The use of genetic epidemiology to guide classification in child and adult psychopathology.
ABSTRACT The goal of this paper is to illustrate the application of the tools of genetic epidemiology, particularly the family study method, to inform the classification of psychiatric disorders in adults and children. The first section describes family studies of adults designed to investigate the causes of comorbidity of anxiety and depression. The analysis of familial traits provides stronger evidence for the validity of certain sub-types of anxiety and mood disorders that co-occur within the same individual and within families. The second section presents an example of the use of the family study method to examine the validity of the autism spectrum disorders (ASD). A review of these studies suggests that the most consistently familial traits in ASD are language and communication skills, insistence on sameness and non-verbal IQ. These are also the traits most commonly associated with the differentiation of autism from Asperger disorder and PDDNOS using both cross-sectional and longitudinal studies. From these data, a new classification system of the ASDs is proposed based on these familial traits.
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ABSTRACT: Animal models indicate that maternal infection during pregnancy can result in behavioral abnormalities and neuropathologies in offspring. We examined the association between maternal inpatient diagnosis with infection during pregnancy and risk of ASD in a Swedish nationwide register-based birth cohort born 1984-2007 with follow-up through 2011. In total, the sample consisted of 2,371,403 persons with 24,414 ASD cases. Infection during pregnancy was defined from ICD codes. In the sample, 903 mothers of ASD cases (3.7%) had an inpatient diagnosis of infection during pregnancy. Logistic regression models adjusted for a number of covariates yielded odds ratios indicating approximately a 30% increase in ASD risk associated with any inpatient diagnosis of infection. Timing of infection did not appear to influence risk in the total Swedish population, since elevated risk of ASD was associated with infection in all trimesters. In a subsample analysis, infections were associated with greater risk of ASD with intellectual disability than for ASD without intellectual disability. The present study adds to the growing body of evidence, encompassing both animal and human studies, that supports possible immune-mediated mechanisms underlying the etiology of ASD.Brain Behavior and Immunity 09/2014; DOI:10.1016/j.bbi.2014.09.001 · 6.13 Impact Factor
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ABSTRACT: Converging evidence from epidemiological, genetic, and animal studies supports the hypothesis that advancing parental age, both of the father and mother, increases the risk of autism spectrum disorders (ASD) in offspring. Paternal age has received considerable attention, with whole-genome sequencing studies linking older fathers to higher rates of de novo mutations and increased risk of ASD. The current evidence suggests that the increased risk of ASD in the offspring of older mothers may be related to mechanisms different from those operating in older fathers. Causal pathways probably involve the interaction of multiple risk factors. Although the etiology of ASD is still poorly understood, studies of parental age provide clues into the genetic and environmental mechanisms that mediate the risk of ASD. Copyright © 2014 Elsevier Ltd. All rights reserved.Trends in Molecular Medicine 02/2015; 21(2). DOI:10.1016/j.molmed.2014.11.005 · 10.11 Impact Factor
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ABSTRACT: Obsessive-compulsive disorder (OCD) often co-occurs with psychotic and bipolar disorders; this comorbidity complicates the clinical management of these conditions. In this population-based longitudinal and multigenerational family study, we examined the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders. Participants were individuals with a diagnosis of OCD (n = 19814), schizophrenia (n = 58336), bipolar disorder (n = 48180), and schizoaffective disorder (n = 14904) included in the Swedish Patient Register between January 1969 and December 2009; their first-, second-, and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. The Swedish Prescribed Drug Register was used to control for the potential effect of medication in the longitudinal analyses. Individuals with OCD had a 12-fold increased risk of having a comorbid diagnosis of schizophrenia and a 13-fold increased risk of bipolar disorder and schizoaffective disorder. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for later diagnosis of all other disorders, and vice versa. The risk of bipolar disorder was reduced, but not eliminated, when the use of selective serotonin reuptake inhibitors was adjusted for. OCD-unaffected first-, second-, and third-degree relatives of probands with OCD had a significantly increased risk for all 3 disorders; the magnitude of this risk decreased as the genetic distance increased. We conclude that OCD is etiologically related to both schizophrenia spectrum and bipolar disorders. The results have implications for current gene-searching efforts and for clinical practice. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: email@example.com.Schizophrenia Bulletin 12/2014; DOI:10.1093/schbul/sbu169 · 8.61 Impact Factor