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Find video protocols related to scientific articles indexed in Pubmed.
No differences in hippocampal volume between carriers and non-carriers of the ApoE ?4 and ?2 alleles in young healthy adolescents.
J. Alzheimers Dis.
PUBLISHED: 10-31-2014
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Alleles of the apolipoprotein E (ApoE) gene are known to modulate the genetic risk for developing late-onset Alzheimer's disease (AD) and have been associated with hippocampal volume differences in AD. However, the effect of these alleles on hippocampal volume in younger subjects has yet to be clearly established. Using a large cohort of more than 1,400 adolescents, this study found no hippocampal volume or hippocampal asymmetry differences between carriers and non-carriers of the ApoE ?4 or ?2 alleles, nor dose-dependent effects of either allele, suggesting that regionally specific effects of these polymorphisms may only become apparent in later life.
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Evidence for a Sex-Dependent MAOA× Childhood Stress Interaction in the Neural Circuitry of Aggression.
Cereb. Cortex
PUBLISHED: 10-22-2014
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Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOA× CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.
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Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence.
J Psychiatr Res
PUBLISHED: 08-27-2014
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Insensitive and unresponsive caregiving during infancy has been linked to externalizing behavior problems during childhood and adolescence. The 7-repeat (7r) allele of the dopamine D4 receptor (DRD4) gene has meta-analytically been associated with a heightened susceptibility to adverse as well as supportive environments. In the present study, we examined long-term effects of early maternal care, DRD4 genotype and the interaction thereof on externalizing and internalizing psychopathology during adolescence. As part of an ongoing epidemiological cohort study, early maternal care was assessed at child's age 3 months during a nursing and playing situation. In a sample of 296 offspring, externalizing and internalizing symptoms were assessed using a psychiatric interview conducted at age 15 years. Parents additionally filled out a questionnaire on their children's psychopathic behaviors. Results indicated that adolescents with the DRD4 7r allele who experienced less responsive and stimulating early maternal care exhibited more symptoms of ADHD and CD/ODD as well as higher levels of psychopathic behavior. In accordance with the hypothesis of differential susceptibility, 7r allele carriers showed fewer ADHD symptoms and lower levels of psychopathic behavior when exposed to especially beneficial early caregiving. In contrast, individuals without the DRD4 7r allele proved to be insensitive to the effects of early maternal care. This study replicates earlier findings with regard to an interaction between DRD4 genotype and early caregiving on externalizing behavior problems in preschoolers. It is the first one to imply continuity of this effect until adolescence.
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Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?
Eur Arch Psychiatry Clin Neurosci
PUBLISHED: 08-23-2014
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With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1 years of follow-up in children and adolescents and mean duration of 0.33 years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH.
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Health-Related Quality of Life and Functional Outcomes from a Randomized-Withdrawal Study of Long-Term Lisdexamfetamine Dimesylate Treatment in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.
CNS Drugs
PUBLISHED: 08-20-2014
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The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention-deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD.
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Global genetic variations predict brain response to faces.
PLoS Genet.
PUBLISHED: 08-14-2014
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Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ? 500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40-50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R(2) = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R(2) = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network.
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Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years.
PLoS ONE
PUBLISHED: 08-13-2014
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Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.
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Evaluation of a head-to-head study of lisdexamfetamine dimesylate and atomoxetine: evaluation of Dittmann RW, Cardo E, Nagy P, et al. Efficacy and safety of lisdexamfetamine dimesylate and atomoxetine in the treatment of attention-deficit/hyperactivity disorder: a head-
Expert Opin Pharmacother
PUBLISHED: 08-01-2014
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Here, we evaluate a report of a head-to-head study of the prodrug stimulant lisdexamfetamine dimesylate (LDX) and the non-stimulant atomoxetine hydrochloride (ATX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). An inadequate response to previous methylphenidate (MPH) treatment was a notable inclusion criterion. The primary efficacy outcome of a more rapid clinical response to LDX than to ATX was predictable from the known properties of the two drugs. However, secondary efficacy outcomes indicated that LDX was significantly more effective than ATX in relieving investigator-rated symptoms of ADHD, with an effect size of 0.56. Safety and tolerability profiles were consistent with the known properties of LDX and ATX. Despite some issues with the study design, the conclusion that LDX is more effective than ATX over the short term appears robust. In addition, the magnitude of improvement with both treatments indicated that previous MPH treatment is not a factor affecting the potential for patients to benefit from LDX or ATX. The results may help to inform clinical practice in Europe, where LDX is approved for treating children and adolescents with ADHD and a previous inadequate response to MPH, and in other regions where generic MPH formulations are typically the first-line therapeutic option.
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Neural and Cognitive Correlates of the Common and Specific Variance Across Externalizing Problems in Young Adolescence.
Am J Psychiatry
PUBLISHED: 07-31-2014
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The authors sought to model the unique and common variance across conduct disorder, substance misuse, and attention deficit hyperactivity disorder (ADHD) and to investigate the neurocognitive factors that relate generally or uniquely to externalizing problems in adolescence.
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The Long-Term Impact of Early Life Poverty on Orbitofrontal Cortex Volume in Adulthood: Results from a Prospective Study Over 25 Years.
Neuropsychopharmacology
PUBLISHED: 07-16-2014
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Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty [0=non-exposed (N=134), 1=exposed (N=33)] and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother-infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8-19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education and current poverty. Individuals exposed to early-life poverty exhibited a lower OFC volume and more CD symptoms. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early-life adversity on brain alterations and highlight the need for programs to decrease income-related disparities.Neuropsychopharmacology accepted article preview online, 15 October 2014. doi:10.1038/npp.2014.277.
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[DMS-5 - attention-deficit/hyperactivity disorder].
Z Kinder Jugendpsychiatr Psychother
PUBLISHED: 07-10-2014
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Modifications to the DSM-5 criteria for the diagnosis of attention-deficit/hyperactivity disorders are described and discussed. The main modifications concern the onset of the disorder, the reduction on the number of criteria fulfilled for a diagnosis in patients aged 17 years or older, and the elimination of autism spectrum disorders as an exclusion criterion for this diagnosis. These changes are mainly welcomed. However, the demanded increase in the age for the latest onset of the disorder may prove to be problematic.
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Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents.
