Abraham Reichenberg

King's College London, Londinium, England, United Kingdom

Are you Abraham Reichenberg?

Claim your profile

Publications (165)970.14 Total impact

  • Sven Sandin, Abraham Reichenberg
    JAMA. 09/2014; 312(11):1155.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome.
    Schizophrenia Research 08/2014; · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
    Nature 07/2014; 511:421-427. · 38.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism's genetic architecture: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.
    Nature genetics. 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental factors remains unresolved. OBJECTIVE To provide estimates of familial aggregation and heritability of ASD. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort including 2 049 973 Swedish children born 1982 through 2006. We identified 37 570 twin pairs, 2 642 064 full sibling pairs, 432 281 maternal and 445 531 paternal half sibling pairs, and 5 799 875 cousin pairs. Diagnoses of ASD to December 31, 2009 were ascertained. MAIN OUTCOMES AND MEASURES The relative recurrence risk (RRR) measures familial aggregation of disease. The RRR is the relative risk of autism in a participant with a sibling or cousin who has the diagnosis (exposed) compared with the risk in a participant with no diagnosed family member (unexposed). We calculated RRR for both ASD and autistic disorder adjusting for age, birth year, sex, parental psychiatric history, and parental age. We estimated how much of the probability of developing ASD can be related to genetic (additive and dominant) and environmental (shared and nonshared) factors. RESULTS In the sample, 14 516 children were diagnosed with ASD, of whom 5689 had autistic disorder. The RRR and rate per 100 000 person-years for ASD among monozygotic twins was estimated to be 153.0 (95% CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed ); for dizygotic twins, 8.2 (95% CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full siblings, 10.3 (95% CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half siblings, 3.3 (95% CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half siblings, 2.9 (95% CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0 (95% CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for autistic disorder but of slightly higher magnitude.We found support for a disease etiology including only additive genetic and nonshared environmental effects. The ASD heritability was estimated to be 0.50 (95% CI, 0.45-0.56) and the autistic disorder heritability was estimated to 0.54 (95% CI, 0.44-0.64). CONCLUSIONS AND RELEVANCE Among children born in Sweden, the individual risk of ASD and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and autistic disorder were estimated to be approximately 50%. These findings may inform the counseling of families with affected children.
    JAMA The Journal of the American Medical Association 05/2014; 311(17):1770-7. · 29.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study is to compare the time trend of reported diagnoses of autism spectrum disorder (ASD), hyperkinetic disorder, Tourette's syndrome, and obsessive-compulsive disorder across four countries after standardizing the study period, diagnostic codes used to define the conditions and statistical analyses across countries. We use a population-based cohort, including all live-born children in Denmark, Finland, Sweden and Western Australia, from January 1, 1990, through December 31, 2007 and followed through December 31, 2011. The main outcome measure is age-specific prevalence of diagnoses reported to population-based registry systems in each country. We observe an increase in age-specific prevalence for reported diagnoses of all four disorders across birth-year cohorts in Denmark, Finland, Sweden, and (for ASD) Western Australia. Our results highlight the increase in the last 20 years in the number of children and families in contact with health care systems for diagnosis and services for an array of childhood neuropsychiatric disorders, a phenomenon not limited to ASD. Also, the age of diagnosis of the studied disorders was often much higher than what is known of the typical age of onset of symptoms, and we observe limited leveling off in the incidence rate with increasing age.
    European Child & Adolescent Psychiatry 05/2014; · 3.70 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Advanced paternal age is robustly associated with several human neuropsychiatric disorders, particularly autism. The precise mechanism(s) mediating the paternal age effect are not known, but they are thought to involve the accumulation of de novo (epi)genomic alterations. In this study we investigate differences in the frontal cortex transcriptome in a mouse model of advanced paternal age. Transcriptomic profiling was undertaken for medial prefrontal cortex tissue dissected from the male offspring of young fathers (2 month old, 4 sires, n = 16 offspring) and old fathers (10 month old, 6 sires, n = 16 offspring) in a mouse model of advancing paternal age. We found a number of differentially expressed genes in the offspring of older fathers, many previously implicated in the aetiology of autism. Pathway analysis highlighted significant enrichment for changes in functional networks involved in inflammation and inflammatory disease, which are also implicated in autism. We observed widespread alterations to the transcriptome associated with advanced paternal age with an enrichment of genes associated with inflammation, an interesting observation given previous evidence linking the immune system to several neuropsychiatric disorders including autism.
    Molecular Autism 03/2014; 5(1):24. · 5.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors.
    The British journal of psychiatry: the journal of mental science 03/2014; · 6.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 01/2014; · 3.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Previous research has shown that people with psychotic disorders have impaired functioning prior to the onset of the illness. The goal of this study is to obtain a detailed, in depth, analysis of the characteristics of premorbid impairment. Methods In this study we examined summaries of interviews with 20 male adolescents who were later diagnosed with non-affective psychotic disorders and compared them to interviews conducted with 20 matched controls without psychiatric disorders. The current study applied a qualitative analysis, performed in the following stages: each interview was read thoroughly by two blinded raters with no a-priori hypothesis, and then key themes and statements were identified and organized into meaningful domains. Afterwards, the frequency of each item was calculated and comparisons between the groups were performed. Results Future non-affective psychotic disorder patients were more likely to be described as strange or different, be involved in violent behavior, experience difficulties in educational functioning and peer integration, deal with problems in everyday functioning and have an avoidant interpersonal conflict resolution style in comparison with matched controls without psychiatric disorders. In addition, future patients experienced more stressful life events and dealt with these stressors more poorly in comparison with controls. Conclusions The findings of this unique historical-prospective qualitative analysis of interviews performed before the onset of psychosis, confirmed previous findings of premorbid abnormality of future non-affective psychosis patients. Using qualitative analysis enabled obtaining a more in-depth understanding of the real-life experience of the premorbid period among patients with non-affective psychotic disorders.
    Schizophrenia Research: Cognition. 01/2014; 1(1):e35–e39.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a ‘cognitive-enhancing’ drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation.
    European Neuropsychopharmacology. 01/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Borderline intellectual functioning is defined by the DSM IV as an IQ range that is between one to two standard deviations below the mean (71<IQ<84), and a considerable percentage of the population is included in this definition (approximately 13.5%). The few studies performed on this group indicate that borderline intellectual functioning is associated with various mental disorders, problems in everyday functioning, social disability and poor academic or occupational achievement. Using data from the Israeli military, we retrieved the social and clinical characteristics of 76,962 adolescents with borderline intellectual functioning and compared their social functioning, psychiatric diagnoses and drug abuse with those of 96,580 adolescents with average IQ (+/−0.25 SD from population mean). The results demonstrated that the borderline intellectual functioning group had higher rates of poor social functioning compared to the control group (OR=1.9, 95% CI=1.85–1.94). Individuals with borderline intellectual functioning were 2.37 times more likely to have a psychiatric diagnosis (95% CI=2.30–2.45) and 1.2 times more likely to use drugs (95% CI=1.07-0.35) than those with average IQ. These results suggest that adolescents with borderline intellectual functioning are more likely to suffer from psychiatric disorders, poor social functioning and drug abuse than those with average intelligence, and that borderline intellectual functioning is a marker of vulnerability to these poor outcomes.
    European Neuropsychopharmacology. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adults with schizophrenia present cognitive impairments, as do individuals at ultra-high risk for the disorder, youth with relatives with schizophrenia spectrum disorders, and children with antecedents of schizophrenia. The present study aimed to determine if impairments in childhood differed depending on the definition of risk and/or on the degree of relatedness to an affected individual, and if impairments were explained by IQ. Four groups of children aged 9-12 years were studied: (1) 13 children with ≥1 first-degree or ≥2 second-degree affected relatives (high familial loading: FHx(H)); (2) 14 with ≥1 affected second-degree relative (lower familial loading: FHx(L)); (3) 32 with well-replicated antecedents of schizophrenia (ASz); and (4) 45 typically-developing (TD) children with neither a positive family history nor antecedents. Compared to TD children, both FHx(H) and ASz children exhibited significantly poorer verbal comprehension, scholastic achievement, and verbal working memory, while FHx(H) children additionally displayed significantly lower full-scale IQ, and verbal memory and executive function impairments. After adjusting statistical analyses for IQ, group differences were attenuated. Relative to TD children, FHx(L) children showed no significant differences in performance. The results imply that impairments in verbal comprehension, scholastic achievement, and verbal working memory may index vulnerability for schizophrenia among children with affected relatives with the disorder and among those with multiple antecedents of the disorder who have no affected relatives. More accurate identification of children at-risk for schizophrenia and the specific deficits that they present provides opportunities for interventions such as cognitive remediation that may impact the development of the illness.
    Journal of Psychiatric Research 12/2013; · 4.09 Impact Factor
  • Sven Sandin, Christina Hultman, Abraham Reichenberg
    JAMA The Journal of the American Medical Association 11/2013; 310(19):2101. · 29.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hoarding disorder is typified by persistent difficulties discarding possessions, resulting in significant clutter that obstructs the individual's living environment and produces considerable functional impairment. The prevalence of hoarding disorder, as defined in DSM-5, is currently unknown. To provide a prevalence estimate specific to DSM-5 hoarding disorder and to delineate the demographic, behavioural and health features that characterise individuals with the disorder. We conducted a two-wave epidemiological study of 1698 adult individuals, originally recruited via the South East London Community Health (SELCoH) study. Participants screening positively for hoarding difficulties in wave 1, and who agreed to be re-contacted for wave 2 (n = 99), underwent in-home psychiatric interviews and completed a battery of self-report questionnaires. Current DSM-5 diagnoses were made via consensus diagnostic procedure. In total, 19 individuals met DSM-5 criteria for hoarding disorder at the time of interview, corresponding to a weighted prevalence of 1.5% (95% CI 0.7-2.2). Those with hoarding disorder were older and more often unmarried (67%). Members of this group were also more likely to be impaired by a current physical health condition (52.6%) or comorbid mental disorder (58%), and to claim benefits as a result of these issues (47.4%). Individuals with hoarding disorder were also more likely to report lifetime use of mental health services, although access in the past year was less frequent. With a lower-bound prevalence of approximately 1.5%, hoarding disorder presents as a condition that affects people of both genders and is associated with substantial adversity.
    The British journal of psychiatry: the journal of mental science 10/2013; · 6.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Most case reports suggest an association between autistic spectrum disorders (ASDs) and celiac disease (CD) or positive CD serologic test results, but larger studies are contradictory. OBJECTIVE To examine the association between ASDs and CD according to small intestinal histopathologic findings. DESIGN AND SETTING Nationwide case-control study in Sweden. MAIN OUTCOMES AND MEASURES Through 28 Swedish biopsy registers, we collected data about 26 995 individuals with CD (equal to villous atrophy, Marsh stage 3), 12 304 individuals with inflammation (Marsh stages 1-2), and 3719 individuals with normal mucosa (Marsh stage 0) but positive CD serologic test results (IgA/IgG gliadin, endomysium, or tissue transglutaminase) and compared them with 213 208 age- and sex-matched controls. Conditional logistic regression estimated odds ratios (ORs) for having a prior diagnosis of an ASD according to the Swedish National Patient Register. In another analysis, we used the Cox proportional hazards regression model to estimate hazard ratios (HRs) for future ASDs in individuals undergoing small intestinal biopsy. RESULTS A prior ASD was not associated with CD (OR, 0.93; 95% CI, 0.51-1.68) or inflammation (OR 1.03; 95% CI, 0.40-2.64) but was associated with a markedly increased risk of having a normal mucosa but a positive CD serologic test result (OR, 4.57; 95% CI, 1.58-13.22). Restricting our data to individuals without a diagnosis of an ASD at the time of biopsy, CD (HR, 1.39; 95% CI, 1.13-1.71) and inflammation (HR, 2.01; 95% CI, 1.29-3.13) were both associated with moderate excess risks of later ASDs, whereas the HR for later ASDs in individuals with normal mucosa but positive CD serologic test results was 3.09 (95% CI, 1.99-4.80). CONCLUSIONS AND RELEVANCE Although this study found no association between CD or inflammation and earlier ASDs, there was a markedly increased risk of ASDs in individuals with normal mucosa but a positive CD serologic test result.
    JAMA Psychiatry 09/2013; · 12.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the relationship between preterm birth, adolescent, and adult psychosocial outcomes, and alterations in gray matter volume. Individuals (n = 73) born at <33 weeks of gestation (very preterm) and 49 controls completed the Child Behavior Checklist (CBCL) at age 15 years to identify 'social immaturity' (SI) cases. Voxel-based morphometry was used to investigate gray matter volumes according to CBCL-SI 'caseness.' The Clinical Interview Schedule-Revised (CIS-R) was administered at age 19 years. Very preterm adolescents were almost 4 times more likely to reach CBCL-SI 'caseness' compared with controls. Ex-preterm SI 'cases' had increased gray matter volume in the fusiform gyrus bilaterally (Talairach coordinates: x = 60, y = -27, z = -30; Z = 3.78; x = -61, y = -35, z = -27; Z = 3.56, after correction for multiple comparisons) compared with ex-preterm SI 'noncases.' Left fusiform volume displayed a stronger correlation with ipsilateral orbitofrontal cortex in SI 'cases' (x = -15, y = 22, z = -26; Z = 3.64). CIS-R total scores were slightly higher in ex-preterm individuals compared with controls. In the whole sample, SI 'cases' in midadolescence also had higher CIS-R scores in adulthood compared with 'noncases' (SI 'cases': mean = 5.7, 95% CI = 4.0-7.4; SI 'noncases': mean = 2.7, 95% CI = 1.1-4.3; F = 6.4, df = 74; P = .013). Ex-preterm adolescents had increased socialization problems in adolescence, which were associated with volumetric alterations in an emotion-processing brain network. Atypical social development is linked to an increased vulnerability to psychiatric disorder.
    The Journal of pediatrics 09/2013; · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE Despite the widespread belief that neuropsychological decline is a cardinal feature of the progression from the premorbid stage to the chronic form of schizophrenia, few longitudinal studies have examined change in neuropsychological functioning from before to after illness onset. The authors examined whether neuropsychological decline is unique to schizophrenia, whether it is generalized or confined to particular mental functions, and whether individuals with schizophrenia also have cognitive problems in everyday life. METHOD Participants were members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed prospectively to age 38, with 95% retention. Assessment of IQ and specific neuropsychological functions was conducted at ages 7, 9, 11, and 13, and again at age 38. Informants also reported on any cognitive problems at age 38. RESULTS Individuals with schizophrenia exhibited declines in IQ and in a range of mental functions, particularly those tapping processing speed, learning, executive function, and motor function. There was little evidence of decline in verbal abilities or delayed memory, however, and the developmental progression of deficits in schizophrenia differed across mental functions. Processing speed deficits increased gradually from childhood to beyond the early teen years, whereas verbal deficits emerged early but remained static thereafter. Neuropsychological decline was specific to schizophrenia, as no evidence of decline was apparent among individuals with persistent depression, children with mild cognitive impairment, individuals matched on childhood risk factors for schizophrenia, and psychiatrically healthy individuals. Informants also noticed more cognitive problems in individuals with schizophrenia. CONCLUSIONS There is substantial neuropsychological decline in schizophrenia from the premorbid to the postonset period, but the extent and developmental progression of decline varies across mental functions. Findings suggest that different pathophysiological mechanisms may underlie deficits in different mental functions.
    American Journal of Psychiatry 09/2013; · 14.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A number of studies have reported that patients with psychosis who use cannabis have better cognitive performance than those who do not. This is surprising as cannabis can impair cognition in healthy subjects. An obvious question is whether the better current performance of psychotic patients who have used cannabis is a reflection of their having a higher premorbid IQ than those psychotic patients who haven't used cannabis. In a sample of patients at their first episode of psychosis, we tested the hypothesis that patients who smoked cannabis would have a higher premorbid IQ than patients who did not. 279 participants (119 patients and 160 healthy controls) were assessed in order to obtain current and premorbid IQ measures and detailed information on cannabis use. We examined the association between cannabis use and both premorbid and current IQ in patients and controls. Patients who had ever smoked cannabis had significantly higher current (p<.001) and premorbid IQ (p=.004) compared to patients who had never used cannabis. This difference was not found among controls. These findings suggest that the better cognitive performance of patients with their first episode of psychosis who have used cannabis compared with those who haven't is due to the better premorbid IQ of the former.
    Schizophrenia Research 08/2013; · 4.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Between 1978 and 2010, approximately 5 million infants were born after in vitro fertilization (IVF) treatments. Yet limited information on neurodevelopment after IVF exists, especially after the first year of life. OBJECTIVE To examine the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring. DESIGN, SETTING, AND PARTICIPANTS A population-based, prospective cohort study using Swedish national health registers. Offspring born between 1982 and 2007 were followed up for a clinical diagnosis of autistic disorder or mental retardation until December 31, 2009. The exposure of interest was IVF, categorized according to whether intracytoplasmic sperm injection (ICSI) for male infertility was used and whether embryos were fresh or frozen. For ICSI, whether sperm were ejaculated or surgically extracted was also considered. MAIN OUTCOMES AND MEASURES Relative risks (RRs) for autistic disorder and mental retardation and rates per 100 000 person-years, comparing spontaneously conceived offspring with those born after an IVF procedure and comparing 5 IVF procedures used in Sweden vs IVF without ICSI with fresh embryo transfer, the most common treatment. We also analyzed the subgroup restricted to singletons. RESULTS Of the more than 2.5 million infants born, 30 959 (1.2%) were conceived by IVF and were followed up for a mean 10 (SD, 6) years. Overall, 103 of 6959 children (1.5%) with autistic disorder and 180 of 15 830 (1.1%) with mental retardation were conceived by IVF. The RR for autistic disorder after any procedure compared with spontaneous conception was 1.14 (95% CI, 0.94-1.39; 19.0 vs 15.6 per 100 000 person-years). The RR for mental retardation was 1.18 (95% CI, 1.01-1.36; 46.3 vs 39.8 per 100 000 person-years). For both outcomes, there was no statistically significant association when restricting analysis to singletons. Compared with IVF without ICSI with fresh embryo transfer, there were statistically significantly increased risks of autistic disorder following ICSI using surgically extracted sperm and fresh embryos (RR, 4.60 [95% CI, 2.14-9.88]; 135.7 vs 29.3 per 100 000 person-years); for mental retardation following ICSI using surgically extracted sperm and fresh embryos (RR, 2.35 [95% CI, 1.01-5.45]; 144.1 vs 60.8 per 100 000 person-years); and following ICSI using ejaculated sperm and fresh embryos (RR, 1.47 [95% CI, 1.03-2.09]; 90.6 vs 60.8 per 100 000 person-years). When restricting the analysis to singletons, the risks of autistic disorder associated with ICSI using surgically extracted sperm were not statistically significant, but the risks associated with ICSI using frozen embryos were significant for mental retardation (with frozen embryos, RR, 2.36 [95% CI, 1.04-5.36], 118.4 vs 50.6 per 100 000 person-years]; with fresh embryos, RR, 1.60 [95% CI, 1.00-2.57], 80.0 vs 50.6 per 100 000 person-years). CONCLUSIONS AND RELEVANCE Compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation. For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI. The prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small.
    JAMA The Journal of the American Medical Association 07/2013; 310(1):75-84. · 29.98 Impact Factor

Publication Stats

5k Citations
970.14 Total Impact Points

Institutions

  • 2007–2014
    • King's College London
      • • Institute of Psychiatry
      • • Department of Psychosis Studies
      • • Department of Psychological Medicine
      Londinium, England, United Kingdom
  • 2003–2014
    • Icahn School of Medicine at Mount Sinai
      • Department of Psychiatry
      Manhattan, New York, United States
  • 2012
    • Academisch Medisch Centrum Universiteit van Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2008–2012
    • Karolinska Institutet
      • Institutionen för medicinsk epidemiologi och biostatistik
      Solna, Stockholm, Sweden
    • ICL
      Londinium, England, United Kingdom
    • Emory University
      • Department of Psychiatry and Behavioral Sciences
      Atlanta, Georgia, United States
  • 2011
    • Temple University
      • Department of Psychology
      Philadelphia, PA, United States
  • 2000–2011
    • Sheba Medical Center
      Gan, Tel Aviv, Israel
    • Bar Ilan University
      • School of Social Work
      Ramat Gan, Tel Aviv, Israel
  • 2010
    • Duke University
      • Department of Psychology and Neuroscience
      Durham, North Carolina, United States
    • Lund University
      • Department of Clinical Sciences
      Lund, Skane, Sweden
  • 2009
    • Harvard University
      Cambridge, Massachusetts, United States
    • Southwest Autism Research & Resource Center
      Phoenix, Arizona, United States
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
  • 2007–2009
    • Ashkelon Academic College
      Majdal, Southern District, Israel
  • 2000–2008
    • Hebrew University of Jerusalem
      • • Department of Psychology
      • • Department of Biological Chemistry
      Jerusalem, Jerusalem District, Israel
  • 2001–2007
    • Tel Aviv University
      • Department of Psychiatry
      Tel Aviv, Tel Aviv, Israel
  • 2004
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 2000–2002
    • Max Planck Institute of Psychiatry
      München, Bavaria, Germany