Unmet support needs in donor sperm treatment: consequences for parents and their donor-children.

RESEARCH QUESTION: Are unmet needs for psychosocial counselling, peer support and friends/family support in parents directly and/or indirectly related to the mental health of parents and their donor-children? DESIGN: A cross-sectional sample of 214 parents participated in this quantitative study via an online questionnaire. The sample comprised mothers and fathers in a heterosexual relationship (n = 85), mothers in a lesbian relationship (n = 67) and single mothers (n = 62). Parents were recruited via three Dutch fertility clinics and four network organizations. Unmet support needs were measured with an adapted version of the Unmet Needs for Parenting Support questionnaire, changing the original items into items about donor conception. The items were derived from a qualitative study and checked by experts in donor conception. The parents' mental health was measured with the Adult Self Report and the donor-children's mental health with the Child Behaviour Checklist. A multigroup mediation analysis was conducted to explore relationships between parents' unmet support needs and their child's mental health, with the parents' mental health as a possible mediator. RESULTS: There were no direct relations between parents' unmet support needs and the mental health of donor-children. Unmet needs for psychosocial counselling, peer support and friends/family support for parents and children's mental health were indirectly related through the mental health of the parents: 0.074 (CI 95%  = 0.013-0.136; P = 0.017), 0.085 (CI 95% = 0.018-0.151; P = 0.036) and 0.063 (CI 95% = 0.019-0.106; P = 0.013), respectively. CONCLUSIONS: We recommend that fertility clinics, network organizations and authorities for infertility counsellors make their support available to parents for extended periods after their treatment. Further qualitative studies are necessary to assess how to relieve unmet support needs during donor sperm treatment.

The Validation of the Selective Mutism Questionnaire for Use in the Dutch Population.

Selective mutism (SM) is an anxiety disorder in children/adolescents, characterized by the absence of speaking in specific social situations, mostly at school. The selective mutism questionnaire (SMQ) is a parent report, internationally used to assess SM symptomatology and treatment outcomes. Since no assessment instrument for SM was available in the Netherlands, our aim was to investigate the psychometric properties of the Dutch translation of the SMQ, through reliability, confirmatory factor, and ROC analyses conducted on data obtained in 303 children (ages 3-17 years; clinical SM group n = 106, control group n = 197). The SMQ turned out to be highly reliable (α = 0.96 in the combined sample; 0.83 within the clinical group) and followed the expected factor structure. We conclude that the Dutch version of the SMQ is a reliable and valid tool both as a screening and clinical instrument to assess SM in Dutch speaking children.

Are Socially Anxious Children Poor or Advanced Mindreaders?

Why are some children more socially anxious than others? One theory holds that socially anxious children are poor mindreaders, which hampers their social interactions; another that socially anxious children are advanced mindreaders leading to heightened self-consciousness in social situations. To test these theories simultaneously, this study (N = 105, ages 8-12) assessed children's mindreading (accuracy in detecting mental states from the eye region), self-consciousness (indexed as physiological blushing during public performance), and social anxiety levels. Results support both theories, showing a quadratic relation between mindreading and social anxiety. Low mindreading was related to clinical levels of social anxiety. High mindreading was related to subclinical levels of social anxiety through blushing. Our findings suggest two social-cognitive pathways to heightened social anxiety.

Testing Syndromes of Psychopathology in Parent and Youth Ratings Across Societies.

As societies become increasingly diverse, mental health professionals need instruments for assessing emotional, behavioral, and social problems in terms of constructs that are supported within and across societies. Building on decades of research findings, multisample alignment confirmatory factor analyses tested an empirically based 8-syndrome model on parent ratings across 30 societies and youth self-ratings across 19 societies. The Child Behavior Checklist for Ages 6-18 and Youth Self-Report for Ages 11-18 were used to measure syndromes descriptively designated as Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule-Breaking Behavior, and Aggressive Behavior. For both parent ratings (N = 61,703) and self-ratings (N = 29,486), results supported aggregation of problem items into 8 first-order syndromes for all societies (configural invariance), plus the invariance of item loadings (metric invariance) across the majority of societies. Supported across many societies in both parent and self-ratings, the 8 syndromes offer a parsimonious phenotypic taxonomy with clearly operationalized assessment criteria. Mental health professionals in many societies can use the 8 syndromes to assess children and youths for clinical, training, and scientific purposes.

No Evidence of Causal Effects of Blood Pressure on Cognition in the Population at Large.

