Molly Nikolas

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Papers by Molly Nikolas

Gene-Environment Interplay in Developmental Psychopathology

Springer eBooks, 2016

Prediction of Attention-Deficit/Hyperactivity Disorder Diagnosis Using Brief, Low-Cost Clinical Measures: A Competitive Model Evaluation

Clinical psychological science, Dec 22, 2022

Proper diagnosis of attention-deficit/hyperactivity disorder (ADHD) is costly, requiring in-depth... more Proper diagnosis of attention-deficit/hyperactivity disorder (ADHD) is costly, requiring in-depth evaluation via interview, multi-informant and observational assessment, and scrutiny of possible other conditions. The increasing availability of data may allow the development of machine-learning algorithms capable of accurate diagnostic predictions using low-cost measures to supplement human decision-making. We report on the performance of multiple classification methods used to predict a clinician-consensus ADHD diagnosis. Methods ranged from fairly simple (e.g., logistic regression) to more complex (e.g., random forest) but emphasized a multistage Bayesian approach. Classifiers were evaluated in two large ( N &gt; 1,000) independent cohorts. The multistage Bayesian classifier provided an intuitive approach consistent with clinical workflows and was able to predict expert consensus ADHD diagnosis with high accuracy (&gt; 86%)—though not significantly better than other methods. Results suggest that parent and teacher surveys are sufficient for high-confidence classifications in the vast majority of cases, but an important minority require additional evaluation for accurate diagnosis.

How Do Child ADHD Symptoms and Oppositionality Impact Parent–Child Interactions When Crossing Virtual Roads?

Journal of Pediatric Psychology, Oct 19, 2021

Objective This study examined how parents and children interact when crossing virtual roads toget... more Objective This study examined how parents and children interact when crossing virtual roads together. We examined (1) whether children's inattention/hyperactivity and oppositionality and children's failure to jointly perform the task interfered with parents' efforts to scaffold children's road-crossing skill and (2) whether experience with the joint road-crossing task impacted children's subsequent performance in a solo road-crossing task. Methods Fifty-five 8-to 10-year-old children with and without attention-deficit/hyperactivity disorder and their parents first jointly crossed a lane of traffic in an immersive pedestrian simulator. Children then completed the same roadcrossing task alone. Parents completed questionnaires about children's symptoms of inattention/ hyperactivity and oppositionality. Results Analyses of the joint road-crossing task showed that when parents and children crossed different gaps, parents suggested and opposed more gaps and were less likely to use a prospective gap communication strategy (i.e., communicating about a crossable gap prior to its arrival). Crossing different gaps was also associated with increased expressions of negative affect among parents and children and an increase in collisions among children. Children's level of parent-reported oppositionality also predicted an increase in child defiance and parental redirection of child behavior. Analyses of children's subsequent crossing performance indicated that parents' use of a prospective gap communication strategy during the joint road-crossing task predicted selection of larger gaps during the solo crossing task. Conclusions Not crossing through the same gap and increased levels of child oppositionality interfered with the scaffolding process, potentially informing future parent-based intervention efforts for increasing children's road-crossing safety.

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Latent class analysis to characterize neonatal risk for neurodevelopmental differences

Journal of Child Psychology and Psychiatry, Jul 15, 2022

BackgroundNeonatal risk factors, such as preterm birth and low birth weight, have been robustly l... more BackgroundNeonatal risk factors, such as preterm birth and low birth weight, have been robustly linked to neurodevelopmental deficits, yet it is still unclear why some infants born preterm and/or low birth weight experience neurodevelopmental difficulties while others do not. The current study investigated this heterogeneity in neurodevelopmental abilities by examining additional neonatal morbidities as risk factors, utilizing latent class analysis to classify neonates into groups based on similar neonatal risk factors, and including neonates from the full spectrum of gestational age.MethodsNeonates who received neonatal care at an academic public hospital during an almost 10‐year period (n = 19,951) were included in the latent class analysis, and 21 neonatal indicators of health were used. Neonatal class, sex, and the interaction between neonatal class and sex were used to examine differences in neurodevelopment at 18 months of age in a typically developing population.ResultsThe best fitting model included five infant classes: healthy, hypoxic, critically ill, minorly ill, and complicated delivery. Scores on the parent‐rated neurodevelopmental measure differed by class such that infants in the critically ill, minorly ill, and complicated delivery classes had lower scores. There was no main effect of sex on the neurodevelopmental measure scores, but the interaction between sex and neonatal class was significant for three out of five neurodevelopmental domains.ConclusionsThe current study extends the understanding of risk factors in neurodevelopment by including several neonatal medical conditions that are often overlooked and by using a person‐centered, as opposed to variable‐centered, approach. Future work should continue to examine risk factors, such as maternal health during pregnancy and medical interventions for newborns, in relation to neonatal risks and neurodevelopment by using a person‐centered approach.

Sluggish Cognitive Tempo as a Transdiagnostic Link Between Adult ADHD and Internalizing Symptoms

Journal of Psychopathology and Behavioral Assessment, Feb 15, 2022

Positive alcohol expectancies mediate associations between ADHD behaviors and alcohol-related problems among college students

Adhd Attention Deficit and Hyperactivity Disorders, Apr 26, 2017

An increasing percentage of college students report being affected by ADHD behaviors, and this po... more An increasing percentage of college students report being affected by ADHD behaviors, and this population is at increased risk of experiencing negative consequences associated with alcohol consumption. However, specific factors motivating alcohol consumption and contributing to negative outcomes among these individuals are not well understood. Recent work suggests alcohol expectancies may interact with ADHD behaviors to influence negative drinking-related outcomes among those with elevated inattention and/or hyperactivity-impulsivity. Seven-hundred-forty emerging adults (M age = 19.13 [SD = 2.25] years; 72.1% female; 85.8% Caucasian) enrolled in two public universities in the Southeast and Midwest USA completed the Brief Comprehensive Effects of Alcohol Survey (B-CEOA) and provided self-reports of ADHD symptoms and drinking-related outcomes. Multiple mediation analyses were conducted to evaluate effects of ADHD behaviors (i.e., hyperactivity-impulsivity, and inattention) and related impairment in major life domains (e.g., social interactions, occupational and educational activities, fulfillment of daily responsibilities) on drinking-related outcomes via positive and negative alcohol expectancies, controlling for sex, age, co-occurring oppositional behaviors, and data collection site. Inattention, hyperactivity-impulsivity, and impairment directly predicted both personal and social problems consequent to alcohol use. Effects of ADHD behaviors and impairment on drinking-related personal and social problems were partially mediated by positive expectancies. Findings are consistent with and extend prior work supporting a role of positive alcohol expectancies in alcohol-related negative outcomes among college students experiencing mild to moderate symptoms of ADHD.

DRD4 Variants Moderate the Impact of Parental Characteristics on Child Attention-Deficit Hyperactivity Disorder: Exploratory Evidence from a Multiplex Family Design

Journal of Abnormal Child Psychology, Jan 30, 2017

Parental ADHD symptomatology and related impairments have been robustly associated with youth ADH... more Parental ADHD symptomatology and related impairments have been robustly associated with youth ADHD across decades of work. Notably, these factors may impede typical development of child self-regulation capabilities through both neurobiological and interpersonal processes. High heritability of estimates for the disorder further suggest that these effects are likely geneticallymediated, at least in part. Variation within the dopamine D4 receptor gene (DRD4) has been shown to moderate parental influences on youth ADHD. Use of a multiplex family design (i.e., samples of families that included multiple affected members) may facilitate identification of additional gene variants of interest and advance understanding of gene-environment interplay in regard to parenting. Thirty multiplex families consisting of 114 individuals (66 youth, 48 parents) completed a multi-stage, multi-informant diagnostic and neurocognitive assessment, measures of parenting, and provided saliva samples for DNA analyses. Sanger sequencing of the DRD4 gene yielded 16 rare variants; a polygenic risk score was computed for both parents and youth. Generalized estimating equations (GEE) examined the predictive effects of parental ADHD symptoms, parental neurocognitive functioning, and poor parenting dimensions on youth ADHD as well as moderation of these effects by parental and youth DRD4 variants. Findings indicated that parental DRD4 variants moderated the impact of parental ADHD and neurocognitive functioning on youth ADHD symptoms. Youth DRD4 variants moderated the impact of parental inconsistent discipline on child ADHD. In all cases, stronger associations were observed for those individuals with more risk variants. These exploratory findings highlight the potential utility of a multiplex family design for examining the interplay between parent and child characteristics in predicting youth outcomes.

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Sex moderates the impact of birth weight on child externalizing psychopathology

Journal of Abnormal Psychology, Feb 1, 2017

Low birth weight (LBW) has consistently been associated with childhood attention deficit/hyperact... more Low birth weight (LBW) has consistently been associated with childhood attention deficit/hyperactivity disorder (ADHD), and a similar association has been found for childhood externalizing disorders, such as oppositional defiant disorder (ODD) and conduct disorder (CD), albeit to a lesser degree. Although the association between LBW and these disorders has been robustly replicated, few studies have adequately controlled for confounding variables, such as parental age at birth and prenatal tobacco use, examined the specificity of the risk of LBW for ADHD symptoms, or investigated potential nonlinear (i.e., quadratic) effects of birth weight (BW). Additionally, the extent to which LBW confers risk for these disorders depending on childhood sex has rarely been examined. The current study examined associations between BW and ADHD, ODD, and CD symptom dimensions as well as the extent to which such associations are moderated by child sex, while also controlling for confounding variables. Significant interactions between sex and BW emerged across all analyses predicting ADHD and externalizing psychopathology, such that associations were stronger in males relative to females. Results remained when controlling for a number of confounds, including parental age, prenatal tobacco use, comorbid psychopathology, as well as other indicators of maternal and child health during the pre- and perinatal period. Both linear and quadratic associations emerged between BW and both hyperactivity and CD symptoms, whereas BW predicted inattention and ODD symptoms in a linear fashion. Future research should continue to investigate the impact of BW on ADHD and externalizing psychopathology, in particular, the biological mechanisms underlying this association. (PsycINFO Database Record

A Meta-Analytic Review of Emotion Regulation Focused Psychosocial Interventions for Adolescents

Clinical Child and Family Psychology Review, Jul 18, 2021

Emotion regulation (ER) is the ability to monitor, evaluate, and modify one's emotional responses... more Emotion regulation (ER) is the ability to monitor, evaluate, and modify one's emotional responses to be appropriate for environmental demands. Poor ER has been considered a transdiagnostic risk factor for a range of internalizing and externalizing disorders and overall decreased well-being in adolescents. A range of evidence-based interventions exist which may improve ER. However, much of the intervention research to date does not include a measure of ER to assess change pre and post treatment, with limited information about the efficacy of these interventions in youth across a range of sample types. There is a clear need for a comprehensive review of the literature examining ER-focused interventions in adolescents with a wide range of presenting disorders. A literature search was originally conducted in January 2020 and an updated search was conducted in February 2021 which elicited 1245 articles, of which 605 were duplicates and were removed. Abstracts of the remaining 640 articles were screened with 121 articles being reviewed in full. Of note, 16 additional articles were identified through references and other sources during this process and were also included in the full review. Of the 137 articles reviewed in full, 41 studies were ultimately included in the present review. The present paper provides a descriptive review of intervention approaches and findings from community prevention programs, programs for war-affected youth, programs for clinical populations, and programs for incarcerated and delinquent adolescents. The overall pooled effect was significantly different from zero based on the pre/post effects [Hedge's g = 0.29, 95% CI (0.22, 0.36)] and the intervention/control effects [Hedge's g = 0.19, 95% CI (0.06-0.32)]. Although neither sex nor age significantly accounted for heterogeneity in effect sizes, there were significant findings for population type (clinical vs. community), with community samples having significantly lower effect sizes on average. Impacts of the different ER measures used and significant methodological variability (e.g., use of control groups, length of intervention) across included studies are discussed. Implications and suggestions for future research are reviewed, specifically, that additional understanding of moderators of effects are needed and that measures used to assess change in ER, both dysregulation and adaptive skill use, may need to more directly align with the intervention's focus and the strategies taught as part of the intervention.

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Sluggish Cognitive Tempo Symptoms Contribute to Heterogeneity in Adult Attention-Deficit Hyperactivity Disorder

Journal of Psychopathology and Behavioral Assessment, Oct 28, 2017

Attention-deficit hyperactivity disorder (ADHD) persists into adulthood in over 50% of cases, alt... more Attention-deficit hyperactivity disorder (ADHD) persists into adulthood in over 50% of cases, although its associated symptom profiles, comorbid problems, and neuropsychological deficits change substantially across development. Sluggish cognitive tempo (SCT) symptoms may contribute to associations between ADHD and comorbid problems and may partially explain the substantial heterogeneity observed in its correlates. 349 adults aged 18-38 years (M = 23.2, SD = 4.5, 54.7% male, 61.03% with ADHD) completed a multi-informant diagnostic procedure and a comprehensive neuropsychological battery. Adults with ADHD (n = 213) were retained for analyses. Latent class analyses (LCA) revealed three profiles of SCT symptoms among those with ADHD, which we classified as minimal, moderate, or severe SCT. Multiple analysis of covariance (MANCOVA) revealed significant differences among these profiles, which remained when controlling for persistence of ADHD symptoms and sex. In general, adults with ADHD combined with SCT symptoms (moderate and severe) had significantly more symptoms of anxiety, depression, and persistent inattention, and had more severe professional and relational impairment compared to ADHD adults without SCT. Compared to those with moderate or minimal SCT symptoms, the severe SCT group had the most symptoms of depression and internalizing disorders, and the most impairment in the domain of daily responsibility. No significant differences based on externalizing symptoms emerged when controlling for sex and persistence of inattention symptoms, suggesting the moderate and severe SCT groups do not simply reflect more symptoms. Moreover, follow-up mediation analyses revealed that SCT might at least partially explain the heterogeneity in ADHD. Findings have implications for refinement of etiological conceptualization, assessment methods, and intervention strategies.

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Parental Involvement Moderates Etiological Influences on Attention Deficit Hyperactivity Disorder Behaviors in Child Twins

Child Development, Sep 26, 2014

Although few would now contest the presence of gene x environment (GxE) effects in the developmen... more Although few would now contest the presence of gene x environment (GxE) effects in the development of child psychopathology, it remains unclear how these effects manifest themselves. Alternative GxE models have been proposed (i.e., diathesis-stress, differential susceptibility, bioecological), each of which has notably different implications for etiology. Child twin studies present a powerful tool for discriminating between these models. The current study examined whether and how parental involvement moderated etiological influences on ADHD within 500 twin pairs aged 6-11 years. Results indicated moderation of genetic and non-shared environmental contributions to ADHD by parental involvement, and moreover, suggested both differential susceptibility and bio-ecological models of GxE. Results highlight the utility of child twin samples in testing different manifestations of GxE effects.

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Does 5HTTLPR Genotype Moderate the Association of Family Environment With Child Attention-Deficit Hyperactivity Disorder Symptomatology?

Journal of Clinical Child and Adolescent Psychology, Jan 20, 2015

Objective-Problematic family dynamics are common among youth with attention-deficit hyperactivity... more Objective-Problematic family dynamics are common among youth with attention-deficit hyperactivity disorder (ADHD). Multiple mechanisms, including diathesis-stress (vulnerability) and differential susceptibility gene × environment interaction effects (G×E), have been proposed to account for this association. G×E effects for ADHD were examined via interactions between a genetic marker hypothesized to influence sensitivity to the environment (the promoter polymorphism of the serotonin transporter gene -5HTTLPR) and family conflict and cohesion in predicting ADHD symptoms. Method-498 youth ages 6-17 years (251 ADHD, 213 non-ADHD) and their parents completed a multi-stage, multi-informant assessment (including parent and youth reports on the Family Environment Scale), and saliva sample collection for genotyping. Linear regression analyses examined interactions between 5HTTLPR genotype and the FES scales of conflict and cohesion reported by parent and child. Criteria laid out by were applied to evaluate diathesis stress versus differential susceptibility G×E mechanisms. Results-Results demonstrated interactions between 5HTTLPR genotype and both conflict and cohesion in predicting inattention, but not hyperactivity-impulsivity. Both interactions were highly consistent with differential susceptibility models of G×E effects. Conclusions-5HTTLPR genotype appeared to moderate the relationship between family conflict/cohesion and inattentive symptoms. Interactions highlight the role of 5HTTLPR genotype as a potential marker of environmental sensitivity and provide support for differential susceptibility models of G×E effects for ADHD.

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Moderators of Neuropsychological Mechanism in Attention-Deficit Hyperactivity Disorder

Journal of Abnormal Child Psychology, Jul 20, 2014

Neuropsychological measures have been proposed as both a way to tap mechanisms and as endophenoty... more Neuropsychological measures have been proposed as both a way to tap mechanisms and as endophenotypes for child ADHD. However, substantial evidence supporting heterogeneity in neuropsychological performance among youth with ADHD as well as apparent effect differences by sex, age, and comorbidity have slowed progress. To address this, it is important to understand sibling effects in relation to these moderators. 461 youth ages 6-17 years (54.8% male, including 251 youth with ADHD, 107 of their unaffected biological siblings, and 103 non-ADHD controls) completed diagnostic interviews and a theoretically informed battery of neuropsychological functioning. A structural equation model was used to consolidate neuropsychological domains. Group differences between unaffected siblings of youth with ADHD and controls across each domain were first examined as the primary endophenotype test for ADHD. Moderation of these effects was evaluated via investigation of interactions between diagnostic group and both proband and individual level characteristics, including sex, age, and comorbidity status. Unaffected siblings performed worse than control youth in the domains of inhibition, response time variability, and temporal information processing. Individual age moderated these effects, such that differences between controls and unaffected siblings were pronounced among younger children (ages 6-10 years) but absent among older youth (ages 11-17 years). Evidence for moderation of effects by proband sex and comorbidity status produced more variable and smaller effects. Results support the utility of inhibition, response time variability, and temporal processing as useful endophenotypes for ADHD in future genetic associations studies of the disorder, but suggest this value will vary by age among unaffected family members.

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A Meta-Analysis of the Association Between Birth Weight and Attention Deficit Hyperactivity Disorder

Journal of Abnormal Child Psychology, Nov 21, 2017

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by... more Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by a constellation of symptoms that includes developmentally inappropriate inattention, impulsivity, and hyperactivity, with symptom onset during childhood (American Psychiatric Association, 2013). ADHD is one of the most common neurodevelopmental disorders, with the prevalence estimated to be between 2.5 and 11 percent in adults and children (

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Neuropsychological performance and attention-deficit hyperactivity disorder subtypes and symptom dimensions

Neuropsychology (journal), 2013

Objective-Characterization of clinical heterogeneity in ADHD remains controversial. Neuropsycholo... more Objective-Characterization of clinical heterogeneity in ADHD remains controversial. Neuropsychological and cognitive studies provides one type of validation data, but too often has considered only a narrow range of functional domains. Method-The current study examined ADHD subtype and presentation differences across a broad range of neurocognitive domains in a large clinically-characterized, community-recruited sample of 498 youth (213 control, 107 ADHD-Primarily Inattentive (ADHD-PI), 137 ADHD-Combined (ADHD-C)), ages 6-17 years. Domains assessed included executive functions, working memory, arousal, processing speed, response variability, and temporal information processing. Results-Youth with ADHD-C performed worse than youth with ADHD-PI in all domains, consistent with a severity model. Performance among a subgroup with a "restrictive inattentive" presentation indicated potential deficits in processing speed relative to other ADHD-PI youth, but no other effects. When all measures were included in the same model, cognitive control (executive functions, working memory, and memory span), arousal, and response variability each provided uniquely incremental statistical prediction of specific symptom dimensions and of subtype/ presentation, but temporal information processing and processing speed did not. suggest the potential to consolidate multiple neurocognitive theories of ADHD, and that such consolidation will apply across putative clinical subtypes or presentations.

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Executive Function in Adolescents With ADHD

Journal of the American Academy of Child and Adolescent Psychiatry, Nov 1, 2007

Objective: The aim of this study was to clarify executive function weakness in attention-deficit/... more Objective: The aim of this study was to clarify executive function weakness in attention-deficit/hyperactivity disorder (ADHD) during adolescence and determine the specificity of executive function weakness to ADHD symptom domains. Method: A total of 182 adolescents (105 boys), ages 13 to 17 years, completed a multistage diagnostic assessment; 85 were diagnosed with ADHD: 43 primarily Inattentive type (ADHD-PI) and 42 Combined type (ADHD-C). Participants completed the Stop, Trail Making, Wisconsin Card Sort, and Stroop tasks. Results: The ADHD group exhibited impaired performance compared with the non-ADHD group on executive function measures (multivariate p < .05); there were no ADHD subtype differences. A composite executive function factor was significantly related to inattentive but not hyperactive-impulsive symptoms. Conclusions: Executive function weakness in adolescent ADHD is specifically related to symptoms of inattention-disorganization. Results are congruent with a dual-pathway model of ADHD cognitive mechanisms.

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Self-regulation in Gender and Sexual Orientation Diverse Adults: Exploring Patterns of Risk and Resilience Using a Person-centered Approach

Journal of LGBTQ Issues in Counseling, Jan 31, 2023

Prediction of ADHD diagnosis using brief, low-cost, clinical measures: a competitive model evaluation

medRxiv (Cold Spring Harbor Laboratory), Dec 30, 2021

Proper diagnosis of ADHD is costly, requiring in-depth evaluation via interview, multi-informant ... more Proper diagnosis of ADHD is costly, requiring in-depth evaluation via interview, multi-informant and observational assessment, and scrutiny of possible other conditions. The increasing availability of data may allow the development of machine-learning algorithms capable of accurate diagnostic predictions using low-cost measures. We report on the performance of multiple classification methods used to predict a clinician-consensus ADHD diagnosis. Classification methods ranged from fairly simple (e.g., logistic regression) to more complex (e.g., random forest), and also included a multi-stage Bayesian approach. All methods were evaluated in two large (N>1000), independent cohorts. The multi-stage Bayesian classifier provides an intuitive approach that is consistent with clinical workflows, and is able to predict ADHD diagnosis with high accuracy (>86%)-though not significantly better than other commonly used classifiers, including logistic regression. Results suggest that data from parent and teacher surveys is sufficient for high-confidence classifications in the vast majority of cases using relatively straightforward methods.

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The Oregon ADHD-1000: A new longitudinal data resource enriched for clinical cases and multiple levels of analysis

Developmental Cognitive Neuroscience, Apr 1, 2023

Multigroup multilevel structure of the child and parent versions of the Positive and Negative Affect Schedule (PANAS) in adolescents with and without ADHD

Psychological Assessment, Apr 1, 2020

The Positive and Negative Affect Schedule (PANAS) has been widely used to assess affect expressio... more The Positive and Negative Affect Schedule (PANAS) has been widely used to assess affect expression. Shortened and adolescent versions of the measure have been created, such as the 10item PANAS for children (PANAS-C). However, affect expression often involves substantial intra-individual variability, and no research has examined within-person differences using the 10-item PANAS-C. Moreover, intra-individual variability is a key characteristic of attentiondeficit/hyperactivity disorder (ADHD), and emotion dysregulation is a key feature of ADHD. The present study examined the factor structure of the 10-item PANAS-C in a sample of adolescents (Mage = 13.17 years) with (n=156) and without (n=139) ADHD. A 3-factor within (positive affect, fear, distress) and a 2-factor between (positive affect, negative affect) model was found to be best fitting using both parent-and adolescent-report. The model demonstrated configural invariance for adolescent-report and scalar invariance for parent-report. These results support the multidimensionality of negative affect in youth with ADHD, even when assessed via the short version PANAS-C. In future work, it will be important to consider the implications of more discrete types of negative affect expression (fear and distress) found across time at the individual level for assessment and intervention practice.

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