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1.
Physiol Rev ; 99(4): 2115-2140, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31507244

RESUMO

Drug consumption is driven by a drug's pharmacological effects, which are experienced as rewarding, and is influenced by genetic, developmental, and psychosocial factors that mediate drug accessibility, norms, and social support systems or lack thereof. The reinforcing effects of drugs mostly depend on dopamine signaling in the nucleus accumbens, and chronic drug exposure triggers glutamatergic-mediated neuroadaptations in dopamine striato-thalamo-cortical (predominantly in prefrontal cortical regions including orbitofrontal cortex and anterior cingulate cortex) and limbic pathways (amygdala and hippocampus) that, in vulnerable individuals, can result in addiction. In parallel, changes in the extended amygdala result in negative emotional states that perpetuate drug taking as an attempt to temporarily alleviate them. Counterintuitively, in the addicted person, the actual drug consumption is associated with an attenuated dopamine increase in brain reward regions, which might contribute to drug-taking behavior to compensate for the difference between the magnitude of the expected reward triggered by the conditioning to drug cues and the actual experience of it. Combined, these effects result in an enhanced motivation to "seek the drug" (energized by dopamine increases triggered by drug cues) and an impaired prefrontal top-down self-regulation that favors compulsive drug-taking against the backdrop of negative emotionality and an enhanced interoceptive awareness of "drug hunger." Treatment interventions intended to reverse these neuroadaptations show promise as therapeutic approaches for addiction.


Assuntos
Comportamento Aditivo , Encéfalo/fisiopatologia , Usuários de Drogas/psicologia , Recompensa , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Animais , Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Plasticidade Neuronal , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/reabilitação
2.
Nat Commun ; 10(1): 3934, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477694

RESUMO

Drug addiction is a chronic relapsing disorder of compulsive drug use. Studies of the neurobehavioral factors that promote drug relapse have yet to produce an effective treatment. Here we take a different approach and examine the factors that suppress-rather than promote-relapse. Adapting Pavlovian procedures to suppress operant drug response, we determined the anti-relapse action of environmental cues that signal drug omission (unavailability) in rats. Under laboratory conditions linked to compulsive drug use and heightened relapse risk, drug omission cues suppressed three major modes of relapse-promotion (drug-predictive cues, stress, and drug exposure) for cocaine and alcohol. This relapse-suppression is, in part, driven by omission cue-reactive neurons, which constitute small subsets of glutamatergic and GABAergic cells, in the infralimbic cortex. Future studies of such neural activity-based cellular units (neuronal ensembles/memory engram cells) for relapse-suppression can be used to identify alternate targets for addiction medicine through functional characterization of anti-relapse mechanisms.


Assuntos
Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , Sinais (Psicologia) , Neurônios/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Alcoolismo/fisiopatologia , Alcoolismo/prevenção & controle , Animais , Cocaína/administração & dosagem , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/prevenção & controle , Condicionamento Operante/fisiologia , Inibidores da Captação de Dopamina/farmacologia , Masculino , Córtex Pré-Frontal/fisiopatologia , Ratos Long-Evans , Ratos Sprague-Dawley , Ratos Transgênicos , Recidiva , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
3.
Neuron ; 103(4): 563-581, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437453

RESUMO

Spike-timing-dependent synaptic plasticity (STDP) is a leading cellular model for behavioral learning and memory with rich computational properties. However, the relationship between the millisecond-precision spike timing required for STDP and the much slower timescales of behavioral learning is not well understood. Neuromodulation offers an attractive mechanism to connect these different timescales, and there is now strong experimental evidence that STDP is under neuromodulatory control by acetylcholine, monoamines, and other signaling molecules. Here, we review neuromodulation of STDP, the underlying mechanisms, functional implications, and possible involvement in brain disorders.