The large body of literature on the association between blood pressure (BP) and cognitive functioning has yielded mixed results, possibly due to the presence of non-linear effects across age, or because BP affects specific brain areas differently, impacting more on some cognitive skills than on others. If a robust association was detected among BP and specific cognitive tasks, the causal nature of reported associations between BP and cognition could be investigated in twin data, which allow a test of alternative explanations, including genetic pleiotropy. The present study first examines the association between BP and cognition in a sample of 1,140 participants with an age range between 10 and 86 years. Linear and quadratic effects of systolic BP (SBP) and diastolic BP (DBP) on cognitive functioning were examined for 17 tests across five functions. Associations were corrected for effects of sex and linear and quadratic effects of age. Second, to test a causal model, data from 123 monozygotic (MZ) twin pairs were analyzed to test whether cognitive functioning of the twins with the higher BP was different from that of the co-twins with lower BP. Associations between BP and cognitive functioning were absent for the majority of the cognitive tests, with the exception of a lower speed of emotion identification and verbal reasoning in subjects with high diastolic BP. In the MZ twin pair analyses, no effects of BP on cognition were found. We conclude that in the population at large, BP level is not associated with cognitive functioning in a clinically meaningful way.

Domain dependent associations between cognitive functioning and regular voluntary exercise behavior.

Regular exercise has often been suggested to have beneficial effects on cognition, but empirical findings are mixed because of heterogeneity in sample composition (age and sex); the cognitive domain being investigated; the definition and reliability of exercise behavior measures; and study design (e.g., observational versus experimental). Our aim was to scrutinize the domain specificity of exercise effects on cognition, while controlling for the other sources of heterogeneity. In a population based sample consisting of 472 males and 668 females (aged 10-86 years old) we administered the Computerized Neurocognitive Battery (CNB), which provided accuracy and speed measures of abstraction and mental flexibility, attention, working memory, memory (verbal, face, and spatial), language and nonverbal reasoning, spatial ability, emotion identification, emotion- and age differentiation, sensorimotor speed, and motor speed. Using univariate and multivariate regression models, CNB scores were associated with participants' average energy expenditure per week (weekly METhours), which were derived from a questionnaire on voluntary regular leisure time exercise behavior. Univariate models yielded generally positive associations between weekly METhours and cognitive accuracy and speed, but multivariate modeling demonstrated that direct relations were small and centered around zero. The largest and only significant effect size (ß = 0.11, p < 0.001) was on the continuous performance test, which measures attention. Our results suggest that in the base population, any chronic effects of voluntary regular leisure time exercise on cognition are limited. Only a relation between exercise and attention inspires confidence.

Assessing genetic influences on behavior: informant and context dependency as illustrated by the analysis of attention problems.

Assessment of genetic influences on behavior depends on context, informants, and study design: We show (analytically) that, conditional on study design, informant specific genetic variance is included in the genetic variance component or in the environmental variance component. To aid the explanation, we present an illustrative empirical analysis of data from the Netherlands Twin Register. Subjects included 1,571 monozygotic and 2,672 dizygotic 12-year-old twin pairs whose attention problems (AP) were rated by their parents, teachers, and themselves. Heritability estimates (h(2)) of AP were about ~0.75 for same informant ratings (mother, father, and same teacher ratings) and ~0.54 for different informants' ratings (different parents', different teachers', and two twins' self-ratings). Awareness of assessment effects is relevant to research into psychiatric disorders. Differences in assessment can account for age effects, such as a drop in heritability of ADHD symptoms. In genome-wide association studies, effects of rating specific genetic influences will be undetectable.

Why Do Bi-Factor Models Outperform Higher-Order g Factor Models? A Network Perspective.

Bi-factor models of intelligence tend to outperform higher-order g factor models statistically. The literature provides the following rivalling explanations: (i) the bi-factor model represents or closely approximates the true underlying data-generating mechanism; (ii) fit indices are biased against the higher-order g factor model in favor of the bi-factor model; (iii) a network structure underlies the data. We used a Monte Carlo simulation to investigate the validity and plausibility of each of these explanations, while controlling for their rivals. To this end, we generated 1000 sample data sets according to three competing models-a bi-factor model, a (nested) higher-order factor model, and a (non-nested) network model-with 3000 data sets in total. Parameter values were based on the confirmatory analyses of the Wechsler Scale of Intelligence IV. On each simulated data set, we (1) refitted the three models, (2) obtained the fit statistics, and (3) performed a model selection procedure. We found no evidence that the fit measures themselves are biased, but conclude that biased inferences can arise when approximate or incremental fit indices are used as if they were relative fit measures. The validity of the network explanation was established while the outcomes of our network simulations were consistent with previously reported empirical findings, indicating that the network explanation is also a plausible one. The empirical findings are inconsistent with the (also validated) hypothesis that a bi-factor model is the true model. In future model selection procedures, we recommend that researchers consider network models of intelligence, especially when a higher-order g factor model is rejected in favor of a bi-factor model.

