Levent Kirisci

• University of Pittsburgh

This study prospectively examined the interplay of culturally ingrained beliefs regarding the benefits of substance use, social milieu featured by disengaged parents and deviant friends, and behavior undercontrol on the development of substance use disorder (SUD) by early adulthood. The sample at baseline consisted of 497 youths between 10 and 12 y...

Introduction Post-Traumatic Stress Disorder (PTSD) entails behavioral changes with increased risk of suicide, and there is no consensus on the preferred antidepressants for treatment of those PTSD patients who are at elevated risk for suicide. Methods We conducted a clinical trial emulation study comparing suicide-related events (SREs) among those...

Background/Objectives: Comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) patients are at a significantly higher risk of adverse outcomes, including opioid use disorder, depression, suicidal behaviors, and death, yet limited treatment options exist for this population. This study aimed to build on previous research by inc...

The present study examined longitudinal trajectory classes and correlates of triarchic psychopathy domains (boldness, meanness, and disinhibition) from age 16 to 22, leveraging Multidimensional Personality Questionnaire (MPQ)-based triarchic scales data gathered on a large community sample ( n s ranging between 483 and 775 across waves) oversampled...

Background Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities. Methods...

Purpose Substance use disorders (SUDs) increase the risk and severity of infectious diseases, including coronavirus disease 2019 (COVID-19). Adults with a co-occurring SUD and psychiatric disorder were studied to elucidate the association between SUD severity and (1) COVID-19 vaccination status, (2) receptivity to a one-session intervention with a...

Background Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities. Methods...

Background Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-ris...

Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. We developed DeepBiomarker2 by leveraging deep learning and natural language processing to analyze lab tests, medication use, diagnosis, social determinants of health (SDoH) parameters, and psychotherapy for outcome prediction. To incre...

Background Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients. Methods We applied DeepBiomarker2 through data integratio...

Objective: Disinhibitory behavior during childhood and adolescence has been frequently shown to amplify the risk for substance use disorder (SUD) in adulthood. This prospective study examined the hypothesis that poor communication with parents and association with deviant peers comprise an SUD-promoting environtype which catalyzes transition of di...

Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the...

The association between physical inactivity and substance use throughout adolescence was prospectively investigated in relation to developing cannabis use disorder (CUD). Physical inactivity and substance use in males (N = 462) and females (N = 178) were measured at 12-14, 16, 19, and 22 years of age in a repeated measures design. A structured diag...

Defining the traits and phenotypes as well as their adequate measurement is critically important for genetic research. This chapter reviews the nature of the traits pertaining to substance use, the variety of related phenotypic definitions, and their influence on research and practice. The binary view on the extreme forms of substance use, commonly...

Because the construct of psychopathy is of chief interest across different disciplines, spanning developmental, clinical, and forensic psychology, its assessment bears far-reaching implications. One prominent contemporary conceptualization of psychopathy, the Triarchic Model, posits that a psychopathic personality encompasses three phenotypic const...

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at high...

Around 800,000 people worldwide die from suicide every year and it’s the 10th leading cause of death in the US. It is of great value to build a mathematic model that can accurately predict suicide especially in high-risk populations. Several different ML-based models were trained and evaluated using features obtained from electronic medical records...

Adolescence and emerging adulthood are developmental periods associated with increased risk taking, including alcohol and substance use and antisocial behaviors. Typical psychological growth from adolescence into early adulthood reflects increases in traits related to psychological regulation (e.g., greater emotional stability and less impulsivity)...

Self-regulation is considered a major predictor of crime and deviant behavior. However, longitudinal research investigating these associations, frequently looked only at the effect of self-regulation on deviant behavior, but not the other way around. The current study argued that deviance may contribute to later problems in self-regulation, and exa...

Objective t To evaluate the accuracy of detecting 16 year old male (N=465) and female (N=162) youths who subsequently manifest opioid use disorder (OUD) at 25 years of age. We hypothesized that the combined measures of two components of etiology, heritable risk and substance use, accurately detect youths who develop OUD. Study design Heritable ris...

A gene expression signature (GES) is a group of genes that shows a unique expression profile as a result of perturbations by drugs, genetic modification or diseases on the transcriptional machinery. The comparisons between GES profiles have been used to investigate the relationships between drugs, their targets and diseases with quite a few success...

Background: The development of person-centered medical education is inscribed within an international programmatic movement toward a medicine focused on the totality of the person. This movement, with broad historical bases, has been maturing since 2008 through conferences with global health institutions, research projects, and academic publication...