Assuntos
Plasticidade Neuronal/fisiologia , Neurotransmissores/fisiologia , Potenciais de Ação , Animais , Astrócitos/fisiologia , Comportamento/fisiologia , Encefalopatias/tratamento farmacológico , Encefalopatias/fisiopatologia , Mapeamento Encefálico , Humanos , Aprendizagem/fisiologia , Consolidação da Memória/fisiologia , Modelos Neurológicos , Terapia de Alvo Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/fisiopatologia , Neurônios/fisiologia , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Terminações Pré-Sinápticas/fisiologia , Receptores de Neurotransmissores/fisiologia , Transdução de Sinais/fisiologia , Especificidade da Espécie , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Fatores de Tempo
4.
BMJ Case Rep ; 12(7)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352378

RESUMO

A 45-year-old man, a regular cocaine user, presented with confusion and unusual behaviour to the emergency room. On examination he was unable to perform simple tasks or follow commands. He was treated for possible central nervous system infection. MRI of the brain showed multiple bilateral T2 hyperintense periventricular and deep white matter foci, best appreciated on FLAIR with contrast enhancement. He continued deteriorating, eventually becoming catatonic with extensor posturing and increased tone, requiring intensive therapy unit management. Repeat MRIs were also noted to show worsening changes. He was treated for a presumed inflammatory leucoencephalopathy with intravenous methylprednisolone, immunoglobulins, as well as plasmapheresis. After 2 weeks, the patient started to show clinical improvement with eventual transfer to a rehabilitation hospital. A year after his first presentation, the patient scored 30 out of 30 on the MMSE and his neurological examination was normal.


Assuntos
Cocaína/efeitos adversos , Confusão/induzido quimicamente , Leucoencefalopatias/fisiopatologia , Transtornos Mentais/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Substância Branca/patologia , Confusão/fisiopatologia , Eletroencefalografia , Humanos , Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/terapia , Imagem por Ressonância Magnética , Masculino , Transtornos Mentais/fisiopatologia , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Plasmaferese , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento
5.
Eur Addict Res ; 25(5): 238-247, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163437

RESUMO

BACKGROUND: The specialized literature provides solid evidence that substance use disorders (SUD) and personality disorders (PD) are interrelated. Given the relative novelty of the Alternative Model for PD, there are still few studies that have analyzed the relationship between the different facets, substance use disorder, and the various consumption profiles. OBJECTIVE: This paper analyzes the relationship between the facets of the Alternative Model for PD and different substance use disorder profiles, using the facet scores obtained in a sample of substance use disorder patients and comparing these with normative scores. A comparison is also conducted between types of patients. METHOD: The Personality Inventory for DSM-5-SF was administered to a sample of 289 patients diagnosed with SUD who began treatment for alcohol (ALC), cannabis (CAN), cocaine (COC), or heroin (HER) use disorder. A latent class analysis was conducted and scores obtained for each of the classes were compared with normative scores. Logistic regression analyzes were carried out to determine which facets and domains show the greatest explanatory capacity of belonging to each latent class. RESULTS: Four patient profiles were identified on the basis of their SUD: polydrug use (POLY), COC-HER, ALC, and CAN. When comparing the groups with the normative population, POLY presented higher scores on all the domains, COC-HER and ALC on all domains except antagonism, and CAN showed higher scores on detachment and psychoticism. The CAN cluster presented lower scores than the other 3 groups in different domains. No statistically significant differences were observed on any domain between the groups POLY and COC - HER, while differences were found between the classes POLY and ALC for the detachment domain. CONCLUSIONS: The results help to identify the personality profiles associated with various SUD profiles. In particular, patients from the groups POLY, COC-HER, and ALC present high scores on pathological facets related to borderline PD and schizotypal PD (all 3), and antisocial PD (POLY), while the CAN cluster is more normalized and its pathological facets are related to the schizotypal PD. Patients with POLY have a greater tendency toward pathological personality, with the involvement of a large number of facets, while COC-HER and ALC show a slightly less severe profile, and CAN users are characterized by lower scores, but high detachment and psychoticism.


Assuntos
Diagnóstico Duplo (Psiquiatria) , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos da Personalidade/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
6.
Behav Processes ; 165: 23-28, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132444

RESUMO

Circadian rhythms organize behavior and physiological processes to be appropriate to the predictable cycle of daily events. These rhythms are entrained by stimuli that provide time of day cues (zeitgebers), such as light, which regulates the sleep-wake cycle and associated rhythms. But other events, including meals, social cues, and bouts of locomotor activity, can act as zeitgebers. Recent evidence shows that most organs and tissues contain cells that are capable of some degree of independent circadian cycling, suggesting the circadian system is broadly and diffusely distributed. Within laboratory studies of behavior, circadian rhythms tend to be treated as a complication to be minimized, but they offer a useful model of predictable shifts in behavioral tendencies. In the present review, we summarize the evidence that formed the basis for a hypothesis that drugs of abuse can entrain circadian rhythms and describe the outcome of a series of experiments designed to test that hypothesis. We propose that such drug-entrained rhythms may contribute to demonstrated daily variations in drug metabolism, tolerance, and sensitivity to drug reward. Of particular importance, these rhythms may be evoked by a single episode of drug taking, strengthen with repeated episodes, and re-emerge after long periods of abstinence, thereby contributing to drug abuse, addiction, and relapse.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Comportamento Alimentar/fisiologia , /farmacologia , Animais , Encéfalo/fisiopatologia , Ritmo Circadiano/fisiologia , Sinais (Psicologia) , Tolerância a Medicamentos , Habituação Psicofisiológica/fisiologia , Humanos , Taxa de Depuração Metabólica/fisiologia , Motivação/efeitos dos fármacos , Motivação/fisiologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
7.
Recenti Prog Med ; 110(5): 230-235, 2019 05.
Artigo em Italiano | MEDLINE | ID: mdl-31140455

RESUMO

Psychiatry and addiction disorders are closely linked, but the current epidemiological and clinical evidence impose us to effectively define the "dependence medicine" (DM) discipline, and to review its management. The need for change is also suggested indirectly by the new DSM-5 which proposes a partial overcoming of the term 'addiction' by introducing the definitions Substances Use Disorders (SUDs), Alcohol Use Disorders (AUDs), and disorders related to behavioral alterations (behavioral disorders): eating disorders, gambling, etc. These disorders can generate organic diseases, psychic, family and social problems. The onset of psycho-pathological diseases, in young poly-dependents, occurs in a high percentage of cases of SUDs and/or AUDs (40-70%); the constant increase of young poly-dependents requires us to avoid psychiatrization as a first approach. For these reasons we suggest a change of management in this field, underlining how the DM combines elements of public health, prevention, internal medicine, clinical pharmacology, neurology 'and even psychiatry'.


Assuntos
Alcoolismo/diagnóstico , Transtornos Mentais/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Alcoolismo/fisiopatologia , Alcoolismo/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Transtornos Mentais/fisiopatologia , Transtornos Mentais/terapia , Saúde Pública , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/terapia
8.
PLoS Genet ; 15(5): e1007834, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31107875

RESUMO

Illicit use of psychostimulants, such as cocaine and methamphetamine, constitutes a significant public health problem. Whereas neural mechanisms that mediate the effects of these drugs are well-characterized, genetic factors that account for individual variation in susceptibility to substance abuse and addiction remain largely unknown. Drosophila melanogaster can serve as a translational model for studies on substance abuse, since flies have a dopamine transporter that can bind cocaine and methamphetamine, and exposure to these compounds elicits effects similar to those observed in people, suggesting conserved evolutionary mechanisms underlying drug responses. Here, we used the D. melanogaster Genetic Reference Panel to investigate the genetic basis for variation in psychostimulant drug consumption, to determine whether similar or distinct genetic networks underlie variation in consumption of cocaine and methamphetamine, and to assess the extent of sexual dimorphism and effect of genetic context on variation in voluntary drug consumption. Quantification of natural genetic variation in voluntary consumption, preference, and change in consumption and preference over time for cocaine and methamphetamine uncovered significant genetic variation for all traits, including sex-, exposure- and drug-specific genetic variation. Genome wide association analyses identified both shared and drug-specific candidate genes, which could be integrated in genetic interaction networks. We assessed the effects of ubiquitous RNA interference (RNAi) on consumption behaviors for 34 candidate genes: all affected at least one behavior. Finally, we utilized RNAi knockdown in the nervous system to implicate dopaminergic neurons and the mushroom bodies as part of the neural circuitry underlying experience-dependent development of drug preference.


Assuntos
Estimulantes do Sistema Nervoso Central/metabolismo , Cocaína/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Genoma de Inseto , Metanfetamina/metabolismo , Transtornos Relacionados ao Uso de Substâncias/genética , Animais , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/metabolismo , Comportamento Alimentar , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Masculino , Corpos Pedunculados/metabolismo , Corpos Pedunculados/fisiopatologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Caracteres Sexuais , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
9.
Genes Brain Behav ; 18(6): e12580, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31099175

RESUMO

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk.


Assuntos
Afro-Americanos/genética , Grupo com Ancestrais do Continente Europeu/genética , Polimorfismo de Nucleotídeo Único , Transtornos Relacionados ao Uso de Substâncias/genética , Estriado Ventral/fisiopatologia , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 3/genética , Loci Gênicos , Humanos , Fenótipo , Recompensa , Transtornos Relacionados ao Uso de Substâncias/etnologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
10.
Eur Addict Res ; 25(4): 173-181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30999293

RESUMO

BACKGROUND: Gamma-hydroxybutyric acid (GHB) is a drug of abuse associated with increased emergency room attendances, due to GHB-induced comas. Withdrawal from GHB often increases social anxiety and is linked to alterations in emotion processing. However, little is known about the effects of GHB-use and GHB-induced comas on affect regulation in humans. OBJECTIVES: We aimed to assess the effect of GHB-use and GHB-induced comas on the affective network. METHOD: We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed self-report questionnaires assessing negative affect (depression, anxiety and stress) and performed an emotional face matching task during functional magnetic resonance imaging to probe activity of the amygdala and the hippocampus. RESULTS: The GHB-Coma group reported higher levels of depression, anxiety, and stress; showed decreased activity of the hippocampus; and increased functional connectivity of the left hippocampus with the left fusiform gyrus and a cluster on the left temporal-parietal-occipital junction, when compared with the 2 other groups. The GHB-NoComa group showed decreased functional connectivity of the left hippocampus with the amygdala in comparison with the No-GHB group. CONCLUSIONS: GHB-use but in particular GHB-induced comas, are associated with altered emotion identification and hippocampal functioning. Awareness campaigns are required to raise consciousness about the adverse effects of GHB-induced comas on affect regulation, despite the absence of subjective side effects.


Assuntos
Sintomas Afetivos , Coma/etiologia , Emoções , Hidroxibutiratos/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Hipocampo/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Países Baixos , Autorrelato , Inquéritos e Questionários
11.
Trends Psychiatry Psychother ; 41(1): 87-93, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30994781

RESUMO

INTRODUCTION: Emotional intelligence (EI) has been defined as the ability to perceive, understand, use and manage emotions. Studying EI could potentially be useful in understanding addictive behaviors as well as for designing and planning interventions. OBJECTIVES: To conduct a critical review on EI impairment in addiction disorders. METHODS: MEDLINE/PubMed, Google Scholar, Cochrane, LILACS, and SciELO databases were searched. Articles that used the standardized Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) instrument to assess EI in people with addictions and healthy controls were selected for the review. RESULTS: We selected seven articles assessing EI and its associations with addiction disorders, mainly alcohol abuse and cocaine dependence. Most studies reported that individuals with addiction disorders had worse EI scores when compared to controls. CONCLUSION: Overall, the studies reviewed demonstrated that addictions are associated with EI deficits, compared to controls. However, aspects such as the small number of addictive disorders analyzed, methodological issues related to instruments for assessment of IE and the lack of follow-up remain significant limitations.


Assuntos
Comportamento Aditivo/fisiopatologia , Inteligência Emocional/fisiologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Humanos
12.
J Abnorm Psychol ; 128(6): 585-595, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30985173

RESUMO

Diagnostic comorbidity is common among psychiatric patients. One approach to obtain an improved understanding of this phenomenon is to explore diagnostic transitions, across time. In the present study, we aim to take this methodology further within the specific context of eating disorders by investigating whether there are individuals who shift not only between different eating disorder symptoms, but also shift to deliberate self-harm and substance use over time, and relations of this to other indicators of mental illness. Retrospective longitudinal registry data from the Swedish Stepwise national quality assurance platform for eating disorders were analyzed, including self-report measurements and clinical assessments. Individuals (N = 3,159 adults) were selected for analysis based on available data at admission and 12 months postadmission, and grouped based on occurrence of a "symptom shift" (defined as a decrease in one symptom and increase in another over time). In this sample of patients, 422 (13%) demonstrated symptom shifting among eating disorder symptoms. As hypothesized, "symptom shifters" were more prone to engage in deliberate self-harm and shifted to both deliberate self-harm and substance use across time. They had higher reported levels of symptoms indicative of mental illness (e.g., anxiety and compulsivity) and more pronounced functional impairment (clinician rated and self-rated), compared to nonshifters. Taken together, this study demonstrates that a subgroup of individuals diagnosed with eating disorder(s) shift between distinct psychiatric symptoms across time, indicating that they may share a common vulnerability to engaging in problem behaviors and a need for a more comprehensive and individualized treatment plan. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Sistema de Registros , Comportamento Autodestrutivo/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Comportamento Autodestrutivo/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Suécia/epidemiologia
13.
Neuron ; 102(1): 48-59, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30946825

RESUMO

Addiction is a disease in which, after a period of recreational use, a subset of individuals develops compulsive use that does not stop even in light of major negative consequences. Here, we review the evidence for underlying epigenetic remodeling in brain in two settings. First, excessive dopamine signaling during drug use may modulate gene expression, altering synaptic function and circuit activity and leading over time to maladaptive behaviors in vulnerable individuals. Second, on a longer timescale, life experience can shape the epigenetic landscape in brain and thereby may contribute to an individual's vulnerability by amplifying drug-induced changes in gene expression that drive the transition to addiction. We conclude by exploring how epigenetic mechanisms might serve as therapeutic targets for addiction treatments.


Assuntos
Encéfalo/metabolismo , Epigênese Genética/genética , Plasticidade Neuronal/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Sinapses/genética , Transmissão Sináptica/genética , Animais , Variação Biológica Individual , Encéfalo/fisiopatologia , Cromatina/metabolismo , Humanos , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Sinapses/metabolismo
14.
Genes Brain Behav ; 18(6): e12577, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31012252

RESUMO

The National Institute on Drug Abuse Genetics and Epigenetics Cross-Cutting Research Team convened a diverse group of researchers, clinicians, and healthcare providers on the campus of the University of California, San Diego, in June 2018. The goal was to develop strategies to integrate genetics and phenotypes across species to achieve a better understanding of substance use disorders through associations between genotypes and addictive behaviors. This conference (a) discussed progress in harmonizing large opioid genetics cohorts, (b) discussed phenotypes that are used for genetics studies in humans, (c) examined phenotypes that are used for genetics studies in animal models, (d) identified synergies and gaps in phenotypic analyses of human and animal models and (e) identified strategies to integrate genetics and genomics data with phenotypes across species. The meeting consisted of panels that focused on phenotype harmonization (Dr. Laura Bierut, Dr. Olivier George, Dr. Dan Larach and Dr. Sesh Mudumbai), translating genetic findings between species (Dr. Elissa Chesler, Dr. Gary Peltz and Dr. Abraham Palmer), interpreting and understanding allelic variations (Dr. Vanessa Troiani and Dr. Tamara Richards) and pathway conservation in animal models and human studies (Dr. Robert Hitzemann, Dr. Huda Akil and Dr. Laura Saba). There were also updates that were provided by large consortia (Dr. Susan Tapert, Dr. Danielle Dick, Dr. Howard Edenberg and Dr. Eric Johnson). Collectively, the conference was convened to discuss progress and changes in genome-wide association studies.


Assuntos
Conferências de Consenso como Assunto , Modelos Animais de Doenças , Genômica/métodos , National Institute on Drug Abuse (U.S.) , Transtornos Relacionados ao Uso de Substâncias/genética , Pesquisa Médica Translacional/métodos , Animais , Genômica/normas , Humanos , Guias de Prática Clínica como Assunto , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Pesquisa Médica Translacional/normas , Estados Unidos
15.
Br J Radiol ; 92(1101): 20180942, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30855982

RESUMO

Substance use disorder is a leading causes of preventable disease and mortality. Drugs of abuse cause molecular and cellular changes in specific brain regions and these neuroplastic changes are thought to play a role in the transition to uncontrolled drug use. Neuroimaging has identified neural substrates associated with problematic substance use and may offer clues to reduce its burden on the patient and society. Here, we provide a narrative review of neuroimaging studies that have examined the structures and circuits associated with reward, cues and craving, learning, and cognitive control in substance use disorders. Most studies use advanced MRI or positron emission tomography (PET). Many studies have focused on the dopamine neurons of the ventral tegmental area, and the regions where these neurons terminate, such as the striatum and prefrontal cortex. Decreases in dopamine receptors and transmission have been found in chronic users of drugs, alcohol, and nicotine. Recent studies also show evidence of differences in structure and function in substance users relative to controls in brain regions involved in salience evaluation, such as the insula and anterior cingulate cortex. Balancing between reward-related bottom-up and cognitive-control-related top-down processes is discussed in the context of neuromodulation as a potential treatment. Finally, some of the challenges for understanding substance use disorder using neuroimaging methods are discussed.


Assuntos
Cognição/fisiologia , Fissura/fisiologia , Aprendizagem/fisiologia , Neuroimagem/métodos , Recompensa , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Sinais (Psicologia) , Humanos , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
17.
J Addict Nurs ; 30(1): 40-48, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829999

RESUMO

Drug abuse adversely affects the health of populations in many counties and contributes immensely to social issues. Schedule III and IV controlled drug abuse is popular in young adults. Medical education is one of the most stressful academic fields for students. The aim of this study was to compare the health differences in body, mind, and spirit among Schedule III and IV controlled drugs users, nursing students, and psychology students. This study uses a cross-sectional comparative study on a convenience sample. Four hundred eleven participants were recruited from three different samples that include Schedule III and IV controlled drug users (n = 211), nursing students (n = 100), and psychology students (n = 100), all from either a drug abuse prevention center or two universities in Southern Taiwan. Relying on the Health of Body, Mind and Spirit Scale, a linear regression model was used to identify the health differences among drug users, nursing students, and psychology students. The results show that drug users scored higher on the physical subscale (ß = -.249, p < .001), the mental subscale (ß = -.120, p < .05), the spiritual subscale (ß = -.154, p < .01), and the Health of Body, Mind and Spirit Scale (ß = -.210, p < .001) than psychology students. The nursing students scored higher on the mental subscale (ß = .146, p < .01) than drug users did. These results could help health staff and instructors understand the differences and improve the physical, mental, and spiritual health among Schedule III and IV controlled drug users, nursing students, and psychology students. Furthermore, future study could further investigate the factors that may affect physical, mental, and spiritual health.


Assuntos
Usuários de Drogas/psicologia , Saúde Mental , Estudantes de Medicina/psicologia , Estudantes de Enfermagem/psicologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Substâncias Controladas , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Autoimagem , Inquéritos e Questionários , Taiwan , Universidades , Adulto Jovem
18.
J Biomed Sci ; 26(1): 21, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782159

RESUMO

BACKGROUND: The most important limitations of morphine in pain therapy are its tolerance and dependence. In this study, we evaluated the protective effect of glucosamine against morphine-induced tolerance and dependence in mice. METHODS: Mice received twice daily morphine (20 mg/kg, s.c.) alone, or along with orally administered glucosamine (500, 1000 and 2000 mg/kg), for 9 continuous days. To assess antinociceptive effect of morphine, percentage of maximal possible effect (%MPE) of animals exposed to thermal stimulus was measured in the hot plate test, 30 min after morphine administration. Test was performed on days 1, 3, 5, 7 and 9. The effect of glucosamine on the naloxone (5 mg/kg, i.p.)-precipitated morphine withdrawal, was also evaluated. Changes in brain gene expression levels of induced nitric oxide synthase (iNOS), enzyme responsible for nitric oxide generation, as well as pro-inflammatory mediator, tumor necrosis alpha (TNF-α) were measured in morphine tolerated animals, as well as after withdrawal by real-time polymerase chain reaction (RT-PCR). Protein content of TNF-α was evaluated via ELISA assay. RESULTS: Tolerance to antinociceptive effect of morphine was developed after 7 days of morphine treatment. The concurrent administration of glucosamine (500, 1000 and 2000 mg/kg) with morphine, significantly inhibited tolerance development, on days 7 and 9. In addition, glucosamine ameliorated the naloxone-precipitated opioid withdrawal symptoms (tremor, jumping, teeth chattering, grooming). However, diarrhea was significantly improved only with the dose of 500 mg/kg. Increased mRNA expression of iNOS as well as TNF-α mRNA expression and protein, after both morphine tolerance and withdrawal, were considerably reduced by glucosamine (1000 mg/kg) in the morphine withdrawal animals. CONCLUSION: These data support the utility of glucosamine in attenuating both tolerance to nociceptive effects of morphine as well as withdrawal-induced behavioral profile. Anti-oxidant and anti-inflammatory effects are responsible, at least in part, for the protective effects of this drug.


Assuntos
Tolerância a Medicamentos , Glucosamina/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Analgésicos/farmacologia , Animais , Ensaio de Imunoadsorção Enzimática , Masculino , Camundongos , Morfina/farmacologia , Óxido Nítrico/genética , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
19.
BMJ Case Rep ; 12(2)2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30737329

RESUMO

A 21-year-old university student studying abroad in the USA presented to the emergency department with double vision, lower extremity weakness with difficulty ambulating and other neuropsychiatric symptoms. MRI of the brain and spinal cord were normal. Vitamin B12 was 78 pg/mL (58 pmol/L, reference 211-911 pg/mL). The patient had been using nitrous oxide capsules used for whipped cream recharging, which she obtained from other students, a few times daily for a month for the purpose of anxiety relief. The patient was not a vegan or vegetarian. The patient was treated with intramuscular vitamin B12 repletion with partial resolution of neurologic symptoms and discharged on vitamin B12 supplementation.


Assuntos
Óxido Nitroso/efeitos adversos , Transtornos Psicóticos/etiologia , Doenças da Medula Espinal/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/complicações , Deficiência de Vitamina B 12/induzido quimicamente , Vitamina B 12/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Diplopia/induzido quimicamente , Aconselhamento Diretivo , Feminino , Humanos , Óxido Nitroso/administração & dosagem , Transtornos Psicóticos/psicologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Adulto Jovem
20.
Genes (Basel) ; 10(2)2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30781888

RESUMO

Post-traumatic stress disorder (PTSD) is an acquired psychiatric disorder with functionally impairing physiological and psychological symptoms following a traumatic exposure. Genetic, epigenetic, and environmental factors act together to determine both an individual's susceptibility to PTSD and its clinical phenotype. In this literature review, we briefly review the candidate genes that have been implicated in the development and severity of the PTSD phenotype. We discuss the importance of the epigenetic regulation of these candidate genes. We review the general epigenetic mechanisms that are currently understood, with examples of each in the PTSD phenotype. Our focus then turns to studies that have examined PTSD in the context of comorbid psychiatric disorders or associated social and behavioral stressors. We examine the epigenetic variation in cases or models of PTSD with comorbid depressive disorders, anxiety disorders, psychotic disorders, and substance use disorders. We reviewed the literature that has explored epigenetic regulation in PTSD in adverse childhood experiences and suicide phenotypes. Finally, we review some of the information available from studies of the transgenerational transmission of epigenetic variation in maternal cases of PTSD. We discuss areas pertinent for future study to further elucidate the complex interactions between epigenetic modifications and this complex psychiatric disorder.


Assuntos
Epigênese Genética , Transtornos Psicóticos/genética , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/fisiopatologia , Comorbidade , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/fisiopatologia , Humanos , Transtornos Psicóticos/fisiopatologia , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Suicídio
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