The longitudinal relationship between fear of movement and physical activity after cardiac hospitalization: A cross lagged panel model.

BACKGROUND: Little is known about the association between fear of movement (kinesiophobia) and objectively measured physical activity (PA), the first 12 weeks after cardiac hospitalization. PURPOSE: To assess the longitudinal association between kinesiophobia and objectively measured PA and to assess the factor structure of kinesiophobia. METHODS: We performed a longitudinal observational study. PA was continuously measured from hospital discharge to 12 weeks using the Personal Activity Monitor. The PAM measures time spent per day in PA-intensity categories: light, moderate and heavy. Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK) at four time points (hospital discharge, 3, 6 and 12 weeks). The longitudinal association between PA-intensity and kinesiophobia was studied with a random intercept cross lagged panel model (RI-CLPM). A RI-CLPM estimates effects from kinesiophobia on objectively measured PA and vice versa (cross-over effects), and autoregressive effects (e.g. kinesiophobia from one occasion to the next). RESULTS: In total, 116 patients (83.6% male) with a median age of 65.5 were included in this study. On no occasion did we find an effect of kinesiophobia on PA and vice versa. Model fit for the original model was poor (X2: = 44.646 P<0.001). Best model fit was found for a model were kinesiophobia was modelled as a stable between factor (latent variable) and PA as autoregressive component (dynamic process) (X2 = 27.541 P<0.12). CONCLUSION: Kinesiophobia and objectively measured PA are not associated in the first 12 weeks after hospital discharge. This study shows that kinesiophobia remained relatively stable, 12 weeks after hospital discharge, despite fluctuations in light to moderate PA-intensity.

On the nature and nurture of intelligence and specific cognitive abilities: the more heritable, the more culture dependent.

To further knowledge concerning the nature and nurture of intelligence, we scrutinized how heritability coefficients vary across specific cognitive abilities both theoretically and empirically. Data from 23 twin studies (combined N = 7,852) showed that (a) in adult samples, culture-loaded subtests tend to demonstrate greater heritability coefficients than do culture-reduced subtests; and (b) in samples of both adults and children, a subtest's proportion of variance shared with general intelligence is a function of its cultural load. These findings require an explanation because they do not follow from mainstream theories of intelligence. The findings are consistent with our hypothesis that heritability coefficients differ across cognitive abilities as a result of differences in the contribution of genotype-environment covariance. The counterintuitive finding that the most heritable abilities are the most culture-dependent abilities sheds a new light on the long-standing nature-nurture debate of intelligence.

The Young Netherlands Twin Register (YNTR): longitudinal twin and family studies in over 70,000 children.

The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.

Physician exhaustion and work engagement during the COVID-19 pandemic: A longitudinal survey into the role of resources and support interventions.

BACKGROUND: Physicians increasingly show symptoms of burnout due to the high job demands they face, posing a risk for the quality and safety of care. Job and personal resources as well as support interventions may function as protective factors when demands are high, specifically in times of crisis such as the COVID-19 pandemic. Based on the Job Demands-Resources theory, this longitudinal study investigated how monthly fluctuations in job demands and job and personal resources relate to exhaustion and work engagement and how support interventions are associated with these outcomes over time. METHODS: A longitudinal survey consisting of eight monthly measures in the period 2020-2021, completed by medical specialists and residents in the Netherlands. We used validated questionnaires to assess job demands (i.e., workload), job resources (e.g., job control), personal resources (e.g., psychological capital), emotional exhaustion, and work engagement. Additionally, we measured the use of specific support interventions (e.g., professional support). Multilevel modeling and longitudinal growth curve modeling were used to analyze the data. RESULTS: 378 medical specialists and residents were included in the analysis (response rate: 79.08%). Workload was associated with exhaustion (γ = .383, p < .001). All job resources, as well as the personal resources psychological capital and self-judgement were associated with work engagement (γs ranging from -.093 to .345, all ps < .05). Job control and psychological capital attenuated the workload-exhaustion relationship while positive feedback and peer support strengthened it (all ps < .05). The use of professional support interventions (from a mental health expert or coach) was related to higher work engagement (estimate = .168, p = .032) over time. Participation in organized supportive group meetings was associated with higher exhaustion over time (estimate = .274, p = .006). CONCLUSIONS: Job and personal resources can safeguard work engagement and mitigate the risk of emotional exhaustion. Professional support programs are associated with higher work engagement over time, whereas organized group support meetings are associated with higher exhaustion. Our results stress the importance of professional individual-level interventions to counteract a loss of work engagement in times of crisis.

