Jessica Agnew-Blais

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

IMPORTANCEnAttention-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.nnnOBJECTIVEnTo investigate childhood risk factors and young adult functioning of individuals with persistent, remitted, and late-onset young adult ADHD.nnnDESIGN, SETTING, AND PARTICIPANTSnThe 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.nnnMAIN OUTCOMES AND MEASURESnAttention-deficit/hyperactivity disorder according to DSM-IV diagnostic criteria in childhood and DSM-5 diagnostic criteria in young adulthood.nnnRESULTSnOf 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.nnnCONCLUSIONS AND RELEVANCEnWe 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.

Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis

BACKGROUNDnBipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder.nnnMETHODSnFor this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features.nnnFINDINGSnWe initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21-3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25-1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10-2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45-5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39-2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41-2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13-1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43-2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45-2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09-1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07-1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88-2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality.nnnINTERPRETATIONnChildhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder.nnnFUNDINGnNone.

Social network media exposure and adolescent eating pathology in Fiji.

BACKGROUNDnMass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure--such as the proliferation of media exposure in an individuals social network--is also associated with eating disorders.nnnAIMSnTo test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji.nnnMETHODnWe assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n=523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE-Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors.nnnRESULTSnBoth direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR=1.60, 95% CI 1.15-2.23 relating social network media exposure to upper-quartile EDE-Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association.nnnCONCLUSIONSnSocial network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations.

Folate, Vitamin B-6, and Vitamin B-12 Intake and Mild Cognitive Impairment and Probable Dementia in the Women's Health Initiative Memory Study

BACKGROUNDnWhether higher B vitamin intake (ie, B-6, B-12, and folate) is protective against cognitive decline in later life remains uncertain. Several prospective, observational studies find higher B vitamin intake to be associated with lower risk of dementia; other studies, including most trials of B vitamin supplementation, have observed no effect on cognition. We examined this question in a large population of older women carefully monitored for development of mild cognitive impairment (MCI) and probable dementia.nnnOBJECTIVEnTo determine whether baseline folate, vitamin B-6, and/or vitamin B-12 intake, alone or in combination, are associated with incident MCI/probable dementia among older women.nnnDESIGNnProspective, longitudinal cohort study. Participants were enrolled between 1993 and 1998, and B vitamin intake was self-reported using a food frequency questionnaire administered at baseline.nnnPARTICIPANTS/SETTINGnPostmenopausal women (N=7,030) free of MCI/probable dementia at baseline in the Womens Health Initiative Memory Study.nnnMAIN OUTCOME MEASURESnOver a mean follow-up of 5.0 years, 238 cases of incident MCI and 69 cases of probable dementia were identified through rigorous screening and expert adjudication.nnnSTATISTICAL ANALYSESnCox proportional hazard models adjusting for sociodemographic and lifestyle factors examined the association of B vitamin intake above and below the Recommended Daily Allowance and incident MCI/probable dementia.nnnRESULTSnFolate intake below the Recommended Daily Allowance at study baseline was associated with increased risk of incident MCI/probable dementia (hazard ratio 2.0, 95% CI 1.3 to 2.9), after controlling for multiple confounders. There were no significant associations between vitamins B-6 or B-12 and MCI/probable dementia, nor any evidence of an interaction between these vitamins and folate intake.nnnCONCLUSIONSnFolate intake below the Recommended Daily Allowance may increase risk for MCI/probable dementia in later life. Future research should include long-term trials of folic acid supplementation to examine whether folate may impart a protective effect on cognition in later life.

Early Childhood IQ Trajectories in Individuals Later Developing Schizophrenia and Affective Psychoses in the New England Family Studies

Individuals who develop schizophrenia in adulthood exhibit, on average, deficits in childhood cognition relative to healthy controls. However, it remains unclear when in childhood such deficits emerge and whether they are stable across childhood or change (increase or decrease) across development. Importantly, whether the trajectory of childhood cognition differs among youth who later develop affective psychoses (AP) vs schizophrenia as adults remains unresolved. Subjects in the Collaborative Perinatal Project were administered the Stanford-Binet IQ test at age 4 and the Wechsler Intelligence Scale for Children at age 7. A total of 9809 (54.7%) participants in the New England Study sites were tested at both ages, including 37 who later developed schizophrenia spectrum psychoses (SSP) and 39 who later developed AP. Logistic regression models examined the association of level of and change in childhood IQ and later SSP or AP. Lower overall childhood IQ was associated with higher risk of SSP. Additionally, there was a small mean increase in IQ in the SSP group relative to a mean decrease in the control group from age 4 to 7 such that positive change in IQ was significantly associated with a higher risk of SSP. Neither overall level nor change in IQ was associated with risk of AP. The results are consistent with neurocognitive impairment throughout early childhood specifically for children who later develop schizophrenia, affirming the theory of atypical neurodevelopment in premorbid schizophrenia.