Background Patient-reported outcomes are essential to understand the relationship between patients’ perception of sedation and clinicians’ assessments of sedation. Objectives To evaluate the association between sedation and agitation indexes and patient-reported outcomes of sedation and analgesia. Methods This prospective, single-center, observat...

Background: Severity of substance use disorder (SUD) is typically evaluated by tabulating the number of symptoms. The resulting estimate of disorder severity is, however, biased due to intercorrelations among symptoms and their unequal salience. Objective. Employing item response theory (IRT) methodology, opioid use disorder symptoms were calibrate...

Text messaging (SMS) interventions incorporating a combination of behavior change techniques can assist reductions in alcohol consumption among young adult hazardous drinkers, but mechanisms of action remain unknown. In this secondary analysis, we test the hypothesis that desire to get drunk (DD) recorded prior to drinking episodes would mediate SM...

Background: Interest in person-centered medicine is growing in response to serious contemporary limitations and distortions in medicine and health care across the world. The development of generic instruments with substantial metric features to appraise progress toward person-centered care is providing instrumentation to advance the emerging field.

Background: This longitudinal study explored the utility of machine learning (ML) methodology in predicting the trajectory of severity of substance use from childhood to thirty years of age using a set of psychological and health characteristics. Design: Boys (N = 494) and girls (N = 206) were recruited using a high-risk paradigm at 10-12 years...

Background: Substance use disorder (SUD) exacts enormous societal costs in the United States, and it is important to detect high-risk youths for prevention. Machine learning (ML) is the method to find patterns and make prediction from data. We hypothesized that ML identifies the health, psychological, psychiatric, and contextual features to predic...

Text message (SMS) interventions can reduce binge drinking in young adults, but optimal behavior change techniques (BCTs) remain unknown. The present study tests the acceptability and preliminary efficacy of different combinations of SMS-delivered BCTs. 149 young adults who screened positive for hazardous drinking completed a baseline survey in the...

Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. The sulfotransferase-mediated sulfation of APAP is widely believed to be a protective mechanism to attenuate the hepatotoxicity of APAP. The cholesterol sulfotransferase SULT2B1b is best known for its activity in catalyzing the sulfoconjugation...

Background: Benzodiazepine-resistant alcohol withdrawal (RAW), defined by a requirement of ≥ 40 mg of diazepam in 1 h, represents a severe form of withdrawal without predictive parameters. This study was designed to identify risk factors associated with RAW versus withdrawal without benzodiazepine resistance (nRAW). Methods: A retrospective cohort...

Purpose Conflicting data exists on the efficacy of antipsychotics for treatment of intensive care unit (ICU) delirium. The purpose of this study was to compare time to delirium resolution for ICU patients who were managed with and without antipsychotics. Materials and methods This retrospective cohort evaluation included patients admitted to 12 IC...

Association of cognitive function and liability to addiction with childhood herpesvirus infections: A prospective cohort study—ERRATUM - Michael M. Vanyukov, Vishwajit L. Nimgaonkar, Levent Kirisci, Galina P. Kirillova, Maureen D. Reynolds, Konasale Prasad, Ralph E. Tarter, Robert H. Yolken

Liability to substance use disorder (SUD) is largely nonspecific to particular drugs and is related to behavior dysregulation, including reduced cognitive control. Recent data suggest that cognitive mechanisms may be influenced by exposure to neurotropic infections, such as human herpesviruses. In this study, serological evidence of exposure to hum...

Since the inception of Person Centered Medicine (PCM) as a programmatic movement, one could find the articulation of science and humanism as a core concept. This revealed a prominent concern for conceptual clarity, illustratively to formulate humanism as the essence of medicine as well as to engage the scientific method as an essential tool. An ong...

Objective: Limited prospective data indicate that premorbid sleep disturbances elevate the risk for subsequent alcohol and other drug problems, yet the implications for subsequent substance involvement trajectories remain unclear. In the present analyses, we examined risk associations between sleep characteristics during late childhood and the ons...

This was a first double-blind, placebo-controlled pilot study to evaluate the efficacy of the novel antidepressant medication mirtazapine for treating both the depressive symptoms and the level of alcohol consumption of subjects with comorbid major depressive disorder and an alcohol use disorder (MDD/AUD). The results of two previous studies of mir...

Person-centered care is increasingly regarded as the gold standard. Although traditionally health care settings have relied solely on the concept of patient satisfaction to evaluate the care of a person’s experience in health care settings, serious doubts have been expressed about the validity or adequacy of this criterion. Satisfaction is unable t...

