A three-factor model of common early onset psychiatric disorders: temperament, adversity, and dopamine.

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.

Externalizing Risk Pathways for Adolescent Substance Use and Its Developmental Onset: A Canadian Birth Cohort Study: Trajectoires de comportements extériorisés et le risque pour l'initiation et l'usage de substances des adolescents : Une étude de cohorte de naissance canadienne.

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.

mGlu5 receptor availability in youth at risk for addictions: effects of vulnerability traits and cannabis use.

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.

Extra-striatal D2/3 receptor availability in youth at risk for addiction.

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).

Mesolimbic connectivity signatures of impulsivity and BMI in early adolescence.

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 (p = 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.

Neurobiological Correlates and Predictors of Two Distinct Personality Trait Pathways to Escalated Alcohol Use.

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.

Process variables predicting changes in adolescent alcohol consumption and mental health symptoms following personality-targeted interventions.

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.

A cluster-randomized controlled trial evaluating the effects of delaying onset of adolescent substance abuse on cognitive development and addiction following a selective, personality-targeted intervention programme: the Co-Venture trial.

AIMS: Substance use and binge drinking during early adolescence are associated with neurocognitive abnormalities, mental health problems and an increased risk for future addiction. The trial aims to evaluate the protective effects of an evidence-based substance use prevention programme on the onset of alcohol and drug use in adolescence, as well as on cognitive, mental health and addiction outcomes over 5 years. DESIGN: Thirty-eight high schools will be recruited, with a final sample of 31 schools assigned to intervention or control conditions (3826 youth). Brief personality-targeted interventions will be delivered to high-risk youth attending intervention schools during the first year of the trial. Control school participants will receive no intervention above what is offered to them in the regular curriculum by their respective schools. SETTING: Public/private French and English high schools in Montreal (Canada). PARTICIPANTS: All grade 7 students (12-13 years old) will be invited to participate. High-risk youth will be identified as those scoring one standard deviation or more above the school mean on one of the four personality subscales of the Substance Use Risk Profile Scale (40-45% youth). MEASUREMENTS: Self-reported substance use and mental health symptoms and cognitive functioning measured annually throughout 5 years. Primary outcomes are the onset of substance use disorders at 4 years post-intervention (year 5). Secondary intermediate outcomes are the onset of alcohol and substance use 2 years post-intervention and neuropsychological functions; namely, the protective effects of substance use prevention on cognitive functions generally, and executive functions and reward sensitivity specifically. CONCLUSION: This longitudinal, cluster-randomized controlled trial will investigate the impact of a brief personality-targeted intervention program on reducing the onset of addiction 4 years-post intervention. Results will tease apart the developmental sequences of uptake and growth in substance use and cognitive development in adolescence using developmentally sensitive neuropsychological measures.

Effects of delaying binge drinking on adolescent brain development: a longitudinal neuroimaging study.

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.

Mechanisms of personality-targeted intervention effects on adolescent alcohol misuse, internalizing and externalizing symptoms.

OBJECTIVE: This study aims to explore the mechanisms of personality-targeted intervention effects on problematic drinking, internalizing and externalizing symptoms. METHOD: As part of a cluster-randomized trial, 1,210 high-risk students (mean age 13.7 years) in 19 London high schools (42.6% White, 54% male) were identified using the Substance Use Risk Profile Scale. Intervention school participants were invited to participate in personality-matched interventions by trained school staff. MacKinnon's products of coefficients method was used to compare 3 complementary mechanism hypotheses, namely, whether early changes in (a) alcohol use, (b) internalizing and externalizing symptoms, or (c) personality during the 6 months postintervention accounted for intervention effects over 2 years. RESULTS: Early intervention effects on drinking behaviors during the 6 months postintervention partially accounted for longer term intervention effects on the onset of binge drinking (95% confidence interval [CI] [-.349, -.062]) and drinking problems (95% CI [-.206, -.016]) over 2 years. Intervention effects on anxiety symptoms and conduct problems were partially mediated by early reductions in depressive symptoms (95% CI [-.013, -.001]; 95% CI [-.047, -.001]), and intervention effects on internalizing symptoms were also partially mediated by reductions in anxiety sensitivity (95% CI [-.003, 0]). CONCLUSIONS: 2-year intervention effects on problematic drinking were largely accounted for by early changes in drinking behaviors, and were not mediated by changes in mental health symptoms or personality risk factors. Early improvements in mood and anxiety sensitivity partially mediated longer term reductions in mental health problems.