ADHD and Sleep Quality: Longitudinal Analyses From Childhood to Early Adulthood in a Twin Cohort

Attention-deficit/hyperactivity disorder (ADHD) is associated with poor sleep quality, but there is more to learn about the longitudinal association and aetiology of this association. We investigated the following: (a) Is there an association between childhood ADHD and poor sleep quality in young adulthood? (b) Is this driven by the long-term effects of childhood ADHD or concurrent associations with ADHD in young adulthood? (c) To what extent do genetic and environmental influences explain the overlap between symptoms of ADHD and poor sleep quality? Participants were from the Environmental Risk Longitudinal Twin Study of 2,232 twin children born in the United Kingdom in 1994–1995. We ascertained ADHD diagnoses at ages 5, 7, 10, 12, and 18. We assessed sleep quality using the Pittsburgh Sleep Quality Index at age 18. We used regression models to examine longitudinal associations and bivariate twin modelling to test genetic and environmental influences. Children with ADHD had poorer sleep quality in young adulthood, but only if their ADHD persisted. Adults with ADHD had more sleep problems than those without ADHD, over and above psychiatric comorbidity and maternal insomnia. ADHD and sleep problems in young adulthood were associated because of genetic (55%) and nonshared environmental influences (45%). Should ADHD remit, children with ADHD do not appear to have an increased risk of later sleep problems. Good quality sleep is important for multiple areas of functioning, and a better understanding of why adults with ADHD have poorer sleep quality will further the goal of improving treatments.

Parental monitoring and knowledge: Testing bidirectional associations with youths’ antisocial behavior

In the present study, we used separate measures of parental monitoring and parental knowledge and compared their associations with youths antisocial behavior during preadolescence, between the ages of 10 and 12. Parental monitoring and knowledge were reported by mothers, fathers, and youths taking part in the Environmental Risk (E-Risk) Longitudinal Twin Study that follows 1,116 families with twins. Information on youths antisocial behavior was obtained from mothers as well as teachers. We report two main findings. First, longitudinal cross-lagged models revealed that greater parental monitoring did not predict less antisocial behavior later, once family characteristics were taken into account. Second, greater youth antisocial behavior predicted less parental knowledge later. This effect of youths behavior on parents knowledge was consistent across mothers, fathers, youths, and teachers reports, and robust to controls for family confounders. The association was partially genetically mediated according to a Cholesky decomposition twin model; youths genetically influenced antisocial behavior led to a decrease in parents knowledge of youths activities. These two findings question the assumption that greater parental monitoring can reduce preadolescents antisocial behavior. They also indicate that parents knowledge of their childrens activities is influenced by youths behavior.

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 interplay of childhood behavior problems and IQ in the development of later schizophrenia and affective psychoses

Schizophrenia and affective psychoses are both associated with impaired social functioning, but the extent to which childhood behavioral impairments are present prior to onset of illness is less well studied. Moreover, the concurrent relationship of childhood behavior problems and premorbid IQ with subsequent psychotic disorder has not been established. We investigated whether childhood behavior problems are associated with increased risk for adult schizophrenia or affective psychosis, independently and in combination with IQ. The study included individuals with schizophrenia (N=47), affective psychoses (N=45) and non-psychotic controls (N=1496) from the New England Family Study. Behavior problems were prospectively assessed from standardized clinician observations at ages 4 and 7. IQ was assessed with the Stanford-Binet at age 4 and the Wechsler Intelligence Scale for Children at age 7. We found externalizing problems at age 4 and externalizing and internalizing problems at age 7 were associated with later schizophrenia, and both internalizing and externalizing problems at ages 4 and 7 were associated with later development of affective psychoses. Lower IQ at ages 4 and 7 was associated with schizophrenia, while lower IQ was associated with affective psychoses at age 7 only. Examined simultaneously, both lower IQ and behavior problems remained associated with risk of schizophrenia, while only behavior problems remained associated with affective psychoses. Behavior problems appear to be a general marker of risk of adult psychotic disorder, while lower childhood IQ is more specific to risk of schizophrenia. Future research should clarify the premorbid evolution of behavior and cognitive problems into adult psychosis.

Auditory Vigilance and Working Memory in Youth at Familial Risk for Schizophrenia or Affective Psychosis in the Harvard Adolescent Family High Risk Study

BACKGROUNDnThe degree of overlap between schizophrenia (SCZ) and affective psychosis (AFF) has been a recurring question since Kraepelins subdivision of the major psychoses. Studying nonpsychotic relatives allows a comparison of disorder-associated phenotypes, without potential confounds that can obscure distinctive features of the disorder. Because attention and working memory have been proposed as potential endophenotypes for SCZ and AFF, we compared these cognitive features in individuals at familial high-risk (FHR) for the disorders.nnnMETHODSnYoung, unmedicated, first-degree relatives (ages, 13-25 years) at FHR-SCZ (n=41) and FHR-AFF (n=24) and community controls (CCs, n=54) were tested using attention and working memory versions of the Auditory Continuous Performance Test. To determine if schizotypal traits or current psychopathology accounted for cognitive deficits, we evaluated psychosis proneness using three Chapman Scales, Revised Physical Anhedonia, Perceptual Aberration, and Magical Ideation, and assessed psychopathology using the Hopkins Symptom Checklist -90 Revised.nnnRESULTSnCompared to controls, the FHR-AFF sample was significantly impaired in auditory vigilance, while the FHR-SCZ sample was significantly worse in working memory. Both FHR groups showed significantly higher levels of physical anhedonia and some psychopathological dimensions than controls. Adjusting for physical anhedonia, phobic anxiety, depression, psychoticism, and obsessive-compulsive symptoms eliminated the FHR-AFF vigilance effects but not the working memory deficits in FHR-SCZ.nnnCONCLUSIONSnThe working memory deficit in FHR-SZ was the more robust of the cognitive impairments after accounting for psychopathological confounds and is supported as an endophenotype. Examination of larger samples of people at familial risk for different psychoses remains necessary to confirm these findings and to clarify the role of vigilance in FHR-AFF. (JINS, 2016, 22, 1026-1037).