Background: A world-wide movement is emerging for person centered medicine and healthcare collaboratively developed by the International College of Person Centered Medicine and a number of global institutions through annual Geneva Conferences and International Congresses as well as scholarly publications. While frequently quoted definitional note h...

The articulation of science and humanism is at the core of Person Centered Medicine (PCM). Thus, applying the scientific method to advance our understanding of health and the improvement of health actions towards the fulfillment of the whole person is a permanent concern of PCM.

Background: Biomedical research and its applications, particularly in complex disorders, have historically been guided by the group-defined disease-oriented perspective rather than a person-centered health-oriented approach. This has been an obstacle to the development of prevention and treatment methods. There is thus a need to redirect studies to...

Background. Item response theory (IRT) based studies conducted on diverse samples showed a single dominant factor for DSM-III-R and DSM-IV substance use disorder (SUD) abuse and dependence symptoms of alcohol, cannabis, sedative, cocaine, stimulants, and opiates use disorders. IRT provides the opportunity, within a person-centered framework, to acc...

Background: Prior medication studies involving individuals with major depression in combination with an alcohol use disorder (MDD/AUD) have mainly focused on SSRI and tricyclic antidepressants, with generally ineffective results. Consequently, effective treatments for that common comorbid condition remain elusive. Mirtazapine is an antidepressant...

Background: The measurement of quality of life as estimate of well being is assuming increasing importance in the evaluation of health and treatment efficacy. Objectives: The aim of this study is to evaluate the applicability, internal structure and clinical patterns of the Multicultural Quality of Life Index (MQLI), a brief, self-rated, culturally...

Objectives: To examine the differential impact of depressive and manic mood states on alcohol craving in patients with bipolar disorder and comorbid alcoholism. Methods: Forty-four men and women, ages 18-65, with DSM-IV-TR comorbid diagnoses of bipolar I disorder and alcohol dependence were assessed over a three-month period to examine the exten...

Objective: This longitudinal investigation examined the hypothesis that subjective experience during consumption of preferred drugs mediates the association of transmissible risk for substance use disorder (SUD) measured in childhood and adolescence, and SUD diagnosis in adulthood. Transmissible risk denotes the psychological characteristics havin...

Objective: This prospective study determined whether temperament before two years of age predicts transmissible risk for substance use disorder (SUD) up to a decade later and SUD outcome in adulthood. Method: Boys between 10 and 12 years of age (N = 482) were tracked to age 22. The previously validated transmissible liability index (TLI) was adm...

Objective: Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult IC...

Objective: Our previous work demonstrated that the Transmissible Liability Index (TLI), an instrument designed as an index of liability for substance use disorder (SUD), is associated with risk of substance use disorder. This longitudinal study assessed whether TLI measured in 10-12-year-olds (late childhood) predicts suicidal behavior from age 12...

Neglect poses a significant risk for children throughout their development and is often linked with serious consequences that reach into adulthood. The Child Neglect Questionnaire (CNQ) fills existing gaps by incorporating multiple perspectives from both parents and the child, as well as measuring the complex phenomenon of neglect multidimensionall...

Transmissible liability index (TLI), developed employing a high-risk design and item response theory, enables quantification of the latent trait of liability to drug use disorders (DUD) in children. TLI has been shown to have high heritability and predict DUD in young adulthood. This study extends prior research and determines the genetic contribut...

Psychological items discriminating children of fathers diagnosed with an illicit drug-related substance use disorder and normal controls are indicators of a unidimensional construct termed transmissible liability index (TLI) (Vanyukov et al., 2009). TLI is a highly heritable (Vanyukov et al., 2009; Hicks, Iacono, McGue, 2012) and valid (Vanyukov et...

ABSTRACT Rapidly occurring changes in law enforcement and licensing of retail outlets to sell marijuana raises the prospect that the population of consumers will expand and accordingly the prevalence of cannabis use disorder (CUD) will increase. This report presents a novel approach to researching CUD etiology joining multivariate and ontogenetic p...

Children and adolescents receive substance abuse prevention messages from various sources throughout their daily lives, from school-based programs, media PSA’s, neighborhood groups and, hopefully, from their parents. Our aim in this analysis was to examine the efficacy of some of these sources of prevention messages in influencing an adolescent to...

Introduction: Our previous work demonstrated that Transmissible Liability Index (TLI), a measure designed to assess liability for substance use disorder (SUD), as measured at age 10-12, is associated with an increased risk of subsequent substance use and of substance use disorder. The current study was designed to assess whether TLI also predicts s...

Substance use disorder (SUD) etiology is characterized by highly heterogeneous ontogenetic pathways which hinder detection of at-risk youth and complicate the development of efficacious universal prevention programs. Recent work at the Center for Education and Drug Abuse Research (CEDAR) has aimed to create clinical tools to screen children for ove...

Introduction. Prevention research can be extended by analyzing newly available secondary data from the Center for Education and Drug Abuse Research (CEDAR). Data are available on 775 families enrolled in prospective investigations into the etiology of substance use disorder (SUD). CEDAR began collecting data on families in 1990 and follow-up data c...

Background: Stress is a well-documented factor in the development of addiction. However, no longitudinal studies to date have assessed the role of stress in mediating the development of substance use disorders (SUD). Our previous results have demonstrated that a measure called Transmissible Liability Index (TLI) assessed during pre-adolescent year...

The estrogen sulfotransferase (EST/SULT1E1) is known to catalyze the sulfoconjugation and deactivation of estrogens. The goal of this study is to determine whether and how EST plays a role in human adipogenesis. By using human primary adipose derived stem cells (ASCs) and whole fat tissues from the abdominal fat of obese and non‐obese subjects, we...

The estrogen sulfotransferase (EST/SULT1E1) is known to catalyze the sulfoconjugation and deactivation of estrogens. The goal of this study is to determine whether and how EST plays a role in human adipogenesis. By using human primary adipose derived stem cells (ASCs) and whole fat tissues from the abdominal subcutaneous fat of obese and non-obese...

Objective: This prospective study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10-12) and development of substance use disorder (SUD) in adulthood (age 22). Method: The Youth Attachment to Parents Scale (YAPS) was developed in 10...

This prospective study investigated pubertal timing and transmissible risk in relation to affiliation with deviant peers on the development of substance use disorder (SUD). Participants were boys (N = 500) ascertained through proband fathers with (N = 250), and without (N = 250) DSM-III-R lifetime diagnosis of SUD who were prospectively tracked fro...

Introduction: Our previous study results demonstrate that TLI, a measure of liability for substance use disorder, as measured at age 10-12, is associated with an increased risk of current drug use at age 19, which in turn is associated with substance use disorder (SUD) at age 22. However, it has been unclear whether life stress moderates that relat...

Introduction: Research has shown that parental depression can increase the likelihood of internalizing and externalizing behavior in their offspring. It is unclear; however, if a threshold effect exists, in that subclinical levels of parental depression can also increase the risk of impairment in offspring. We hypothesized that subclinical parental...

Background: Risk for substance use disorder is frequently transmitted across generations due to significant heritability. Objective: This longitudinal study tests the hypothesis that initial exposure to cannabis in youths having high transmissible risk is a signal event promoting development of cannabis use disorder (CUD). Methods: At age 22,...

Background: Knowledge of where substance use and other such behavioral problems frequently occur has aided policing, public health, and urban planning strategies to reduce such behaviors. Identifying locales characterized by high childhood neurobehavioral disinhibition (ND), a strong predictor of substance use and consequent disorder (SUD), may li...

AimsA brief screen requiring 3–4 min administration time was developed to detect adolescents qualifying for current substance use disorder (SUD) and those who will subsequently manifest SUD by early adulthood.Methods The revised Drug Use Screening Inventory (DUSI-R; Tarter, 1990) was administered to 329 boys on three occasions (ages 12–14, 15–17 an...

Background: Prevention of substance use disorder (SUD) is impeded by the large number, complexity and idiosyncratic configuration of etiological factors. Effective prevention of SUD is feasible however when intervention resources are prioritized to individuals who are objectively determined as high risk and tailored to their specific characteristi...

Cognitive Behavioral Therapy (CBT) is a commonly used therapy among persons with major depressive disorder (MDD) and also among those with alcohol use disorders (AUD). However, less is known regarding the efficacy of CBT for treating persons with co-occurring disorders involving both MDD and an AUD. Studies assessing the efficacy of CBT in adolesce...

Background: To date, few studies have been conducted evaluating predictors of treatment seeking for substance use disorders as persons make the transition from preadolescence (a period of very low substance use) to young adulthood (a period of peak substance use). The few studies of this area which have been conducted to date have generally been l...

The retinoid-related orphan receptors (RORs) were postulated to have functions in tissue development and circadian rhythm. In this study, we revealed a novel function of RORα (NR1F1) and RORγ (NR1F3) in regulating the human hydroxysteroid sulfotransferase (SULT2A1), a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydro...

