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1.
Am J Geriatr Psychiatry ; 28(7): 780-783, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32359882
2.
JAMA Netw Open ; 3(3): e200910, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32167568

RESUMO

Importance: Impulsivity during periods of abstinence is a critical symptom of patients who use methamphetamine (MA). Objective: To evaluate changes in impulse inhibition elicited by repetitive transcranial magnetic stimulation (rTMS) in patients with MA addiction. Design, Setting, and Participants: This randomized clinical trial was conducted in Da Lian Shan Addiction Rehabilitation Center, Nanjing, China, from December 1, 2018, to April 20, 2019. Effects of the intervention were examined at 3 time points: after a single session (day 1), 24 hours after 10 repeated sessions (day 11), and at 3 weeks of follow-up (day 31). Men with MA addiction and healthy male control participants were recruited for this study. Data analysis was performed from March 2019 to October 2019. Interventions: Patients who use MA were randomized to undergo sham rTMS (36 patients) and or 1-Hz rTMS (37 patients) to the left prefrontal cortex, receiving daily TMS treatments for 10 consecutive days. Main Outcomes and Measures: The primary outcome was impulse inhibition, which is primarily embodied by accuracy reduction (ie, accuracy cost) from standard to deviant trials in a 2-choice oddball task (80% standard and 20% deviant trials). Result: The study included 73 men with MA addiction (mean [SD] age, 38.49 [7.69] years) and 33 male healthy control participants without MA addiction (mean [SD] age, 35.15 [9.68] years). The mean (SD) duration of abstinence for the men with MA addiction was 9.27 (4.61) months. Compared with the control group, patients with MA addiction exhibited greater impulsivity (accuracy cost, 3.3% vs 6.2%). The single session of 1-Hz rTMS over the left prefrontal cortex significantly increased accuracy from 91.4% to 95.7% (F1,36 = 9.58; P < .001) and reaction time delay from 50 milliseconds to 77 milliseconds (F1,36 = 22.66; P < .001) in deviant trials. These effects were seen consistently after 10 sessions of 1-Hz rTMS treatment (day 11 vs day 1, t26 = 1.59; P = .12), and the behavioral improvement was maintained at least for 3 weeks after treatment (day 31 vs day 1, t26 = 0.26; P = .80). These improvement effects of impulse inhibition were coupled with a reduction in addictive symptoms as measured by cue-induced craving. The pretest accuracy cost was positively correlated with the change in impulse inhibition (r = 0.615; P < .001) and change in craving (r = 0.334; P = .01), suggesting that these 2 behaviors may be modified simultaneously. Conclusions and Relevance: These findings suggest that repeated rTMS sessions have sustained effects on impulse inhibition in patients with MA addiction and provide novel data on impulsivity management strategies for addiction rehabilitation. Trial Registration: ChiCTR-ROC-16008541.


Assuntos
Comportamento Aditivo , Cognição/fisiologia , Metanfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cognição/efeitos dos fármacos , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
3.
Midwifery ; 83: 102641, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32066050

RESUMO

The aim of this study is to explore factors that determine infant removal by Child Protective Services and placement in out of home care, for methamphetamine-using women receiving pregnancy care with Western Australia Women and Newborn Drug and Alcohol Service. METHOD: A prospective cohort study of 112 methamphetamine-using women attending Women and Newborn Drug and Alcohol Service for pregnancy care from 2015 to 2018 was undertaken. Maternal methamphetamine use was assessed during each trimester of pregnancy using a standardised assessment tool. Drug use was by maternal self-report. Involvement of Western Australia's Department for Child Protection and Family Support and removal from maternal care were recorded. Infant development was formally assessed at 12 months with Griffiths Mental Development Scales. The comparison was made between three groups: those women who had no involvement with Child Protection, those for whom Child Protection was involved but the child remained in maternal care and those women who had their infants removed from their care. A comparison between Aboriginal and non-Aboriginal women was also undertaken. RESULTS: Of the 110 infants born to 112 women, 33 (30.3%) of infants were removed from maternal custody after delivery. Overall 60 (53.5%) of women had Child Protection involvement. Aboriginal women were overrepresented in our population 59 (52.7%) and 24 out of the 33 infants were Aboriginal were removed and placed into out of home care. Infants were removed from women with a high level of risk factors associated with MA use including those who were homeless, in prison, unemployed or continued high use of MA, mental health issues. Aboriginal infants were at increased risk of removal. Children removed from maternal care had a trend towards poorer developmental attainment at around 12 months compared to those who remained with their mother. Infants who were removed by the Child protection had lower general quotients (p = 0.132) than infants who had no involvement or some involvement. CONCLUSION: Infants removed from maternal care were more likely to be from women with high use, adverse social factors and born to mothers who identified as being Aboriginal. Resources are required that work intensively with families to reduce the number of infants being removed from maternal care to overcome the risks and challenges of addiction. IMPLICATIONS FOR PRACTICE: Resources that provide long term support and community-based models that offer a comprehensive range of maternal-child services and in-home-support would be more effective in keeping families together.


Assuntos
Serviços de Proteção Infantil/estatística & dados numéricos , Metanfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Serviços de Proteção Infantil/métodos , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Metanfetamina/farmacologia , Gravidez , Estudos Prospectivos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos , Austrália Ocidental
4.
BMC Palliat Care ; 19(1): 8, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937289

RESUMO

BACKGROUND: There is little information about how healthcare professionals feel about providing palliative care for patients with a substance use disorder (SUD). Therefore, this study aims to explore: 1) the problems and needs experienced by healthcare professionals, volunteers and experts-by-experience (HCP/VE) during their work with patients with SUD in a palliative care trajectory and; 2) to make suggestions for improvements using the quality of care model by Donabedian (Structure, Process, Outcome). METHODS: A qualitative study was conducted, consisting of six focus group interviews which consisted of HCP/VE working with patients with SUD in a palliative care phase. At the end of the focus group interviews, participants structured and summarized their experiences within a Strengths, Weaknesses, Opportunities and Threats (SWOT) framework. Interview transcripts (other than the SWOT) were analysed by the researchers following procedures from the Grounded Theory Approach ('Grounded Theory Lite'). SWOT-findings were not subjected to in-depth analysis. RESULTS: HCP/VE stated that within the Structure of care, care networks are fragmented and HCP/VE often lack knowledge about patients' multiplicity of problems and the time to unravel these. Communication with this patient group appears limited. The actual care-giving Process requires HCP/VE a lot of creativity and time spent seeking for cooperation with other caregivers and appropriate care settings. The latter is often hindered by stigma. Since no formalized knowledge is available, care-delivery is often exclusively experience-based. Pain-medication is often ineffective due to active substance use. Finally, several Outcomes were brought forward: Firstly, a palliative care phase is often identified only at a late stage. Secondly, education and a (mobile) team of expertise are desired. Thirdly, care for the caregivers themselves is often de-prioritized. CONCLUSIONS: Better integration and collaboration between the different professionals with extensive experience in addiction, palliative and general curative care is imperative to assure good palliative care for patients with SUD. Currently, the resources for this care appear to be insufficient. Development of an educational program and social mapping may be the first steps in improving palliative care for patients with severe SUD.


Assuntos
Pessoal de Saúde/psicologia , Cuidados Paliativos/métodos , Transtornos Relacionados ao Uso de Substâncias/complicações , Medicina do Vício , Adulto , Idoso , Atitude do Pessoal de Saúde , Feminino , Grupos Focais/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/tendências , Pesquisa Qualitativa , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Voluntários/psicologia
5.
Psychopharmacology (Berl) ; 237(4): 1183-1194, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31927603

RESUMO

RATIONALE: In order to understand mechanisms underlying tolerance and dependence following chronic benzodiazepine treatments, quantitative and reproducible behavioral models of these phenomena are required. OBJECTIVES: This research evaluated the ability of chronic treatment with a commonly prescribed benzodiazepine, alprazolam, to induce tolerance to sedative effects and physical dependence using a novel set of behavioral measurements in rhesus monkeys. METHODS: Four female rhesus monkeys (Macaca mulatta) were implanted with chronic intravenous catheters and administered i.v. alprazolam (1.0 mg/kg every 4 h, 38 days total). Quantitative observation measures were obtained during the 38 days of treatment. Acute administration of the benzodiazepine receptor antagonist flumazenil (0.1, 0.3 mg/kg, i.v.) was given to assess precipitated withdrawal. On day 39, saline was substituted for alprazolam and withdrawal signs were assessed for 7 days. RESULTS: Maximal sedation ("deep sedation") was evident on day 1 but was not significantly different from baseline levels by day 4 and was absent for the remainder of the 38 days of treatment. A milder form of sedation, "rest/sleep posture," emerged by day 3 and did not decline over 38 days. Cessation of alprazolam treatment resulted in significant withdrawal signs (nose rub, vomit, procumbent posture, tremor/jerk, rigid posture) that dissipated by day 3. These signs also were observed with flumazenil (0.3 mg/kg). CONCLUSIONS: Chronic alprazolam treatment resulted in rapid tolerance to some behaviors (e.g., deep sedation) but no tolerance to others (e.g., rest/sleep posture). Physical dependence was observed via both spontaneous and precipitated withdrawal. Based on previous research, these phenomena may reflect differential plasticity at GABAA receptor subtypes.


Assuntos
Alprazolam/administração & dosagem , Tolerância a Medicamentos/fisiologia , Hipnóticos e Sedativos/administração & dosagem , Síndrome de Abstinência a Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Animais , Feminino , Infusões Intravenosas , Macaca mulatta , Masculino , Síndrome de Abstinência a Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
6.
Brain Cogn ; 138: 105495, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31877434

RESUMO

In this paper we show how addiction can be thought of as the outcome of learning. We look to the increasingly influential predictive processing theory for an account of how learning can go wrong in addiction. Perhaps counter intuitively, it is a consequence of this predictive processing perspective on addiction that while the brain plays a deep and important role in leading a person into addiction, it cannot be the whole story. We'll argue that predictive processing implies a view of addiction not as a brain disease, but rather as a breakdown in the dynamics of the wider agent-environment system. The environment becomes meaningfully organised around the agent's drug-seeking and using behaviours. Our account of addiction offers a new perspective on what is harmful about addiction. Philosophers often characterise addiction as a mental illness because addicts irrationally shift in their judgement of how they should act based on cues that predict drug use. We argue that predictive processing leads to a different view of what can go wrong in addiction. We suggest that addiction can prove harmful to the person because as their addiction progressively takes hold, the addict comes to embody a predictive model of the environment that fails to adequately attune them to a volatile, dynamic environment. The use of an addictive substance produces illusory feedback of being well-attuned to the environment when the reality is the opposite. This can be comforting for a person inhabiting a hostile niche, but it can also prove to be harmful to the person as they become skilled at living the life of an addict, to the neglect of all other alternatives. The harm in addiction we'll argue is not to be found in the brains of addicts, but in their way of life.


Assuntos
Comportamento Aditivo/fisiopatologia , Teoria Psicológica , Recompensa , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Humanos
7.
BMJ Case Rep ; 12(12)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31826904

RESUMO

Involuntary movements can be a troublesome condition and represent a real challenge for emergency doctors, particularly for patients of paediatric age. We report a case of a 17-year-old boy with painful involuntary movements mostly affecting his mouth and lower limbs, but also the trunk. After reviewing the patient's history, it was revealed that the adolescent had had acute alcohol intoxication with severe acute agitation and therefore was given a single dose of 10 mg intravenous haloperidol. The concealment of the recent event posed serious difficulties in reaching the diagnosis. When the diagnosis of haloperidol-induced acute dystonia was made, 3 mg of intravenous biperiden was promptly administered with complete clinical resolution in 15 min.


Assuntos
Intoxicação Alcoólica/sangue , Antipsicóticos/uso terapêutico , Distonia/induzido quimicamente , Haloperidol/efeitos adversos , Agitação Psicomotora/etiologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Adolescente , Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/fisiopatologia , Biperideno/uso terapêutico , Distonia/tratamento farmacológico , Distonia/fisiopatologia , Serviço Hospitalar de Emergência , Feminino , Haloperidol/uso terapêutico , Humanos , Parassimpatolíticos/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Resultado do Tratamento
9.
Medicina (Kaunas) ; 55(12)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31756995

RESUMO

Background and objectives: The perfusion index (PI) indicates the ratio of pulsatile blood flow in peripheral tissue to non-pulsatile blood flow. This study was performed to examine the blood perfusion status of tissues and organs of patients using synthetic cannabinoids (SCs). Materials and Methods: The records of patients aged 17 or over presenting to the adult emergency department due to SC use between 1 January 2016 and 31 December 2017 were examined in this single-center, retrospective, cross-sectional study. Examined factors included time from consumption of SC to presentation to the emergency department, as well as simultaneously determined systolic and diastolic blood pressures, heart rate (beats per min), Glasgow Coma Score (GCS), and PI values. Patients were divided into two groups, A and B, depending on the amount of time that had elapsed between SC consumption and presentation to the emergency department, and statistical data were compared. Results: The mean PI value in Group A was lower than that in Group B. Therefore, we concluded that peripheral tissue and organ blood perfusion is lower in the first 2 h following SC consumption than after 2 h. Systolic, diastolic, and mean arterial blood pressure and mean GCS values were also statistically significantly lower in Group A than in Group B. Conclusions: A decreased PI value may be an early sign of reduced-perfusion organ damage. PI is a practical and useful parameter in the early diagnosis of impaired organ perfusion and in monitoring tissue hypoxia leading to organ failure.


Assuntos
Canabinoides/efeitos adversos , Índice de Perfusão , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adolescente , Adulto , Idoso , Pressão Sanguínea/fisiologia , Estudos Transversais , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Pulsátil/fisiologia , Estudos Retrospectivos
10.
Neurol India ; 67(5): 1220-1224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31744946

RESUMO

Addiction is a major cause of mortality and morbidity. Apart from psychotropic substances, alcohol and nicotine remain the common addictive materials responsible for the majority of deaths. Conventional conservative therapies are beneficial to certain populations, but the majority may require interventional treatments such as deep brain stimulation (DBS) in view of increasing mortality from drug abuse in recent years. We present a brief review on a novel neuromodulation target of the nucleus accumbens (NA) and its promising role in the management of addiction. The three stages of the addiction cycle are known to be mediated by dopaminergic pathways located in the mesolimbic dopamine system with connections to dorsal striatum, extended amygdala, cingulate gyrus, orbitofrontal cortex, prefrontal cortex, and ventral tegmental area. Recent advanced neuroimaging in humans and several animal studies demonstrated NA to be a vital anatomical area modulating this network. DBS of NA in animals reduced addictive behavior to alcohol, cocaine, and other narcotics significantly. The accidental observation that DBS of NA for psychiatric illnesses induced relief from addiction to alcohol and smoking has encouraged further research of late. Bilateral NA ablative surgery had shown nonrelapse in more than 50% of cases. Small series of patients have benefited so far from DBS of NA, but larger numbers are required to provide evidence-based treatment. The modulation of dopaminergic pathways through DBS of NA as a valid treatment for addiction is substantiated extensively by animal studies and also in a few clinical studies. However, this needs to be validated by a well-structured, multicenter controlled study in a large group of patients suffering from substance abuse.


Assuntos
Estimulação Encefálica Profunda/métodos , Núcleo Accumbens/fisiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Animais , Humanos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
11.
PLoS One ; 14(11): e0224363, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31697698

RESUMO

This pilot quasi-experimental trial tested a gender-responsive cognitive behavioral group intervention with 87 court-involved female adolescents (5 juvenile courts) who were at indicated risk for substance use disorder. Participants in the intervention (n = 57) received twice weekly group sessions for 10 weeks (20 sessions) focused on building emotional, thought and behavior regulation skills and generalizing these skills to relationally-based scenarios (GOAL: Girls Only Active Learning). Youth in the control condition (n = 30) received services as usual, which included non-gender-specific aggression management training, individual counseling and no services. The GOAL program was found to be acceptable to youth and parents and feasible to implement within a juvenile court setting using skilled facilitators. Compared to services as usual, the program significantly and meaningfully reduced self-reported delinquent behavior (ß = 0.84, p < 0.05) over 6 months, and exhibited trend level effects for reduced substance use (ß = 0.40, p = 0.07). The program had mixed or no effects on family conflict and emotion regulation skills. These findings are discussed in light of treatment mechanisms and gender-responsive services.


Assuntos
Transtorno da Personalidade Antissocial/prevenção & controle , Cognição/fisiologia , Emoções/fisiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Adolescente , Transtorno da Personalidade Antissocial/fisiopatologia , Transtorno da Personalidade Antissocial/psicologia , Comportamento/fisiologia , Criança , Conflito Familiar/psicologia , Feminino , Humanos , Aprendizagem/fisiologia , Projetos Piloto , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
12.
Int Rev Neurobiol ; 147: 269-280, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607357

RESUMO

Exercise intervention has long been used as one adjunctive treatment for drug abuse. Both animal studies and human trials suggest that exercise training effectively prevents addiction formation, suppresses drug-seeking behaviors, and ceases addictions. Moreover, exercise improves both mental and cognitive deficits that commonly occur during drug withdrawal. Those observations are supported by neurobiological studies in which exercise training modulates several neural networks including the dopaminergic reward system, and regulates neurogenesis and spinogenesis that affect cognitive behaviors and mental health. In sum, exercise training is a safe and effective way to relieve substance abuse, although both intervention guideline and biomarkers warrants further investigation.


Assuntos
Encéfalo/fisiologia , Terapia por Exercício/métodos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Humanos
13.
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
14.
Cogn Neuropsychiatry ; 24(6): 421-433, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31554497

RESUMO

Introduction: The objectives were to identify a latent factor of cognitive reserve (CR) assessed by self-rating of cognitively stimulating activities, to analyze the association between this factor and educational attainment, and to test whether CR moderates the association between polysubstance use and neurocognitive disorder (NCD). Methods: Cross-sectional data of 753 participants was collected in Mexico City. A questionnaire for self-rating of stimulating activities (work/education, leisure, physical, social, usual- and current environments) was designed. Confirmatory factor analysis was performed to test unifactoriality. This CR factor was then used within a structural equation model of moderation between recent- and years of substance use and indicators of NCD (Montreal Cognitive Assessment and an interview for subjective cognitive deficits). Results: We found acceptable goodness-of-fit values for the unifactorial model, but no association of this factor with educational attainment, nor with recent- and years of substance use (suggesting independence of CR and severity of neuropathology). We did not find a moderation effect of CR between substance use and indicators of NCD; CR was negatively associated with subjective cognitive deficits only. Conclusions: Moderation effect of self-rated CR should be further tested using direct measures of substance-induced neuropathology. Measurement of self-rated CR may complement self-reported cognitive examination.


Assuntos
Atividades Cotidianas , Reserva Cognitiva/fisiologia , Atividades de Lazer , Transtornos Neurocognitivos/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato
15.
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
16.
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 , Reforço Psicológico , 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
17.
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
18.
Neuroimage ; 200: 313-331, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31229660

RESUMO

Aberrant patterns of brain functional connectivity in the default mode network (DMN) have been observed across different classes of substance use disorder (SUD) and are associated with craving and relapse. In addicted individuals resting functional connectivity (RSFC) of the anterior DMN, which participates in attribution of personal value and emotional regulation, tends to be decreased, whereas RSFC of the posterior DMN, which directs attention to the internal world, tends to be increased. Aberrant RSFC within the DMN is believed to contribute to impaired self-awareness, negative emotions and to ruminations in addiction. Additionally, the disrupted connectivity between DMN and cortical regions involved with executive function, memory and emotion could be critical to drug-taking regardless of negative consequences and to stress-triggered relapse. At the system level, the dynamics of DMN interactions with the executive control and the salience networks are also disturbed in addiction. The DMN is prominently engaged during the withdrawal and preoccupation phases of the addiction cycle at the expense of the executive control network and with an enhanced participation of the salience network. In contrast, DMN prominence appears to be transitorily decreased during the intoxication phases. There is also growing evidence that disruption of the DMN in addiction reflects in part changes in dopaminergic, glutamatergic, and GABAergic signaling associated with acute and chronic drug use. Findings are starting to reveal DMN RSFC as a potential biomarker for predicting clinical outcomes in SUD and identify the DMN as a promising target for the treatment of addiction.


Assuntos
Córtex Cerebral/fisiopatologia , Função Executiva/fisiologia , Rede Nervosa/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Humanos
19.
PLoS One ; 14(6): e0218469, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216319

RESUMO

OBJECTIVE: Although there is evidence that Attention Deficit Hyperactivity Disorder (ADHD) symptoms are positively related to alcohol use and related problems among young adults, little research has examined the mechanisms that might explain this association. In response, this study examined the mediating effects of coping and enhancement drinking motives on the prospective associations between ADHD symptoms and alcohol outcomes. METHOD: Participants (N = 4,536) were young men from the Cohort Study on Substance Use Risk Factors. Measures of ADHD symptoms and those of drinking motives, heavy episodic drinking (HED) and alcohol use disorder symptoms were used from the baseline and 15-month follow-up assessments. RESULTS: Findings indicated that the associations of ADHD-inattention symptoms with alcohol use disorder (AUD) symptoms and with HED were partially and completely mediated through drinking motives, respectively, whereas drinking motives did not mediate the ADHD-hyperactivity/impulsivity-symptoms-alcohol outcomes associations. CONCLUSION: Results indicated that coping and enhancement motives partially explained the ADHD-inattention symptoms-subsequent alcohol outcomes association. These findings suggest that interventions targeting enhancement and coping motives may help prevent problematic drinking among young men with elevated ADHD-inattention symptoms.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Transtornos Relacionados ao Uso de Álcool/complicações , Transtornos Relacionados ao Uso de Álcool/fisiopatologia , Transtorno da Personalidade Antissocial/complicações , Transtorno da Personalidade Antissocial/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Estudos de Coortes , Depressão/complicações , Depressão/epidemiologia , Etanol/efeitos adversos , Humanos , Comportamento Impulsivo/fisiologia , Masculino , Motivação/fisiologia , Estudos Prospectivos , Fatores de Risco , Estudantes , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto Jovem
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