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1.
Am J Drug Alcohol Abuse ; 46(3): 357-367, 2020 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31730369

RESUMO

BACKGROUND: While attentional bias modification therapy (ABMT) alters drug-related behaviors in some substance users, results have been mixed in individuals with cocaine use disorders (CUD). OBJECTIVES: The current study examined whether ABMT affected brain functioning during independent measures of cue reactivity (i.e., cocaine versus food cues) and cognitive control (i.e., incongruent versus congruent trials), and whether brain activity was associated with baseline or post-intervention cocaine use. METHODS: 37 participants (62% male) were randomly assigned to ABMT or control therapy. Clinical and neuroimaging assessments occurred at baseline and immediately post-intervention, with additional clinical testing at 2 weeks and 3 months following intervention. Cocaine use was assessed through self-report. RESULTS: Slower reaction times and increased functional activation (prefrontal cortex, posterior parietal cortex) were observed for incongruent versus congruent stimuli and increased functional activation for cocaine relative to food videos (ventral striatum, dorsolateral prefrontal cortex and orbitofrontal cortex). The default-mode network (DMN) was not deactivated during exposure to cocaine videos. The degree of activation during cocaine relative to food cues was associated with baseline cocaine use (insula only) and reduction in use following treatment (insula and anterior DMN) above and beyond clinical variables. Cognitive control network activity was not associated with cocaine use at baseline or following treatment. ABMT therapy did not differentially affect cocaine use or functional activation during either task. CONCLUSION: Current results suggest a relationship between cue reactivity network activation and cocaine use, but question the efficacy of ABMT in changing brain function during cue reactivity or cognitive control tasks.


Assuntos
Viés de Atenção , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cognição , Sinais (Psicologia) , Tempo de Reação , Adolescente , Adulto , Comportamento Aditivo , Encéfalo/fisiopatologia , Condicionamento Psicológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adulto Jovem
2.
Addict Biol ; 23(1): 412-424, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28231626

RESUMO

Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke - Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, ß = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD.


Assuntos
Encéfalo/diagnóstico por imagem , Fumar Cigarros/tratamento farmacológico , Sinais (Psicologia) , Alimentos , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Tabagismo/diagnóstico por imagem , Vareniclina/uso terapêutico , Adolescente , Adulto , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Abandono do Hábito de Fumar , Tabagismo/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
3.
Am J Drug Alcohol Abuse ; 44(1): 103-112, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27892692

RESUMO

BACKGROUND: Depression may contribute to increased drinking in individuals with alcohol use disorder. Although Alcoholics Anonymous (AA) attendance predicts drinking reductions, there is conflicting information regarding the intermediary role played by reductions in depression. OBJECTIVES: We explored whether AA attendance reduces depressive symptoms, the degree to which improvement in depression results in reductions in drinking, and in which subgroups these effects occur. METHODS: 253 early AA affiliates (63% male) were recruited and assessed at baseline 3, 6, 9, 12, 18, and 24 months. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18, and 24 months. AA attendance and alcohol use outcomes were obtained with the Form 90. Mediation analyses were performed at early (3, 6, and 9 months) and late (12, 18, and 24 months) follow-up to investigate the degree to which reductions in depression mediated the effect of AA attendance on drinking, controlling for concurrent drinking. In addition, a series of moderated mediation analyses were performed using baseline depression severity as a moderator. RESULTS: At early follow-up, reductions in depression (6 months) mediated the effects of AA attendance (3 months) on later drinking (drinks per drinking day) (9 months) (b = -0.02, boot CI [-0.055, -0.0004]), controlling for drinking at 6 months. Baseline depression severity did not moderate the degree to which BDI mediated the effects of AA attendance on alcohol use (ps > .05). CONCLUSION: These findings provide further evidence that depression reduction is a mechanism by which AA attendance leads to reductions in alcohol use. Improving depression may help reduce alcohol use in individuals with AUD, and AA attendance may be an effective way to achieve that goal.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Alcoólicos Anônimos , Alcoolismo/psicologia , Depressão/psicologia , Cooperação do Paciente , Adulto , Alcoolismo/complicações , Depressão/complicações , Feminino , Seguimentos , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
4.
Am J Drug Alcohol Abuse ; 42(5): 490-499, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27184605

RESUMO

BACKGROUND: Anxiety is common among persons with alcohol use disorder during early abstinence from alcohol. Although benzodiazepines are effective for short-term treatment of anxiety, they are rarely used beyond acute detoxification due to concerns about misuse or interactions with alcohol. OBJECTIVES: We conducted an open-label trial to explore the effects of coadministering lorazepam and disulfiram to alcohol-dependent patients with anxiety disorder symptoms. The rationale for this model is to minimize the risks of the benzodiazepine, while also potentially enhancing adherence to disulfiram. METHODS: Forty-one participants with DSM-IV alcohol dependence who also met syndromal criteria for anxiety disorder with or without co-occurring major depressive syndrome initiated treatment with lorazepam (starting dose 0.5 mg three times daily) and disulfiram (starting dose 500 mg three times weekly). Participants received 16 weeks of monitored pharmacotherapy with manualized medical management. RESULTS: Adherence to treatment decreased steadily with time (85.4% at 4 weeks, 36.6% at 16 weeks). Participants showed significant increases in percent abstinent days during treatment and at 24 weeks follow-up. Large reductions in anxiety, depression, and craving were observed during treatment, and improvement remained significant at 24 weeks. Duration of adherence with disulfiram strongly predicted abstinence at 16 weeks. There was no evidence of misuse of lorazepam or dose escalation during the study. CONCLUSION: Lorazepam can be safely used for short-term treatment of anxiety in combination with disulfiram treatment of alcohol use disorder. However, it is not clear that making lorazepam dispensing contingent on adherence to disulfiram enhances retention in disulfiram treatment.


Assuntos
Alcoolismo/tratamento farmacológico , Transtornos de Ansiedade/tratamento farmacológico , Dissulfiram/uso terapêutico , Lorazepam/uso terapêutico , Adulto , Alcoolismo/complicações , Fissura/efeitos dos fármacos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Dissulfiram/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Lorazepam/efeitos adversos , Masculino , Adesão à Medicação/estatística & dados numéricos , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
5.
Am J Drug Alcohol Abuse ; 42(4): 459-68, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27184297

RESUMO

BACKGROUND: Attentional bias (i.e., differences in reaction time between drug and neutral cues) has been associated with a variety of drug-use behaviors (e.g., craving, abstinence). Reduction of bias may ultimately reduce use. OBJECTIVE: The current study examined whether attentional bias modification therapy (ABMT) reduced the frequency of drug use behaviors in individuals with cocaine use disorder (CUD). METHOD: Participants (n = 37) were randomly assigned to ABMT or control therapy, which systematically varied how frequently probes replaced neutral (ABMT = 100%; control therapy = 50%) relative to drug stimuli. Each intervention included 5 training sessions comprising a total of 2640 trials over 4 weeks. Clinical assessments occurred at baseline, post-intervention, 2 weeks and 3 months posttreatment. RESULTS: There were no baseline differences between groups on drug-use behaviors or other clinical measures. Contrary to predictions, both groups exhibited slower rather than faster reaction times for cocaine stimuli (p = 0.005) at baseline, with no relationship between bias and baseline measures of drug-use behavior. CONCLUSIONS: ABMT was not more effective than our control therapy at reducing attentional bias, reducing craving or changing other drug use behaviors. Current results suggest additional replication studies are needed to assess ABMT's efficacy in reducing drug-use behaviors in CUD.


Assuntos
Viés de Atenção , Terapia Comportamental , Transtornos Relacionados ao Uso de Cocaína/terapia , Adulto , Comportamento Aditivo/terapia , Feminino , Humanos , Masculino , Tempo de Reação , Adulto Jovem
6.
Pain Med ; 16(11): 2121-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25989475

RESUMO

OBJECTIVE: Previous work suggests that the perception of pain is subjective and dependent on individual differences in physiological, emotional, and cognitive states. Functional magnetic resonance imaging (FMRI) studies have used both stimulus-related (nociceptive properties) and percept-related (subjective experience of pain) models to identify the brain networks associated with pain. Our objective was to identify the network involved in processing subjective pain during cold stimuli. METHODS: The current FMRI study directly contrasted a stimulus-related model with a percept-related model during blocks of cold pain stimuli in healthy adults. Specifically, neuronal activation was modelled as a function of changes in stimulus intensity vs as a function of increasing/decreasing levels of subjective pain corresponding to changes in pain ratings. In addition, functional connectivity analyses were conducted to examine intrinsic correlations between three proposed subnetworks (sensory/discriminative, affective/motivational, and cognitive/evaluative) involved in pain processing. RESULTS: The percept-related model captured more extensive activation than the stimulus-related model and demonstrated an association between higher subjective pain and activation in expected cortical (dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, insula, dorsal anterior cingulate cortex [dACC] extending into pre-supplementary motor area) and subcortical (thalamus, striatum) areas. Moreover, connectivity results supported the posited roles of dACC and insula as key relay sites during neural processing of subjective pain. In particular, anterior insula appeared to link sensory/discriminative regions with regions in the other subnetworks, and dACC appeared to serve as a hub for affective/motivational, cognitive/evaluative, and motor subnetworks. CONCLUSIONS: Using a percept-related model, brain regions involved in the processing of subjective pain during the application of cold stimuli were identified. Connectivity analyses identified linkages between key subnetworks involved in processing subjective pain.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Imageamento por Ressonância Magnética , Dor/fisiopatologia , Tálamo/fisiopatologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto Jovem
7.
Subst Use Misuse ; 50(1): 40-52, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25290463

RESUMO

Individuals with alcohol use disorders (AUDs) have deficits in cognitive control, but how they change with treatment is unclear. Seven patients with AUD and anxiety from an open-label trial of disulfiram plus lorazepam performed a multisensory Stroop task during fMRI (both pre and post initiation of treatment), and were compared to nine healthy controls (HCs) (n = 16; Albuquerque, NM; years 2009-2012). Evoked BOLD signal and resting state functional connectivity were compared (HC vs. AUD; Scan 1 vs. Scan 2). AUD demonstrated hyperactivity and altered connectivity in the cognitive control network compared to HC, but treatment did not normalize function.


Assuntos
Alcoolismo/tratamento farmacológico , Ansiolíticos/uso terapêutico , Cognição/efeitos dos fármacos , Lorazepam/uso terapêutico , Adulto , Alcoolismo/psicologia , Atenção/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/efeitos dos fármacos , Teste de Stroop
8.
Rev Neurosci ; 25(1): 1-24, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24361772

RESUMO

Cognitive control refers to the internal representation, maintenance, and updating of context information in the service of exerting control over thoughts and behavior. Deficits in cognitive control likely contribute to difficulty in maintaining abstinence in individuals with alcohol use disorders (AUD). In this article, we define three cognitive control processes in detail (response inhibition, distractor interference control, and working memory), review the tasks measuring performance in these areas, and summarize the brain networks involved in carrying out these processes. Next, we review evidence of deficits in these processes in AUD, including both metrics of task performance and functional neuroimaging. Finally, we explore the clinical relevance of these deficits by identifying predictors of clinical outcome and markers that appear to change (improve) with treatment. We observe that individuals with AUD experience deficits in some, but not all, metrics of cognitive control. Deficits in cognitive control may predict clinical outcome in AUD, but more work is necessary to replicate findings. It is likely that performance on tasks requiring cognitive control improves with abstinence, and with some psychosocial and medication treatments. Future work should clarify which aspects of cognitive control are most important to target during treatment of AUD.


Assuntos
Alcoolismo/complicações , Transtornos Cognitivos/etiologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Transtornos Cognitivos/patologia , Função Executiva , Humanos , Inibição Psicológica , Memória de Curto Prazo/fisiologia
10.
Am J Drug Alcohol Abuse ; 38(1): 81-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21936751

RESUMO

BACKGROUND: Attrition in studies of substance use disorder treatment is problematic, potentially introducing bias into data analysis. OBJECTIVES: This study aimed to determine the effect of participant compensation amounts on rates of missing data and observed rates of drug use. METHODS: We performed a secondary analysis of a clinical trial of buprenorphine/naloxone among 152 treatment-seeking opioid-dependent subjects aged 15-21 during participation in a randomized trial. Subjects were randomized to a 2-week detoxification with buprenorphine/naloxone (DETOX; N = 78) or 12 weeks buprenorphine/naloxone (BUP; N = 74). Participants were compensated $5 for weekly urine drug screens and self-reported drug use information and $75 for more extensive assessments at weeks 4, 8, and 12. RESULTS: Though BUP assignment decreased the likelihood of missing data, there were significantly less missing data at 4, 8, and 12 weeks than other weeks, and the effect of compensation on the probability of urine screens being positive was more pronounced in DETOX subjects. CONCLUSION: These findings suggest that variations in the amount of compensation for completing assessments can differentially affect outcome measurements, depending on treatment group assignment. SCIENTIFIC SIGNIFICANCE: Adequate financial compensation may minimize bias when treatment condition is associated with differential dropout and may be a cost-effective way to reduce attrition. Moreover, active users may be more likely than non-active users to drop out if compensation is inadequate, especially in control groups or in groups who are not receiving active treatment.


Assuntos
Ensaios Clínicos como Assunto/economia , Transtornos Relacionados ao Uso de Opioides/economia , Remuneração , Sujeitos da Pesquisa/economia , Adolescente , Buprenorfina/uso terapêutico , Análise Custo-Benefício , Coleta de Dados , Feminino , Humanos , Masculino , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/psicologia , Pacientes Desistentes do Tratamento , Projetos de Pesquisa , Sujeitos da Pesquisa/psicologia , Resultado do Tratamento , Adulto Jovem
11.
Hum Brain Mapp ; 32(6): 947-61, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20578173

RESUMO

Age-related deficits have been demonstrated in working memory performance and in the dopamine system thought to support it. We performed positron emission tomography (PET) scans on 12 younger (mean 22.7 years) and 19 older (mean 65.8 years) adults using the radiotracer 6-[(18)F]-fluoro-L-m-tyrosine (FMT), which measures dopamine synthesis capacity. Subjects also underwent functional magnetic resonance imaging (fMRI) while performing a delayed recognition working memory task. We evaluated age-related fMRI activity differences and examined how they related to FMT signal variations in dorsal caudate within each age group. In posterior cingulate cortex and precuneus (PCC/Pc), older adults showed diminished fMRI deactivations during memory recognition compared with younger adults. Greater task-induced deactivation (in younger adults only) was associated both with higher FMT signal and with worse memory performance. Our results suggest that dopamine synthesis helps modulate default network activity in younger adults and that alterations to the dopamine system may contribute to age-related changes in working memory function.


Assuntos
Envelhecimento/fisiologia , Mapeamento Encefálico , Corpo Estriado/diagnóstico por imagem , Dopamina/biossíntese , Memória de Curto Prazo/fisiologia , Idoso , Idoso de 80 Anos ou mais , Corpo Estriado/metabolismo , Radioisótopos de Flúor , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tirosina/análogos & derivados , Adulto Jovem
12.
Brain Imaging Behav ; 14(2): 586-598, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31115861

RESUMO

Impairment in cognitive control in alcohol use disorder (AUD) contributes to difficulty controlling alcohol use and, in many populations, difficulties with emotion regulation. However, the most reliable and robust marker of clinically-relevant deficits in cognitive control in AUD is unclear. Our aims were to measure relationships between BOLD signal during a Stroop task and AUD severity and change in BOLD signal and change in drinking over three weeks. We also aimed to explore the relationships between BOLD signal and subjective negative affect. Thirty-three individuals with AUD underwent a multisensory Stroop task during functional magnetic resonance imaging (fMRI), as well as a battery of neuropsychological tests and self-report assessments of negative affect and AUD severity. Greater activation in temporal gyrus and cerebellum during incongruent trials compared to congruent trials was observed, and percent signal change (incongruent minus congruent) in both clusters was positively correlated with AUD severity and self-reported negative affect. Neuropsychological task performance and self-reported impulsivity were not highly correlated with AUD severity. Hierarchical regression analyses indicated that percent signal change (incongruent minus congruent) in cerebellum was independently associated with negative affect after controlling for recent and chronic drinking. In a subset of individuals (n = 23) reduction in cerebellar percent signal change (incongruent minus congruent) was correlated with increases in percent days abstinent over 3 weeks. BOLD activation during this Stroop task may therefore be an important objective marker of AUD severity and negative affect. The potential importance of the cerebellum in emotion regulation and AUD severity is highlighted.


Assuntos
Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Cognição/fisiologia , Adulto , Afeto/efeitos dos fármacos , Alcoolismo/metabolismo , Encéfalo/fisiopatologia , Cerebelo/fisiopatologia , Feminino , Humanos , Comportamento Impulsivo/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Teste de Stroop
13.
Neuroimage Clin ; 26: 102162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32037283

RESUMO

BACKGROUND: Higher levels of anxiety, negative affect, and impaired emotion regulation are associated with alcohol use disorder (AUD) and contribute to relapse and worse treatment outcomes. Prazosin, while typically used to treat post-traumatic stress disorder (PTSD) and other anxiety disorders, has shown promise for treating AUD. In order to better understand these underlying neural processes in individuals with AUD, our aims in this study were to measure brain activation during an anticipatory anxiety task before treatment to determine whether observed patterns supported previous work. We then aimed to measure the effects of prazosin on patients with AUD and explore whether greater baseline anticipatory anxiety (as measured by subjective and neural measures) predicts better treatment outcomes. METHODS: Thirty-four individuals seeking treatment for AUD participated in a six-week placebo-controlled study of prazosin and underwent an anticipatory anxiety task during fMRI scans at baseline and three weeks. Alcohol use over six weeks was measured. RESULTS: Greater levels of subjective anxiety and deactivation in posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC) were observed during high-threat stimuli compared to low-threat stimuli. Compared to placebo, prazosin reduced subjective anxiety to high-threat stimuli but there were no observed significant effects of prazosin on brain activation during the task. However, AUD patients with greater vmPFC deactivation during high threat relative to low threat and patients with low baseline anticipatory anxiety during the task had worse clinical outcomes on prazosin. CONCLUSIONS: Deactivation in PCC and vmPFC to high-threat stimuli replicated previous work and shows promise for further study as a marker for AUD. Although prazosin did not affect brain activation in the regions of interest during the anticipatory anxiety task, subjective levels of anxiety and brain activation in vmPFC predicted treatment outcomes in individuals with AUD undergoing treatment with prazosin, highlighting individuals more likely to benefit from prazosin than others.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Alcoolismo/tratamento farmacológico , Alcoolismo/fisiopatologia , Antecipação Psicológica/fisiologia , Ansiedade/fisiopatologia , Giro do Cíngulo/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Prazosina/farmacologia , Córtex Pré-Frontal/fisiopatologia , Adolescente , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Adulto , Alcoolismo/diagnóstico por imagem , Antecipação Psicológica/efeitos dos fármacos , Ansiedade/diagnóstico por imagem , Ansiedade/tratamento farmacológico , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prazosina/administração & dosagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Adulto Jovem
14.
J Neurosci ; 28(52): 14320-8, 2008 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-19109513

RESUMO

Past research has demonstrated that performance on frontal lobe-dependent tasks is associated with dopamine system integrity and that various dopamine system deficits occur with aging. The positron emission tomography (PET) radiotracer 6-[(18)F]fluoro-l-m-tyrosine (FMT) is a substrate of the dopamine-synthesizing enzyme, aromatic amino acid decarboxylase (AADC). Studies using 6-[(18)F]fluorodopa (FDOPA) (another AADC substrate) to measure how striatal PET signal and age relate have had inconsistent outcomes. The varying results occur in part from tracer processing that renders FDOPA signal subject to aspects of postrelease metabolism, which may themselves change with aging. In contrast, FMT remains a purer measure of AADC function. We used partial volume-corrected FMT PET scans to measure age-related striatal dopamine synthesis capacity in 21 older (mean, 66.9) and 16 younger (mean, 22.8) healthy adults. We also investigated how striatal FMT signal related to a cognitive measure of frontal lobe function. Older adults showed significantly greater striatal FMT signal than younger adults. Within the older group, FMT signal in dorsal caudate (DCA) and dorsal putamen was greater with age, suggesting compensation for deficits elsewhere in the dopamine system. In younger adults, FMT signal in DCA was lower with age, likely related to ongoing developmental processes. Younger adults who performed worse on tests of frontal lobe function showed greater FMT signal in right DCA, independent of age effects. Our data suggest that higher striatal FMT signal represents nonoptimal dopamine processing. They further support a relationship between striatal dopamine processing and frontal lobe cognitive function.


Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Corpo Estriado/metabolismo , Dopamina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Descarboxilases de Aminoácido-L-Aromático/metabolismo , Corpo Estriado/irrigação sanguínea , Corpo Estriado/diagnóstico por imagem , Di-Hidroxifenilalanina/metabolismo , Feminino , Radioisótopos de Flúor/metabolismo , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Tomografia por Emissão de Pósitrons/métodos , Análise de Regressão , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-29953936

RESUMO

Substance use disorders (SUD) are diseases of the brain, characterized by aberrant functioning in the neural circuitry of the brain. Resting state functional connectivity (rsFC) can illuminate these functional changes by measuring the temporal coherence of low-frequency fluctuations of the blood oxygenation level-dependent magnetic resonance imaging signal in contiguous or non-contiguous regions of the brain. Because this data is easy to obtain and analyze, and therefore fairly inexpensive, it holds promise for defining biological treatment targets in SUD, which could help maximize the efficacy of existing clinical interventions and develop new ones. In an effort to identify the most likely "treatment targets" obtainable with rsFC we summarize existing research in SUD focused on 1) the relationships between rsFC and functionality within important psychological domains which are believed to underlie relapse vulnerability 2) changes in rsFC from satiety to deprived or abstinent states 3) baseline rsFC correlates of treatment outcome and 4) changes in rsFC induced by treatment interventions which improve clinical outcomes and reduce relapse risk. Converging evidence indicates that likely "treatment target" candidates, emerging consistently in all four sections, are reduced connectivity within executive control network (ECN) and between ECN and salience network (SN). Other potential treatment targets also show promise, but the literature is sparse and more research is needed. Future research directions include data-driven prediction analyses and rsFC analyses with longitudinal datasets that incorporate time since last use into analysis to account for drug withdrawal. Once the most reliable biological markers are identified, they can be used for treatment matching, during preliminary testing of new pharmacological compounds to establish clinical potential ("target engagement") prior to carrying out costly clinical trials, and for generating hypotheses for medication repurposing.


Assuntos
Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Descanso , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/terapia , Ensaios Clínicos como Assunto/métodos , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética/tendências , Resultado do Tratamento
16.
J Addict Med ; 12(5): 339-345, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29664896

RESUMO

OBJECTIVES: The noradrenergic system plays an important role in the pathophysiology of alcohol use disorder (AUD). Medications in this class may reduce drinking. Our aims were to investigate this in a unique sample of individuals with AUD. METHODS: Thirty-six individuals with AUD were randomized to treatment with prazosin, an alpha-1 noradrenergic antagonist, or placebo, for 6 weeks (target daily dose 16 mg). Hierarchical linear modeling was used to examine the effect of treatment group on rate of change in primary (drinks per week [DPW]) and several secondary outcome measures. RESULTS: Prazosin did not significantly affect rate of reduction in alcohol use in the intent to treat sample (n = 36) compared with placebo, but did significantly increase the rate of reduction in DPW in an optimal treatment exposure subgroup (beta = -0.3; P = 0.01; event rate ratio 0.74; confidence interval 0.59, 0.93; n = 27). Poor adherence and tolerability may have contributed to null effects. Diastolic blood pressure (DBP) moderated the effects of treatment group on rate of reduction in drinks per drinking day, supporting previous work in doxazosin, another alpha-1 antagonist. Specifically, prazosin was associated with greater rates of reduction in drinking compared with placebo in individuals with high but not low DBP. CONCLUSIONS: Our findings do not support the clinical utility of prazosin for all treatment-seeking AUD, but post hoc analyses indicate that it might have some efficacy in individuals who can tolerate it. Further work exploring the clinical utility of DBP as a treatment matching variable, and defining optimal values using sensitivity and specificity analyses, is warranted.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Alcoolismo/tratamento farmacológico , Prazosina/uso terapêutico , Adulto , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade
17.
Soc Sci Med ; 64(8): 1600-10, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17267087

RESUMO

This qualitative study analyzes the explanatory models employed by parents whose children have been diagnosed with attention deficit hyperactivity disorder (ADHD) and the ways in which these explanatory models change as they seek help for their child's problem. In-depth interviews were conducted with 24 parents recruited from a list of children who had been diagnosed with ADHD at a community-based child development center (CDC) in Goa, India. The most frequent reasons for consulting the CDC were educational difficulties. Despite having received an ADHD diagnosis and reporting significant adverse impact of the child's behavior, most parents were reluctant to accept the biomedical explanatory model or even consider their child's difficulties as an illness. Instead, parents most commonly attributed causality to psychological models, learning and memory difficulties, and to models which emphasized either the volitional or non-volitional nature of the problem, or to attribute blame of self or spouse. Interventions most commonly used were educational and religious; consultation with the CDC was the last resort for many parents. We conclude that cultural attitudes towards mental illness significantly affect parental perception and behavior in response to interventions by biomedical practitioners for child mental health problems in developing countries.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Atitude Frente a Saúde , Países em Desenvolvimento , Pais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adulto , Criança , Comportamento Infantil/psicologia , Serviços de Saúde da Criança/estatística & dados numéricos , Terapias Complementares , Características Culturais , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Religião , Instituições Acadêmicas , Meio Social , Fatores Socioeconômicos
18.
Psychopharmacology (Berl) ; 234(23-24): 3417-3429, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28889258

RESUMO

RATIONALE AND OBJECTIVE: Varenicline has gained a reputation as the optimal intervention for treatment resistant smokers, yet more than half of those who try it do not succeed. To better understand individual differences in the effectiveness of varenicline, this study evaluates the effectiveness of varenicline for smoking cessation in a double-blind, placebo-controlled, randomized clinical trial and examines the influence of psychological factors on treatment outcome. METHOD: Two hundred five cigarette smokers interested in quitting were randomly assigned to 12 weeks of varenicline or placebo. Outcomes examined were CO-confirmed continuous abstinence for the past month, average number of cigarettes smoked per day, and 7-day point prevalence. RESULTS: Varenicline-treated participants were more likely than placebo to achieve continuous abstinence at the end of treatment (OR = 3.29; RR = 2.62), and 7-day point prevalence rates showed an effect of medication at each time point. Participants in both groups significantly reduced their smoking during the course of treatment and follow-up, and the medication by visit interaction was significant in the expected direction. Impulsivity and personality style emerged as moderators of the relationship between medication condition and treatment outcome. CONCLUSIONS: In addition to replicating efficacy results for varenicline versus placebo, the present study shows that the efficacy of pharmacotherapy is influenced by psychological factors. In an era where pharmacotherapy is often perceived as the "silver bullet," we are reminded that smoking cessation is a dynamic process and intervention must be adaptable to address individual differences.


Assuntos
Agonistas Nicotínicos/uso terapêutico , Abandono do Hábito de Fumar/métodos , Fumar/tratamento farmacológico , Fumar/psicologia , Vareniclina/uso terapêutico , Adulto , Benzazepinas/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Fumar Tabaco/tratamento farmacológico , Resultado do Tratamento
19.
Psychiatry Res Neuroimaging ; 265: 45-53, 2017 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-28525877

RESUMO

Altered resting state functional connectivity (rsFC) and functional network connectivity (FNC), which is a measure of coherence between brain networks, may be associated with nicotine use disorder (NUD). We hypothesized that higher connectivity between insula and 1) dorsal anterior cingulate cortex (dACC) and 2) dorsolateral prefrontal cortex (dlPFC) would predict better treatment outcomes. We also performed an exploratory analysis of the associations between FNC values between additional key frontal and striatal regions and treatment outcomes. One hundred and forty four individuals with NUD underwent a resting state session during functional MRI prior to randomization to treatment with varenicline (n=82) or placebo. Group independent component analysis (ICA) was utilized to extract individual subject components and time series from intrinsic connectivity networks in aforementioned regions, and FNC between all possible pairs were calculated. Higher FNC between insula and dACC (rho=0.21) was significantly correlated with lower levels of baseline smoking quantity but did not predict treatment outcome upon controlling for baseline smoking. Higher FNC between putamen and dACC, caudate and dACC, and caudate and dlPFC significantly predicted worse treatment outcome in participants reporting high subjective withdrawal before the scan. FNC between key regions hold promise as biomarkers to predict outcome in NUD.


Assuntos
Encéfalo/efeitos dos fármacos , Rede Nervosa/efeitos dos fármacos , Tabagismo/tratamento farmacológico , Vareniclina/uso terapêutico , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiopatologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Agonistas Nicotínicos/uso terapêutico , Fumar/fisiopatologia , Tabagismo/diagnóstico por imagem , Tabagismo/fisiopatologia , Resultado do Tratamento
20.
Am J Psychiatry ; 173(4): 344-61, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26771738

RESUMO

Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity.


Assuntos
Encéfalo/fisiopatologia , Emoções/fisiologia , Vias Neurais/fisiopatologia , Autocontrole/psicologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Afeto , Tonsila do Cerebelo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Cognição , Neuroimagem Funcional , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
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