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101. sj-docx-1-css-10.1177_24705470221083700 - Supplemental material for A Novel Approach to Link Genetics and Human MRI Identifies AKAP7-Dependent Subicular/Prefrontal Functional Connectivity as Altered in Suicidality

Author

Poblete, Guillermo, Nguyen, Tien, Gosnell, Savannah, Sofela, Olutayo, Patriquin, Michelle, Mathew, Sanjay J., Swann, Alan, Nielsen, David A., Kosten, Thomas R., and Salas, Ramiro

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 111799 Public Health and Health Services not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, sj-docx-1-css-10.1177_24705470221083700 for A Novel Approach to Link Genetics and Human MRI Identifies AKAP7-Dependent Subicular/Prefrontal Functional Connectivity as Altered in Suicidality by Guillermo Poblete, Tien Nguyen, Savannah Gosnell, Olutayo Sofela, Michelle Patriquin, Sanjay J. Mathew, Alan Swann, David A. Nielsen, Thomas R. Kosten and Ramiro Salas in Chronic Stress

Published
2022
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102. FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder

Author

Cruz, Bryan, Vozella, Valentina, Carper, Benjamin A., Xu, Joy C., Kirson, Dean, Hirsch, Shawn, Nolen, Tracy, Bradley, Lauren, Fain, Katie, Crawford, Meg, Kosten, Thomas R., Zorrilla, Eric P., and Roberto, Marisa

Abstract

Post-traumatic stress disorder (PTSD) leads to enhanced alcohol drinking and development of alcohol use disorder (AUD). Identifying shared neural mechanisms might help discover new therapies for PTSD/AUD. Here, we employed a rat model of comorbid PTSD/AUD to evaluate compounds that inhibit FK506-binding protein 51 (FKBP5), a co-chaperone modulator of glucocorticoid receptors implicated in stress-related disorders. Male and female rats received a familiar avoidance-based shock stress followed by voluntary alcohol drinking. We then assessed trauma-related behaviors through sleep bout cycles, hyperarousal, fear overgeneralization, and irritability. To evaluate the role of stress and alcohol history on the sensitivity to FKBP5 inhibitors, in two separate studies, we administered two FKBP5 inhibitors, benztropine (Study 1) or SAFit2 (Study 2). FKBP5 inhibitors were administered on the last alcohol drinking session and prior to each trauma-related behavioral assessment. We also measured plasma corticosterone to assess the actions of FKBP5 inhibitors after familiar shock stress and alcohol drinking. Benztropine reduced alcohol preference in stressed males and females, while aggressive bouts were reduced in benztropine-treated stressed females. During hyperarousal, benztropine reduced several startle response outcomes across stressed males and females. Corticosterone was reduced in benztropine-treated stressed males. The selective FKBP5 inhibitor, SAFit2, reduced alcohol drinking in stressed males but not females, with no differences in irritability. Importantly, SAFit2 decreased fear overgeneralization in stressed males and females. SAFit2 also reduced corticosterone across stressed males and females. Neither FKBP5 inhibitor changed sleep bout structure. These findings indicate that FKBP5 inhibitors modulate stress-related alcohol drinking and partially modulate trauma-related behaviors. This work supports the hypothesis that targeting FKBP5 may alleviate PTSD/AUD comorbidity.

Published
2023
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107. A Systematic Review and Meta-Analysis on Prevalence of and Risk Factors Associated With Depression, Anxiety and Insomnia in Infectious Diseases, Including COVID-19: A Call to Action

Author

Yuan, Kai, primary, Zheng, Yong-Bo, additional, Wang, Yi-Jie, additional, Sun, Yan-Kun, additional, Gong, Yi-Miao, additional, Huang, Yue-Tong, additional, Chen, Xuan, additional, Liu, Xiao-Xing, additional, Zhong, Yi, additional, Su, Si-Zhen, additional, Gao, Nan, additional, Lu, Yi-Long, additional, Wang, Zhe, additional, Liu, Wei-Jian, additional, Que, Jian-Yu, additional, Yang, Ying-Bo, additional, Zhang, An-Yi, additional, Jing, Meng-Ni, additional, Yuan, Chen-Wei, additional, Zeng, Na, additional, Vitiello, Michael V., additional, Patel, Vikram, additional, Fazel, Seena, additional, Minas, Harry, additional, Thornicroft, Graham, additional, Fan, Teng-Teng, additional, Lin, Xiao, additional, Yan, Wei, additional, Shi, Le, additional, Shi, Jie, additional, Kosten, Thomas R., additional, Bao, Yan-Ping, additional, and Lu, Lin, additional

Published
2022
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109. Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression in the VA Health Care System