J Neural Transm
PUBLISHED: 06-24-2014
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Enhanced endocannabinoid signaling has been implicated in typically adolescent behavioral features such as increased risk-taking, impulsivity and novelty seeking. Research investigating the impact of genetic variants in the cannabinoid receptor 1 gene (CNR1) and of early rearing conditions has demonstrated that both factors contribute to the prediction of impulsivity-related phenotypes. The present study aimed to test the hypothesis of an interaction of the two most studied CNR1 polymorphisms rs806379 and rs1049353 with early psychosocial adversity in terms of affecting impulsivity in 15-year-olds from an epidemiological cohort sample followed since birth. In 323 adolescents (170 girls, 153 boys), problems of impulse control and novelty seeking were assessed using parent-report and self-report, respectively. Exposure to early psychosocial adversity was determined in a parent interview conducted at the age of 3 months. The results indicated that impulsivity increased following exposure to early psychosocial adversity, with this increase being dependent on CNR1 genotype. In contrast, while individuals exposed to early adversity scored higher on novelty seeking, no significant impact of genotype or the interaction thereof was detected. This is the first evidence to suggest that the interaction of CNR1 gene variants with the experience of early life adversity may play a role in determining adolescent impulsive behavior. However, given that the reported findings are obtained in a high-risk community sample, results are restricted in terms of interpretation and generalization. Future research is needed to replicate these findings and to identify the mediating mechanisms underlying this effect.
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No differences in ventral striatum responsivity between adolescents with a positive family history of alcoholism and controls.
Addict Biol
PUBLISHED: 06-07-2014
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Individuals with alcohol-dependent parents show an elevated risk of developing alcohol-related problems themselves. Modulations of the mesolimbic reward circuit have been postulated as a pre-existing marker of alcoholism. We tested whether a positive family history of alcoholism is correlated with ventral striatum functionality during a reward task. All participants performed a modified version of the monetary incentive delay task while their brain responses were measured with functional magnetic resonance imaging. We compared 206 healthy adolescents (aged 13-15) who had any first- or second-degree relative with alcoholism to 206 matched controls with no biological relative with alcoholism. Reward anticipation as well as feedback of win recruited the ventral striatum in all participants, but adolescents with a positive family history of alcoholism did not differ from their matched peers. Also we did not find any correlation between family history density and reward anticipation or feedback of win. This finding of no differences did not change when we analyzed a subsample of 77 adolescents with at least one parent with alcohol use disorder and their matched controls. Because this result is in line with another study reporting no differences between children with alcohol-dependent parents and controls at young age, but contrasts with studies of older individuals, one might conclude that at younger age the effect of family history has not yet exerted its influence on the still developing mesolimbic reward circuit.
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An evaluation of the pharmacokinetics of methylphenidate for the treatment of attention-deficit/ hyperactivity disorder.
Expert Opin Drug Metab Toxicol
PUBLISHED: 05-26-2014
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Methylphenidate (MPH) plays a principal role in the multimodal treatment of attention-deficit/hyperactivity disorder (ADHD). Controlled studies have demonstrated an effective reduction in the core symptoms of the disorder following MPH therapy, although long-term studies also demonstrate that the therapeutic benefits dissipate in the absence of combined psychosocial interventions.
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A Matter of Time: The Influence of Recording Context on EEG Spectral Power in Adolescents and Young Adults with ADHD.
Brain Topogr
PUBLISHED: 05-16-2014
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Elevated theta or theta/beta ratio is often reported in attention deficit hyperactivity disorder (ADHD), but the consistency across studies and the relation to hypoarousal are increasingly questioned. Reports of elevated delta related to maturational lag and of attenuated beta activity are less well replicated. Some critical inconsistencies could relate to differences in recording context. We examined if resting-state EEG power or global field synchronization (GFS) differed between recordings made at the beginning and end of a 1.5 h testing session in 76 adolescents and young adults with ADHD, and 85 controls. In addition, we aimed to examine the effect of IQ on any potential group differences. Both regional and midline electrodes yielded group main effects for delta, trends in theta, but no differences in alpha or theta/beta ratio. An additional group difference in beta was detected when using regions. Group by time interactions in delta and theta became significant when controlling for IQ. The ADHD group had higher delta and theta power at time-1, but not at time-2, whereas beta power was elevated only at time-2. GFS did not differ between groups or condition. We show some ADHD-control differences on EEG spectral power varied with recording time within a single recording session, with both IQ and electrode selection having a small but significant influence on observed differences. Our findings demonstrate the effect of recording context on resting-state EEG, and highlight the importance of accounting for these variables to ensure consistency of results in future studies.
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Effect of prenatal exposure to tobacco smoke on inhibitory control: neuroimaging results from a 25-year prospective study.
JAMA Psychiatry
PUBLISHED: 05-16-2014
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There is accumulating evidence relating maternal smoking during pregnancy to attention-deficit/hyperactivity disorder (ADHD) without elucidating specific mechanisms. Research investigating the neurobiological underpinnings of this disorder has implicated deficits during response inhibition. Attempts to uncover the effect of prenatal exposure to nicotine on inhibitory control may thus be of high clinical importance.
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Intrauterine exposure to cigarette smoke is associated with increased ghrelin concentrations in adulthood.
Neuroendocrinology
PUBLISHED: 04-29-2014
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The appetite-stimulating hormone ghrelin is a fundamental regulator of human energy metabolism. A series of studies support the notion that long-term appetite and weight regulation may be already programmed in early life and it could be demonstrated that the intrauterine environment affects the ghrelin system of the offspring. Animal studies have also shown that intrauterine programming of orexigenic systems persists even until adolescence/adulthood.
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Neuropsychosocial profiles of current and future adolescent alcohol misusers.
Nature
PUBLISHED: 04-23-2014
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A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.
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Sex differences in COMT polymorphism effects on prefrontal inhibitory control in adolescence.
Neuropsychopharmacology
PUBLISHED: 04-03-2014
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Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level-dependent (BOLD) activation are robust; however, despite observations that COMT is estrogenically catabolized, sex differences in its prefrontal repercussions remain unclear. Here, in a large sample of healthy adolescents stratified by sex and Val(158)Met genotype (n=1133), we examine BOLD responses during performance of the stop-signal task in right-hemispheric prefrontal regions fundamental to inhibitory control. A significant sex-by-genotype interaction was observed in pre-SMA during successful-inhibition trials and in both pre-SMA and inferior frontal cortex during failed-inhibition trials with Val homozygotes displaying elevated activation compared with other genotypes in males but not in females. BOLD activation in the same regions significantly mediated the relationship between COMT genotype and inhibitory proficiency as indexed by stop-signal reaction time in males alone. These sexually dimorphic effects of COMT on inhibitory brain activation have important implications for our understanding of the contrasting patterns of prefrontally governed psychopathology observed in males and females.
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Dimensions of manic symptoms in youth: psychosocial impairment and cognitive performance in the IMAGEN sample.