Age at the time of first alcohol and cannabis use was investigated in relation to a measure of transmissible (intergenerational) risk for addiction in childhood and development of alcohol use disorder (AUD) and cannabis use disorder (CUD). It was hypothesized that age at the time of first experience with either substance mediates the association be...

Background: Research has shown involvement of hormones of the hypothalamic pituitary adrenal (HPA) axis and hypothalamic pituitary gonadal (HPG) axis in the regulation of behaviors that contribute to SUD risk and its intergenerational transmission. Neighborhood environment has also been shown to relate to hormones of these two neuroendocrine syste...

This article discusses human individuality within a lifespan developmental perspective. The practical application of an individual differences framework for diagnosis, prevention and treatment of addiction is described. A brief overview of the methods conducive to knowledge development within the rubric of person-centered medicine that are availabl...

Employed as a quantitative measure of substance use disorder (SUD) risk, the transmissible liability index (TLI) can be useful for detecting youths requiring prevention intervention. This study was conducted to develop and evaluate a computer adaptive test (CAT) version of the TLI to identifying individuals at risk for SUD. In the first sample (N=4...

An evaluation of risk factors for adverse drug events in critically ill patients has not been previously studied. The purpose of this original study was to determine risk factors for adverse drug events in critically ill adult patients. This retrospective case-control study includes patients who were admitted to the intensive care unit during a 7.5...

This study was conducted to test whether non-normative socialization mediates the association between transmissible risk measured in childhood and cannabis use disorder manifested by young adulthood, and whether the sequence of drug use initiation ("gateway", i.e., consuming legal drugs before cannabis, or the reverse) increases accuracy of predict...

Two competing concepts address the development of involvement with psychoactive substances: the "gateway hypothesis" (GH) and common liability to addiction (CLA). The literature on theoretical foundations and empirical findings related to both concepts is reviewed. The data suggest that drug use initiation sequencing, the core GH element, is variab...

Background: Previous cross-sectional studies involving adults suggest that sexually transmitted diseases (STD) such as cocaine use disorders and opioid use disorders are associated with the development of sexually transmitted diseases (STD). However, it is less clear whether cannabis use disorders (CUD) are associated with the development of STDs,...

Objective: This study compared the acute phase (12-week) and the long-term (1 year) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the cannabis use of youth with comorbid major depressive disorder (MDD) and an cannabis use disorder (CUD)(cannabis dependence or cannabis abuse). We hypothesized that fluoxetine...

Toward meeting the need for a measure of individual differences in substance use disorder (SUD) liability that is grounded in the multifactorial model of SUD transmission, this investigation tested to what degree transmissible SUD risk is better measured using the continuous Transmissible Liability Index (TLI) (young adult version) compared to alte...

AIM: This study determined the extent to which alcohol and marijuana use during adolescence mediates the relation between transmissible risk for substance use disorder (SUD) and lifetime number of different types of violent offenses. METHODS: The transmissible liability index was administered to 359 10-12 year old youths who were tracked to 22 year...

PURPOSE: The factors that distinguish adolescent male and female substance abusers with and without legal problems were investigated. METHOD: Youths (N = 4,071) admitted for substance abuse treatment were administered the revised Drug Use Screening Inventory (DUSI-R) to measure severity of health, behavior, and social adjustment problems. RESULTS:...

Successful management and implementation of the diverse functions of the International Network of Person-Centered Medicine (INPCM) require a comprehensive and efficient informational base to advance quality of patient care though timely and rapid distribution of knowledge via publications, conferences, and education programs in concert with catalyz...

This study examined the contribution of transmissible risk, in conjunction with family and peer contextual factors during childhood and adolescence, on the development of cannabis use disorder in adulthood. The family high-risk design was used to recruit proband fathers with and without substance use disorder and track their sons longitudinally fro...

The revised Drug Use Screening Inventory (DUSI-R) is a self-report questionnaire designed to quantify the severity of problems that are commonly associated with consumption of alcohol and other drugs. This study extends research conducted on the US population to determine whether the DUSI-R's substance abuse scale discriminates Brazilian youths in...

The authors examined both the nonspecific effects of psychopathology and the interactions of alcohol use disorders with other specific comorbid psychiatric conditions in an adolescent population on perceived self-efficacy to resist heavy drinking. The results suggest that nonspecific psychopathology, manifested in the form of any common psychiatric...

Problem awareness and treatment readiness are factors that influence treatment-seeking behavior, and thus, morbidity and outcome. The authors elucidated patterns of problem awareness and treatment readiness among hospitalized dually diagnosed patients by administering the Problem Awareness and Readiness for Treatment subscales of the Alcohol Use In...