Jasmin Wertz

Evaluation of the Persistence, Remission, and Emergence of Attention-Deficit/Hyperactivity Disorder in Young Adulthood

IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) is now recognized to occur in adulthood and is associated with a range of negative outcomes. However, less is known about the prospective course of ADHD into adulthood, the risk factors for its persistence, and the possibility of its emergence in young adulthood in nonclinical populations. OBJECTIVE To investigate childhood risk factors and young adult functioning of individuals with persistent, remitted, and late-onset young adult ADHD. DESIGN, SETTING, AND PARTICIPANTS The study sample was the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in England and Wales from January 1, 1994, to December 4, 1995. Evaluation of childhood ADHD (ages 5, 7, 10, and 12 years) included prenatal and perinatal factors, clinical characteristics, and aspects of the family environment. Among participants aged 18 years, ADHD symptoms and associated impairment, overall functioning, and other mental health disorders were examined. Data analysis was conducted from February 19 to September 10, 2015. MAIN OUTCOMES AND MEASURES Attention-deficit/hyperactivity disorder according to DSM-IV diagnostic criteria in childhood and DSM-5 diagnostic criteria in young adulthood. RESULTS Of 2232 participants in the E-Risk Study, 2040 were included in the present analysis. In total, 247 individuals met diagnostic criteria for childhood ADHD; of these, 54 (21.9%) also met diagnostic criteria for the disorder at age 18 years. Persistence was associated with more symptoms (odds ratio [OR], 1.11 [95% CI, 1.04-1.19]) and lower IQ (OR, 0.98 [95% CI, 0.95-1.00]). At age 18 years, individuals with persistent ADHD had more functional impairment (school/work: OR, 3.30 [95% CI, 2.18-5.00], home/with friends: OR, 6.26 [95% CI, 3.07-12.76]), generalized anxiety disorder (OR, 5.19 [95% CI, 2.01-13.38]), conduct disorder (OR, 2.03 [95% CI, 1.03-3.99]), and marijuana dependence (OR, 2.88 [95% CI, 1.07-7.71]) compared with those whose ADHD remitted. Among 166 individuals with adult ADHD, 112 (67.5%) did not meet criteria for ADHD at any assessment in childhood. Results from logistic regressions indicated that individuals with late-onset ADHD showed fewer externalizing problems (OR, 0.93 [95% CI, 0.91-0.96]) and higher IQ (OR, 1.04 [95% CI, 1.02-1.07]) in childhood compared with the persistent group. However, at age 18 years, those with late-onset ADHD demonstrated comparable ADHD symptoms and impairment as well as similarly elevated rates of mental health disorders. CONCLUSIONS AND RELEVANCE We identified heterogeneity in the DSM-5 young adult ADHD population such that this group consisted of a large, late-onset ADHD group with no childhood diagnosis, and a smaller group with persistent ADHD. The extent to which childhood-onset and late-onset adult ADHD may reflect different causes has implications for genetic studies and treatment of ADHD.

Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells

Background: The increasingly recognized role of inflammation in the pathogenesis and prognosis of depression has led to a renewed focus on the immunomodulatory properties of compounds with antidepressant action. Studies have, so far, explored such properties in human blood samples and in animal models. Methods: Here we used the more relevant model of human hippocampal progenitor cells exposed to an inflammatory milieu, induced by treatment with IL-1β. This increased the levels of a series of cytokines and chemokines produced by the cells, including a dose- and time-dependent increase of IL-6. We investigated the immunomodulatory properties of four monoaminergic antidepressants (venlafaxine, sertraline, moclobemide, and agomelatine) and two omega-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]). Results: We found that venlafaxine and EPA were anti-inflammatory: venlafaxine decreased IL-6, with a trend for decreases of IL-8 and IP-10, while EPA decreased the levels of IL-6, IL-15, IL-1RA, and IP-10. These effects were associated with a corresponding decrease in NF-kB activity. Unexpectedly, sertraline and DHA had pro-inflammatory effects, with sertraline increasing IFN-α and IL-6 and DHA increasing IL-15, IL-1RA, IFN-α, and IL-6, though these changes were also associated with a decrease in NF-kB activity, suggesting distinct modes of action. Agomelatine and moclobemide had no effect on IL-6 secretion. Conclusions: These observations indicate that monoaminergic antidepressants and n-3 PUFAs have distinctive effects on immune processes in human neural cells. Further characterization of these actions may enable more effective personalization of treatment based on the inflammatory status of patients.

