David Goldman
National Institutes of Health, Lab of Neurogenetics, Faculty Member
The endocannabinoid system plays an important role in reward and addiction. One of the two main endocannabinoid neurotransmitters, anandamide, is metabolized by fatty acid amide hydrolase, an enzyme with a functional genetic polymorphism... more
The endocannabinoid system plays an important role in reward and addiction. One of the two main endocannabinoid neurotransmitters, anandamide, is metabolized by fatty acid amide hydrolase, an enzyme with a functional genetic polymorphism (FAAH Pro129Thr, rs324420). The Thr129 allele has been linked to problem drug and alcohol use, but the association has not been widely replicated and may be stronger for clinical measures of severity rather than categorical diagnosis. In the present study, we sought to determine whether the Thr129 allele was associated with both alcohol dependence (AD) diagnosis and severity in a sample of 1434 European American and African American individuals, 952 of whom were diagnosed with lifetime AD. Participants were genotyped for FAAH rs324420, and ancestry was determined via a genome-wide panel of ancestry informative markers. Subjects participated in Structured Clinical Interviews for psychiatric disorders and 90-day Timeline Followback interviews to asses...
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Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent... more
Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (-703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (-703 G/T) and rs2129575 (p⩽0...
Research Interests: Biology, Neuropsychopharmacology, Magnetic Resonance Spectroscopy, Medicine, Prefrontal Cortex, and 15 moreHumans, Internal Medicine, Female, Male, Panic Disorder, Genetic Association Studies, Middle Aged, Genotype, Adult, Linkage Disequilibrium, Psychiatric Status Rating Scales, Gabaergic, alleles, Medical and Health Sciences, and Genetic predisposition to disease
Central serotonergic (5-HT) function is implicated in pathways to alcohol dependence, including dysphoria manifested by symptoms of anxiety and depression. However, little is known about genetic variation in central 5-HT function and its... more
Central serotonergic (5-HT) function is implicated in pathways to alcohol dependence, including dysphoria manifested by symptoms of anxiety and depression. However, little is known about genetic variation in central 5-HT function and its potential impact on temperament and behavior in persons with a family history of alcoholism (FH+). We tested 314 healthy young adults (23.5 years of age, 57% female; 193 FH- and 121 FH+) enrolled in the Oklahoma Family Health Patterns project, a study of alcoholism risk in relation to temperament and behavioral dyscontrol. Dysphoria was assessed using the Eysenck neuroticism and Beck depression scales, and Cloninger's Tridimensional Personality Questionnaire. Risk taking was assessed with the Iowa Gambling Task (IGT) and Balloon Analogue Response Task (BART). All subjects were genotyped for a functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4). FH+ subjects with the gain-of-function 5-HTTLPR genot...
Research Interests: Psychology, Clinical Psychology, Risk Taking, Medicine, Humans, and 15 morePersonality Assessment Inventory, Neuroticism, Alcoholism, Female, Serotonin Transporter, Male, Dysphoria, Oklahoma, Clinical Sciences, Mood Disorders, Harm Avoidance, Neurosciences, Case Control Studies, Psychiatric Status Rating Scales, and Personality Inventory
Research Interests: Genetics, Clinical Psychology, Food Science, Eating Disorders, Medicine, and 15 moreAnorexia Nervosa, Bulimia Nervosa, Anxiety, Humans, Female, Exercise, Animal Model, Eating, Activity, Adult, Eating Disorder, ANXIETY, Endophenotype, Eating Disorder Not Otherwise Specified, and Medical and Health Sciences
The A1 allele of the DRD2/ANKK1 Taq1A polymorphism (rs1800497) is associated with reduced striatal D2/3 receptor binding in healthy individuals (Con) as well as depression and addiction. However, the effect of rs1800497 on D2/3 receptor... more
The A1 allele of the DRD2/ANKK1 Taq1A polymorphism (rs1800497) is associated with reduced striatal D2/3 receptor binding in healthy individuals (Con) as well as depression and addiction. However, the effect of rs1800497 on D2/3 receptor binding in depressed patients as well as the SNP's effect on D2/3 binding during reward-associated dopamine release is unknown. Twelve unmedicated patients with major depressive disorder (MDD) and 24 Con completed PET scans with [11C]raclopride, once without receiving monetary rewards (baseline) and once while winning money. In Con, the A1 allele was associated with reduced baseline binding potential (BPND) in the middle caudate and ventral striatum. However, in MDD patients the A1 allele was associated with increased baseline BPND in these regions. There were no significant associations between rs1800497 and change in BPND during reward-associated dopamine release. Conceivably, the A1 allele predisposes to depression and addiction via its effect...
Research Interests: Endocrinology, Psychology, Neuropsychopharmacology, Positron Emission Tomography, Medicine, and 15 moreBrain, Humans, Internal Medicine, Major Depressive Disorder, Gambling, Female, Male, Phenotype, Middle Aged, Genotype, Adult, Allele, Case Control Studies, Dopamine antagonists, and Medical and Health Sciences
Objective:To describe menstrual disturbance in eating disorders (ED).Method:We describe menstrual history in 1,705 women and compare eating, weight, and psychopathological traits across menstrual groups.Results:Menstrual dysfunction... more
Objective:To describe menstrual disturbance in eating disorders (ED).Method:We describe menstrual history in 1,705 women and compare eating, weight, and psychopathological traits across menstrual groups.Results:Menstrual dysfunction occurred across all eating disorder subtypes. Individuals with normal menstrual history and primary amenorrhea reported the highest and lowest lifetime body mass index (BMI), respectively. Normal menstruation and oligomenorrhea groups reported greater binge eating, vomiting, and appetite suppressant use. Amenorrhea was associated with lower caloric intake and higher exercise. Harm avoidance, novelty seeking, perfectionism, and obsessionality discriminated among menstrual status groups. No differences in comorbid Axis I and II disorders were observed.Conclusion:Menstrual dysfunction is not limited to any eating disorder subtype. BMI, caloric intake, and exercise were strongly associated with menstrual function. Menstrual status is not associated with como...
Research Interests: Eating Disorders, Behavior, Adolescent, Medicine, Comorbidity, and 15 moreAnorexia Nervosa, Bulimia Nervosa, Humans, Female, Menstrual Cycle, Body Mass Index, Eating, Adult, Eating Disorder, Binge eating, Harm Avoidance, Cross Sectional Studies, Amenorrhea, Medical and Health Sciences, and Genetic predisposition to disease
Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely... more
Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availabilityin vivoas measured with [11C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to sal...
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Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging,... more
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging, and regulated secretion of this neurotrophin. The human prefrontal cortex (PFC) shows lifelong neuroplastic adaption implicating the Val66Met BDNF polymorphism in the recovery of higher-order executive functions after traumatic brain injury (TBI). In this study, we examined the effect of this BDNF polymorphism on the recovery of executive functioning after TBI. We genotyped a sample of male Vietnam combat veterans consisting of a frontal lobe lesion group with focal penetrating head injuries and a non-head-injured control group for the Val66Met BDNF polymorphism. The Delis–Kaplan Executive Function System as a standardized psychometric battery was administrated to examine key domains of executive functions. The results revealed that the Met allele b...
Research Interests: Neuroscience, Psychology, Traumatic Brain Injury, Medicine, Prefrontal Cortex, and 15 moreLinear models, Neuroplasticity, Humans, Male, Executive Functions, The, Middle Aged, Methionine, Neurotrophic Factors, Frontal Lobe, Brain injuries, Recovery of Function, Psychology and Cognitive Sciences, Valine, and Medical and Health Sciences
Research Interests: Endocrinology, Neuroscience, Psychology, Pain, Medicine, and 15 moreNucleus Accumbens, Dopamine, Humans, Internal Medicine, Caudate Nucleus, Female, Male, Mood Disorders, Adult, Genetic variation, Dopaminergic Neurons, dopaminergic, Corpus striatum, Psychology and Cognitive Sciences, and Medical and Health Sciences
Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (DA) cells within the ventral tegmental area (VTA)/nucleus accumbens (NAc) circuitry appear to be a candidate mechanism for the neuroadaptive changes that follow stress and... more
Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (DA) cells within the ventral tegmental area (VTA)/nucleus accumbens (NAc) circuitry appear to be a candidate mechanism for the neuroadaptive changes that follow stress and reward responses in animal models. However, the role of theBDNFgene variants in responses to salient cues through DA neurotransmission in humans remains unexplored. Here, we studied the effect of the common functionalBDNFVal66Met (rs6265) polymorphism on rewarding experiences in the striatum and DA-mediated responses to stress. Seventy-two healthy controls were genotyped for theBDNFVal66Met polymorphism and underwent the monetary incentive delay task during an functional magnetic resonance imaging (fMRI) session. Forty-nine of them also underwent a sustained pain challenge with and without placebo administration with potential analgesic properties during PET measures of DA D2/3-receptor-mediated neurotransmission. Neuroimaging results revealed a sign...
Research Interests: Neuroscience, Psychology, Pain, Magnetic Resonance Imaging, Medicine, and 15 moreNucleus Accumbens, Brain Mapping, Humans, Functional Magnetic Resonance Imaging, Female, Male, Genotype, Adult, Physiological Stress Markers, Dopaminergic Neurons, Neuropsychological Tests, dopaminergic, Corpus striatum, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Genetics, Bipolar Disorder, Biology, Medicine, Psychiatric Genetics, and 13 moreSignal Transduction, Humans, Major Depressive Disorder, Female, Male, Genetic Association Studies, Gene Regulatory Networks, Clinical Sciences, Mood Disorders, Adult, Neurosciences, Gene expression profiling, and Genetic predisposition to disease
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Objective: To evaluate the relationship of the tryptophan hydroxylase (TPH) genotype to suicidality by the study of surviving monozygotic (MZ) cotwins of twins who committed suicide. Method: Twenty-four surviving Swedish MZ twins whose MZ... more
Objective: To evaluate the relationship of the tryptophan hydroxylase (TPH) genotype to suicidality by the study of surviving monozygotic (MZ) cotwins of twins who committed suicide. Method: Twenty-four surviving Swedish MZ twins whose MZ cotwins had committed suicide were compared to 158 demographically sampled Swedish general population controls for TPH alleles. We also examined serotonin transporter alleles. Results: The living MZ cotwins of suicide victims had a significantly higher TPH 17 779C allele frequency than controls. No significant difference was observed for serotonin transporter alleles. Conclusion: These results, in a small sample, suggest the possibility that the 17 779C allele of the TPH gene may be associated with an increased risk of suicide. Further studies in larger samples are needed.
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Research Interests: Genetics, Chemistry, Behavioral Medicine, Comorbidity, Biological Sciences, and 15 moreDopamine, Humans, Haplotypes, Alcoholism, Male, Heroin Dependence, African Americans, Alcohol dependence, Genotype, Adult, Interaction effect, Drug Dependence, alleles, Medical and Health Sciences, and Genetic predisposition to disease
Research Interests: Suicide, Medicine, Humans, Child, Child Abuse, and 15 moreFemale, Male, Genetic Association Studies, African Americans, Middle Aged, Questionnaires, Genotype, Adult, Single Nucleotide Polymorphism, Sex Factors, Psychiatric, Logistic Models, Psychology and Cognitive Sciences, Gene frequency, and Medical and Health Sciences
Research Interests: Complementary and Alternative Medicine, Biology, Biological Chemistry, American Indian, Alcoholism, and 15 moreDNA Extraction, Ethanol, Genetic linkage analysis, Alcohol Consumption, Enzyme, Alcohol dependence, Binge drinking, Clinical Data, Gene Family, Allele, Genetic Markers, Alcohol Dehydrogenase, Aldehyde Dehydrogenase, Association Analysis, and Gene frequency
The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous... more
The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1 (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability. The present study explores whether those observations extend to the neuronal processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and a preliminary sample of 16 unmedicated patients with MDD who completed a functional magnetic resonance imaging scan while viewing blocks of positive, negative, and neutral words. In addition, potential mediating factors such as early life stress, sex, personality traits, and negative memory bias were examined. Robust differences in blood oxygenation level-dependent (BOLD) signal were found in healthy controls (A allele carriers > GG-hom...
Research Interests: Neuroscience, Psychology, Magnetic Resonance Imaging, Aging, Medicine, and 15 moreEmotions, Hippocampus, Humans, Genetic Testing, Major Depressive Disorder, Functional Magnetic Resonance Imaging, Female, Male, Amygdala, Aged, Middle Aged, Adult, Genetic variation, Psychiatric, and Medical and Health Sciences
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This analysis is a follow‐up to an earlier investigation of 182 genes selected as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN). As those initial case–control results revealed no statistically... more
This analysis is a follow‐up to an earlier investigation of 182 genes selected as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN). As those initial case–control results revealed no statistically significant differences in single nucleotide polymorphisms, herein, we investigate alternative phenotypes associated with AN. In 1762 females, using regression analyses, we examined the following: (i) lowest illness‐related attained body mass index; (ii) age at menarche; (iii) drive for thinness; (iv) body dissatisfaction; (v) trait anxiety; (vi) concern over mistakes; and (vii) the anticipatory worry and pessimism versus uninhibited optimism subscale of the harm avoidance scale. After controlling for multiple comparisons, no statistically significant results emerged. Although results must be viewed in the context of limitations of statistical power, the approach illustrates a means of potentially identifying genetic variants conferring susceptibility t...
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Research Interests: Neuroscience, Psychology, Cognitive Science, Personality, Magnetic Resonance Imaging, and 15 moreMedicine, Emotions, Dopamine, Humans, Haplotypes, Functional Magnetic Resonance Imaging, Female, Male, Cortex, Middle Aged, Genotype, Adult, Functional Neuroimaging, Neurosciences, and Dorsolateral Prefrontal Cortex
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Research Interests: Genetics, Eating Disorders, Anorexia Nervosa, Bulimia Nervosa, Biological Sciences, and 15 moreBiological Psychiatry, Humans, Female, Biological, Genetic determinism, Body Mass Index, Genotype, Adult, Disordered Eating, Eating Disorder, Large Scale, Bulimia, Linkage Analysis, Genetic factors, and Eating Disorder Not Otherwise Specified
Research Interests: Clinical Psychology, Eating Disorders, Adolescent, Medicine, Anorexia Nervosa, and 15 moreBulimia Nervosa, Humans, Female, Male, Obsessive Compulsive Disorder, Differential Diagnosis, Feeding Behavior, Adult, Latent Class Analysis, Body Weight, Eating Disorder, Binge Eating Disorder, Archives General Psychiatry, Latent class model, and Medical and Health Sciences
Research Interests: Magnetic Resonance Imaging, Gene expression, Emotions, Brain Mapping, Brain, and 15 moreHumans, Major Depressive Disorder, Haplotypes, Functional Magnetic Resonance Imaging, Female, Amygdala, Arousal, Genotype, Adult, Genetic variation, Cross Sectional Studies, Archives General Psychiatry, Anterior cingulate cortex, Case Control Studies, and Genetic predisposition to disease
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Research Interests: Genetics, Demography, Addiction, Humans, Child, and 15 moreAfrican American, Child Abuse, Female, Male, Drug Addiction, American, African Americans, Genotype, Ethnic Group, Genetic variation, Genetic Markers, Life Change Events, healthcare disparities, Medical and Health Sciences, and Genetic predisposition to disease
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Aggressive disorders are moderately heritable; therefore, identification of genetic influences is important. The X-linked MAOA gene, encoding the MAOA enzyme, has a functional 30 bp repeat polymorphism in the promoter region (MAOA-LPR)... more
Aggressive disorders are moderately heritable; therefore, identification of genetic influences is important. The X-linked MAOA gene, encoding the MAOA enzyme, has a functional 30 bp repeat polymorphism in the promoter region (MAOA-LPR) that has been shown to influence aggression. Childhood trauma is a known risk factor for numerous psychopathologies in adulthood including aggressive behaviors. We investigated the interactive effect of MAOA-LPR genotype and a history of childhood trauma in predicting aggressive behaviors in a prisoner population. A total of 692 male prisoners were genotyped for MAOA-LPR with genotypes grouped into high and low transcriptional activity. Participant evaluations included measures of aggression (Brown-Goodwin Lifetime History of Aggression, BGHA), hostility (Buss-Durkee Hostility Inventory), impulsivity (Barratt Impulsiveness Scale), violence directed toward self and others, and childhood trauma [Childhood Trauma Questionnaire (CTQ)]. MAOA-LPR interacted...
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Hepatocellular carcinoma (HCC) has high mortality and no adequate treatment. Endocannabinoids interact with hepatic cannabinoid 1 receptors (CB1Rs) to promote hepatocyte proliferation in liver regeneration by inducing cell cycle proteins... more
Hepatocellular carcinoma (HCC) has high mortality and no adequate treatment. Endocannabinoids interact with hepatic cannabinoid 1 receptors (CB1Rs) to promote hepatocyte proliferation in liver regeneration by inducing cell cycle proteins involved in mitotic progression, including Forkhead Box M1. Because this protein is highly expressed in HCC and contributes to its genesis and progression, we analyzed the involvement of the endocannabinoid/CB1R system in murine and human HCC. Postnatal diethylnitrosamine treatment induced HCC within 8 months in wild-type mice but fewer and smaller tumors in CB1R(-/-) mice or in wild-type mice treated with the peripheral CB1R antagonist JD5037, as monitored in vivo by serial magnetic resonance imaging. Genome-wide transcriptome analysis revealed CB1R-dependent, tumor-induced up-regulation of the hepatic expression of CB1R, its endogenous ligand anandamide, and a number of tumor-promoting genes, including the GRB2 interactome as well as Forkhead Box ...
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Aggressive disorders are moderately heritable; therefore, identification of genetic influences is important. The X-linked MAOA gene, encoding the MAOA enzyme, has a functional 30 bp repeat polymorphism in the promoter region (MAOA-LPR)... more
Aggressive disorders are moderately heritable; therefore, identification of genetic influences is important. The X-linked MAOA gene, encoding the MAOA enzyme, has a functional 30 bp repeat polymorphism in the promoter region (MAOA-LPR) that has been shown to influence aggression. Childhood trauma is a known risk factor for numerous psychopathologies in adulthood including aggressive behaviors. We investigated the interactive effect of MAOA-LPR genotype and a history of childhood trauma in predicting aggressive behaviors in a prisoner population. A total of 692 male prisoners were genotyped for MAOA-LPR with genotypes grouped into high and low transcriptional activity. Participant evaluations included measures of aggression (Brown-Goodwin Lifetime History of Aggression, BGHA), hostility (Buss-Durkee Hostility Inventory), impulsivity (Barratt Impulsiveness Scale), violence directed toward self and others, and childhood trauma [Childhood Trauma Questionnaire (CTQ)]. MAOA-LPR interacted...
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The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using whole genome sequencing of mRNA transcripts (RNA-Seq) and... more
The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using whole genome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine- and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between ...
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Hepatocellular carcinoma (HCC) has high mortality and no adequate treatment. Endocannabinoids interact with hepatic cannabinoid 1 receptors (CB1Rs) to promote hepatocyte proliferation in liver regeneration by inducing cell cycle proteins... more
Hepatocellular carcinoma (HCC) has high mortality and no adequate treatment. Endocannabinoids interact with hepatic cannabinoid 1 receptors (CB1Rs) to promote hepatocyte proliferation in liver regeneration by inducing cell cycle proteins involved in mitotic progression, including Forkhead Box M1. Because this protein is highly expressed in HCC and contributes to its genesis and progression, we analyzed the involvement of the endocannabinoid/CB1R system in murine and human HCC. Postnatal diethylnitrosamine treatment induced HCC within 8 months in wild-type mice but fewer and smaller tumors in CB1R(-/-) mice or in wild-type mice treated with the peripheral CB1R antagonist JD5037, as monitored in vivo by serial magnetic resonance imaging. Genome-wide transcriptome analysis revealed CB1R-dependent, tumor-induced up-regulation of the hepatic expression of CB1R, its endogenous ligand anandamide, and a number of tumor-promoting genes, including the GRB2 interactome as well as Forkhead Box ...
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The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using whole genome sequencing of mRNA transcripts (RNA-Seq) and... more
The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using whole genome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine- and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between ...
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Research Interests: Psychology, Medicine, Humans, Child, Child Abuse, and 15 moreFemale, Serotonin Transporter, Male, African Americans, Middle Aged, Questionnaires, Genotype, Adult, Genetic Polymorphism, Chi Square Distribution, Psychiatric, Substance-Related Disorders, Psychology and Cognitive Sciences, Gene frequency, and Medical and Health Sciences
Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of... more
Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque ge...
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Research Interests: Genetics, Clinical Psychology, Eating Disorders, Comorbidity, Anorexia Nervosa, and 15 moreBulimia Nervosa, Anxiety, Female, Body Mass Index, Eating, Adult, Femme, Eating Disorder, ANXIETY, Harm Avoidance, Hombre, Age of Onset, Anorexie mentale, Eating Disorder Not Otherwise Specified, and conducta sexual
Research Interests: Genetics, Clinical Psychology, Eating Disorders, Comorbidity, Anorexia Nervosa, and 15 moreBulimia Nervosa, Anxiety, Female, Body Mass Index, Eating, Adult, Femme, Eating Disorder, ANXIETY, Harm Avoidance, Hombre, Age of Onset, Anorexie mentale, Eating Disorder Not Otherwise Specified, and conducta sexual
ABSTRACT
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The low self-administration (LS)/Kgras (LS) and high self-administration (HS)/Kgras (HS) rat lines were generated by selective breeding for low- and high-intravenous cocaine self-administration, respectively, from a common outbred Wistar... more
The low self-administration (LS)/Kgras (LS) and high self-administration (HS)/Kgras (HS) rat lines were generated by selective breeding for low- and high-intravenous cocaine self-administration, respectively, from a common outbred Wistar stock (Crl:WI). This trait has remained stable after 13 generations of breeding. The objective of the present study is to compare cocaine preference, neurotransmitter release, and dopamine receptor activation in LS and HS rats. Levels of dopamine, acetylcholine, and cocaine were measured in the nucleus accumbens (NA) shell of HS and LS rats by tandem mass spectrometry of microdialysates. Cocaine-induced locomotor activity and conditioned-place preference were compared between LS and HS rats. HS rats displayed greater conditioned-place preference scores compared to LS and reduced basal extracellular concentrations of dopamine and acetylcholine. However, patterns of neurotransmitter release did not differ between strains. Low-dose cocaine increased lo...
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The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood,... more
The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-e...