Impact of kinesiophobia on initiation of cardiac rehabilitation: a prospective cohort path analysis.

OBJECTIVES: To identify factors associated with kinesiophobia (fear of movement) after cardiac hospitalisation and to assess the impact of kinesiophobia on cardiac rehabilitation (CR) initiation. DESIGN: Prospective cohort study. SETTING: Academic Medical Centre, Department of Cardiology. PARTICIPANTS: We performed a prospective cohort study in cardiac patients recruited at hospital discharge. In total, 149 patients (78.5% male) with a median age of 65 years were included, of which 82 (59%) were referred for CR. PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed kinesiophobia with the Tampa Scale for Kinesiophobia (TSK). For this study, the total score was used (range 13-52). We assessed baseline factors (demographics, cardiac disease history, questionnaire data on anxiety, biopsychosocial complexity and self-efficacy) associated with kinesiophobia using linear regression with backward elimination. For linear regression, the standardised beta (ß) was reported. Prospectively, the impact of kinesiophobia on probability of CR initiation, in the first 3 months after hospital discharge (subsample referred for CR), was assessed with logistic regression. For logistic regression, the OR was reported. RESULTS: Moderate and severe levels of kinesiophobia were found in 22.8%. In the total sample, kinesiophobia was associated with cardiac anxiety (ß=0.33, 95% CI: 0.19 to 0.48), social complexity (ß=0.23, 95% CI: 0.06 to 0.39) and higher education (ß=-0.18, 95% CI: -0.34 to -0.02). In those referred for CR, kinesiophobia was negatively associated with self-efficacy (ß=-0.29, 95% CI: -0.47 to -0.12) and positively with cardiac anxiety (ß=0.43, 95% CI: 0.24 to 0.62). Kinesiophobia decreased the probability of CR initiation (OR Range13-52 points =0.92, 95% CI: 0.85 to 0.99). CONCLUSION: In patients hospitalised for cardiovascular disease, kinesiophobia is associated with cardiac anxiety, social complexity, educational level and self-efficacy. Kinesiophobia decreased the likelihood of CR initiation with 8% per point on the TSK.

Effectiveness of 'Tackle Your Tics', a brief, intensive group-based exposure therapy programme for children with tic disorders: study protocol of a randomised controlled trial.

INTRODUCTION: This paper outlines the study protocol for the Dutch Tackle Your Tics study in youth with tic disorders. Tourette syndrome and chronic tic disorders are prevalent neurodevelopmental disorders, placing considerable burden on youth and their families. Behavioural treatment is the first-line, evidence-based intervention for tic disorders, but tic reduction and availability remain relatively low. Patient associations stress the need for more accessible high-quality treatments, also focusing on improving quality of life. Therefore, the brief, intensive group-based treatment Tackle Your Tics was developed. METHODS AND ANALYSIS: Tackle Your Tics is a 4-day intensive and comprehensive group-based intervention for children and adolescents (9-17 years) with Tourette syndrome or a chronic tic disorder. The programme encompasses exposure and response prevention treatment and additional supporting components (coping strategies, relaxation exercises and parent support). To study the effectiveness of Tackle Your Tics and identify predictors/moderators at baseline, a single-blinded randomised controlled trial (n=104) is conducted, comparing Tackle Your Tics (n=52) with a waiting list condition lasting 3 months (n=52). Assessments are performed at similar time points for both groups: at baseline, after 4 weeks, and at 3 and 6 months of follow-up, on tic severity, quality of life and other psychosocial variables. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the medical ethical committee of the Amsterdam Medical Centre (METC nr NL66340.018.18, v3 June 2020). Findings will be presented on national and international conferences, peer-reviewed scientific journals, patient organisation meetings and public media. Patient representatives are fully integrated as part of the research team. If Tackle Your Tics proves to be effective, it can expand evidence-based treatment possibilities for children and adolescents with tic disorders. Identifying the psychosocial predictors/moderators for the effectiveness of this intervention can provide personalised treatment advice in the future. TRIAL REGISTRATION NUMBER: NL8052.

Nonlinear epigenetic variance: review and simulations.