Social Isolation and Mental Health at Primary and Secondary School Entry: A Longitudinal Cohort Study

Objective We tested whether children who are socially isolated early in their schooling develop mental health problems in early adolescence, taking into account their mental health and family risk at school entry. Method We used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 children born in England and Wales in 1994 and 1995. We measured social isolation using mothers’ and teachers’ reports at ages 5 and 12 years. We assessed mental health symptoms via mothers’ and teachers’ ratings at age 5 and self-report measures at age 12. We collected mother-reported information about the family environment when children were 5 years old. We conducted regression analyses to test concurrent and longitudinal associations between early family factors, social isolation, and mental health difficulties. Results At both primary and secondary school, children who were socially isolated experienced greater mental health difficulties. Children with behavioral problems or attention-deficit/hyperactivity disorder (ADHD) symptoms at age 5 years had an elevated risk of becoming more socially isolated at age 12. However, children who were isolated at age 5 did not have greater mental health symptoms at age 12, over and above pre-existing difficulties. Conclusion Although social isolation and mental health problems co-occur in childhood, early isolation does not predict worse mental health problems later on. However, children who exhibit problematic behaviors may struggle to cope with the social challenges that accompany their progression through the early school years.

Etiology of Pervasive versus Situational Antisocial Behaviors: A Multi-informant Longitudinal Cohort Study.

The aim of this study was to disentangle pervasive from situational antisocial behaviors using multiple informants, and to investigate their genetic and environmental etiologies in preadolescence and across time. Antisocial behaviors were assessed in 2,232 twins from the Environmental Risk (E‐Risk) Longitudinal Twin Study at ages 5 and 12. Pervasive antisocial behaviors were defined as behaviors that mothers, teachers, interviewers, and twins themselves agreed on. Results from a psychometric model indicated that the variation in childrens pervasive antisocial behaviors was mostly accounted for by familial influences that originated in childhood, whereas situational behaviors were explained by newly emerging nonshared environmental and genetic influences. This study shows that childrens pervasive and situational antisocial behaviors have distinct etiologies that could guide research and treatment.

Invited commentary on . . . Psychiatric resilience: longitudinal twin study

The study of resilience may lead to the identification of new targets for prevention and intervention, yet there has been little research on why some people, but not others, show resilience after facing stressful life events. New research in this issue shows that resilience is equally explained by genetic and environmental influences, and that individual experiences and situational factors are both important in shaping resilient responses to stress. These findings could inform the development of interventions that enhance psychiatric resilience after exposure to adversity.

Genetic analysis of social-class mobility in five longitudinal studies

Significance Genome-wide association study (GWAS) discoveries about educational attainment have raised questions about the meaning of the genetics of success. These discoveries could offer clues about biological mechanisms or, because children inherit genetics and social class from parents, education-linked genetics could be spurious correlates of socially transmitted advantages. To distinguish between these hypotheses, we studied social mobility in five cohorts from three countries. We found that people with more education-linked genetics were more successful compared with parents and siblings. We also found mothers’ education-linked genetics predicted their children’s attainment over and above the children’s own genetics, indicating an environmentally mediated genetic effect. Findings reject pure social-transmission explanations of education GWAS discoveries. Instead, genetics influences attainment directly through social mobility and indirectly through family environments. A summary genetic measure, called a “polygenic score,” derived from a genome-wide association study (GWAS) of education can modestly predict a person’s educational and economic success. This prediction could signal a biological mechanism: Education-linked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents’ position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother’s polygenic score predicted her child’s attainment over and above the child’s own polygenic score, suggesting parents’ genetics can also affect their children’s attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals’ family-of-origin environments and their social mobility.

