pinecone/core-2020-05-10-deduplication huggingface dataset:
Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and meta-analysis

IMPORTANCE Schizophrenia has a complex etiology influenced both by genetic and nongenetic factors but disentangling these factors is difficult. OBJECTIVE To estimate (1) how strongly the risk for schizophrenia relates to the mutual effect of the polygenic risk score, parental socioeconomic status, and family history of psychiatric disorders; (2) the fraction of cases that could be prevented if no one was exposed to these factors; (3) whether family background interacts with an individual\u27s genetic liability so that specific subgroups are particularly risk prone; and (4) to what extent a proband\u27s genetic makeup mediates the risk associated with familial background. DESIGN, SETTINGS, AND PARTICIPANTS We conducted a nested case-control study based onDanish population-based registers. The study consisted of 866 patients diagnosed as having schizophrenia between January 1, 1994, and December 31, 2006, and 871 matched control individuals. Genome-wide data and family psychiatric and socioeconomic background information were obtained from neonatal biobanks and national registers. Results from a separate meta-analysis (34 600 cases and 45 968 control individuals) were applied to calculate polygenic risk scores. EXPOSURES Polygenic risk scores, parental socioeconomic status, and family psychiatric history. MAIN OUTCOMES AND MEASURES Odds ratios (ORs), attributable risks, liability R2 values, and proportions mediated. RESULTS Schizophrenia was associated with the polygenic risk score (OR, 8.01; 95%CI, 4.53-14.16 for highest vs lowest decile), socioeconomic status (OR, 8.10; 95%CI, 3.24-20.3 for 6 vs no exposures), and a history of schizophrenia/psychoses (OR, 4.18; 95%CI, 2.57-6.79). The R2 values were 3.4%(95%CI, 2.1-4.6) for the polygenic risk score, 3.1%(95%CI, 1.9-4.3) for parental socioeconomic status, and 3.4%(95%CI, 2.1-4.6) for family history. Socioeconomic status and psychiatric history accounted for 45.8% (95%CI, 36.1-55.5) and 25.8% (95%CI, 21.2-30.5) of cases, respectively. There was an interaction between the polygenic risk score and family history (P = .03). A total of 17.4%(95%CI, 9.1-26.6) of the effect associated with family history of schizophrenia/psychoses was mediated through the polygenic risk score. CONCLUSIONS AND RELEVANCE Schizophrenia was associated with the polygenic risk score, family psychiatric history, and socioeconomic status. Our study demonstrated that family history of schizophrenia/psychoses is partly mediated through the individual\u27s genetic liability
Attention-Deficit/Hyperactivity Disorder trajectories from childhood to young adulthood: evidence from a birth cohort supporting a late-onset syndrome

IMPORTANCE  The requirement of a childhood onset has always been a key criterion for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults, but recently this requirement has become surrounded by controversy.  OBJECTIVE  To investigate whether impaired young adults with ADHD symptoms always have a childhood-onset disorder in a population-based longitudinal study.  DESIGN, SETTING, AND PARTICIPANTS  Participants belonged to the 1993 Pelotas Birth Cohort Study, including 5249 individuals born in Pelotas, Brazil, in 1993. They were followed up to 18 to 19 years of age, with 81.3% retention. The data analysis was performed between August 8, 2015, and February 5, 2016.  MAIN OUTCOMES AND MEASURES  The ADHD status was first ascertained at 11 years of age using a screening instrument (hyperactivity subscale of the Strength and Difficulties Questionnaire) calibrated for a DSM-IV ADHD diagnosis based on clinical interviews with parents using the Development and Well-Being Assessment. At 18 to 19 years of age, ADHD diagnosis was derived using DSM-5 criteria, except age at onset. We estimated the overlap between these groups assessed at 11 and 18 to 19 years of age and the rates of markers of impairment in these 2 groups compared with those without ADHD.  RESULTS  At 11 years of age, childhood ADHD (C-ADHD) was present in 393 individuals (8.9%). At 18 to 19 years of age, 492 individuals (12.2%) fulfilled all DSM-5 criteria for young adult ADHD (YA-ADHD), except age at onset. After comorbidities were excluded, the prevalence of YA-ADHD without comorbidities decreased to 256 individuals (6.3%). Children with C-ADHD had a male preponderance not observed among children without ADHD (251 [63.9%] vs 1930 [47.9%] male, P < .001), whereas the YA-ADHD group had a female preponderance (192 [39.0%] vs 1786 [50.4%] male, P < .001). Both groups had increased levels of impairment in adulthood, as measured by traffic incidents, criminal behavior, incarceration, suicide attempts, and comorbidities. However, only 60 children (17.2%) with ADHD continued to have ADHD as young adults, and only 60 young adults (12.6%) with ADHD had the disorder in childhood.  CONCLUSIONS AND RELEVANCE  The findings of this study do not support the assumption that adulthood ADHD is necessarily a continuation of childhood ADHD. Rather, they suggest the existence of 2 syndromes that have distinct developmental trajectories
Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial

Importance  A promising treatment to prevent onset and improve outcomes in patients at ultrahigh risk for psychosis is dietary supplementation with long-chain ω-3 polyunsaturated fatty acids (PUFAs).  Objective  To determine whether treatment with ω-3 PUFAs in combination with a high-quality psychosocial intervention (cognitive behavioral case management [CBCM]) is more effective than placebo plus CBCM.  Design, Setting, and Participants  NEURAPRO, a double-blind, placebo-controlled, randomized clinical trial, was conducted from March 1, 2010, to September 30, 2014, in 10 specialized early psychosis treatment services in Australia, Asia, and Europe. The primary analysis used the intention-to-treat approach.  Interventions  A daily dose of 1.4 g of ω-3 PUFAs or placebo (paraffin oil), plus 20 or fewer sessions of CBCM over the 6-month study period.  Main Outcomes and Measures  The primary outcome was transition to psychosis status at 6 months. The secondary outcomes were general levels of psychopathology and functioning, as assessed by the Brief Psychiatric Rating Scale (BPRS) (range, 24-168), Scale for the Assessment of Negative Symptoms (SANS) (range, 0-125), Montgomery-Åsberg Depression Rating Scale (MADRS) (range, 0-60), Young Mania Rating Scale (YMRS) (range, 0-44), Social and Occupational Functioning Assessment Scale (SOFAS) (range, 0-100), and the Global Functioning: Social and Role scale (range, 0-10). For SOFAS and Global Functioning: Social and Role scale, higher scores were better; for other measures, lower scores were better.  Results  In this study of 304 adults at ultrahigh risk for psychotic disorders, 153 (50.3%) received ω-3 PUFAs and 151 (49.7%) received placebo. In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The Kaplan-Meier-estimated 6-month transition rates were 5.1% (95% CI, 1.3%-8.7%) in the control group and 6.7% (95% CI, 2.3%-10.8%) in the ω-3 PUFA group. At 12 months, the rates were 11.2% (95% CI, 5.5%-16.7%) in the control group and 11.5% (95% CI, 5.8%-16.9%) in the ω-3 PUFA group. No significant difference was observed between the transition rates of both groups (hazard ratio, 1.1; 95% CI, 0.55-2.23; P = .76, stratified log-rank test).  Conclusions and Relevance  This trial clearly failed to replicate the findings of the original single-center trial. The most likely explanation is that ω-3 PUFAs lack efficacy under these conditions. However, the lower-than-expected transition rate may have prevented a test of the main hypothesis. Given the substantial symptomatic and functional improvement in both groups, the other treatments received (ie, CBCM and antidepressants) likely produced a ceiling effect beyond which ω-3 PUFAs, even if effective, could not be shown to confer additional benefits. Nevertheless, the main conclusion is that ω-3 PUFAs are not effective under conditions where good quality, evidence-based psychosocial treatment is available.  Trial Registration  anzctr.org.au Identifier: 12608000475347
Antecedents of new-onset major depressive disorder in adolescence: a longitudinal familial high-risk study

Importance: Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational outcomes.\ud
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Objectives: To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents.\ud
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Design, Setting, and Participants: This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean [SD] age of 12.4 [2.0] years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up.\ud
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Main Outcomes and Measures: The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score.\ud
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Results: On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (β = 0.12, P = .03) and fear and/or anxiety (β = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (β = −0.08, P = .14) and low mood (β = −0.03, P = .65) were not. The results were similar for the DSM-IV symptom count at follow-up. All the measured familial/genetic and social risk indicators directly influenced risk for new-onset MDD rather than indirectly through acting on dimensional clinical antecedents.\ud
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Conclusions and Relevance: There are multiple pathways to first-onset adolescent depression in individuals at familial risk. Irritability and fear/anxiety may be additional clinical phenomena to be included as targets in primary preventive interventions focusing on the child. In addition to targeting these phenomena in parents and children, depression prevention methods in high-risk groups may need to take into consideration social risks, such as poverty and psychosocial adversity
D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: A systematic review and meta-analysis of individual participant data

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                  174490.pdf (publisher's version ) (Open Access)Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.10 p
Concurrent and longitudinal contribution of exposure to bullying in childhood to mental health: the role of vulnerability and resilience

Importance: Exposure to bullying is associated with poor mental health. However, the degree to which observed associations reflect direct detrimental contributions of exposure to bullying to mental health remains uncertain, as noncausal relationships may arise from genetic and environmental confounding (eg, preexisting vulnerabilities). Determining to what extent exposure to bullying contributes to mental health is an important concern, with implications for primary and secondary interventions.\ud
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Objective: To characterize the concurrent and longitudinal contribution of exposure to bullying to mental health in childhood and adolescence using a twin differences design to strengthen causal inference.\ud
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Design, Setting, and Participants: Participants were drawn from the Twins Early Development Study, a population-based cohort recruited from population records of births in England and Wales between January 1, 1994, and December 31, 1996. Data collection took place when the participants were between 11 and 16 years of age from December 1, 2005, to January 31, 2013. Data analysis was conducted from January 1, 2016, to June 20, 2017.\ud
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Exposures: Participants completed the Multidimensional Peer-Victimization Scale at 11 and 14 years of age.\ud
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Main Outcomes and Measures: Mental health assessments at 11 and 16 years of age included anxiety, depression, hyperactivity and impulsivity, inattention, conduct problems, and psychotic-like experiences (eg, paranoid thoughts or cognitive disorganization).\ud
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Results: The 11 108 twins included in the final sample (5894 girls and 5214 boys) were a mean age of 11.3 years at the first assessment and 16.3 years at the last assessment. The most stringent twin differences estimates (monozygotic) were consistent with causal contribution of exposure to bullying at 11 years to concurrent anxiety, depression, hyperactivity and impulsivity, inattention, and conduct problems. Effects decreased over time; that is, substantial concurrent contributions to anxiety (β = 0.27; 95% CI, 0.22-0.33) persisted for 2 years (β = 0.12; 95% CI, 0.04-0.20) but not 5 years. Direct contributions to paranoid thoughts and cognitive disorganization persisted for 5 years.\ud
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Conclusions and Relevance: This study is the largest to date to characterize the contribution of exposure to bullying in childhood to mental health using a twin differences design and multi-informant, multiscale data. Stringent evidence of the direct detrimental contribution of exposure to bullying in childhood to mental health is provided. Findings also suggest that childhood exposure to bullying may partly be viewed as a symptom of preexisting vulnerabilities. Finally, the dissipation of effects over time for many outcomes highlights the potential for resilience in children who were bullied. In addition to programs that aim to reduce exposure to bullying, interventions may benefit from addressing preexisting vulnerabilities and focus on resilience
Association of Environment With the Risk of Developing Psychotic Disorders in Rural Populations:Findings from the Social Epidemiology of Psychoses in East Anglia Study

Importance: Social determinants are important risk factors for the development of first-episode psychosis (FEP); their effects in rural areas are largely unknown. Objective: To investigate neighborhood-level factors associated with FEP in a large, predominantly rural population-based cohort. Design, Setting, and Participants: This study extracted data on referrals for treatment of potential FEP at 6 Early-Intervention Psychosis services from the Social Epidemiology of Psychoses in East Anglia naturalistic cohort study data set, which covered a population of more than 2 million people in a rural area in the East of England for a period of 3.5 years. All individuals aged 16 to 35 years who presented to Early-Intervention Psychosis services and met diagnostic criteria for first episodes of nonaffective psychoses and affective psychoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes F20-33) were included (n = 631). Persons whose disorders had an organic basis (diagnostic codes F06.X) and those meeting the criteria for substance-induced psychosis (diagnostic codes F1X.5) were excluded. We derived 4 neighborhood-level exposures from a routine population data set using exploratory factor analysis (racial/ethnic diversity, deprivation, urbanicity, and social isolation) and investigated intragroup racial/ethnic density and fragmentation. Main Outcomes and Measures: Multilevel Poisson regression was performed to determine associations between incidence rates and neighborhood-level factors, after adjustment for individual factors. Results were reported as incidence rate ratios (IRRs). Results: The study included 631 participants who met criteria for FEP and whose median age at first contact was 23.8 years (interquartile range, 19.6-27.6 years); 416 of 631 (65.9%) were male. Crude incidence of FEP was calculated as 31.2 per 100 000 person-years (95% CI, 28.9-33.7). Incidence varied significantly between neighborhoods after adjustment for age, sex, race/ethnicity, and socioeconomic status. For nonaffective psychoses, incidence was higher in neighborhoods that were more economically deprived (IRR, 1.13; 95% CI, 1.06-1.20) and socially isolated (IRR, 1.11; 95% CI, 1.04-1.19). It was lower in more racially/ethnically diverse neighborhoods (IRR, 0.94; 95% CI, 0.87-1.00). Higher intragroup racial/ethnic density (IRR, 0.97; 95% CI, 0.94-1.00) and lower intragroup racial/ethnic fragmentation (IRR, 0.98; 95% CI, 0.96-1.00) were associated with a reduced risk of affective psychosis. Conclusions and Relevance: Spatial variation in the incidence of nonaffective and affective psychotic disorders exists in rural areas. This suggests that the social environment contributes to psychosis risk across the rural-urban gradient
Individual and Area-Based Socioeconomic Factors Associated With Dementia Incidence in England

<b>IMPORTANCE</b> <p>Lower educational attainment is associated with a higher risk of dementia.\ud
However, less clear is the extent to which other socioeconomic markers contribute to\ud
dementia risk.</p>\ud
<b>OBJECTIVE</b> <p>To examine the relationship of education, wealth, and area-based deprivation\ud
with the incidence of dementia over the last decade in England and investigate differences\ud
between people born in different periods.</p>\ud
<b>DESIGN, SETTING, AND PARTICIPANTS</b> <p>Data from the English Longitudinal Study of Ageing, a\ud
prospective cohort study that is representative of the English population, were used to\ud
investigate the associations between markers of socioeconomic status (wealth quintiles and\ud
the index of multiple deprivation) and dementia incidence. To investigate outcomes\ud
associated with age cohorts, 2 independent groups were derived using a median split (born\ud
between 1902-1925 and 1926-1943).</p>\ud
<b>MAIN OUTCOMES AND MEASURES</b> <p>Dementia as determined by physician diagnosis and the\ud
Informant Questionnaire on Cognitive Decline in the Elderly.</p>\ud
<b>RESULTS</b> <p>A total of 6220 individuals aged 65 years and older enrolled in the study (median\ud
[interquartile range] age at baseline, 73.2 [68.1-78.3] years; 3410 [54.8%] female). Of these,\ud
463 individuals (7.4%) had new cases of dementia ascertained in the 12 years between\ud
2002-2003 and 2014-2015. In the cohort born between 1926 and 1943, the hazard of\ud
developing dementia was 1.68 times higher (hazard ratio [HR] = 1.68 [95%CI, 1.05-2.86]) for\ud
those in the lowest wealth quintile compared with those in the highest quintile, independent\ud
of education, index of multiple deprivation, and health indicators. Higher hazards were also\ud
observed for those in the second-highest quintile of index of multiple deprivation (HR = 1.62\ud
[95%CI, 1.06-2.46]) compared with those in the lowest (least deprived) quintile.</p>\ud
<b>CONCLUSIONS AND RELEVANCE</b> <p>In an English nationally representative sample, the incidence\ud
of dementia appeared to be socioeconomically patterned primarily by the level of wealth.\ud
This association was somewhat stronger for participants born in later years.</p