J Child Psychol Psychiatry
PUBLISHED: 03-25-2014
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It has been reported that mania may be associated with superior cognitive performance. In this study, we test the hypothesis that manic symptoms in youth separate along two correlated dimensions and that a symptom constellation of high energy and cheerfulness is associated with superior cognitive performance.
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Findings from the observational COMPLY study in children and adolescents with ADHD: core symptoms, ADHD-related difficulties, and patients' emotional expression during psychostimulant or nonstimulant ADHD treatment.
Atten Defic Hyperact Disord
PUBLISHED: 03-22-2014
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The aim of this study was to explore the course of attention-deficit/hyperactivity disorder (ADHD) core symptoms, ADHD-related difficulties, and emotional expression during ADHD pharmacotherapy and associations between them. This prospective, observational study examines pediatric patients with ADHD who newly initiated stimulant, atomoxetine or a combination of both treatments. Data were collected at baseline; weeks 1, 2, and 4; and months 3, 6, 9, and 12. Physicians rated ADHD core symptoms using the ADHD Rating Scale (ADHD-RS); patients, parents, and physicians rated ADHD-related difficulties using the Global Impression of Perceived Difficulties (GIPD) Scale; and patients and parents rated emotional expression using the Expression of Emotion Scale for Children (EESC). Results were analyzed using mixed model repeated measures. Associations are presented by Spearman's correlations. Overall, 504 patients, mean age 9.6 years, 72.6 % males, were analyzed. Fifty percent of patients started atomoxetine, 49.0 % stimulant and 1 % a combination of both. ADHD-RS, GIPD, and EESC scores decreased significantly in both monotherapy groups. Correlations between ADHD-RS and parent- or physician-rated GIPD scores were at-best moderate and increased over time but remained low to moderate for patient-rated GIPD [patient, r = 0.43 (95 % CI 0.34, 0.51); parent, r = 0.58 (0.50, 0.64); physician, r = 0.55 (0.48, 0.62)]. Correlations between ADHD-RS and patient- or parent-rated EESC scores were low at baseline (r < 0.2) and increased over time mostly for parent ratings [patient, r = 0.35 (0.26, 0.44); parent, r = 0.41 (0.32, 0.50)]. These data support the effectiveness of ADHD pharmacotherapy. The at-best moderate correlations between ADHD core symptoms and ADHD-related difficulties or emotional expression assessed by different raters indicate potentially important patient outcomes beyond core symptoms.
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DRD2/ANKK1 polymorphism modulates the effect of ventral striatal activation on working memory performance.
Neuropsychopharmacology
PUBLISHED: 03-14-2014
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Motivation is important for learning and cognition. Although dopaminergic (D2) transmission in the ventral striatum (VS) is associated with motivation, learning, and cognition are more strongly associated with function of the dorsal striatum, including activation in the caudate nucleus. A recent study found an interaction between intrinsic motivation and the DRD2/ANKK1 polymorphism (rs1800497), suggesting that A-carriers of rs1800497 are significantly more sensitive to motivation in order to improve during working memory (WM) training. Using data from the two large-scale imaging genetic data sets, IMAGEN (n=1080, age 13-15 years) and BrainChild (n?300, age 6-27), we investigated whether rs1800497 is associated with WM. In the IMAGEN data set, we tested whether VS/caudate activation during reward anticipation was associated with WM performance and whether rs1800497 and VS/caudate activation interact to affect WM performance. We found that rs1800497 was associated with WM performance in IMAGEN and BrainChild. Higher VS and caudate activation during reward processing were significantly associated with higher WM performance (p<0.0001). An interaction was found between the DRD2/ANKK1 polymorphism rs1800497 and VS activation during reward anticipation on WM (p<0.01), such that carriers of the minor allele (A) showed a significant correlation between VS activation and WM, whereas the GG-homozygotes did not, suggesting that the effect of VS BOLD on WM is modified by inter-individual genetic differences related to D2 dopaminergic transmission.
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Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1.
J Child Psychol Psychiatry
PUBLISHED: 02-13-2014
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Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.
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Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume.
Brain Struct Funct
PUBLISHED: 02-07-2014
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Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.
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Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults.
Brain Struct Funct
PUBLISHED: 02-04-2014
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Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder.
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Interaction between prenatal stress and dopamine D4 receptor genotype in predicting aggression and cortisol levels in young adults.
Psychopharmacology (Berl.)
PUBLISHED: 02-01-2014
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Considerable evidence suggests that genetic factors combine with environmental influences to impact on the development of aggressive behavior. A genetic variant that has repeatedly been reported to render individuals more sensitive to the presence of adverse experiences, including stress exposure during fetal life, is the seven-repeat allele of the dopamine D4 receptor (DRD4) gene.
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Sequential inhibitory control processes assessed through simultaneous EEG-fMRI.
Neuroimage
PUBLISHED: 01-16-2014
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Inhibitory response control has been extensively investigated in both electrophysiological (ERP) and hemodynamic (fMRI) studies. However, very few multimodal results address the coupling of these inhibition markers. In fMRI, response inhibition has been most consistently linked to activation of the anterior insula and inferior frontal cortex (IFC), often also the anterior cingulate cortex (ACC). ERP work has established increased N2 and P3 amplitudes during NoGo compared to Go conditions in most studies. Previous simultaneous EEG-fMRI imaging reported association of the N2/P3 complex with activation of areas like the anterior midcingulate cortex (aMCC) and anterior insula. In this study we investigated inhibitory control in 23 healthy young adults (mean age=24.7, n=17 for EEG during fMRI) using a combined Flanker/NoGo task during simultaneous EEG and fMRI recording. Separate fMRI and ERP analysis yielded higher activation in the anterior insula, IFG and ACC as well as increased N2 and P3 amplitudes during NoGo trials in accordance with the literature. Combined analysis modelling sequential N2 and P3 effects through joint parametric modulation revealed correlation of higher N2 amplitude with deactivation in parts of the default mode network (DMN) and the cingulate motor area (CMA) as well as correlation of higher central P3 amplitude with activation of the left anterior insula, IFG and posterior cingulate. The EEG-fMRI results resolve the localizations of these sequential activations. They suggest a general role for allocation of attentional resources and motor inhibition for N2 and link memory recollection and internal reflection to P3 amplitude, in addition to previously described response inhibition as reflected by the anterior insula.
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Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood.
Eur Neuropsychopharmacol
PUBLISHED: 01-14-2014
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Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders.
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Maintenance of efficacy of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder: randomized-withdrawal study design.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 01-06-2014
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In this phase 3 extension study, the long-term maintenance of efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) was evaluated using a randomized-withdrawal study design.
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Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial.
Neuropsychiatr Dis Treat
PUBLISHED: 01-01-2014
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Following the approval of lisdexamfetamine dimesylate (LDX) in several European countries for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with an inadequate response to methylphenidate (MPH) treatment, the aim of the present analysis was to establish the response to LDX in subgroups of patients with different ADHD medication histories.
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Positive association of video game playing with left frontal cortical thickness in adolescents.
PLoS ONE
PUBLISHED: 01-01-2014
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Playing video games is a common recreational activity of adolescents. Recent research associated frequent video game playing with improvements in cognitive functions. Improvements in cognition have been related to grey matter changes in prefrontal cortex. However, a fine-grained analysis of human brain structure in relation to video gaming is lacking. In magnetic resonance imaging scans of 152 14-year old adolescents, FreeSurfer was used to estimate cortical thickness. Cortical thickness across the whole cortical surface was correlated with self-reported duration of video gaming (hours per week). A robust positive association between cortical thickness and video gaming duration was observed in left dorsolateral prefrontal cortex (DLPFC) and left frontal eye fields (FEFs). No regions showed cortical thinning in association with video gaming frequency. DLPFC is the core correlate of executive control and strategic planning which in turn are essential cognitive domains for successful video gaming. The FEFs are a key region involved in visuo-motor integration important for programming and execution of eye movements and allocation of visuo-spatial attention, processes engaged extensively in video games. The results may represent the biological basis of previously reported cognitive improvements due to video game play. Whether or not these results represent a-priori characteristics or consequences of video gaming should be studied in future longitudinal investigations.
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Severe affective and behavioral dysregulation in youths is associated with a proinflammatory state.
Z Kinder Jugendpsychiatr Psychother
PUBLISHED: 11-19-2013
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A heritable behavioral phenotype, the so-called Dysregulation Profile (DP), characterized by extreme scores on the syndrome scales Anxious/Depressed (A/D), Attention Problems (AP), and Aggressive Behavior (AGG), has been identified on the Child Behavior Checklist (CBCL). It characterizes children with severe affective and behavioral dysregulation. The present study examined possible alterations of the inflammatory system in CBCL-DP using a clinical sample of n = 133 children and adolescents.
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Interaction of neurodevelopmental pathways and synaptic plasticity in mental retardation, autism spectrum disorder and schizophrenia: Implications for psychiatry.
World J. Biol. Psychiatry
PUBLISHED: 09-30-2013
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Objectives. Schizophrenia (SCZ), autism spectrum disorder (ASD) and mental retardation (MR) are psychiatric disorders with high heritability. They differ in their clinical presentation and in their time course of major symptoms, which predominantly occurs for MR and ASD during childhood and for SCZ during young adult age. Recent findings with focus on the developmental neurobiology of these disorders emphasize shared mechanisms of common origin. These findings propose a continuum of genetic risk factors impacting on synaptic plasticity with MR causing impairments in global cognitive abilities, ASD in social cognition and SCZ in both global and social cognition. Methods. We assess here the historical developments that led to the current disease concepts of the three disorders. We then analyse, based on the functions of genes mutated in two or three of the disorders, selected mechanisms shared in neurodevelopmental pathways and synaptic plasticity. Results. The analysis of the psychopathological constructs supports the existence of three distinct clinical entities but also elaborates important associations. Similarly, there are common mechanisms especially in global and social cognition. Conclusions. We discuss implications from this integrated view on MR, ASD and SCZ for child & adolescent and adult psychiatry in pathophysiology and research perspectives.
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[Diagnostic of ADHD in childhood and adolescence with the K-SADS-PL].
Prax Kinderpsychol Kinderpsychiatr
PUBLISHED: 09-17-2013
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Attention Deficit-/Hyperactivity Disorder (ADHD) is one of the most prevalent psychiatric disorders in childhood and adolescence, often accompanied by comorbid disorders. A high standard of diagnostic assessment combined with a demand for valid diagnostic instruments is necessary. The K-SADS-PL is an established semi-structured interview, focusing on the categorical assessment of psychiatric disorders. The aim of the following study was to examine specific characteristics of ADHD symptomatology including functional and behavioral assessment. Therefore correlations between the result in a diagnostic interview (K-SADS-PL) and different ADHD-specific instruments were performed. Groups were formed (exposed vs. unexposed), based on the diagnostic finding in the K-SADS-PL. Group-specific test score differences were calculated and compared by multivariate analyses of covariance. Children with ADHD showed a significantly higher impact of conduct and emotional problems than the unexposed group. Health related quality of life was more impaired in children and families suffering from ADHD which refers to the relevance of family-oriented psychotherapy.
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Aversive Learning in Adolescents: Modulation by Amygdala-Prefrontal and Amygdala-Hippocampal Connectivity and Neuroticism.
Neuropsychopharmacology
PUBLISHED: 09-06-2013
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Neuroticism involves a tendency for enhanced emotional and cognitive processing of negative affective stimuli and a propensity to worry and be anxious. It is known that this trait modulates fear learning and the activation of brain regions involved in it such as the amygdala, hippocampus, and prefrontal cortex and their connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents participated in functional magnetic resonance imaging (fMRI) of aversive pavlovian differential delay conditioning. An unpleasant sound served as unconditioned stimulus (US) and pictures of neutral male faces as conditioned stimuli (CS+ followed by the US in 50% of the cases; CS- never followed by the US). During acquisition (CS+/- differentiation), higher levels of neuroticism were associated with a stronger interaction between the right amygdala and the right hippocampus as well as the right amygdala and prefrontal cortical regions, specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. The association of stronger conditionability of fear and connectivity of brain regions related to consolidation of fear associations and neuroticism points to underlying mechanisms of the enhanced propensity for anxiety disorders in highly neurotic participants. This is especially important in adolescence, a vulnerable time for the onset of mental disorders such as anxiety disorders.Neuropsychopharmacology advance online publication, 13 November 2013; doi:10.1038/npp.2013.287.
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Simultaneous EEG and fMRI reveals a causally connected subcortical-cortical network during reward anticipation.
J. Neurosci.
PUBLISHED: 09-06-2013
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Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL?VS?SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.
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Do you see what I see? Sex differences in the discrimination of facial emotions during adolescence.
Emotion
PUBLISHED: 08-05-2013
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During adolescence social relationships become increasingly important. Establishing and maintaining these relationships requires understanding of emotional stimuli, such as facial emotions. A failure to adequately interpret emotional facial expressions has previously been associated with various mental disorders that emerge during adolescence. The current study examined sex differences in emotional face processing during adolescence. Participants were adolescents (n = 1951) with a target age of 14, who completed a forced-choice emotion discrimination task. The stimuli used comprised morphed faces that contained a blend of two emotions in varying intensities (11 stimuli per set of emotions). Adolescent girls showed faster and more sensitive perception of facial emotions than boys. However, both adolescent boys and girls were most sensitive to variations in emotion intensity in faces combining happiness and sadness, and least sensitive to changes in faces comprising fear and anger. Furthermore, both sexes overidentified happiness and anger. However, the overidentification of happiness was stronger in boys. These findings were not influenced by individual differences in the level of pubertal maturation. These results indicate that male and female adolescents differ in their ability to identify emotions in morphed faces containing emotional blends. The findings provide information for clinical studies examining whether sex differences in emotional processing are related to sex differences in the prevalence of psychiatric disorders within this age group. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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Health-related quality of life and functional outcomes from a randomized, controlled study of lisdexamfetamine dimesylate in children and adolescents with attention deficit hyperactivity disorder.
CNS Drugs
PUBLISHED: 07-30-2013
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Optimal management of attention deficit hyperactivity disorder (ADHD) aims not only to ameliorate patients symptoms, but also to improve health-related quality of life (HRQL) and functioning. A pivotal, 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in ten European countries demonstrated that the stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well-tolerated treatment for symptoms of ADHD.
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Randomized parcellation based inference.
Neuroimage
PUBLISHED: 07-11-2013
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Neuroimaging group analyses are used to relate inter-subject signal differences observed in brain imaging with behavioral or genetic variables and to assess risks factors of brain diseases. The lack of stability and of sensitivity of current voxel-based analysis schemes may however lead to non-reproducible results. We introduce a new approach to overcome the limitations of standard methods, in which active voxels are detected according to a consensus on several random parcellations of the brain images, while a permutation test controls the false positive risk. Both on synthetic and real data, this approach shows higher sensitivity, better accuracy and higher reproducibility than state-of-the-art methods. In a neuroimaging-genetic application, we find that it succeeds in detecting a significant association between a genetic variant next to the COMT gene and the BOLD signal in the left thalamus for a functional Magnetic Resonance Imaging contrast associated with incorrect responses of the subjects from a Stop Signal Task protocol.
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Mothers prenatal stress and their childrens antisocial outcomes - a moderating role for the Dopamine D4 Receptor (DRD4) gene.
J Child Psychol Psychiatry
PUBLISHED: 07-11-2013
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Maternal distress during pregnancy has been linked to aggressive behavior in offspring. This effect has been interpreted in terms of fetal programming. The 7-repeat (7r) allele of a VNTR polymorphism in exon III of the human dopamine receptor D4 (DRD4) has consistently been associated with externalizing behavior problems, especially in the presence of adverse environmental factors. So far, it is not known whether the DRD4 genotype moderates the effect of prenatal maternal stress on the development of childhood antisocial behavior.
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Oxytocin Receptor Genotype Modulates Ventral Striatal Activity to Social Cues and Response to Stressful Life Events.
Biol. Psychiatry
PUBLISHED: 07-01-2013
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Common variants in the oxytocin receptor gene (OXTR) have been shown to influence social and affective behavior and to moderate the effect of adverse experiences on risk for social-affective problems. However, the intermediate neurobiological mechanisms are not fully understood. Although human functional neuroimaging studies have reported that oxytocin effects on social behavior and emotional states are mediated by amygdala function, animal models indicate that oxytocin receptors in the ventral striatum (VS) modulate sensitivity to social reinforcers. This study aimed to comprehensively investigate OXTR-dependent brain mechanisms associated with social-affective problems.
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A post hoc comparison of the effects of lisdexamfetamine dimesylate and osmotic-release oral system methylphenidate on symptoms of attention-deficit hyperactivity disorder in children and adolescents.
CNS Drugs
PUBLISHED: 06-27-2013
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There are limited head-to-head data comparing the efficacy of long-acting amfetamine- and methylphenidate-based psychostimulants as treatments for individuals with attention-deficit hyperactivity disorder (ADHD). This post hoc analysis provides the first parallel-group comparison of the effect of lisdexamfetamine dimesylate (lisdexamfetamine) and osmotic-release oral system methylphenidate (OROS-MPH) on symptoms of ADHD in children and adolescents.
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Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking.
JAMA Psychiatry
PUBLISHED: 06-21-2013
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Higher rates of substance use and dependence have been observed in the offspring of mothers who smoked during pregnancy. Animal studies indicate that prenatal exposure to nicotine alters the development of brain areas related to reward processing, which might be a risk factor for substance use and addiction later in life. However, no study has examined the effect of maternal smoking on the offsprings brain response during reward processing.
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Evaluation of a computer-based neuropsychological training in children with attention-deficit hyperactivity disorder (ADHD).
NeuroRehabilitation
PUBLISHED: 05-08-2013
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We report the effects of a computer-based neuropsychological training in children with Attention-Deficit Hyperactivity Disorder (ADHD). We hypothesized that a specific training focusing on attentional dysfunction would result in an improvement of inattention, observable in test performance, behavior and performance during experimental school lessons and in parent and teacher ratings of the related core symptom.
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Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized, controlled trial.
Eur Child Adolesc Psychiatry
PUBLISHED: 05-04-2013
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Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6-17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment - placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).
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High loading of polygenic risk for ADHD in children with comorbid aggression.
Am J Psychiatry
PUBLISHED: 04-20-2013
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OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.
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Individual treatment response in attention-deficit/hyperactivity disorder: broadening perspectives and improving assessments.
Expert Rev Neurother
PUBLISHED: 04-03-2013
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Attention-deficit/hyperactivity disorder (ADHD) is a highly complex disorder with multiple treatment options. Impairments associated with ADHD, rather than symptoms defining the disorder, are the primary reason for referral of individuals to clinical services; consequently, they should also be key targets for intervention. Impairments are moderated by factors such as comorbidities, family environment and intelligence quotient, and particular challenges may vary between patients. The understanding of patient and family treatment preferences, as well as identification of treatment needs and goals, should drive future clinical practice. This review addresses the assessment of ADHD treatment goals and outcomes in clinical practice, and discusses changes in future clinical research studies necessary to progress the utilization of an individualized medicine approach in ADHD.
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Neural mechanisms of attention-deficit/hyperactivity disorder symptoms are stratified by MAOA genotype.
Biol. Psychiatry
PUBLISHED: 03-19-2013
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Attention-deficit/hyperactivity disorder (ADHD) is characterized by deficits in reward sensitivity and response inhibition. The relative contribution of these frontostriatal mechanisms to ADHD symptoms and their genetic determinants is largely unexplored.
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Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 03-17-2013
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Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P = 0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P = 0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P = 0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHDs etiology.
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Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 03-13-2013
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Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD.
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Impact of pubertal stage at first drink on adult drinking behavior.
Alcohol. Clin. Exp. Res.
PUBLISHED: 03-08-2013
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Early alcohol use is one of the strongest predictors of later alcohol use disorders, with early use usually taking place during puberty. Many researchers have suggested drinking during puberty as a potential biological basis of the age at first drink (AFD) effect. However, the influence of the pubertal phase at alcohol use initiation on subsequent drinking in later life has not been examined so far.
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From gene to brain to behavior: schizophrenia-associated variation in AMBRA1 alters impulsivity-related traits.
Eur. J. Neurosci.
PUBLISHED: 02-26-2013
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Recently, genome-wide association between schizophrenia and an intronic variant in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level-dependent (BOLD) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity-related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis (n = 848) and a functional magnetic resonance imaging (fMRI) task (n = 512). Various aspects of impulsivity were assessed using the Temperament and Character Inventory-Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition Neuropsychological Test Automated Battery, and the Stop Signal Task (SST) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito-frontal target region during the SST, which declined to trend status after Family Wise Error correction. Our findings support the hypothesis that the schizophrenia-related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level.
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Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies.
BMC Psychiatry
PUBLISHED: 02-24-2013
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The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed.The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection.
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Association of PER2 genotype and stressful life events with alcohol drinking in young adults.
PLoS ONE
PUBLISHED: 02-13-2013
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Clock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking.
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Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.
, S Hong Lee, Stephan Ripke, Benjamin M Neale, Stephen V Faraone, Shaun M Purcell, Roy H Perlis, Bryan J Mowry, Anita Thapar, Michael E Goddard, John S Witte, Devin Absher, Ingrid Agartz, Huda Akil, Farooq Amin, Ole A Andreassen, Adebayo Anjorin, Richard Anney, Verneri Anttila, Dan E Arking, Philip Asherson, Maria H Azevedo, Lena Backlund, Judith A Badner, Anthony J Bailey, Tobias Banaschewski, Jack D Barchas, Michael R Barnes, Thomas B Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Mònica Bayés, Frank Bellivier, Sarah E Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B Binder, Donald W Black, Douglas H R Blackwood, Cinnamon S Bloss, Michael Boehnke, Dorret I Boomsma, Gerome Breen, René Breuer, Richard Bruggeman, Paul Cormican, Nancy G Buccola, Jan K Buitelaar, William E Bunney, Joseph D Buxbaum, William F Byerley, Enda M Byrne, Sian Caesar, Wiepke Cahn, Rita M Cantor, Miguel Casas, Aravinda Chakravarti, Kimberly Chambert, Khalid Choudhury, Sven Cichon, C Robert Cloninger, David A Collier, Edwin H Cook, Hilary Coon, Bru Cormand, Aiden Corvin, William H Coryell, David W Craig, Ian W Craig, Jennifer Crosbie, Michael L Cuccaro, David Curtis, Darina Czamara, Susmita Datta, Geraldine Dawson, Richard Day, Eco J De Geus, Franziska Degenhardt, Srdjan Djurovic, Gary J Donohoe, Alysa E Doyle, Jubao Duan, Frank Dudbridge, Eftichia Duketis, Richard P Ebstein, Howard J Edenberg, Josephine Elia, Sean Ennis, Bruno Etain, Ayman Fanous, Anne E Farmer, I Nicol Ferrier, Matthew Flickinger, Eric Fombonne, Tatiana Foroud, Josef Frank, Barbara Franke, Christine Fraser, Robert Freedman, Nelson B Freimer, Christine M Freitag, Marion Friedl, Louise Frisén, Louise Gallagher, Pablo V Gejman, Lyudmila Georgieva, Elliot S Gershon, Daniel H Geschwind, Ina Giegling, Michael Gill, Scott D Gordon, Katherine Gordon-Smith, Elaine K Green, Tiffany A Greenwood, Dorothy E Grice, Magdalena Gross, Detelina Grozeva, Weihua Guan, Hugh Gurling, Lieuwe de Haan, Jonathan L Haines, Hakon Hakonarson, Joachim Hallmayer, Steven P Hamilton, Marian L Hamshere, Thomas F Hansen, Annette M Hartmann, Martin Hautzinger, Andrew C Heath, Anjali K Henders, Stefan Herms, Ian B Hickie, Maria Hipolito, Susanne Hoefels, Peter A Holmans, Florian Holsboer, Witte J Hoogendijk, Jouke-Jan Hottenga, Christina M Hultman, Vanessa Hus, Andrés Ingason, Marcus Ising, Stéphane Jamain, Edward G Jones, Ian Jones, Lisa Jones, Jung-Ying Tzeng, Anna K Kähler, René S Kahn, Radhika Kandaswamy, Matthew C Keller, James L Kennedy, Elaine Kenny, Lindsey Kent, Yunjung Kim, George K Kirov, Sabine M Klauck, Lambertus Klei, James A Knowles, Martin A Kohli, Daniel L Koller, Bettina Konte, Ania Korszun, Lydia Krabbendam, Robert Krasucki, Jonna Kuntsi, Phoenix Kwan, Mikael Landén, Niklas Långström, Mark Lathrop, Jacob Lawrence, William B Lawson, Marion Leboyer, David H Ledbetter, Phil H Lee, Todd Lencz, Klaus-Peter Lesch, Douglas F Levinson, Cathryn M Lewis, Jun Li, Paul Lichtenstein, Jeffrey A Lieberman, Dan-Yu Lin, Don H Linszen, Chunyu Liu, Falk W Lohoff, Sandra K Loo, Catherine Lord, Jennifer K Lowe, Susanne Lucae, Donald J MacIntyre, Pamela A F Madden, Elena Maestrini, Patrik K E Magnusson, Pamela B Mahon, Wolfgang Maier, Anil K Malhotra, Shrikant M Mane, Christa L Martin, Nicholas G Martin, Manuel Mattheisen, Keith Matthews, Morten Mattingsdal, Steven A McCarroll, Kevin A McGhee, James J McGough, Patrick J McGrath, Peter McGuffin, Melvin G McInnis, Andrew McIntosh, Rebecca McKinney, Alan W McLean, Francis J McMahon, William M McMahon, Andrew McQuillin, Helena Medeiros, Sarah E Medland, Sandra Meier, Ingrid Melle, Fan Meng, Jobst Meyer, Christel M Middeldorp, Lefkos Middleton, Vihra Milanova, Ana Miranda, Anthony P Monaco, Grant W Montgomery, Jennifer L Moran, Daniel Moreno-De-Luca, Gunnar Morken, Derek W Morris, Eric M Morrow, Valentina Moskvina, Pierandrea Muglia, Thomas W Mühleisen, Walter J Muir, Bertram Müller-Myhsok, Michael Murtha, Richard M Myers, Inez Myin-Germeys, Michael C Neale, Stan F Nelson, Caroline M Nievergelt, Ivan Nikolov, Vishwajit Nimgaonkar, Willem A Nolen, Markus M Nöthen, John I Nurnberger, Evaristus A Nwulia, Dale R Nyholt, Colm O'Dushlaine, Robert D Oades, Ann Olincy, Guiomar Oliveira, Line Olsen, Roel A Ophoff, Urban Osby, Michael J Owen, Aarno Palotie, Jeremy R Parr, Andrew D Paterson, Carlos N Pato, Michele T Pato, Brenda W Penninx, Michele L Pergadia, Margaret A Pericak-Vance, Benjamin S Pickard, Jonathan Pimm, Joseph Piven, Danielle Posthuma, James B Potash, Fritz Poustka, Peter Propping, Vinay Puri, Digby J Quested, Emma M Quinn, Josep Antoni Ramos-Quiroga, Henrik B Rasmussen, Soumya Raychaudhuri, Karola Rehnström, Andreas Reif, Marta Ribasés, John P Rice, Marcella Rietschel, Kathryn Roeder, Herbert Roeyers, Lizzy Rossin, Aribert Rothenberger, Guy Rouleau, Douglas Ruderfer, Dan Rujescu, Alan R Sanders, Stephan J Sanders, Susan L Santangelo, Joseph A Sergeant, Russell Schachar, Martin Schalling, Alan F Schatzberg, William A Scheftner, Gerard D Schellenberg, Stephen W Scherer, Nicholas J Schork, Thomas G Schulze, Johannes Schumacher, Markus Schwarz, Edward Scolnick, Laura J Scott, Jianxin Shi, Paul D Shilling, Stanley I Shyn, Jeremy M Silverman, Susan L Slager, Susan L Smalley, Johannes H Smit, Erin N Smith, Edmund J S Sonuga-Barke, David St Clair, Matthew State, Michael Steffens, Hans-Christoph Steinhausen, John S Strauss, Jana Strohmaier, T Scott Stroup, James S Sutcliffe, Peter Szatmari, Szabocls Szelinger, Srinivasa Thirumalai, Robert C Thompson, Alexandre A Todorov, Federica Tozzi, Jens Treutlein, Manfred Uhr, Edwin J C G van den Oord, Gerard van Grootheest, Jim van Os, Astrid M Vicente, Veronica J Vieland, John B Vincent, Peter M Visscher, Christopher A Walsh, Thomas H Wassink, Stanley J Watson, Myrna M Weissman, Thomas Werge, Thomas F Wienker, Ellen M Wijsman, Gonneke Willemsen, Nigel Williams, A Jeremy Willsey, Stephanie H Witt, Wei Xu, Allan H Young, Timothy W Yu, Stanley Zammit, Peter P Zandi, Peng Zhang, Frans G Zitman, Sebastian Zöllner, Bernie Devlin, John R Kelsoe, Pamela Sklar, Mark J Daly, Michael C O'Donovan, Nicholas Craddock, Patrick F Sullivan, Jordan W Smoller, Kenneth S Kendler, Naomi R Wray.
Nat. Genet.
PUBLISHED: 02-10-2013
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Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohns disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
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Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments.
Am J Psychiatry
PUBLISHED: 01-31-2013
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Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments.
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An inventory of European data sources for the long-term safety evaluation of methylphenidate.
Eur Child Adolesc Psychiatry
PUBLISHED: 01-29-2013
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To compile an inventory of European healthcare databases with potential to study long-term effects of methylphenidate (MPH) in patients with attention deficit hyperactivity disorder (ADHD). Potential databases were identified through expert opinion, the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, and literature search. An online survey was conducted among database providers/coordinators to ascertain the databases appropriateness for inclusion into the inventory. It included questions about database characteristics, sample size, availability of information on drug exposure, clinical data and accessibility. Forty-two databases from 11 countries were identified and their coordinators invited to participate; responses were obtained for 22 (52.4 %) databases of which 15 record ADHD diagnoses. Eleven had sufficient data on ADHD diagnosis, drug exposure, and at least one type of outcome information (symptoms/clinical events, weight, height, blood pressure, heart rate) to assess MPH safety. These were Aarhus University Prescription Database, Danish National Birth Cohort (Denmark); German Health Interview and Examination Survey for Children and Adolescents; Health Search Database Thales, Italian ADHD Register, Lombardy Region ADHD Database (Italy); Avon Longitudinal Study of Parents and Children, General Practice Research Database, The Health Improvement Network, QResearch (UK) and IMS Disease Analyzer (UK, Germany, France). Of the 20 databases with no responses, information on seven from publications and/or websites was obtained; Pedianet and the Integrated Primary Care Information database were considered suitable. Many European healthcare databases can be used for multinational long-term safety studies of MPH. Methodological research is underway to investigate the feasibility of their pooling and analysis.
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European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder.
Eur Neuropsychopharmacol
PUBLISHED: 01-15-2013
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This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ? 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.
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The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing.
Bipolar Disord
PUBLISHED: 01-07-2013
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OBJECTIVES: Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents. METHODS: We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed. RESULTS: Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing. CONCLUSION: Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined.
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Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents.
J Child Psychol Psychiatry
PUBLISHED: 01-07-2013
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Medication is an important element of therapeutic strategies for ADHD. While medications for ADHD are generally well-tolerated, there are common, although less severe, as well as rare but severe adverse events AEs during treatment with ADHD drugs. The aim of this review is to provide evidence- and expert-based guidance concerning the management of (AEs) with medications for ADHD.
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Maternal stimulation in infancy predicts hypothalamic-pituitary-adrenal axis reactivity in young men.
J Neural Transm
PUBLISHED: 01-04-2013
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Evidence from animal research has demonstrated the effect of early maternal care on the offsprings endocrine and behavioral stress response in adulthood. The present prospective study investigates, in humans, the long-term impact of maternal responsiveness and stimulation during early mother-child interaction on adrenocorticotropic hormone (ACTH) and cortisol response to a psychosocial laboratory stressor in adulthood. The data are from an epidemiological cohort study of the long-term outcome of early risk factors assessed at birth. At age 3 months, mothers and infants were videotaped during a 10-min standardized nursing and playing situation and evaluated by trained raters for maternal stimulation and infant and maternal responsiveness. At age 19 years, 270 participants (146 females, 124 males) completed the Trier Social Stress Test. The results indicated that less maternal stimulation during early interaction at age 3 months predicted diminished plasma ACTH and cortisol increase in response to acute psychosocial stress in male, but not female offspring. In contrast, maternal responsiveness was found to be unrelated to hypothalamic-pituitary-adrenal (HPA) reactivity. In accordance with the findings from animal research, the present study provides prospective evidence in humans of a long-term association between early maternal interaction behavior and the offsprings hormonal stress response in young adulthood, suggesting that poor maternal stimulation in early infancy may result in reduced HPA axis reactivity to an acute psychosocial stressor in males.
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Comorbidities in ADHD children treated with methylphenidate: a database study.
BMC Psychiatry
PUBLISHED: 01-04-2013
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Methylphenidate (MPH) is the most common drug treatment of attention deficit / hyperactivity disorder (ADHD) in children. Treatment with MPH is contraindicated in the presence of certain psychiatric, cerebro- and cardiovascular conditions. We assessed MPH treatment prevalence and incidence and the frequency of comorbid conditions related to these contraindications in new MPH users compared to a control group without ADHD and ADHD medication.
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A phenotypic structure and neural correlates of compulsive behaviors in adolescents.
PLoS ONE
PUBLISHED: 01-01-2013
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A compulsivity spectrum has been hypothesized to exist across Obsessive-Compulsive disorder (OCD), Eating Disorders (ED), substance abuse (SA) and binge-drinking (BD). The objective was to examine the validity of this compulsivity spectrum, and differentiate it from an externalizing behaviors dimension, but also to look at hypothesized personality and neural correlates.
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Twin and sibling studies using health insurance data: the example of attention deficit/hyperactivity disorder (ADHD).
PLoS ONE
PUBLISHED: 01-01-2013
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Twin studies are used to assess the contribution of genetic factors to the aetiology of diseases. To show the feasibility of such research on the basis of health insurance data, we analysed twin and sibling data on the attention deficit/hyperactivity disorder (ADHD) in the German Pharmacoepidemiological Research Database (GePaRD).
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Determinants of early alcohol use in healthy adolescents: the differential contribution of neuroimaging and psychological factors.
Neuropsychopharmacology
PUBLISHED: 11-23-2011
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Individual variation in reward sensitivity may have an important role in early substance use and subsequent development of substance abuse. This may be especially important during adolescence, a transition period marked by approach behavior and a propensity toward risk taking, novelty seeking and alteration of the social landscape. However, little is known about the relative contribution of personality, behavior, and brain responses for prediction of alcohol use in adolescents. In this study, we applied factor analyses and structural equation modeling to reward-related brain responses assessed by functional magnetic resonance imaging during a monetary incentive delay task. In addition, novelty seeking, sensation seeking, impulsivity, extraversion, and behavioral measures of risk taking were entered as predictors of early onset of drinking in a sample of 14-year-old healthy adolescents (N=324). Reward-associated behavior, personality, and brain responses all contributed to alcohol intake with personality explaining a higher proportion of the variance than behavior and brain responses. When only the ventral striatum was used, a small non-significant contribution to the prediction of early alcohol use was found. These data suggest that the role of reward-related brain activation may be more important in addiction than initiation of early drinking, where personality traits and reward-related behaviors were more significant. With up to 26% of explained variance, the interrelation of reward-related personality traits, behavior, and neural response patterns may convey risk for later alcohol abuse in adolescence, and thus may be identified as a vulnerability factor for the development of substance use disorders.
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The hierarchical factor model of ADHD: invariant across age and national groupings?
J Child Psychol Psychiatry
PUBLISHED: 11-15-2011
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To examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and sibling samples, across three different instruments and across parent and teacher informants. Specific consideration was given to factorial invariance analyses across different ages and different countries in the ADHD sample.
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Drugs as instruments from a developmental child and adolescent psychiatric perspective.
Behav Brain Sci
PUBLISHED: 11-15-2011
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Developmental, epidemiological, and neurobiological studies indicate that the adaptive and maladaptive functions, as well as immediate and long-term consequences of drug use, may vary by age. Early initiation seems to be associated with a reduced ability to use drugs purposely in a temporally stable, non-addictive manner. Prevention strategies should consider social environmental factors and aim to delay age at initiation.
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Neuropsychological outcomes across the day in children with attention-deficit/hyperactivity disorder treated with atomoxetine: results from a placebo-controlled study using a computer-based continuous performance test combined with an infra-red motion-tra
J Child Adolesc Psychopharmacol
PUBLISHED: 11-02-2011
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The effect of atomoxetine (ATX) on executive function has been assessed by means of questionnaires only. The aim of this study was therefore to evaluate the efficacy of ATX using standard variables of a computer-based continuous performance test (cb-CPT) combined with an infra-red motion-tracking device at different times of the day. One hundred twenty-eight girls and boys aged 6 to 12 years with a diagnosis of ADHD according to DSM-IV-TR criteria were randomized in the study. The primary efficacy measures were the q-scores of the cb-CPT combined with an infra-red motion-tracking device. The test comprises 13 neuropsychological variables that can be taken to reflect hyperactivity, inattention, or impulsivity. One hundred five patients completed the study (ATX group: n=54; placebo group: n=51). ATX (target dose 1.2?mg/kg/day) over 8 weeks was significantly superior to placebo in reducing hyperactivity, inattention, and impulsivity as measured by q-scores of 10 primary variables of the cb-CPT. Both groups of patients showed a circadian pattern of neuropsychological outcomes across the day as reflected by the cb-CPT combined with an infra-red motion-tracking device. In summary, this study demonstrated a positive effect of ATX on some aspects of executive function, inhibitory control, and hyperactivity compared with placebo.
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Early smoking onset may promise initial pleasurable sensations and later addiction.
Addict Biol
PUBLISHED: 10-04-2011
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There is converging evidence suggesting a particular susceptibility to the addictive properties of nicotine among adolescents. The aim of the current study was to prospectively ascertain the relationship between age at first cigarette and initial smoking experiences, and to examine the combined effects of these characteristics of adolescent smoking behavior on adult smoking. It was hypothesized that the association between earlier age at first cigarette and later development of nicotine dependence may, at least in part, be attributable to differences in experiencing pleasurable early smoking sensations. Data were drawn from the participants of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study from birth to adulthood. Structured interviews at age 15, 19 and 22 years were conducted to assess the age at first cigarette, early smoking experiences and current smoking behavior in 213 young adults. In addition, the participants completed the Fagerström Test for Nicotine Dependence. Adolescents who smoked their first cigarette at an earlier age reported more pleasurable sensations from the cigarette, and they were more likely to be regular smokers at age 22. The age at first cigarette also predicted the number of cigarettes smoked and dependence at age 22. Thus, both the age of first cigarette and the pleasure experienced from the cigarette independently predicted aspects of smoking at age 22.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.