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Introduction
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Publications
Publications (676)
Experimental cognitive tests are designed to measure particular cognitive domains, although evidence supporting test validity is often limited. The Consortium for Neuropsychiatric Phenomics test battery administered 23 experimental and traditional neuropsychological tests to a large sample of community volunteers ( n = 1,059) and patients with psyc...
Importance: Cigarette smoking remains the leading preventable cause of death worldwide, leading to development of new therapeutics, such as repetitive transcranial magnetic stimulation (rTMS).
Objective: To optimize treatment, we compared three TMS targets to evaluate the effects on cigarette craving and withdrawal, and on within- and between-netwo...
Neuroimaging research has identified significant effects of oral contraceptive pills (OCPs) on brain networks. A wide variety of approaches have been employed, largely in observational samples, with few converging results. This study was designed to replicate and expand this previous work using a randomized, double-blind, placebo-controlled crossov...
Background
The group-I metabotropic glutamate receptor subtype five (mGlu5) has been implicated in methamphetamine exposure in animals, and in human cognition. Because people with Methamphetamine Use Disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance....
Importance
In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessmen...
Objective
Individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit deficits in reward-based learning, which have important implications for behavioral regulation. Prior research has shown that these individuals show altered patterns of risky decision-making, which may be partially explained as a function of dysfunctional reactivity...
Introduction
There are growing concerns about commonly inflated effect sizes in small neuroimaging studies, yet no study has addressed recalibrating effect size estimates for small samples. To tackle this issue, we propose a hierarchical Bayesian model to adjust the magnitude of single-study effect sizes while incorporating a tailored estimation of...
Background
Alcohol consumption is a leading cause of morbidity and mortality worldwide, disproportionately affecting young men. Heavy episodic drinking is particularly prevalent among men, with this behavior peaking between the ages of 20 and 24.
Aims
We sought to identify dimensions of decision-making in men that would predict the development of...
Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warran...
Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n = 1138) comprised healthy pa...
Background:
Negative affect and craving during abstinence from cigarettes predict resumption of smoking. Therefore, understanding their neural substrates may guide development of new interventions. Negative affect and craving have traditionally been linked to functions of the brain's threat and reward networks, respectively. However, given the rol...
Nicotine dependence is a major predictor of relapse in people with Tobacco Use Disorder (TUD). Accordingly, therapies that reduce nicotine dependence may promote sustained abstinence from smoking. The insular cortex has been identified as a promising target in brain-based therapies for TUD, and has three major sub-regions (ventral anterior, dorsal...
Background:
Escalating misuse of amphetamine-type stimulants, mainly methamphetamine, has led to a staggering rise in associated overdose deaths and a pressing need to understand the basis of methamphetamine use disorder (MUD). MUD is characterized by disadvantageous decision-making, and people with MUD perform below controls on the Balloon Analog...
Background:
Methamphetamine misuse, a surging cause of morbidity and mortality worldwide, identifies Methamphetamine Use Disorder (MUD) as a critical public health problem. Treatment for MUD typically is sought during early abstinence when patients are experiencing cognitive difficulties that may hamper their engagement in treatment and recovery....
Introduction
Denial, or lack of awareness of problems related to substance misuse, is a common feature of drug use disorders and can affect engagement in treatment and recovery. This study tested for association of denial with severity of symptoms used in the diagnosis of Methamphetamine Dependence.
Methods
This secondary analysis used data from 6...
Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n=1138) comprised healthy part...
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients who misuse alcohol, especially in the context of comorbid depressive symptoms. Deficits in impulse control and decision-making are linked to routine alcohol consumption and alcohol dependence. The goal of this study was to determine the effects of a single dose of...
Methamphetamine use is surging globally as a cause of morbidity and mortality. Treatment is typically sought in early abstinence, when craving and depressive symptoms are intense, contributing to relapse and poor outcomes. To advance an understanding of this problem and identify therapeutic targets, we conducted a retrospective analysis of brain st...
Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and...
Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete rep...
Introduction
Cannabis use disorder (CUD) is a growing public health concern, and is highly comorbid with negative affective conditions such as anxiety and depression. Late adolescence and early adulthood represents a time of rapid emotion regulation development, as well as the onset of anxiety, mood, and substance use disorders, especially CUD. Mal...
Background and aims
Graph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol....
Background
Nicotine and illicit stimulants are very addictive substances. Although associations between grey matter and dependence on stimulants have been frequently reported, white matter correlates have received less attention.
Methods
Eleven international sites ascribed to the ENIGMA-Addiction consortium contributed data from individuals with d...
Decision-making strategies shift during normal aging and can profoundly affect wellbeing. Although overweighing losses compared to gains, termed “loss aversion,” plays an important role in choice selection, the age trajectory of this effect and how it may be influenced by associated changes in brain structure remain unclear. We therefore investigat...
The insular cortex has been identified as a promising target in brain-based therapies for Tobacco Use Disorder, and has three major sub-regions (ventral anterior, dorsal anterior, and posterior) that serve distinct functional networks. How these subregions and associated networks contribute to nicotine dependence has not been well understood, and t...
Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had...
Objectives:
Contingency management is a promising intervention for Methamphetamine Use Disorder (MUD).Impaired executive function may decrease adherence to such treatment, but there are few data on whether impairment in executive function predicts treatment outcomes. We therefore evaluated whether baseline performance on tests of executive functio...
Currently available therapies for smoking cessation have limited efficacy, and potential treatments that target specific brain regions are under evaluation, with a focus on the insula. The ventral and dorsal anterior subregions of the insula serve distinct functional networks, yet our understanding of how these subregions contribute to smoking beha...
Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorde...
Background
Cigarette craving, which can negatively impact smoking cessation, is reportedly stronger in women than in men when they initiate abstinence from smoking. Identifying approaches to counteract craving in people of different sexes may facilitate the development of personalized treatments for Tobacco Use Disorder, which disproportionally aff...
Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alongside a variety of mood alterat...
Methamphetamine abuse leads to devastating consequences, including addiction, crime, and death. Despite decades of research, no medication has been approved by the U.S. Food and Drug Administration for the treatment of Methamphetamine Use Disorder. Thus, there is a need for new therapeutic approaches. Animal studies demonstrate that methamphetamine...
Brain asymmetry reflects left‐right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are differ...
Background: Brain structural findings in chronic methamphetamine users have been inconsistent. Identifying contributing influences (e.g., sex, abstinence duration) can help clarify the clinical course of recovery.
Objectives: We studied the effects of long-term methamphetamine abstinence on gray-matter volume. Our hypothesis was that smaller volume...
Background
Risky decision-making is an important facet of addiction. Individuals with alcohol dependence show abnormalities in gambling and other risk-taking tasks. In one such measure, the Balloon Analogue Risk Task (BART), participants sequentially choose to pump a virtual balloon to increase potential reward while the risk of explosion increases...
Background
Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been many promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, heterogeneities in participant characteristics, task design, craving a...
To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega‐analysis of previously published datasets from 2,034 AD and comparison participants spanni...
Chronic methamphetamine use is linked to abnormalities in brain structure, which may reflect neurotoxicity related to metabolism of the drug. As the cytochrome P450 2D6 (CYP2D6) enzyme is central to the metabolism of methamphetamine, genotypic variation in its activity may moderate effects of methamphetamine on brain structure and function. This st...
Introduction: The amygdala is known to play a role in mediating emotion and possibly addiction. We used probabilistic tractography (PT) to evaluate whether structural connectivity of the amygdala to the brain reward network is associated with impulsive choice and tobacco smoking.
Methods: Diffusion and structural MRI scans were obtained from 197 he...
