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... Larry Davidson, Connie M. Nickou, Peter Lynch, ... There is mounting evidence that early treatment of schizophrenia may affect the course of the illness, and preliminary research appears promising (Carbone et al., 1999; Edwards et... more
... Larry Davidson, Connie M. Nickou, Peter Lynch, ... There is mounting evidence that early treatment of schizophrenia may affect the course of the illness, and preliminary research appears promising (Carbone et al., 1999; Edwards et al., 1998; Johannessen, 1998; Larsen & ...
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Research Interests: Psychology, Clinical Psychology, Brain Imaging, Addiction, Magnetic Resonance Imaging, and 15 moreMedicine, Motivation, Clinical Practice, Brain, Humans, Alcoholism, Stress response, Psychological Intervention, Craving, Arousal, Street Drugs, Psychological Stress, SECONDARY PREVENTION, Substance-Related Disorders, and Substance Withdrawal Syndrome
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This study examined the role of depressive symptoms in the context of specific demographic and individual treatment characteristics in predicting drug abstinence at discharge from outpatient substance abuse treatment. Data from 827... more
This study examined the role of depressive symptoms in the context of specific demographic and individual treatment characteristics in predicting drug abstinence at discharge from outpatient substance abuse treatment. Data from 827 clients entering a large public funded outpatient substance abuse treatment program were analyzed using logistic regression to assess the effects of depressive symptoms on drug abstinence status at discharge. Analyses on the effects of gender, race, age, education level, frequency of drug use, insurance status, referral source, and length of stay in treatment on drug abstinence status at discharge were also conducted. Higher depressive symptom scores significantly predicted a decreased likelihood of clients' abstinence at discharge even after accounting for other significant demographic and treatment variables such as insurance status, race, age, primary drug of choice, frequency of drug use at admission and length of stay in treatment. The findings suggest that depression symptoms are an important factor affecting successful substance abuse treatment outcomes. Treatment approaches that address depressive symptoms are likely to enhance substance abuse treatment outcomes in real world clinical settings.
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This study examined whether differential response patterns are associated with the emotions of fear and anger as compared to neutral and physical action imagery conditions in 27 right-handed male volunteers screened for imagery ability... more
This study examined whether differential response patterns are associated with the emotions of fear and anger as compared to neutral and physical action imagery conditions in 27 right-handed male volunteers screened for imagery ability and alexithymia. Fear, anger, neutral, and action states were significantly differentiated on the basis of autonomic measures and facial electromyographic (EMG) responses. Discriminant function analyses (DFAs) using autonomic and facial EMG measures conducted separately on data from two experimental sessions revealed 78% and 72% correct classification of fear and anger, and neutral conditions, respectively. Cross-validation of the DFA using discriminant weights of the first session to classify the second session data led to a 66.5% correct classification of the fear and anger, and neutral imagery conditions. The combined average of both sessions revealed an 84% correct classification rate. Further, when subjective ratings were added to the discriminant function as a manipul...
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Research Interests: Bipolar Disorder, Biology, Medicine, Gene expression, Humans, and 14 moreMicroarray, Female, Male, Bipolar, Gene, Clinical Sciences, Middle Aged, Adult, Bipolar Disorders, Neurosciences, Gene expression profiling, Down-Regulation, reverse transcriptase polymerase chain reaction, and Peripheral blood
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Empirical findings from human laboratory and brain-imaging studies are consistent with clinical observations and indicate that chronic alcohol-related dysfunction in emotional and stress responses plays a role in motivation to consume... more
Empirical findings from human laboratory and brain-imaging studies are consistent with clinical observations and indicate that chronic alcohol-related dysfunction in emotional and stress responses plays a role in motivation to consume alcohol in people with alcohol use disorders. Recent findings on differences in stress responsivity in alcohol-dependent versus nondependent social drinkers demonstrate alterations in stress pathways that partially may explain the significant contribution of stress-related mechanisms on craving and relapse susceptibility. These findings have significant implications for clinical practice, including (1) the development of novel brain and stress biology-related measures of relapse risk that could serve as biomarkers to identify those most at risk of alcohol relapse during early recovery from alcoholism; and (2) the development of novel interventions that target stress-related effects on the motivation to drink alcohol and on relapse outcomes.