Personality, Attentional Biases towards Emotional Faces and Symptoms of Mental Disorders in an Adolescent Sample.

OBJECTIVE: To investigate the role of personality factors and attentional biases towards emotional faces, in establishing concurrent and prospective risk for mental disorder diagnosis in adolescence. METHOD: Data were obtained as part of the IMAGEN study, conducted across 8 European sites, with a community sample of 2257 adolescents. At 14 years, participants completed an emotional variant of the dot-probe task, as well two personality measures, namely the Substance Use Risk Profile Scale and the revised NEO Personality Inventory. At 14 and 16 years, participants and their parents were interviewed to determine symptoms of mental disorders. RESULTS: Personality traits were general and specific risk indicators for mental disorders at 14 years. Increased specificity was obtained when investigating the likelihood of mental disorders over a 2-year period, with the Substance Use Risk Profile Scale showing incremental validity over the NEO Personality Inventory. Attentional biases to emotional faces did not characterise or predict mental disorders examined in the current sample. DISCUSSION: Personality traits can indicate concurrent and prospective risk for mental disorders in a community youth sample, and identify at-risk youth beyond the impact of baseline symptoms. This study does not support the hypothesis that attentional biases mediate the relationship between personality and psychopathology in a community sample. Task and sample characteristics that contribute to differing results among studies are discussed.

Brain serotonin synthesis in MDMA (ecstasy) polydrug users: an alpha-[(11) C]methyl-l-tryptophan study.

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.

Developmental association of prosocial behaviour with aggression, anxiety and depression from infancy to preadolescence.

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.

A methodological comparison of the Porges algorithm, fast Fourier transform, and autoregressive spectral analysis for the estimation of heart rate variability in 5-month-old infants.

Little empirical evidence exists on the comparability of heart rate variability (HRV) quantification methods commonly used in infants. The aim was to compare three methods of HRV estimation: (1) fast Fourier transform (FFT), (2) autoregressive (AR), and (3) the Porges methods. HRV was estimated in 63 healthy 5-month-old infants. HRV parameters were strongly correlated across methods (.92-.99) but yielded significantly different mean HRV estimates (Porges method > FFT > AR). There was no systematic bias over the whole range of values between the two spectral approaches, while differences between the Porges method and the spectral estimates were systematically greater for larger values. Additional comparative studies are needed to explore the between-method agreement across a range of physiological conditions.

Differential striatal dopamine responses following oral alcohol in individuals at varying risk for dependence.

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.

The effect of acute tryptophan depletion on mood and impulsivity in polydrug ecstasy users.

RATIONALE: Several studies suggest users of 3,4-methylenedioxymethamphetamine (ecstasy) have low levels of serotonin. Low serotonin may make them susceptible to lowered mood. OBJECTIVE: This work aims to study the acute effects on mood and impulsivity of lowering serotonin levels with acute tryptophan depletion in polydrug ecstasy users and to determine whether effects were different in men and women. METHODS: In a double-blind cross-over study, participants who had used ecstasy at least 25 times (n = 13) and nonuser controls (n = 17) received a tryptophan-deficient amino acid mixture and a control amino acid mixture containing tryptophan, at least 1 week apart. Mood was measured using the profile of mood states, and impulsivity was measured with the Go/No-Go task. RESULTS: The main result shows that a lowering of mood after acute tryptophan depletion occurred only in female polydrug ecstasy users (n = 7), relative to controls (n = 9). Results from the Go/No-Go task suggested that impulsivity was not increased by acute tryptophan depletion in polydrug ecstasy users. LIMITATION: The group sizes were small, when males and females were considered separately. CONCLUSIONS: Women polydrug ecstasy users appear to be more susceptible than men to the effects of lowered serotonin levels. If use of ecstasy alone or in conjunction with other drugs causes progressive damage of serotonin neurons, women polydrug ecstasy users may become susceptible to clinical depression.

Two-year impact of personality-targeted, teacher-delivered interventions on youth internalizing and externalizing problems: a cluster-randomized trial.

OBJECTIVE: To assess the 2-year impact of teacher-delivered, brief, personality-targeted interventions on internalizing and externalizing symptoms in an adolescent U.K. sample. METHOD: This cluster-randomized trial was run in 19 London schools (N = 1,024 adolescents). Trained school-based professionals delivered two 90-minute, CBT-based group interventions targeting 1 of 4 personality-risk profiles: anxiety sensitivity, hopelessness, impulsivity, or sensation seeking. Self-report depression, anxiety, and conduct disorder symptoms were assessed at 6-month intervals. RESULTS: Interventions were associated with significantly reduced depressive, anxiety, and conduct symptoms (p < .05) over 2 years in the full sample, reduced odds of severe depressive symptoms (odds ratio [OR] = 0.74, CI = 0.58-0.96), and conduct problems (OR = 0.79, CI = 0.65-0.96), and a nonsignificant reduction in severe anxiety symptoms (OR = 0.79, CI = 0.59-1.05). Evaluating a priori personality-specific hypotheses revealed strong evidence for impulsivity-specific effects on severe conduct problems, modest evidence of anxiety sensitivity-specific effects on severe anxiety, and no evidence for hopelessness-specific effects on severe depressive symptoms. CONCLUSIONS: Brief, personality-targeted interventions delivered by educational professionals can have a clinically significant impact on mental health outcomes in high-risk youth over 2 years, as well as personality-specific intervention effects in youth most at risk for a particular problem, particularly for youth with high levels of impulsivity. Clinical trial registration information-Adventure: The Efficacy of Personality-Targeted Interventions for Substance Misuse and Other Risky Behaviors as Delivered by Educational Professionals.

Influence of the OPRM1 A118G polymorphism on alcohol-induced euphoria, risk for alcoholism and the clinical efficacy of naltrexone.

Alcohol-use disorders are thought to be heterogeneous in etiology, pathophysiology and response to treatment. One hypothesized contributor to this variability is the common A118G polymorphism of the µ-opioid receptor gene, OPRM1. This article critically evaluates the evidence that the A118G substitution affects subjective, behavioral and neurobiological responses to alcohol and the opioid receptor antagonist, naltrexone. Although screening of patients in a clinical setting remains premature, results suggest the A118G substitution may influence one etiological pathway to alcoholism, for which naltrexone pharmacotherapy is more effective.

The dopamine augmenter L-DOPA does not affect positive mood in healthy human volunteers.

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans.

Serotonergic contribution to boys' behavioral regulation.

OBJECTIVES: Animal and human adult studies reveal a contribution of serotonin to behavior regulation. Whether these findings apply to children is unclear. The present study investigated serotonergic functioning in boys with a history of behavior regulation difficulties through a double-blind, acute tryptophan supplementation procedure. METHOD: Participants were 23 boys (age 10 years) with a history of elevated physical aggression, recruited from a community sample. Eleven were given a chocolate milkshake supplemented with 500 mg tryptophan, and 12 received a chocolate milkshake without tryptophan. Boys engaged in a competitive reaction time game against a fictitious opponent, which assessed response to provocation, impulsivity, perspective taking, and sharing. Impulsivity was further assessed through a Go/No-Go paradigm. A computerized emotion recognition task and a staged instrumental help incident were also administered. RESULTS: Boys, regardless of group, responded similarly to high provocation by the fictitious opponent. However, boys in the tryptophan group adjusted their level of responding optimally as a function of the level of provocation, whereas boys in the control group significantly decreased their level of responding towards the end of the competition. Boys in the tryptophan group tended to show greater perspective taking, tended to better distinguish facial expressions of fear and happiness, and tended to provide greater instrumental help to the experimenter. CONCLUSIONS: The present study provides initial evidence for the feasibility of acute tryptophan supplementation in children and some effect of tryptophan supplementation on children's behaviors. Further studies are warranted to explore the potential impact of increased serotonergic functioning on boys' dominant and affiliative behaviors.