Background
Radioligands for the translocator protein (TSPO) 18 kDa have been used with positron emission tomography (PET) to assess neuroinflammation and microglial activation in psychiatric disorders. One study using this approach showed substantial TSPO elevation throughout the brain in chronic methamphetamine users following long-term abstinence...
Alexithymia is a vulnerability factor for physical and mental illness that can significantly influence the daily function of alcohol-dependent patients. The aim of this study was to examine the indirect effect of obsessive thoughts and compulsive behaviors involving alcohol craving on the relationship between alexithymia, quality of life (QoL) of p...
Background: Emerging evidence suggests that opioid receptor antagonists, such as naltrexone, are effective pharmacotherapies for alcohol, opioid, and possibly stimulant use disorders. It is posited that naltrexone exerts its effects, in part, by increasing functional connectivity between neural reward circuitry and frontal systems implicated in exe...
Background:
Negative emotional states contribute to cigarette smoking, and difficulties in regulating these states can hinder smoking cessation. Understanding the neural bases of these difficulties in smokers may facilitate development of novel therapies for Tobacco Use Disorder.
Methods:
Thirty-seven participants (18 smokers, 19 nonsmokers; 16-...
Background
Individuals with substance use disorders exhibit maladaptive decision-making on the Iowa Gambling Task (IGT), which involves selecting from card decks differing in the magnitudes of rewards, and the frequency and magnitude of losses. We investigated whether baseline IGT performance could predict responses to contingency management (CM) b...
Background
Cognitive traits demonstrate significant genetic correlations with many psychiatric disorders and other health-related traits. Many neuropsychiatric and neurodegenerative disorders are marked by cognitive deficits. Therefore, genome-wide association studies (GWAS) of general cognitive ability might suggest potential targets for nootropic...
Background
Multiple psychopathologies feature impaired clinical insight. Emerging evidence suggests that insight problems may similarly characterize addiction, perhaps due to aberrant functioning of self-referential brain circuitry, including the rostral anterior cingulate and ventromedial prefrontal cortices (rACC/vmPFC). We developed a new fMRI t...
Background
The search for neuroimaging biomarkers of alcohol use disorder (AUD) has primarily been restricted to significance testing in small datasets of low diversity. To identify neurobiological markers beyond individual differences, it may be useful to develop classification models for AUD. The ever-increasing quantity of neuroimaging data dema...
Molecular and functional imaging techniques have been used and combined with pharmacological probes to evaluate the role of dopamine in impulsivity. Overall, strong evidence links striatal dopaminergic function with impulsivity, measured by self-reports and laboratory tests of cognitive control and reward-based decision-making. The combination of m...
Introduction and aims:
As South Africa, especially the Western Cape Province, faces an epidemic of methamphetamine use disorder, therapeutic approaches suited to the South African context are needed. This secondary analysis assessed retention and methamphetamine abstinence outcomes in response to an 8-week pilot contingency management (CM) interve...
Background:
Premenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls.
Methods:
Thirty-six wome...
We previously reported that L-DOPA effects on reward-based decision-making in a randomized, placebo-controlled, double-blind, crossover study were consistent with an inverted U-shaped function whereby both low and high extremes of dopamine signaling are associated with high-impulsive choice. To test this hypothesis, we performed [18F]DOPA positron...
Studies of risk for psychotic symptoms in methamphetamine users have focused primarily on drug use immediately before symptoms had appeared. Here we assessed factors reflecting characteristics of lifetime methamphetamine use before the appearance of psychotic symptoms. Four hundred ninety-five methamphetamine users (322 men, 173 women) were studied...
While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and subst...
Objectives: Despite the prevalence of methamphetamine-associated psychosis, how characteristics of drug use affect the severity and clinical course, and its optimal treatments have not been established. We addressed these questions, assessing clinical features of methamphetamine-associated psychosis, and compared it with primary psychosis.
Methods:...