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Stress is associated with an increased intake of palatable foods and with weight gain, particularly in overweight women. Stress, food and body mass index (BMI) have been separately shown to affect amygdala activity. However, it is not... more
Stress is associated with an increased intake of palatable foods and with weight gain, particularly in overweight women. Stress, food and body mass index (BMI) have been separately shown to affect amygdala activity. However, it is not known whether stress influences amygdala responses to palatable foods, and whether this response is associated with chronic stress or BMI. A total of 14 overweight and obese women participated in a functional magnetic resonance imaging (fMRI) scan as they consumed a palatable milkshake during script-driven, autobiographical, guided imagery of stressful and neutral-relaxing scenarios. We report that a network including insula, somatomotor mouth area, ventral striatum and thalamus responds to milkshake receipt, but none of these areas are affected by stress. In contrast, whereas the left amygdala responds to milkshake irrespective of condition, the right amygdala responds to milkshake only under stressful conditions. Moreover, this right amygdala respons...
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Understanding the biologic systems that underlie the relationship between stress and alcohol consumption may lead to better prevention efforts and more effective treatments for alcoholism. Clinical laboratory studies offer a unique... more
Understanding the biologic systems that underlie the relationship between stress and alcohol consumption may lead to better prevention efforts and more effective treatments for alcoholism. Clinical laboratory studies offer a unique opportunity to examine these relationships by using a controlled environment to study how an acute stressor affects alcohol drinking and alcohol craving, how individuals in recovery or those at risk for alcoholism may respond differently to stressors relative to control subjects, and how alcohol differentially affects stress reactivity in these groups. This article reviews some of the most common physical, psychological, and pharmacological stressors used in stress-induction studies designed to reveal details about the relationship between stress reactivity and alcohol use and abuse.
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While emotion dysregulation represents an important mechanism underpinning psychological responses to trauma, little research has investigated this in refugees. In the current study, we examined the mediating role of emotion dysregulation... more
While emotion dysregulation represents an important mechanism underpinning psychological responses to trauma, little research has investigated this in refugees. In the current study, we examined the mediating role of emotion dysregulation in the relationship between refugee experiences (trauma and living difficulties) and psychological outcomes. Participants were 134 traumatized treatment-seeking refugees who completed measures indexing trauma exposure, post-migration living difficulties, difficulties in emotion regulation, posttraumatic stress disorder, depression, and explosive anger. Findings revealed distinctive patterns of emotion dysregulation associated with each of these psychological disorders. Results also indicated that emotion regulation difficulties mediated the association between both trauma and psychological symptoms, and living difficulties and psychological symptoms. Limitations include a cross-sectional design and the use of measures that had not been validated ac...
Research Interests: Psychology, Cognitive Science, Anger, Depression, Culture, and 15 moreEmotions, Humans, Affective Disorders, Personality Assessment Inventory, Female, Personality and Individual Differences, Male, Depressive Disorder, Interpersonal Relations, Middle Aged, Adult, Psychiatric, Cross Sectional Studies, Life Change Events, and Medical and Health Sciences
The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in the development of cancer. No in-depth studies of the involvement of this system in breast cancer (BC) have been carried out, and the action exerted by the... more
The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in the development of cancer. No in-depth studies of the involvement of this system in breast cancer (BC) have been carried out, and the action exerted by the drug aprepitant on BC cells is currently unknown. We show the involvement of this system in human BC cell lines: i) these cells express mRNA for the NK-1 receptor; ii) they overexpress NK-1 receptors; iii) the NK-1 receptor is involved in their viability; iv) SP induces their proliferation; v) NK-1 receptor antagonists block SP-induced mitogen stimulation of these cells; vi) the specific antitumor action of such antagonists on these cells occurs through the NK-1 receptor; and vii) BC cell death is due to apoptosis. We also found NK-1 receptors and SP in all human BC samples studied. The NK-1 receptor may be a promising target in the treatment of BC and NK-1 receptor antagonists could be candidates as a new antitumor drug in the treatment of BC.
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Research Interests: Neuroscience, Psychology, Magnetic Resonance Imaging, Medicine, Brain Mapping, and 13 moreResponse Inhibition, Humans, Cerebral Cortex, Female, Male, Reaction Time, Regression Analysis, The, Adult, Neural pathways, Psychomotor Performance, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Psychology, Adolescent, Fatigue, Medicine, Biomechanics of strength and conditioning, and 15 moreMuscle strength, Humans, Chronic Disease, Female, Male, Resistance Training, Young Adult, Questionnaires, Time Factors, Exercise Test, Psychological Stress, Myalgia, Isometric Contraction, Recovery of Function, and Adiposity
Research Interests: Psychology, Cognitive Science, Law, Criminal Law, Forensic psychiatry, and 12 moreCriminal Psychology, Medicine, Comorbidity, Antisocial Personality Disorder, Humans, Crime, United States, Mental Disorders, Clinical Sciences, Psychotropic Drugs, Substance-Related Disorders, and Psychiatric Status Rating Scales
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Research Interests: Psychology, Clinical Psychology, Anxiety, Humans, Cues, and 15 moreAlcoholism, Female, Male, Ethanol, Craving, Middle Aged, Adult, Adrenocorticotropic Hormone, ANXIETY, Psychological Stress, Archives General Psychiatry, Case Control Studies, Adrenal glands, hydrocortisone, and Medical and Health Sciences
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Research Interests: Psychology, Psychopharmacology, Animal Studies, Risk, Medicine, and 14 moreDrug Use, Humans, Substance Abuse, Stress response, Animals, Drug abuse, Recurrence, Empirical evidence, Neural pathways, Psychological Stress, Substance-Related Disorders, Psychology and Cognitive Sciences, Stress Physiological, and Medical and Health Sciences
The Belle detector at the KEKB electron-positron collider has collected almost 1 billion Y(4S) events in its decade of operation. Super-KEKB, an upgrade of KEKB is under construction, to increase the luminosity by two orders of magnitude... more
The Belle detector at the KEKB electron-positron collider has collected almost 1 billion Y(4S) events in its decade of operation. Super-KEKB, an upgrade of KEKB is under construction, to increase the luminosity by two orders of magnitude during a three-year shutdown, with an ultimate goal of 8E35 /cm^2 /s luminosity. To exploit the increased luminosity, an upgrade of the Belle detector has been proposed. A new international collaboration Belle-II, is being formed. The Technical Design Report presents physics motivation, basic methods of the accelerator upgrade, as well as key improvements of the detector.
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Our society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to... more
Our society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed “epigenetic clocks” such as GrimAge have shown utility in predicting biological age and mortality. Here, we assessed the impact of cumulative stress, stress physiology, and resilience on accelerated aging in a community sample (N = 444). Cumulative stress was associated with accelerated GrimAge (P = 0.0388) and stress-related physiologic measures of adrenal sensitivity (Cortisol/ACTH ratio) and insulin resistance (HOMA). After controlling for demographic and behavioral factors, HOMA correlated with accelerated GrimAge (P = 0.0186). Remarkably, psychological resilience factors of emotion regulation and self-co...
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The United States is facing an alarming and increasing obesity epidemic. Stress is associated with obesity, but specific longitudinal effects of life trauma on weight gain have not been assessed. Here we examined if life trauma and... more
The United States is facing an alarming and increasing obesity epidemic. Stress is associated with obesity, but specific longitudinal effects of life trauma on weight gain have not been assessed. Here we examined if life trauma and chronic stress predicted weight gain while also measuring the impact of body mass index (BMI). Life trauma and chronic stress were assessed with the Cumulative Adversity Interview (CAI). Weight and BMI were captured repeatedly over a two-year period. Results show significant increases in weight gain over time. Individuals with obesity (IOb) reported significantly higher levels of life trauma at the onset compared to overweight (IOw) and lean individuals (Il). Greater numbers of trauma events were associated with increased weight gain for both IOb and IOw but not for Il. Increased chronic stress was not consistently associated with weight gain over time. Current findings suggest the need to address trauma coping, especially in vulnerable individuals to prevent greater weight gain and curb obesity-related health outcomes.
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While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and... more
While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited. This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy. Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use. Lower perceived stress and presence of substance-use initiation were r...
Research Interests: Psychology and Medicine
The anterior cingulate cortex (ACC) is critical for both stress and inhibitory control processes and has been implicated in childhood trauma. This prospective study tested the hypothesis that early trauma moderates the association between... more
The anterior cingulate cortex (ACC) is critical for both stress and inhibitory control processes and has been implicated in childhood trauma. This prospective study tested the hypothesis that early trauma moderates the association between inhibitory control during late childhood and ACC stress reactivity during adolescence. Sixty-four adolescents were stratified into higher- or lower-childhood-trauma groups. Inhibitory control was indicated by fewer errors on a Stroop Color-Word task. Personalized stress cues during functional magnetic resonance imaging assessed neural correlates of stress in adolescents. Using a priori-defined anterior (rCZa) and posterior rostral cingulate zones of the ACC, associated with Stroop Color-Word task performance in prior meta-analyses, Stroop errors correlated inversely with activation in the rCZa during stress-cue exposure (r = -.23, p = .04). Childhood trauma moderated the association between Stroop errors and rCZa stress reactivity (interaction = -1...
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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,... more
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 the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions de...
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Across cultures and throughout history, human beings have reported a variety of spiritual experiences and the concomitant perceived sense of union that transcends one's ordinary sense of self. Nevertheless, little is known about the... more
Across cultures and throughout history, human beings have reported a variety of spiritual experiences and the concomitant perceived sense of union that transcends one's ordinary sense of self. Nevertheless, little is known about the underlying neural mechanisms of spiritual experiences, particularly when examined across different traditions and practices. By adapting an individualized guided-imagery task, we investigated neural correlates of personally meaningful spiritual experiences as compared with stressful and neutral-relaxing experiences. We observed in the spiritual condition, as compared with the neutral-relaxing condition, reduced activity in the left inferior parietal lobule (IPL), a result that suggests the IPL may contribute importantly to perceptual processing and self-other representations during spiritual experiences. Compared with stress cues, responses to spiritual cues showed reduced activity in the medial thalamus and caudate, regions associated with sensory a...
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Background: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence... more
Background: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. Methods: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. Results: The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also show...
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Prenatal cocaine exposure (PCE) is associated with risk-taking behaviors, including increased initiation of substance use in adolescence. The neurobiological underpinnings of these behaviors in adolescents with PCE are not well... more
Prenatal cocaine exposure (PCE) is associated with risk-taking behaviors, including increased initiation of substance use in adolescence. The neurobiological underpinnings of these behaviors in adolescents with PCE are not well understood. The goal of this study was to compare diffusion-weighted imaging data between adolescents with and without PCE using crossing-fiber models, which may provide more comprehensive estimates of white-matter microstructure within regions of multiple (e.g., primary and secondary) fiber orientations. Thirty-nine PCE individuals and 17 comparably aged prenatally non-drug-exposed (NDE) youths were recruited from a longitudinal cohort followed since birth. White matter was examined using tensor-derived and crossing-fiber models. Whole-brain investigations were performed, as were analyses on seven white-matter regions, which included the splenium, body and genu of the corpus callosum, bilateral cingulum, and the right and left superior longitudinal fasciculu...
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Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity... more
Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC), mid (MCC) and posterior cingulate cortex (PCC), voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC re...
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Chronic stress has a significant impact on obesity. However, how stress influences obesity remains unclear. We conducted an epigenome-wide DNA methylation association analysis of obesity (N=510) and examined whether cumulative stress... more
Chronic stress has a significant impact on obesity. However, how stress influences obesity remains unclear. We conducted an epigenome-wide DNA methylation association analysis of obesity (N=510) and examined whether cumulative stress influenced the DNA methylation on body weight. We identified 20 CpG sites associated with body mass index at the false discovery rate q<0.05, including a novel site, cg18181703, in suppressor of cytokine signaling 3 (SOCS3) gene (coefficient β=-0.0022, FDR q=4.94×10(-5)). The interaction between cg18181703 and cumulative adverse life stress contributed to variations in body weight (p=0.002). Individuals with at least five major life events and lower methylation of cg1818703 showed a 1.38-fold higher risk of being obese (95%CI: 1.17-1.76). Our findings suggest that aberrant in DNA methylation is associated with body weight and that methylation of SOCS3 moderates the effect of cumulative stress on obesity.
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Increased attention bias toward drug-related cues over non-drug-related intrinsically pleasant reinforcers is a hallmark of drug addiction. In this study we used the late positive potential (LPP) to investigate whether such increased... more
Increased attention bias toward drug-related cues over non-drug-related intrinsically pleasant reinforcers is a hallmark of drug addiction. In this study we used the late positive potential (LPP) to investigate whether such increased attention bias toward drug-related relative to non-drug-related cues changes over a protracted period of reduced drug use in treatment-seeking individuals with a cocaine use disorder (CUD). Treatment-seeking individuals with CUD and matched healthy controls passively viewed a series of pleasant, neutral and drug-related pictures while their event-related potentials were recorded at baseline (≤ 3 weeks after treatment initiation) and at 6-month follow-up (only CUD). We included 19 treatment-seeking individuals with CUD and 18 matched controls in our analyses. The results showed a reversal in attention bias (i.e., LPP amplitude) from baseline (i.e., drug > pleasant) to follow-up (i.e., pleasant > drug) driven by an increased attentional engagement w...
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Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive... more
Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classifi...
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Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of... more
Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery ...