RESUMO
OBJECTIVE: Only a minority of drug and alcohol users develops a substance use disorder. Previous studies suggest that this differential vulnerability commonly reflects a developmental trajectory characterized by diverse externalizing behaviors. In this study, we examined the relation between child and adolescent externalizing behaviors and adolescent substance use in a prospectively followed Canadian birth cohort, accounting for the temporal sequence of a wide variety of contributing factors. METHODS: Two hundred and forty-two adolescents followed since birth (date range: 1996 to 2012) were assessed on externalizing behavior (age 17 months to 16 years), alcohol and cannabis use at age 16, age of alcohol use onset, family history of substance use problems, family functioning (age 11 to 15), sensation seeking (age 16), prenatal substance exposure, socioeconomic status (age 1 to 9), and sex. RESULTS: Age of alcohol use onset was predicted by a family history of substance use problems, externalizing traits from ages 6 to 10 and 11 to 16, sensation seeking at age 16, prenatal alcohol and tobacco exposure and family functioning at ages 11 to 15. High frequencies of alcohol and cannabis use at age 16 were both predicted by externalizing traits from ages 11 to 16, a family history of substance use problems and sensation seeking after controlling for other individual, environmental and familial variables. The association between familial substance use problems and substance use during adolescence was partially mediated by externalizing traits from age 11 to 16. CONCLUSIONS: The present findings provide prospective evidence for a developmental risk pathway for adolescent substance use, potentially identifying those who could benefit from early interventions.
Assuntos
Coorte de Nascimento , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Canadá/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Gravidez , Estudos Prospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Across age groups, differences in connectivity of the mesolimbic and the prefrontal cortex co-vary with trait impulsivity and sensation-seeking. Impulsivity and sensation-seeking are also known to increase during early adolescence as maturation of subcortical structures outpaces that of the prefrontal cortex. While an imbalance between the striatum and prefrontal cortex is considered a normal developmental process, higher levels of adolescent impulsivity and sensation-seeking are associated with an increased risk for diverse problems, including obesity. To determine how the relationship between sensation-seeking, impulsivity and body mass index (BMI) is related to shared neural correlates we measured their relationships with the connectivity of nuclei in the striatum and dopaminergic midbrain in young adolescents. Data were collected from 116 children between the ages of 12 and 14, and included resting state functional magnetic resonance imaging, personality measures from the Substance Use Risk Profile Scale, and BMI Z-score for age. The shared variance for the connectivity of regions of interest in the substantia nigra, ventral tegmental area, ventral striatum and sub-thalamic nucleus, personality measures and BMI Z-score for age, were analyzed using partial least squares correlation. This analysis identified a single significant striato-limbic network that was connected with the substantia nigra, ventral tegmental area and sub-thalamic nuclei (pâ¯=â¯0.002). Connectivity within this network which included the hippocampi, amygdalae, parahippocampal gyri and the regions of interest, correlated positively with impulsivity and BMI Z-score for age and negatively with sensation-seeking. Together, these findings emphasize that, in addition to the well-established role that frontostriatal circuits play in the development of adolescent personality traits, connectivity of limbic regions with the striatum and midbrain also impact impulsivity, sensation-seeking and BMI Z-score in adolescents.
Assuntos
Índice de Massa Corporal , Corpo Estriado/fisiologia , Comportamento Impulsivo , Córtex Pré-Frontal/fisiologia , Adolescente , Criança , Corpo Estriado/diagnóstico por imagem , Feminino , Humanos , Análise dos Mínimos Quadrados , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
BACKGROUND: Onset of alcohol use by 14 relative to 21 years of age strongly predicts elevated risk for severe alcohol use problems, with 27% versus 4% of individuals exhibiting alcohol dependence within 10 years of onset. What remains unclear is whether this early alcohol use (i) is a marker for later problems, reflected as a pre-existing developmental predisposition, (ii) causes global neural atrophy or (iii) specifically disturbs neuro-maturational processes implicated in addiction, such as executive functions or reward processing. Since our group has demonstrated that a novel intervention program targeting personality traits associated with adolescent alcohol use can prevent the uptake of drinking and binge drinking by 40 to 60%, a crucial question is whether prevention of early onset alcohol misuse will protect adolescent neurodevelopment and which domains of neurodevelopment can be protected. METHODS: A subsample of 120 youth at high risk for substance misuse and 30 low-risk youth will be recruited from the Co-Venture trial (Montreal, Canada) to take part in this 5-year follow-up neuroimaging study. The Co-Venture trial is a community-based cluster-randomised trial evaluating the effectiveness of school-based personality-targeted interventions on substance use and cognitive outcomes involving approximately 3800 Grade 7 youths. Half of the 120 high-risk participants will have received the preventative intervention program. Cognitive tasks and structural and functional neuroimaging scans will be conducted at baseline, and at 24- and 48-month follow-up. Two functional paradigms will be used: the Stop-Signal Task to measure motor inhibitory control and a modified version of the Monetary Incentive Delay Task to evaluate reward processing. DISCUSSION: The expected results should help identify biological vulnerability factors, and quantify the consequences of early alcohol abuse as well as the benefits of early intervention using brain metrics.
Assuntos
Comportamento do Adolescente , Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo , Consumo Excessivo de Bebidas Alcoólicas , Encéfalo/diagnóstico por imagem , Adolescente , Desenvolvimento do Adolescente , Consumo de Bebidas Alcoólicas/prevenção & controle , Canadá , Feminino , Seguimentos , Neuroimagem Funcional , Humanos , Estudos Longitudinais , Masculino , Neuroimagem , Personalidade , Fatores de RiscoRESUMO
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[(11) C]methyl-l-tryptophan ((11) C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional (11) C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized (11) C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized (11) C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized (11) C-AMT trapping in the brainstem and pre-frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms.
Assuntos
Encéfalo/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Serotonina/metabolismo , Transtornos Relacionados ao Uso de Substâncias/patologia , Triptofano/análogos & derivados , Adulto , Antidepressivos de Segunda Geração/sangue , Antidepressivos de Segunda Geração/farmacologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Mapeamento Encefálico , Feminino , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Autorrelato , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Triptofano/sangue , Triptofano/farmacologia , Adulto JovemRESUMO
BACKGROUND: Research on associations between children's prosocial behaviour and mental health has provided mixed evidence. The present study sought to describe and predict the joint development of prosocial behaviour with externalizing and internalizing problems (physical aggression, anxiety and depression) from 2 to 11 years of age. METHOD: Data were drawn from the National Longitudinal Survey of Children and Youth (NLSCY). Biennial prosocial behaviour, physical aggression, anxiety and depression maternal ratings were sought for 10,700 children aged 0 to 9 years at the first assessment point. RESULTS: While a negative association was observed between prosociality and physical aggression, more complex associations emerged with internalizing problems. Being a boy decreased the likelihood of membership in the high prosocial trajectory. Maternal depression increased the likelihood of moderate aggression, but also of joint high prosociality/low aggression. Low family income predicted the joint development of high prosociality with high physical aggression and high depression. CONCLUSIONS: Individual differences exist in the association of prosocial behaviour with mental health. While high prosociality tends to co-occur with low levels of mental health problems, high prosociality and internalizing/externalizing problems can co-occur in subgroups of children. Child, mother and family characteristics are predictive of individual differences in prosocial behaviour and mental health development. Mechanisms underlying these associations warrant future investigations.
Assuntos
Agressão/psicologia , Ansiedade/psicologia , Desenvolvimento Infantil , Depressão/psicologia , Comportamento Social , Fatores Etários , Criança , Comportamento Infantil/psicologia , Pré-Escolar , Família/psicologia , Feminino , Humanos , Lactente , Estudos Longitudinais , MasculinoRESUMO
BACKGROUND: The neurobiology of risk for alcohol use disorders (AUDs) remains poorly understood. Individual differences in vulnerability, though, have been indicated by subjective responses to alcohol ingestion and personality traits. METHODS: To investigate the relationship between these features and striatal dopamine (DA) responses to alcohol, we studied 26 healthy young social drinkers (21.3 ± 3.0 years old; 10.7 ± 8.8 drinks/wk) at varying risk for alcoholism. Each participant received 2 positron emission tomography [(11) C]raclopride scans after administration of either placebo or oral alcohol (1 ml/kg body weight of 94% alcohol, 0.75 g/kg) in a randomized and counterbalanced design. RESULTS: Subjects with high-risk subjective responses to alcohol had more family members with AUDs, greater alcohol use problems, and, in response to the alcohol challenge, significant decreases in [(11) C]raclopride binding indicative of increased extracellular DA. In contrast, low-risk subjects exhibited increases in [(11) C]raclopride binding in response to alcohol. The results were similar when risk groups were based on personality traits, although statistically less robust. CONCLUSIONS: Changes in striatal DA in response to alcohol ingestion may be a neurobiological marker of vulnerability to AUDs.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Alcoolismo/diagnóstico , Alcoolismo/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Individualidade , Administração Oral , Adolescente , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/psicologia , Biomarcadores/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
Commonly comorbid early onset psychiatric disorders might reflect the varying expression of overlapping risk factors. The mediating processes remain poorly understood, but three factors show some promise: adolescent externalizing traits, early life adversity, and midbrain dopamine autoreceptors. To investigate whether these features acquire greater predictive power when combined, a longitudinal study was conducted in youth who have been followed since birth. Cohort members were invited to participate based on externalizing scores between 11 to 16 years of age. At age 18 (age 18.5 ± 0.6 y.o.), 52 entry criteria meeting volunteers had a 90-min positron emission tomography scan with [18F]fallypride, completed the Childhood Trauma Questionnaire, and were assessed with the Structured Clinical Interview for DSM-5. The three-factor model identified those with a lifetime history of DSM-5 disorders with an overall accuracy of 90.4% (p = 2.4 × 10-5) and explained 91.5% of the area under the receiver operating characteristic curve [95% CI: .824, 1.000]. Targeting externalizing disorders specifically did not yield a more powerful model than targeting all disorders (p = 0.54). The model remained significant when including data from participants who developed their first disorders during a three-year follow-up period (p = 3.5 × 10-5). Together, these results raise the possibility that a combination of temperamental traits, childhood adversity, and poorly regulated dopamine transmission increases risk for diverse, commonly comorbid, early onset psychiatric problems, predicting this susceptibility prospectively.
Assuntos
Dopamina , Transtornos Mentais , Adolescente , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Estudos Longitudinais , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/epidemiologia , Temperamento , Adulto JovemRESUMO
BACKGROUND: Few pharmacological treatments for alcohol dependence are available. Moreover, the best supported treatment, naltrexone hydrochloride, appears to work for only some. METHODS: To investigate potential predictors of these differential responses, 40 social drinkers (20 women) were administered 6 days of treatment with naltrexone vs. placebo in a double-blind, counterbalanced, crossover design. At the end of each treatment period, participants received a single dose of their preferred alcoholic beverage followed by the opportunity to work for additional alcohol units using a progressive ratio (PR) breakpoint paradigm. All subjects but one were genotyped for the A118G polymorphism of the mu opioid receptor gene (OPRM1). RESULTS: Naltrexone decreased the ethanol-induced 'euphoria' to a priming dose of alcohol in two subgroups: (i) in women, and (ii) in subjects with the A118G polymorphism of the mu opioid receptor gene (OPRM1). Naltrexone did not decrease motivation to work for additional alcoholic beverages on the PR task regardless of gender or genotype. CONCLUSIONS: The results add to the evidence that naltrexone decreases positive subjective effects of alcohol, with preferential effects in distinct subgroups. Similar effects in heavier drinkers might decrease alcohol use.
Assuntos
Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/genética , Naltrexona/uso terapêutico , Caracteres Sexuais , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/farmacologia , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Autoadministração , Adulto JovemRESUMO
AIMS: Widely varying estimates of treatment effects have been reported in randomized controlled trials (RCTs) investigating the efficacy of behavioural interventions for smoking cessation. Previous meta-analyses investigating behavioural interventions have important limitations and do not include recently published RCTs. We undertook a meta-analysis of RCTs to synthesize the treatment effects of four behavioural interventions, including minimal clinical intervention (brief advice from a healthcare worker), and intensive interventions, including individual, group, and telephone counselling. METHODS AND RESULTS: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline, and PsycINFO databases. We included only RCTs that reported biochemically validated smoking cessation outcomes at 6 and/or 12 months after the target quit date. Outcomes were aggregated using hierarchical Bayesian random-effects models. We identified 50 RCTs, which randomized n = 26 927 patients (minimal clinical intervention: 9 RCTs, n = 6456; individual counselling: 23 RCTs, n = 8646; group counselling: 12 RCTs, n = 3600; telephone counselling: 10 RCTs, n = 8225). The estimated mean treatment effects were minimal clinical intervention [odds ratio (OR) 1.50, 95% credible interval (CrI) 0.84-2.78], individual counselling (OR 1.49, 95% CrI 1.08-2.07), group counselling (OR 1.76, 95% CrI 1.11-2.93), and telephone counselling (OR 1.58, 95% CrI 1.15-2.29). CONCLUSION: Intensive behavioural interventions result in substantial increases in smoking abstinence compared with control. Although minimal clinical intervention may increase smoking abstinence, there is insufficient evidence to draw strong conclusions regarding its efficacy.
Assuntos
Terapia Comportamental/métodos , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados UnidosRESUMO
The excitatory neurotransmitter glutamate has been implicated in experience-dependent neuroplasticity and drug-seeking behaviors. Type 5 metabotropic glutamate (mGlu5) receptors might be particularly important. They are critically involved in synaptic plasticity and their availability has been reported to be lower in people with alcohol, tobacco, and cocaine use disorders. Since these reductions could reflect effects of drug use or pre-existing traits, we used positron emission tomography to measure mGlu5 receptor availability in young adults at elevated risk for addictions. Fifty-nine participants (age 18.5 ± 0.6) were recruited from a longitudinal study that has followed them since birth. Based on externalizing traits that predict future substance use problems, half were at low risk, half were at high risk. Cannabis use histories varied markedly and participants were divided into three subgroups: zero, low, and high use. Compared to low risk volunteers, those at elevated risk had lower [11C]ABP688 binding potential (BPND) values in the striatum, amygdala, insula, and orbitofrontal cortex (OFC). Cannabis use by risk group interactions were observed in the striatum and OFC. In these regions, low [11C]ABP688 BPND values were only seen in the high risk group that used high quantities of cannabis. When these high risk, high cannabis use individuals were compared to all other participants, [11C]ABP688 BPND values were lower in the striatum, OFC, and insula. Together, these results provide evidence that mGlu5 receptor availability is low in youth at elevated risk for addictions, particularly those who frequently use cannabis.
Assuntos
Cannabis , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Cannabis/metabolismo , Radioisótopos de Carbono , Humanos , Estudos Longitudinais , Tomografia por Emissão de Pósitrons , Receptor de Glutamato Metabotrópico 5/metabolismo , Adulto JovemRESUMO
The neurobiological traits that confer risk for addictions remain poorly understood. However, dopaminergic function throughout the prefrontal cortex, limbic system, and upper brainstem has been implicated in behavioral features that influence addiction vulnerability, including poor impulse control, and altered sensitivity to rewards and punishments (i.e., externalizing features). To test these associations in humans, we measured type-2/3 dopamine receptor (DA2/3R) availability in youth at high vs. low risk for substance use disorders (SUDs). In this study, N = 58 youth (18.5 ± 0.6 years) were recruited from cohorts that have been followed since birth. Participants with either high (high EXT; N = 27; 16 F/11 M) or low pre-existing externalizing traits (low EXT; N = 31; 20 F/11 M) underwent a 90-min positron emission tomography [18F]fallypride scan, and completed the Barratt Impulsiveness Scale (BIS-11), Substance Use Risk Profile scale (SURPS), and Sensitivity to Punishment (SP) and Sensitivity to Reward (SR) questionnaire. We found that high vs. low EXT trait participants reported elevated substance use, BIS-11, SR, and SURPS impulsivity scores, had a greater prevalence of psychiatric disorders, and exhibited higher [18F]fallypride binding potential (BPND) values in prefrontal, limbic and paralimbic regions, even when controlling for substance use. Group differences were not evident in midbrain dopamine cell body regions, but, across all participants, low midbrain BPND values were associated with low SP scores. Together, the results suggest that altered DA2/3R availability in terminal extra-striatal and dopamine cell body regions might constitute biological vulnerability traits, generating an EXT trajectory for addictions with and without co-occurring alterations in punishment sensitivity (i.e., an internalizing feature).
Assuntos
Corpo Estriado , Receptores de Dopamina D2 , Adolescente , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Humanos , Comportamento Impulsivo , Tomografia por Emissão de Pósitrons , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismoRESUMO
OBJECTIVES: To longitudinally describe prosocial behaviour development from childhood to adolescence, using multiple informants within Canadian and Italian samples. METHOD: Participants in Study 1 were 1037 boys from low socioeconomic status (SES) areas in Montreal, Canada, for whom yearly teacher and mother reports were obtained between the ages of 10 and 15. Participants in Study 2 were 472 children (209 girls) from Genzano, Italy, for whom yearly self and teacher reports were obtained between the ages of 10 and 14. Developmental trajectories were estimated from ratings by each informant to identify subgroups of children following distinct courses of prosocial development. RESULTS: In Study 1, three trajectory groups (low/declining 53%, high/declining 16%, high/steep declining 31%) were identified from teacher ratings, while five trajectories (low/stable 7%, low/declining 19%, moderate/stable 41%, high/declining 24%, high/stable 9%) were identified from mother ratings. Small but significant associations were observed between mother and teacher ratings. In Study 2, three trajectory groups (low/stable 9%, moderate/stable 50%, high/stable 42%) were identified from self-ratings, while four trajectory groups (low/stable 8%, moderate/declining 48%, high/declining 37%, increasing 7%) were identified from teacher ratings. Small but significant associations were observed between self- and teacher ratings. CONCLUSIONS: The present studies investigated levels of prosocial behaviours from childhood to adolescence, using a multi-informant, cross-cultural perspective. All but one of the developmental trajectories identified were characterised by stable or declining levels of prosocial behaviours. Further research longitudinally investigating prosociality across developmental periods is needed to clarify prosocial behaviour development over time.
Assuntos
Desenvolvimento do Adolescente , Desenvolvimento Infantil , Comparação Transcultural , Comportamento Social , Adolescente , Fatores Etários , Canadá , Criança , Feminino , Humanos , Itália , Estudos Longitudinais , Masculino , Determinação da Personalidade , Classe Social , Meio SocialRESUMO
Rough-and-tumble play (RTP) is a common form of play between fathers and children. It has been suggested that RTP can contribute to the development of selfregulation. This study addressed the hypothesis that the frequency of father-child RTP is related to the frequency of physically aggressive behavior in early childhood. This relationship was expected to be moderated by the dominance relationship between father and son during play. Eighty-five children between the ages of 2 and 6 years were videotaped during a free-play session with their fathers in their homes and questionnaire data was collected about father-child RTP frequency during the past year. The play dyads were rated for the degree to which the father dominated play interactions. A significant statistical interaction revealed that RTP frequency was associated with higher levels of physical aggression in children whose fathers were less dominant. These results indicate that RTP is indeed related to physical aggression, though this relationship is moderated by the degree to which the father is a dominant playmate.
Assuntos
Agressão/psicologia , Relações Pai-Filho , Controle Interno-Externo , Jogos e Brinquedos , Pré-Escolar , Dominação-Subordinação , Feminino , Humanos , Masculino , Fatores de Risco , Socialização , Inquéritos e Questionários , Gravação de VideoteipeRESUMO
Intoxicated aggression is both a dangerous and a costly problem for society, with alcohol being involved in over 50% of violent crimes, and the cost of alcohol-consumption-related crime being estimated at $205 billion in the United States alone. First, the authors reviewed the substantial evidence for the connection between alcohol consumption and aggression, and then they examined the risk factors for this problem. These included societal/cultural factors, such as availability and alcohol expectancies, and individual factors, such as demographic characteristics, personality, comorbid disorders, individual differences in response to alcohol, and cognitive functioning. Finally, interventions were suggested focusing on policy, alcohol sellers, treatments for alcohol abuse and dependency, anger management, pharmacology, and low executive functioning. Further efforts are still needed to target interventions to specific risk factors.
Assuntos
Agressão/efeitos dos fármacos , Agressão/psicologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/prevenção & controle , Humanos , Fatores de RiscoRESUMO
OBJECTIVE: To clarify dopamine's role in alcohol self-administration in a heterogeneous sample of drinkers using acute phenylalanine/tyrosine depletion (APTD). METHODS: Sixteen men with variable drinking histories were characterized on their ethanol-induced cardiac response, a marker previously proposed to index dopamine system reactivity and vulnerability to alcohol abuse. During separate sessions participants were administered (i) a nutritionally balanced (BAL) amino acid (AA) mixture, (ii) a mixture lacking the dopamine precursors, phenylalanine and tyrosine, and (iii) APTD followed by the dopamine precursor, L-DOPA. Five hours after AA administration, participants could earn units of alcohol using a progressive ratio breakpoint task. RESULTS: Alcohol self-administration was reduced in the APTD and APTD+L-DOPA conditions relative to the BAL condition. In both cases the changes were predicted by ethanol-induced cardiac change. CONCLUSIONS: The motivation to drink is likely regulated by more than one neurobiological mechanism. Individual differences in cardiac responsivity to ethanol might provide a peripheral marker of responsiveness to pharmacological manipulations of dopamine.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/psicologia , Dopamina/metabolismo , Etanol/administração & dosagem , Individualidade , Adulto , Aminoácidos/administração & dosagem , Análise de Variância , Dopaminérgicos/administração & dosagem , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Levodopa/administração & dosagem , Masculino , Fenilalanina/deficiência , Autoadministração , Tirosina/deficiênciaRESUMO
BACKGROUND: The delineation of the behavioral neurobiological mechanisms underlying the heterogeneous pathways for alcohol use disorders (AUDs) is ostensibly imperative for the development of more cost-effective treatments predicated on better understanding of this complex psychopathology. METHODS: 1) Forty-eight high anxiety sensitive (HAS) and high sensation seeking (HSS) psychopathology-free emerging adults (mean (SD) age: 20.4 (1.9) years) completed a Face Emotion Processing Task and a social stress paradigm (Montreal Imaging Stress Task) during functional magnetic resonance imaging sessions with and without alcohol ingestion (1ml/kg of 95% USP alcohol, p.o.). Drug and alcohol use was reassessed during follow-up interviews 2-3years later. OUTCOMES: The effects of alcohol (versus placebo) ingestion depended upon the task and risk group. In response to negative (versus neutral) faces, alcohol diminished amygdala (AMYG) activations in HAS but not HSS subjects. In response to psychosocial evaluative stress, alcohol enhanced activations of the medial orbitofrontal cortex (mOFC), perigenual anterior cingulate cortex, and nucleus accumbens in HAS male subjects (HASMS), but decreased mOFC activity in HSS male subjects (HSSMS). At follow-up, a greater alcohol versus placebo differential for threat-related AMYG activations predicted escalating drinking and/or illicit drug use among HAS but not HSS participants, whereas a greater differential for mOFC activations during acute social stress predicted escalating substance use among HSS but not HAS participants. INTERPRETATION: This double dissociation provides evidence of distinct neurobiological profiles in a priori identified personality trait-based risk groups for AUDs, and links these signatures to clinically relevant substance use outcomes at follow-up. AUD subtypes might benefit from motivationally and personality-specific ameliorative and preventative interventions.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Sistema Nervoso/patologia , Personalidade , Comportamento , Demografia , Emoções , Face , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Autorrelato , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
BACKGROUND: Dopaminergic neurotransmission is implicated in externalizing behavior problems, such as aggression and hyperactivity. Externalizing behavior is known to be negatively associated with cognitive ability. Activation of dopamine D4 receptors appears to inhibit the functioning of the prefrontal cortex, a brain region implicated in cognitive ability. The 7-repeat allele of the dopamine D4 receptor gene produces less efficient receptors, relative to other alleles, and this may alter the effects of dopamine on cognitive function. OBJECTIVE: To examine the influence of a polymorphism in the third exon of the dopamine D4 receptor gene on the association between externalizing behavior and IQ. DESIGN: In 1 community sample and 2 clinical samples, the presence or absence of the 7-repeat allele was examined as a moderator of the association between externalizing behavior and IQ; the strength of this effect across samples was estimated meta-analytically. PATIENTS: Eighty-seven boys from a longitudinal community study, 48 boys referred clinically for aggression, and 42 adult males diagnosed with attention-deficit/hyperactivity disorder. MAIN OUTCOME MEASURES: IQ scores and observer ratings of externalizing behavior were taken from existing data sets. RESULTS: Among individuals lacking the 7-repeat allele, externalizing behavior was negatively correlated with IQ (mean r = -0.43; P<.001). Among individuals having at least 1 copy of the 7-repeat allele, externalizing behavior and IQ were uncorrelated (mean r = 0.02; P = .45). The difference between these correlations was significant (z = -2.99; P<.01). CONCLUSIONS: Allelic variation of the dopamine D4 receptor gene appears to be a genetic factor moderating the association between externalizing behavior and cognitive ability. This finding may help to elucidate the adaptive value of the 7-repeat allele.
Assuntos
Agressão/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtornos do Comportamento Infantil/genética , Inteligência/genética , Polimorfismo Genético , Córtex Pré-Frontal/fisiologia , Receptores de Dopamina D4/genética , Adolescente , Adulto , Alelos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Genótipo , Humanos , Inteligência/classificação , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade/estatística & dados numéricos , Receptores de Dopamina D4/fisiologia , Sequências de Repetição em Tandem/genética , Escalas de Wechsler/estatística & dados numéricosRESUMO
Studies 1 and 2 assessed performance on a battery of dorsolateral prefrontal cognitive ability (D-PFCA) tests, personality, psychometric intelligence, and academic performance (AP) in 2 undergraduate samples. In Studies 1 and 2, AP was correlated with D-PFCA (r=.37, p<.01, and r=.33, p<.01, respectively), IQ (r=.24, p<.05, and r=.38, p<.01, respectively), and Conscientiousness (r=.26, p<.05, and r=.37, p<.01, respectively). D-PFCA remained significant in regression analyses controlling for intelligence (or g) and personality. Studies 3 and 4 assessed D-PFCA, personality, and workplace performance among (a) managerial-administrative workers and (b) factory floor workers at a manufacturing company. Prefrontal cognitive ability correlated with supervisor ratings of manager performance at values of r ranging from .42 to .57 (ps<.001), depending on experience, and with factory floor performance at pr=.21 (p=.02), after controlling for experience, age, and education. Conscientiousness correlated with factory floor performance at r=.23.
Assuntos
Logro , Mobilidade Ocupacional , Cognição/fisiologia , Inteligência , Personalidade , Córtex Pré-Frontal/fisiologia , Local de Trabalho , Humanos , Resolução de Problemas , Estudos ProspectivosRESUMO
Given the central role of perseverative chasing in problem gambling, the present study sought to find evidence for three hypothesized components of perseveration in problem gamblers: reward-sensitivity dominance, deficient inhibition of reward-seeking behavior, and working memory deficits. This was the first attempt to examine working memory deficits in problem gamblers using a conditional association task, which is associated with posterior-dorsolateral prefrontal functioning. In a sample that was not in treatment, and representative in terms of comorbidity, problem gamblers performed significantly worse on the conditional association working memory tasks after controlling for general memory function, compared to demographically-matched controls. This is significant because deficits in the dorsolateral prefrontal region have been consistently associated with perseveration, which suggests that problem gamblers' perseverative chasing may be associated with a working memory deficit. Problem gamblers were not significantly higher than at-risk gamblers in terms of reward-sensitivity dominance (measured as a personality trait in terms of extraversion) suggesting that it may not be specifically associated with problem gambling. Sensation-seeking was also not associated with problem gambling in a sample that corrected for the methodological problems of previous studies which examined it. The need for gambling research to focus specifically on the perseverative inability to stop gambling is emphasized, and the present findings of specific working memory deficits in problem gamblers suggest the need for further examination of working memory as a potential risk factor for problem gambling. We propose that subsequent studies examine working memory in terms of the self-regulatory capacity for goal maintenance where attention must specifically be allocated to resist interference.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Transtornos da Memória/epidemiologia , Transtornos da Memória/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Recompensa , Adulto , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Comorbidade , Lobo Frontal/fisiopatologia , Humanos , Masculino , Memória , Transtornos da Memória/terapia , OntárioRESUMO
OBJECTIVE: This study aims to identify key process variables that are associated with changes in alcohol consumption and mental health symptoms over 12months following personality-targeted interventions in youth. METHOD: 154 high-risk youth (aged 12-13years) in 7 Montreal high schools were identified using the Substance Use Risk Profile Scale and participated in personality-matched interventions. Preliminary process variables were identified using a combination of psychotherapy process variables and youth-generated (qualitative) feedback immediately post-intervention. RESULTS: Learning, skill development and a positive group experience were key to positive behavioural change. Youth-generated feedback independently accounted for 12-25% of the variance in the change in alcohol use and mental health symptoms over 12months. Changes in cognitive distortions and self-esteem accounted for somewhat less of the variance in alcohol use (0-9%), but a moderate-to-large portion of the variance in changes in mental health symptoms (up to 44%). CONCLUSIONS: The study findings highlight candidate process variables relevant to future implementations of this program that might inform change processes relevant to brief interventions with youth more generally. This study suggests that youth experiences can indicate proximal measures of program efficacy, and has implications for the dissemination of this brief intervention program. Clinical Trial registered on www.ClinicalTrials.gov, "Does Delaying Adolescent Substance Use Lead to Improved Cognitive Function and Reduce Risk for Addiction", study NCT01655615.