In einer randomisierten, placebokontrollierten, doppelblinden Crossover-Studie konnten wir zeigen, dass L-DOPA-Effekte auf Entscheidungsverhalten (Belohnungsaufschub, Risikoverhalten bei Gewinnen, Verlustaversion) mit einer umgekehrten U-Funktion in Einklang zu bringen ist, in der eine niedrige als auch eine hohe Dopaminaktivität mit impulsiven Ent...
Background: Alexithymia is a personality trait associated with emotion regulation difficulties. Up to 67% of alcohol-dependent patients in treatment have alexithymia. Objectives: The objective of this study was to investigate the direct and indirect effects of alexithymia, negative mood (stress, anxiety, and depression) and alcohol craving on alcoh...
Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and edu...
Background: Cannabis is the most widely used illicit substance worldwide, and legalization for recreational and medical purposes has substantially increased its availability and use in the United States.Objectives: Decades of research have suggested that recreational cannabis use confers risk for cognitive impairment across various domains, and str...
Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted...
Background: Buprenorphine, a treatment for Opioid Use Disorder, has liability for diversion and abuse. Use of single high doses of buprenorphine that are supervised avoid issues with diversion that occur with unsupervised or take home doses. Such doses have the potential to act as an initial opioid detox, facilitate transition to opioid antagonists...
Research has indicated a major role of dopamine in decision-making processes, but the underlying mechanisms remain largely unknown due to inconsistency in effects of dopaminergic drugs. To clarify the impact of dopamine on impulsive choice, we administered 150 mg L-DOPA to 87 healthy adults in a randomized, placebo-controlled, double-blind, crossov...
Background
Selective serotonin reuptake inhibitors are often used in alcohol use disorders. Clinical trials with selective serotonin reuptake inhibitors for alcohol use disorders, however, have yielded mixed results. The goal of this project was to assess whether a single i.v. dose of a selective serotonin reuptake inhibitor reduces craving for alc...
Rationale
Attentional bias toward drug-related stimuli is a feature of drug addiction that is linked to craving and drug-seeking behavior.
Objectives/method
An attentional bias modification (ABM) program was tested in 42 methamphetamine-dependent clients (DSM-IV criteria) receiving residential treatment for their drug use. Participants were random...
Liability to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational...
Background: Buprenorphine, a treatment for Opioid Use Disorder, has liability for diversion and abuse. Use of single high doses of buprenorphine that are supervised avoid issues with diversion that occur with unsupervised or take home doses. Such doses have the potential to act as an initial opioid detox, facilitate transition to opioid antagonists...
Background
Opioid use disorder is one of the most prevalent addiction problems worldwide. Buprenorphine is used as a medication to treat this disorder, but in countries where buprenorphine is unavailable in combination with naloxone, diversion can be a problem if the medication is given outside a hospital setting.
Objective
The objective of this r...
Rationale
Microglia are the main immune cells in the central nervous system and participate in neuroinflammation. When activated, microglia express increased levels of the translocator protein 18 kDa (TSPO), thereby making TSPO availability a marker for neuroinflammation. Using positron emission tomography (PET) scanning, our group recently demonst...
Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term eff...
Objective::
Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of...
Mesolimbic dopaminergic function influences addiction through effects on reinforcement learning, decision-making, and impulsivity. This review covers sex differences in dopaminergic neurochemistry, their hormonal and genetic determinants, and how differences in dopaminergic tone interact with sex and/or ovarian hormone status to affect cognitive fu...
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports , Vol. 21, 2017, 2597–2613). Specifically, Hill offered severa...
Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,86...
Background:
Although nicotine alters serotonergic neurochemistry, clinical trials of serotonergic medications for smoking cessation have provided mixed results. Understanding the role of serotonergic dysfunction in tobacco use disorder may advance development of novel pharmacotherapies.
Methods:
Functional magnetic resonance imaging was used to...
General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cogn...