Adolescent Victimization and Early-Adult Psychopathology: Approaching Causal Inference Using a Longitudinal Twin Study to Rule Out Noncausal Explanations:

Adolescence is the peak age for both victimization and mental disorder onset. Previous research has reported associations between victimization exposure and many psychiatric conditions. However, causality remains controversial. Within the Environmental Risk Longitudinal Twin Study, we tested whether seven types of adolescent victimization increased risk of multiple psychiatric conditions and approached causal inference by systematically ruling out noncausal explanations. Longitudinal within-individual analyses showed that victimization was followed by increased mental health problems over a childhood baseline of emotional/behavioral problems. Discordant-twin analyses showed that victimization increased risk of mental health problems independent of family background and genetic risk. Both childhood and adolescent victimization made unique contributions to risk. Victimization predicted heightened generalized liability (the “p factor”) to multiple psychiatric spectra, including internalizing, externalizing, and thought disorders. Results recommend violence reduction and identification and treatment of adolescent victims to reduce psychiatric burden.

Genetics and crime: Integrating new genomic discoveries into psychological research about antisocial behavior

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

From Childhood Conduct Problems to Poor Functioning at Age 18 Years: Examining Explanations in a Longitudinal Cohort Study

Objective Childhood conduct problems are associated with poor functioning in early adulthood. We tested a series of hypotheses to understand the mechanisms underlying this association. Method We used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 twins born in England and Wales in 1994 and 1995, followed up to age 18 years with 93% retention. Severe conduct problems in childhood were assessed at ages 5, 7, and 10 years using parent and teacher reports. Poor functioning at age 18 years, including cautions and convictions, daily cigarette smoking, heavy drinking, and psychosocial difficulties, was measured through interviews with participants and official crime record searches. Results Participants 18 years old with versus without a childhood history of severe conduct problems had greater rates of each poor functional outcome, and they were more likely to experience multiple poor outcomes. This association was partly accounted for by concurrent psychopathology in early adulthood, as well as by early familial risk factors, both genetic and environmental. Childhood conduct problems, however, continued to predict poor outcomes at age 18 years after accounting for these explanations. Conclusion Children with severe conduct problems display poor functioning at age 18 years because of concurrent problems in early adulthood and familial risk factors originating in childhood. However, conduct problems also exert a lasting effect on young people’s lives independent of these factors, pointing to early conduct problems as a target for early interventions aimed at preventing poor functional outcomes.

The developmental nature of the victim-offender overlap

PurposeIt is well-established that victims and offenders are often the same people, a phenomenon known as the victim-offender overlap, but the developmental nature of this overlap remains uncertain. In this study, we drew from a developmental theoretical framework to test effects of genetics, individual characteristics, and routine-activity-based risks. Drawing from developmental literature, we additionally tested the effect of an accumulation of adverse childhood experiences (ACEs).MethodsData came from the Environmental Risk (E-Risk) Study, a representative UK birth cohort of 2232 twins born in 1994–1995 and followed to age 18 (with 93% retention). Crime victimization and offending were assessed through self-reports at age 18 (but findings replicated using crime records). We used the classical twin study method to decompose variance in the victim-offender overlap into genetic and environmental components. We used logistic regression to test the effects of childhood risk factors.ResultsIn contrast to past twin studies, we found that environment (as well as genes) contributed to the victim-offender overlap. Our logistic regression results showed that childhood low self-control and childhood antisocial behavior nearly doubled the odds of becoming a victim-offender, compared to a victim-only or an offender-only. Each additional ACE increased the odds of becoming a victim-offender, compared to a victim-only or an offender-only, by approximately 12%, pointing to the importance of cumulative childhood adversity.ConclusionsThis study showed that the victim-offender overlap is, at least partially, developmental in nature and predictable from personal childhood characteristics and an accumulation of many adverse childhood experiences.