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Friendship and social functioning following early institutional rearing: The role of ADHD symptoms.
Humphreys KL, Gabard-Durnam L, Goff B, Telzer EH, Flannery J, Gee DG, Park V, Lee SS, Tottenham N
(2019) Dev Psychopathol 31: 1477-1487
MeSH Terms: Adolescent, Aggression, Attention Deficit Disorder with Hyperactivity, Child, Child, Institutionalized, Female, Friends, Humans, Male, Peer Group, Social Adjustment, Social Behavior
Show Abstract · Added March 3, 2020
Early institutional rearing is associated with increased risk for subsequent peer relationship difficulties, but the underlying mechanisms have not been identified. Friendship characteristics, social behaviors with peers, normed assessments of social problems, and social cue use were assessed in 142 children (mean age = 10.06, SD = 2.02; range 7-13 years), of whom 67 were previously institutionalized (PI), and 75 were raised by their biological families. Anxiety and attention-deficit/hyperactivity disorder (ADHD) symptoms, often elevated among PI children, were examined as potential mediators of PI status and baseline social functioning and longitudinal follow-ups (2 and 4 years later). Twenty-seven percent of PI children fell above the Child Behavior Checklist Social Problems cutoff. An examination of specific social behaviors with peers indicated that PI and comparison children did not differ in empathic concern or peer social approach, though parents were more likely to endorse aggression/overarousal as a reason that PI children might struggle with friendships. Comparison children outperformed PI children in computerized testing of social cue use learning. Finally, across these measures, social difficulties exhibited in the PI group were mediated by ADHD symptoms with predicted social problems assessed 4 years later. These findings show that, when PI children struggle with friendships, mechanisms involving attention and behavior regulation are likely contributors.
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MeSH Terms
Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence.
Humphreys KL, Watts EL, Dennis EL, King LS, Thompson PM, Gotlib IH
(2019) J Abnorm Child Psychol 47: 421-432
MeSH Terms: Adolescent, Adverse Childhood Experiences, Attention Deficit Disorder with Hyperactivity, Child, Female, Humans, Magnetic Resonance Imaging, Male, Stress, Psychological, Temporal Lobe, Time Factors, White Matter
Show Abstract · Added March 3, 2020
Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.
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12 MeSH Terms
Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model.
Dai H, Jackson CR, Davis GL, Blakely RD, McMahon DG
(2017) J Neurodev Disord 9: 38
MeSH Terms: Animals, Attention Deficit Disorder with Hyperactivity, Biomarkers, Disease Models, Animal, Dopamine, Dopamine Plasma Membrane Transport Proteins, Electroretinography, Female, Male, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Transgenic, Retina, Vision, Ocular
Show Abstract · Added February 9, 2018
BACKGROUND - Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes. To understand the broader impact of ADE on ADHD, noninvasive measures sensitive to DAT reversal are needed.
METHODS - Here, we explored this question through ERG-based analysis of retinal light responses, as well as HPLC measurements of retinal DA in DAT Val559 mice.
RESULTS - Male mice homozygous (HOM) for the DAT Val559 variant demonstrated increased, light-adapted ERG b-wave amplitudes compared to wild type (WT) and heterozygous (HET) mice, whereas dark-adapted responses were indistinguishable across genotypes. The elevated amplitude of the photopic light responses in HOM mice could be mimicked in WT mice by applying D and D DA receptor agonists and suppressed in HOM mice by introducing D antagonist, supporting elevated retinal DA signaling arising from ADE. Following the challenge with amphetamine, WT exhibited an increase in light-adapted response amplitudes, while HOM did not. Total retinal DA content was similar across genotypes. Interestingly, female DAT Val559 HOM animals revealed no significant difference in photopic ERG responses when compared with WT and HET littermates.
CONCLUSIONS - These data reveal that noninvasive, in vivo evaluation of retinal responses to light can reveal physiological signatures of ADE, suggesting a possible approach to the segregation of neurobehavioral disorders based on the DAT-dependent control of DA signaling.
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14 MeSH Terms
Evaluating the consistency of scales used in adult attention deficit hyperactivity disorder assessment of college-aged adults.
Saleh A, Fuchs C, Taylor WD, Niarhos F
(2018) J Am Coll Health 66: 98-105
MeSH Terms: Adult, Attention Deficit Disorder with Hyperactivity, Female, Humans, Male, Mass Screening, Psychiatric Status Rating Scales, Retrospective Studies, Self-Assessment, Severity of Illness Index, Students, Universities, Young Adult
Show Abstract · Added March 14, 2018
OBJECTIVE - Neurocognitive evaluations are commonly integrated with clinical assessment to evaluate adult Attention Deficit Hyperactivity Disorder (ADHD). Study goal is to identify measures most strongly related to ADHD diagnosis and to determine their utility in screening processes.
PARTICIPANTS - 230 students who were evaluated at the Vanderbilt University Psychological and Counseling Center between July 2013 and October 2015.
METHODS - We retrospectively examined charts, including clinical diagnosis, family history, childhood parental reported and current self-reported ADHD symptoms, psychiatric comorbidities, and continuous performance test (CPT).
RESULT - Positive report of childhood and current ADHD symptoms, and lack of comorbid psychiatric symptoms were strongly associated with clinical diagnosis. CPT results were not associated with an ADHD diagnosis. The absence of reported childhood and current ADHD symptoms may serve as a contradictory marker for ADHD diagnosis.
CONCLUSION - Clinical assessment of ADHD symptoms and ADHD childhood history, but not CPT, contributes to an accurate diagnosis of ADHD in college-aged adults.
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13 MeSH Terms
Risky decision-making in children with and without ADHD: A prospective study.
Humphreys KL, Tottenham N, Lee SS
(2018) Child Neuropsychol 24: 261-276
MeSH Terms: Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Decision Making, Female, Humans, Male, Prospective Studies, Risk-Taking
Show Abstract · Added March 3, 2020
Learning from past decisions can enhance successful decision-making. It is unclear whether difficulties in learning from experience may contribute to risky decision-making, which may be altered among individuals with attention-deficit/hyperactivity disorder (ADHD). This study follows 192 children with and without ADHD aged 5 to 10 years for approximately 2.5 years and examines their risky decision-making using the Balloon Emotional Learning Task (BELT), a computerized assessment of sequential risky decision-making in which participants pump up a series of virtual balloons for points. The BELT contains three task conditions: one with a variable explosion point, one with a stable and early explosion point, and one with a stable and late explosion point. These conditions may be learned via experience on the task. Contrary to expectations, ADHD status was not found to be related to greater risk-taking on the BELT, and among younger children ADHD status is in fact associated with reduced risk-taking. In addition, the typically-developing children without ADHD showed significant learning-related gains on both stable task conditions. However, the children with ADHD demonstrated learning on the condition with a stable and early explosion point, but not on the condition with the stable and late explosion point, in which more pumps are required before learning when the balloon will explode. Learning during decision-making may be more difficult for children with ADHD. Because adapting to changing environmental demands requires the use of feedback to guide future behavior, negative outcomes associated with childhood ADHD may partially reflect difficulties in learning from experience.
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CATEGORICAL DIAGNOSIS OF EXTREME HYPERACTIVITY, IMPULSIVITY, AND INATTENTION IN VERY YOUNG CHILDREN.
Gleason MM, Humphreys KL
(2016) Infant Ment Health J 37: 476-85
MeSH Terms: Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Humans, Impulsive Behavior, Infant, Vocabulary, Controlled
Show Abstract · Added March 3, 2020
Severe hyperactivity and impulsivity are common reasons for referral to infant mental health services. Past versions of ZERO TO THREE's () diagnostic nosology, the Diagnostic Classification of Mental and Developmental Disorders in Infancy and Early Childhood (DC:0-3), did not address this clinical issue because it had been addressed in other nosologies. These general diagnostic nosologies describe attention deficit hyperactivity disorder (ADHD), but with little attention to developmentally specific aspects of the diagnosis in very young children. Categorical diagnosis related to hyperactivity and impulsivity in very young children warrants careful review of existing literature. Explicit attention must be paid to ensure that categorical diagnoses serve to describe syndromes that cause significant impairment to the family to allow children and families to access effective supports and ensure that behaviors typical of the developmental level are not described as pathologic. This article reviews proposed diagnostic criteria for ADHD and overactivity disorder of toddlerhood as well as the rationale for the criteria and evidence supporting validity and reliability of the diagnoses in very young children. Clinical implications also are presented.
© 2016 Michigan Association for Infant Mental Health.
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Psychopathology in young children in two types of foster care following institutional rearing.
Tibu F, Humphreys KL, Fox NA, Nelson CA, Zeanah CH
(2014) Infant Ment Health J 35: 123-31
MeSH Terms: Attention Deficit Disorder with Hyperactivity, Child, Institutionalized, Child, Preschool, Female, Foster Home Care, Humans, Male, Mental Disorders, Psychopathology, Sex Factors
Show Abstract · Added March 3, 2020
Institutional rearing of young children has been demonstrated to increase risk for a broad range of psychiatric disorders and other impairments. This has led many countries to consider or to invest in foster care. However, no study to date has explored potential differences in psychiatric symptoms in children placed in different types of foster care. We assessed internalizing disorders, externalizing disorders, and attention deficit hyperactivity disorder (ADHD) in 54-month-old children living with foster families. We compared one group of children living in high-quality foster families who had benefited from specialized training and support to another group of children placed with government-sponsored foster care in Bucharest, Romania. After controlling for duration of time spent in foster care, there was a main group effect in predicting ADHD (p = .021) and a marginal group × gender interaction effect. No effects were noted for signs of externalizing disorders. There was, however, a significant group × gender interaction effect of signs of internalizing disorders (p = .007), with the girls in high-quality foster care having less severe symptomatology than did their counterparts in the government-sponsored group. Governments must invest in quality interventions for their most vulnerable citizens to prevent serious and potentially lasting problems.
© 2014 Michigan Association for Infant Mental Health.
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Single-quantum-dot tracking reveals altered membrane dynamics of an attention-deficit/hyperactivity-disorder-derived dopamine transporter coding variant.
Kovtun O, Sakrikar D, Tomlinson ID, Chang JC, Arzeta-Ferrer X, Blakely RD, Rosenthal SJ
(2015) ACS Chem Neurosci 6: 526-34
MeSH Terms: Amphetamine, Attention Deficit Disorder with Hyperactivity, Cell Membrane, Central Nervous System Stimulants, Diffusion, Dopamine Plasma Membrane Transport Proteins, HEK293 Cells, Humans, Microscopy, Confocal, Microscopy, Fluorescence, Mutation, Quantum Dots, Time-Lapse Imaging
Show Abstract · Added September 28, 2015
The presynaptic, cocaine- and amphetamine-sensitive dopamine (DA) transporter (DAT, SLC6A3) controls the intensity and duration of synaptic dopamine signals by rapid clearance of DA back into presynaptic nerve terminals. Abnormalities in DAT-mediated DA clearance have been linked to a variety of neuropsychiatric disorders, including addiction, autism, and attention deficit/hyperactivity disorder (ADHD). Membrane trafficking of DAT appears to be an important, albeit incompletely understood, post-translational regulatory mechanism; its dysregulation has been recently proposed as a potential risk determinant of these disorders. In this study, we demonstrate a link between an ADHD-associated DAT mutation (Arg615Cys, R615C) and variation on DAT transporter cell surface dynamics, a combination only previously studied with ensemble biochemical and optical approaches that featured limited spatiotemporal resolution. Here, we utilize high-affinity, DAT-specific antagonist-conjugated quantum dot (QD) probes to establish the dynamic mobility of wild-type and mutant DATs at the plasma membrane of living cells. Single DAT-QD complex trajectory analysis revealed that the DAT 615C variant exhibited increased membrane mobility relative to DAT 615R, with diffusion rates comparable to those observed after lipid raft disruption. This phenomenon was accompanied by a loss of transporter mobilization triggered by amphetamine, a common component of ADHD medications. Together, our data provides the first dynamic imaging of single DAT proteins, providing new insights into the relationship between surface dynamics and trafficking of both wild-type and disease-associated transporters. Our approach should be generalizable to future studies that explore the possibilities of perturbed surface DAT dynamics that may arise as a consequence of genetic alterations, regulatory changes, and drug use that contribute to the etiology or treatment of neuropsychiatric disorders.
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13 MeSH Terms
Circadian modulation of dopamine levels and dopaminergic neuron development contributes to attention deficiency and hyperactive behavior.
Huang J, Zhong Z, Wang M, Chen X, Tan Y, Zhang S, He W, He X, Huang G, Lu H, Wu P, Che Y, Yan YL, Postlethwait JH, Chen W, Wang H
(2015) J Neurosci 35: 2572-87
MeSH Terms: Animals, Animals, Genetically Modified, Attention Deficit Disorder with Hyperactivity, Avoidance Learning, Behavior, Animal, Circadian Rhythm, Dopamine, Dopaminergic Neurons, Impulsive Behavior, Larva, Mice, Motor Activity, NIH 3T3 Cells, Period Circadian Proteins, Tyrosine 3-Monooxygenase, Zebrafish, Zebrafish Proteins
Show Abstract · Added February 20, 2015
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children and adults. While ADHD patients often display circadian abnormalities, the underlying mechanisms are unclear. Here we found that the zebrafish mutant for the circadian gene period1b (per1b) displays hyperactive, impulsive-like, and attention deficit-like behaviors and low levels of dopamine, reminiscent of human ADHD patients. We found that the circadian clock directly regulates dopamine-related genes monoamine oxidase and dopamine β hydroxylase, and acts via genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum. We then found that Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine, thereby showing highly conserved roles of the circadian clock in ADHD. Our studies demonstrate that disruption of a circadian clock gene elicits ADHD-like syndrome. The circadian model for attention deficiency and hyperactive behavior sheds light on ADHD pathogenesis and opens avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder.
Copyright © 2015 the authors 0270-6474/15/352572-16$15.00/0.
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Misuse of stimulant medication among college students: a comprehensive review and meta-analysis.
Benson K, Flory K, Humphreys KL, Lee SS
(2015) Clin Child Fam Psychol Rev 18: 50-76
MeSH Terms: Achievement, Attention Deficit Disorder with Hyperactivity, Central Nervous System Stimulants, College Fraternities and Sororities, Humans, Motivation, Peer Group, Prescription Drug Misuse, Prevalence, Risk Factors, Students, Substance-Related Disorders, Universities
Show Abstract · Added March 3, 2020
The misuse of stimulant medication among college students is a prevalent and growing problem. The purpose of this review and meta-analysis is to summarize the current research on rates and demographic and psychosocial correlates of stimulant medication misuse among college students, to provide methodological guidance and other ideas for future research, and to provide some preliminary suggestions for preventing and reducing misuse on college campuses. Random-effects meta-analysis found that the rate of stimulant medication misuse among college students was estimated at 17 % (95 % CI [0.13, 0.23], p < .001) and identified several psychological variables that differentiated misusers and nonusers, including symptoms of attention-deficit/hyperactivity disorder, problems associated with alcohol use, and marijuana use. A qualitative review of the literature also revealed that Greek organization membership, academic performance, and other substance use were associated with misuse. Students are misusing primarily for academic reasons, and the most common source for obtaining stimulant medication is peers with prescriptions. Interpretation of findings is complicated by the lack of a standard misuse definition as well as validated tools for measuring stimulant misuse. The relation between stimulant medication misuse and extra curricular participation, academic outcomes, depression, and eating disorders requires further investigation, as do the reasons why students divert or misuse and whether policies on college campuses contribute to the high rates of misuse among students. Future research should also work to develop and implement effective prevention strategies for reducing the diversion and misuse of stimulant medication on college campuses.
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