We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addition to our review, we present simulation studies of nonlinear epigenetic variance using a computational model of neuronal network development. In each simulation study, time series for monozygotic and dizygotic twins were generated and analysed using conventional behaviour genetic modelling. In the results of these analyses, the nonlinear epigenetic variance was subsumed under the non-shared environmental component. As is commonly found in behaviour genetic studies, observed heritabilities and unique environmentabilities increased with time, whereas common environmentabilities decreased. The fact that the phenotypic effects of nonlinear epigenetic processes appear as unsystematic variance in conventional twin analyses complicates the identification and quantification of the ultimate genetic and environmental causes of individual differences. We believe that nonlinear dynamical system theories provide a challenging perspective on the development of individual differences, which may enrich behaviour genetic studies.

Consequences of a network view for genetic association studies.

Cramer et al's proposal to view mental disorders as the outcome of network dynamics among symptoms obviates the need to invoke latent traits to explain co-occurrence of symptoms and syndromes. This commentary considers the consequences of such a network view for genetic association studies.

How to Compare Psychometric Factor and Network Models.

In memory of Dr. Dennis John McFarland, who passed away recently, our objective is to continue his efforts to compare psychometric networks and latent variable models statistically. We do so by providing a commentary on his latest work, which he encouraged us to write, shortly before his death. We first discuss the statistical procedure McFarland used, which involved structural equation modeling (SEM) in standard SEM software. Next, we evaluate the penta-factor model of intelligence. We conclude that (1) standard SEM software is not suitable for the comparison of psychometric networks with latent variable models, and (2) the penta-factor model of intelligence is only of limited value, as it is nonidentified. We conclude with a reanalysis of the Wechlser Adult Intelligence Scale data McFarland discussed and illustrate how network and latent variable models can be compared using the recently developed R package Psychonetrics. Of substantive theoretical interest, the results support a network interpretation of general intelligence. A novel empirical finding is that networks of intelligence replicate over standardization samples.

Neural Correlates of Adolescent Irritability and Its Comorbidity With Psychiatric Disorders.

OBJECTIVE: Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. We examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2,024 14-year-old adolescents from 5 European countries. METHOD: The Development and Well-Being Assessment (DAWBA) was used to assess attention-deficit/hyperactivity disorder, major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder. Three items from the DAWBA, selected as close matches to the Affective Reactivity Index, were used to assess irritability. Structural magnetic resonance imaging was examined using whole-brain voxel-based morphometry analysis, and functional magnetic resonance imaging was examined during a stop signal task of inhibitory control. Imaging data were included in structural equation models to examine the direct and indirect associations between irritable mood and comorbid DSM diagnoses. RESULTS: Whole-brain voxelwise analysis showed that adolescent irritable mood was associated with less gray matter volume and less neural activation underlying inhibitory control in frontal and temporal cortical areas (cluster-correction at p < .05). Structural equation models suggested that part of the observed smaller gray matter volume was exclusively driven by irritability separate from direct relationships between generalized anxiety disorder (or attention-deficit/hyperactivity disorder, major depressive disorder, or oppositional defiant disorder) and gray matter volume. CONCLUSION: This study identifies adolescent irritability as an independent construct and points to a neurobiological correlate to irritability that is an important contributing feature to many psychopathological disorders.

The moderating role of SES on genetic differences in educational achievement in the Netherlands.

Parental socioeconomic status (SES) is a strong predictor of children's educational achievement (EA), with an increasing effect throughout development. Inequality in educational outcomes between children from different SES backgrounds exists in all Western countries. It has been proposed that a cause of this inequality lies in the interplay between genetic effects and SES on EA, which might depend on society and the equality of the education system. This study adopted two approaches, a classical twin design and polygenic score (PGS) approach, to address the effect of parental SES on EA in a large sample of 12-year-old Dutch twin pairs (2479 MZ and 4450 DZ twin pairs with PGSs for educational attainment available in 2335 children) from the Netherlands Twin Register (NTR). The findings of this study indicated that average EA increased with increasing parental SES. The difference in EA between boys and girls became smaller in the higher SES groups. The classical twin design analyses based on genetic covariance structure modeling pointed to lower genetic, environmental, and thus phenotypic variation in EA at higher SES. Independent from a child's PGS, parental SES predicted EA. However, the strength of the association between PGS and EA did not depend on parental SES. In a within-family design, the twin with a higher PGS scored higher on EA than the co-twin, demonstrating that the effect of the PGS on EA was at least partly independent from parental SES. To conclude, EA depended on SES both directly and indirectly, and SES moderated the additive genetic and environmental components of EA. Adding information from PGS, in addition to parental SES, improved the prediction of children's EA.

Low Smoking Exposure, the Adolescent Brain, and the Modulating Role of CHRNA5 Polymorphisms.

BACKGROUND: Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown. METHODS: Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and drug-use assessments. Additional assessments were conducted at 16 years of age. RESULTS: Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968. CONCLUSIONS: These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive.