOI: 10.1016/j.physbeh.2016.06.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 06/10/2016] [Accepted: 06/11/2016] [Indexed: 12/23/2022]
Abstract
Anxiety is believed to influence ethanol use human in alcoholics. Studies using laboratory animals suggested an interaction between oxytocin and the behavioral effects of ethanol. Our previous study implicated a potential role for the oxytocin receptor (OxtR) in regulating ethanol-conditioned place preference. Here, we examined anxiety and the behavioral responses to ethanol in C57BL/6 mice stereotaxically injected in the nucleus accumbens (NAcc) with lentiviral vectors expressing an empty vector (Mock) or the OxtR cDNA. For anxiety we used the elevated-plus maze, the open-field and the marble-burying tests and for ethanol we used the two-bottle choice paradigm, the wire-hanging and ethanol-induced loss-of-righting-reflex tests. We found that, compared to Mock, OxtR overexpression led to anxiolytic-like behavior without altering spontaneous locomotor activity. Most importantly, we found that, relative to Mock controls, increased expression of the OxtR in the NAcc led to decreased ethanol consumption and preference in the two-bottle choice protocol and increased resistance to ethanol-induced sedation. We also compared the consequence of OxtR modulation on the consumption and preference of saccharin and quinine and found that the two experimental groups did not differ for any tastant. These results provide further evidence that the oxytocin system contributes to the regulation of ethanol drinking and sensitivity and position OxtR as a central molecular mediator of ethanol's effects within the mesolimbic system. Taken together, the current findings suggest that OxtR manipulation may be a relevant strategy to address ethanol use disorders.
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Stapinski LA, Rapee RM, Sannibale C, Teesson M, Haber PS, Baillie AJ. The Clinical and Theoretical Basis for Integrated Cognitive Behavioral Treatment of Comorbid Social Anxiety and Alcohol Use Disorders. COGNITIVE AND BEHAVIORAL PRACTICE 2015. [DOI: 10.1016/j.cbpra.2014.05.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Abstract
AbstractDiagnostic issues in ADHD are examined from two perspectives. Firstly the long-term outcome of ADHD is one indicator of predictive validity of the concept and of its importance. At the same time, the role of comorbid conditions is fundamental to the prognosis of children with ADHD and emphasises the need for thorough assessment and careful differential diagnosis. The range of adult sequelae of ADHD is so broad as to have major implications for the delineation of adult ADHD, and suggestions are made as to how it cannot just be seen as a direct translation of the childhood symptoms. Given the high genetic component to ADHD, our work in ATAP (the Australian Twin ADHD Project) is used to examine three issues in the diagnosis of ADHD, namely that it is inherited as a behavioural dimension, not as a discrete category that there is some genetic and behavioural independence of the Hyperactivity-Impulsivity and Inattention symptom clusters, and that ADHD should not be seen as a consequence of learning problems (or the reverse). Because the concept of ADHD has undergone so many revisions since 1980, there remains much scope for input to a more definitive formulation with particular reference to age and gender differences.
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43
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Lee KM, Coehlo M, McGregor HA, Waltermire RS, Szumlinski KK. Binge alcohol drinking elicits persistent negative affect in mice. Behav Brain Res 2015; 291:385-398. [PMID: 26048424 PMCID: PMC4513951 DOI: 10.1016/j.bbr.2015.05.055] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 05/26/2015] [Accepted: 05/31/2015] [Indexed: 01/21/2023]
Abstract
Cessation from chronic alcohol abuse often produces a dysphoric state that can persist into protracted withdrawal. This dysphoric state is theorized to function as a negative reinforcer that maintains excessive alcohol consumption and/or precipitates relapse in those struggling to abstain from alcohol. However, we know relatively little regarding the impact of cessation from binge drinking on behavioral measures of negative affect and related neurobiology. Male C57BL/6J mice were given access to unsweetened 20% alcohol for 6 weeks under modified Drinking-in-the-dark procedures, followed by behavioral testing beginning either 1 or 21 days into withdrawal. Mice were administered a behavioral test battery consisting of: the elevated plus maze, light/dark box, novel object test, marble burying test, Porsolt forced swim test and sucrose preference test to assess anxiogenic and depressive signs. Egr1 immunostaining was used to quantify cellular activity within the central nucleus of the amygdala (CEA), basolateral amygdala (BLA), bed nucleus of the stria terminalis (BNST), and the nucleus accumbens (Acb) shell (AcbSh) and core (AcbC). Compared to water controls, alcohol-drinking mice exhibited higher indices of emotionality in the majority of behavioral assays. The hyper-emotionality exhibited by binge drinking mice was apparent at both withdrawal time-points and correlated with higher Egr1+ cell counts in the CEA and BNST, compared to controls. These data show that affective symptoms emerge very early after cessation of binge drinking and persist into protracted withdrawal. A history of binge drinking is capable of producing enduring neuroadaptations within brain circuits mediating emotional arousal.
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Affiliation(s)
- Kaziya M Lee
- Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA
| | - Michal Coehlo
- Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA
| | - Hadley A McGregor
- Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA
| | - Ryan S Waltermire
- Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA
| | - Karen K Szumlinski
- Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
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Mitchell IJ, Gillespie SM, Abu-Akel A. Similar effects of intranasal oxytocin administration and acute alcohol consumption on socio-cognitions, emotions and behaviour: Implications for the mechanisms of action. Neurosci Biobehav Rev 2015; 55:98-106. [PMID: 25956250 DOI: 10.1016/j.neubiorev.2015.04.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Revised: 04/15/2015] [Accepted: 04/25/2015] [Indexed: 12/22/2022]
Abstract
Oxytocin (OT) plays a critical role in the formation of long lasting social attachments across a range of mammalian species. Raising intracerebral OT levels by intranasal administration of the neuropeptide (inOT) can also have pronounced effects on human sociocognitive functioning. inOT has been associated with increasing altruism, generosity, empathy and trust while decreasing fear, anxiety and stress reactions via neural mechanisms which are yet to be fully elucidated. The observation of the prosocial effects of OT has led to speculation about the role the peptide might play in some psychiatric conditions and debate as to its potential therapeutic uses. Here we note the great similarity in the sociocognitive effects that can be induced by inOT and the effects of acute consumption of modest does of alcohol. We further reflect on how both compounds may act on limbic and prefrontal cortical structures to increase GABAergic transmission, thereby facilitating the release of prepotent responses, that is, more automatic responses which are associated with earlier developmental stages.
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Affiliation(s)
- Ian J Mitchell
- School of Psychology, University of Birmingham, Birmingham B152TT, UK
| | | | - Ahmad Abu-Akel
- School of Psychology, University of Birmingham, Birmingham B152TT, UK
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45
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Cognitive-Behavior Therapy for Concurrent Anxiety and Alcohol Use Disorder: A Randomized Control Trial. Int J Ment Health Addict 2015. [DOI: 10.1007/s11469-014-9529-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Barkley-Levenson AM, Crabbe JC. Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark selected mice. Alcohol 2015; 49:29-36. [PMID: 25515706 DOI: 10.1016/j.alcohol.2014.07.022] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 07/17/2014] [Accepted: 07/17/2014] [Indexed: 11/18/2022]
Abstract
Alcohol use disorders and anxiety disorders are highly comorbid in humans. In rodent lines selected for alcohol drinking, differences in anxiety-like behavior are also seen. The High Drinking in the Dark (HDID) lines of mice are selectively bred for drinking to intoxication during limited access to alcohol, and these mice represent a genetic model of risk for binge-like drinking. The present studies investigated whether these selected lines differ from control (HS) mice in basal anxiety behavior or in anxiolytic response to alcohol. We also assessed the genetic correlation between alcohol drinking in the dark (DID) and basal anxiety-like behavior using existing inbred strain data. Mice of both sexes and HDID replicates (HDID-1 and HDID-2) were tested on an elevated zero maze immediately following a DID test. In general, HDID mice showed more time spent in the open arms after drinking alcohol than HS mice, and open-arm time was significantly correlated with blood alcohol concentration. HDID-1 male mice also showed less anxiety-like behavior at baseline (water-drinking controls). In a separate experiment, HDID-1 and HS mice were tested for anxiolytic dose-response to acute alcohol injections. Both genotypes showed increasing time spent in the open arms with increasing alcohol doses, and HDID-1 and female mice had greater open-arm time across all doses. HDID-1 control males showed lower anxiety-like behavior than the HS control males. Inbred strain data analysis also showed no significant genetic relationship between alcohol DID and anxiety. These findings suggest that HDID selection has not produced systematic changes in anxiety-like behavior or sensitivity to alcohol-induced anxiolysis, though there is a tendency in the male mice of the first replicate toward reduced basal anxiety-like behavior. Therefore, anxiety state and sensitivity to alcohol's anxiolytic effects do not appear to contribute significantly to the high drinking behavior of the HDID mice.
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Affiliation(s)
- Amanda M Barkley-Levenson
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; Portland Alcohol Research Center, VA Medical Center, Portland, OR 97239, USA.
| | - John C Crabbe
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA; Portland Alcohol Research Center, VA Medical Center, Portland, OR 97239, USA
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Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours. Int J Neuropsychopharmacol 2014; 17:1207-20. [PMID: 24528596 PMCID: PMC4140694 DOI: 10.1017/s1461145714000054] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Recent studies have demonstrated the involvement of epigenetic mechanisms in psychiatric disorders, including alcoholism. Here, we investigated the effects of histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) on amygdaloid HDAC-induced histone deacetylation and neuropeptide Y (NPY) expression and on anxiety-like and alcohol-drinking behaviours in alcohol-preferring (P) and -non-preferring (NP) rats. It was found that P rats displayed higher anxiety-like and alcohol-drinking behaviours, higher amygdaloid nuclear, but not cytosolic, HDAC activity, which was associated with increased HDAC2 protein levels and deficits in histone acetylation and NPY expression in the central (CeA) and medial nucleus of amygdala (MeA), as compared to NP rats. TSA treatment attenuated the anxiety-like and alcohol-drinking behaviours, with concomitant reductions in amygdaloid nuclear, but not cytosolic HDAC activity, and HDAC2, but not HDAC4, protein levels in the CeA and MeA of P rats, without effect in NP rats. TSA treatment also increased global histone acetylation (H3-K9 and H4-K8) and NPY expression in the CeA and MeA of P, but not in NP rats. Histone H3 acetylation within the NPY promoter was also innately lower in the amygdala of P rats compared with NP rats; which was normalized by TSA treatment. Voluntary ethanol intake in P, but not NP rats, produced anxiolytic effects and decreased the HDAC2 levels and increased histone acetylation in the CeA and MeA. These results suggest that higher HDAC2 expression-related deficits in histone acetylation may be involved in lower NPY expression in the amygdala of P rats, and operative in controlling anxiety-like and alcohol-drinking behaviours.
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48
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Abdollahnejad R, Delfabbro P, Denson L. Psychiatric co-morbidity in problem and pathological gamblers: investigating the confounding influence of alcohol use disorder. Addict Behav 2014; 39:566-72. [PMID: 24315782 DOI: 10.1016/j.addbeh.2013.11.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Revised: 10/15/2013] [Accepted: 11/04/2013] [Indexed: 11/19/2022]
Abstract
Pathological gambling is known to be associated with a higher than average prevalence of psychological co-morbidities including a range of psychiatric conditions. A problem with much of this literature, however, is that such problems are also frequently found in populations affected by alcohol use disorder, which is common in populations of pathological gamblers. Accordingly, the principal aim of this study was to profile the comorbidities present in a sample of pathological gamblers, comparing those who did, and did not, additionally meet criteria for alcohol use disorder. A sample of 140 community-recruited regular gamblers completed a number of measures including the Mini International Neuropsychiatric Interview, the Personality Diagnostic Questionnaire, NORC DSM-IV Screen Self-Administered and the Alcohol Use Disorders Identification Test. Comparisons showed that most psychiatric conditions (and in particular personality disorders) were significantly more prevalent in those with a dual diagnosis, followed by problem gamblers and then by those with neither disorder. This suggests that high rates of psychiatric illness in pathological gambling may be strongly influenced by co-occurring alcohol problems.
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Affiliation(s)
| | - Paul Delfabbro
- School of Psychology, University of Adelaide, Australia.
| | - Linley Denson
- School of Psychology, University of Adelaide, Australia
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49
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Acevedo MB, Nizhnikov ME, Molina JC, Pautassi RM. Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats. Behav Brain Res 2014; 265:203-15. [PMID: 24583190 DOI: 10.1016/j.bbr.2014.02.032] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 02/18/2014] [Accepted: 02/19/2014] [Indexed: 01/24/2023]
Abstract
It is yet unclear if ethanol-induced motor stimulation in the open field (OF) merely reflects psychomotor stimulating effects of the drug or if this stimulation is driven or modulated by ethanol's antianxiety properties. In the present study, adolescent rats were administered with different ethanol doses or remained untreated. They were sequentially assessed in the OF, elevated plus maze (EPM), and light-dark box (LDB) and then assessed for ethanol intake. The aims were to assess the relationship between measures of ethanol-induced activity and anxiolysis, analyze ethanol intake as a function of prior ethanol exposure, and associate behavioral responsiveness in these apparatus with ethanol intake during adolescence. The results suggested that the enhanced exploration of the OF observed after 2.5 and 3.25 g/kg ethanol reflected a motor-stimulating effect that appeared to be relatively independent of anxiolysis. The 1.25 g/kg dose induced motor stimulation in the OF and anti-anxiety effects in the EPM, but these effects were relatively independent. The 0.5 g/kg ethanol dose exerted significant anxiolytic effects in the EPM in the absence of stimulating effects in the OF. A multivariate regression analysis indicated that adolescents with a higher frequency of rearing behavior in the OF, higher percentage of open arm entries in the EPM, and lower propensity to enter the central area of the OF exhibited greater ethanol intake. These results indicate that the OF is a valid procedure for the measurement of ethanol-induced stimulation, and provide information toward characterizing subpopulations of adolescents at risk for initiating alcohol drinking.
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Affiliation(s)
- María Belén Acevedo
- Instituto de Investigación Médica M. y M. Ferreyra (INIMEC - CONICET), Córdoba C.P. 5000, Argentina.
| | - Michael E Nizhnikov
- Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY 13902-6000, USA
| | - Juan C Molina
- Instituto de Investigación Médica M. y M. Ferreyra (INIMEC - CONICET), Córdoba C.P. 5000, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba C.P. 5000, Argentina
| | - Ricardo Marcos Pautassi
- Instituto de Investigación Médica M. y M. Ferreyra (INIMEC - CONICET), Córdoba C.P. 5000, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba C.P. 5000, Argentina
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50
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Krishnan HR, Sakharkar AJ, Teppen TL, Berkel TDM, Pandey SC. The epigenetic landscape of alcoholism. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2014; 115:75-116. [PMID: 25131543 DOI: 10.1016/b978-0-12-801311-3.00003-2] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, hold great therapeutic potential in the treatment and prevention of alcoholism.
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Affiliation(s)
- Harish R Krishnan
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
| | - Amul J Sakharkar
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
| | - Tara L Teppen
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
| | - Tiffani D M Berkel
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
| | - Subhash C Pandey
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois, USA.
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