Author

Bigdeli, Tim B., primary, Voloudakis, Georgios, additional, Barr, Peter B., additional, Gorman, Bryan, additional, Genovese, Giulio, additional, Peterson, Roseann E., additional, Burstein, David E., additional, Velicu, Vlad I., additional, Li, Yuli, additional, Gupta, Rishab, additional, Mattheisen, Manuel, additional, Tomasi, Simone, additional, Rajeevan, Nallakkandi, additional, Sayward, Frederick, additional, Radhakrishnan, Krishnan, additional, Natarajan, Sundar, additional, Malhotra, Anil K., additional, Shi, Yunling, additional, Zhao, Hongyu, additional, Kosten, Thomas R., additional, Concato, John, additional, O’Leary, Timothy J., additional, Przygodzki, Ronald, additional, Gleason, Theresa, additional, Pyarajan, Saiju, additional, Brophy, Mary, additional, Program (MVP), Million Veteran, additional, Siever, Larry J., additional, Huang, Grant D., additional, Muralidhar, Sumitra, additional, Gaziano, J. Michael, additional, Aslan, Mihaela, additional, Fanous, Ayman H., additional, Harvey, Philip D., additional, and Rousos, Panos, additional

Published
2022
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110. Are We Making Any Progress in Treatment and Attitudes?

Author

Kosten, Thomas R.

Subjects
United States. Centers for Disease Control and Prevention, Medical societies, Medical personnel, Criminal justice, Administration of, Health, Psychology and mental health
Abstract

About 50 years ago (1968) in an early edition of Resident Physician, a progenitor of Psychiatric Times, Herbert Berger, MD (Chairman of the Committee on Alcoholism and Narcotic Addiction, New [...]

Published
2020

124. Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment

Author

Kosten, Thomas R. and Baxter, Louis E.

Subjects
Analgesics, Opioid, Behavior, Addictive, Treatment Outcome, Cost of Illness, Opiate Substitution Treatment, Secondary Prevention, Humans, Review Article, Opioid-Related Disorders, Substance Withdrawal Syndrome
Abstract

Background and Objectives The opioid crisis has taken an immense toll in the United States. On average, five lives are lost to an opioid overdose every hour of the day; estimated costs associated with opioid misuse exceed $500 billion annually. Illicit opioid discontinuation is the first step in the treatment of opioid use disorder (OUD), and transition to an opioid agonist may initiate treatment. However, discontinuation to abstinence from either OUD directly or following agonist treatment results in severely distressing opioid withdrawal symptoms (OWS). Methods This review evaluated studies on the etiology, burden, and management of OWS. Results Noradrenergic hyperactivity generates many OWS. These OWS can cause patients to relapse during early opioid discontinuation. While agonist therapies are generally first‐line for moderate or severe OUD and reduce OWS, prescribing restrictions can limit their availability. Discussion and Conclusions Non‐opioid medications to treat OWS provides a gateway into long‐term treatment with naltrexone or psychosocial therapies. For opioid dependent patients without OUD, non‐opioid treatments like α‐2 adrenergic agonists can facilitate opioid tapering. Scientific Significance For the millions who are physically dependent on opioids, new treatments for OWS can enhance recovery from OUD and prevent relapse. (© 2019 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc.;XX:1–8)

Published
2019

129. Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System.

Author

Bigdeli, Tim B., Voloudakis, Georgios, Barr, Peter B., Gorman, Bryan R., Genovese, Giulio, Peterson, Roseann E., Burstein, David E., Velicu, Vlad I., Li, Yuli, Gupta, Rishab, Mattheisen, Manuel, Tomasi, Simone, Rajeevan, Nallakkandi, Sayward, Frederick, Radhakrishnan, Krishnan, Natarajan, Sundar, Malhotra, Anil K., Shi, Yunling, Zhao, Hongyu, and Kosten, Thomas R.

Abstract

Importance: Serious mental illnesses, including schizophrenia, bipolar disorder, and depression, are heritable, highly multifactorial disorders and major causes of disability worldwide.Objective: To benchmark the penetrance of current neuropsychiatric polygenic risk scores (PRSs) in the Veterans Health Administration health care system and to explore associations between PRS and broad categories of human disease via phenome-wide association studies.Design, Setting, and Participants: Extensive Veterans Health Administration's electronic health records were assessed from October 1999 to January 2021, and an embedded cohort of 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder were found. The performance of schizophrenia, bipolar disorder, and major depression PRSs were compared in participants of African or European ancestry in the Million Veteran Program (approximately 400 000 individuals), and associations between PRSs and 1650 disease categories based on ICD-9/10 billing codes were explored. Last, genomic structural equation modeling was applied to derive novel PRSs indexing common and disorder-specific genetic factors. Analysis took place from January 2021 to January 2022.Main Outcomes and Measures: Diagnoses based on in-person structured clinical interviews were compared with ICD-9/10 billing codes. PRSs were constructed using summary statistics from genome-wide association studies of schizophrenia, bipolar disorder, and major depression.Results: Of 707 299 enrolled study participants, 459 667 were genotyped at the time of writing; 84 806 were of broadly African ancestry (mean [SD] age, 58 [12.1] years) and 314 909 were of broadly European ancestry (mean [SD] age, 66.4 [13.5] years). Among 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder, 8962 (95.6%) were correctly identified using ICD-9/10 codes (2 or more). Among those of European ancestry, PRSs were robustly associated with having received a diagnosis of schizophrenia (odds ratio [OR], 1.81 [95% CI, 1.76-1.87]; P < 10-257) or bipolar disorder (OR, 1.42 [95% CI, 1.39-1.44]; P < 10-295). Corresponding effect sizes in participants of African ancestry were considerably smaller for schizophrenia (OR, 1.35 [95% CI, 1.29-1.42]; P < 10-38) and bipolar disorder (OR, 1.16 [95% CI, 1.11-1.12]; P < 10-10). Neuropsychiatric PRSs were associated with increased risk for a range of psychiatric and physical health problems.Conclusions and Relevance: Using diagnoses confirmed by in-person structured clinical interviews and current neuropsychiatric PRSs, the validity of an electronic health records-based phenotyping approach in US veterans was demonstrated, highlighting the potential of PRSs for disentangling biological and mediated pleiotropy. [ABSTRACT FROM AUTHOR]

Published
2022
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135. Clinical Management of Cannabis Complications

Author

Kosten, Thomas R. and Verrico, Christopher D.

Subjects
Medical marijuana -- Complications and side effects, Health, Psychology and mental health
Abstract

This Special Report contains articles about cannabis use and its potential complications, including cannabis use disorder (CUD). The first piece highlights the use of cannabinoids among the geriatric population. Cannabis [...]

Published
2021

147. Efficacy of opiate maintenance therapy and adjunctive interventions for opioid dependence with comorbid cocaine use disorders: a systematic review and meta-analysis of controlled clinical trials

Author

Castells, Xavier, Kosten, Thomas R., Capella, Dolors, Vidal, Xavier, Colom, Joan, and Casas, Miguel

Subjects
Cocaine abuse -- Care and treatment, Cocaine abuse -- Research, Methadone maintenance -- Usage, Methadone maintenance -- Patient outcomes, Methadone maintenance -- Research, Meta-analysis -- Usage, Health, Psychology and mental health
Published
2009

148. Time-dependent neuroendocrine alterations and drug craving during the first month of abstinence in heroin addicts

Author

Shi, Jie, Li, Su-xia, Zhang, Xiao-li, Wang, Xi, Le Foll, Bernard, Zhang, Xiang-Yang, Kosten, Thomas R., and Lu , Lin

Subjects
Adrenocortical hormones -- Physiological aspects, Adrenocortical hormones -- Research, Hydrocortisone -- Physiological aspects, Hydrocortisone -- Research, Beta-endorphin -- Physiological aspects, Beta-endorphin -- Research, Neuropeptides -- Physiological aspects, Neuropeptides -- Research, Heroin habit -- Physiological aspects, Heroin habit -- Research, Leptin -- Physiological aspects, Leptin -- Research, Drug withdrawal symptoms -- Patient outcomes, Drug withdrawal symptoms -- Research, Health, Psychology and mental health
Published
2009

149. Family support and employment as predictors of smoking cessation success: a randomized, double-blind, placebo-controlled trial of nicotine sublingual tablets in Chinese smokers

Author

Sun, Hong-Qiang, Guo, Song, Chen, Da-Fang, Jiang, Zuo-Ning, Liu, Yu, Di, Xiao-Lan, Yang, Fu-De, Zhang, Xiang-Yang, Kosten, Thomas R., and Lu, Lin

Subjects
Smoking cessation programs -- Methods, Smoking cessation programs -- Patient outcomes, Smoking cessation programs -- Research, Domestic relations -- Influence, Domestic relations -- Research, Health, Psychology and mental health
Published
2009

150. Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine

Author

Haile, Colin N., Kosten, Thomas R., and Kosten, Therese A.

Subjects
Drug abuse -- Care and treatment, Drug abuse -- Methods, Drug abuse -- Patient outcomes, Drug abuse -- Research, Pharmacogenetics -- Research, Drug therapy -- Patient outcomes, Drug therapy -- Research, Dopamine receptors -- Physiological aspects, Health, Psychology and mental health
Published
2009

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