The use of genetic epidemiology to guide classification in child and adult psychopathology

ArticleinInternational Review of Psychiatry 19(5):483-96 · November 2007with11 Reads
DOI: 10.1080/09540260701563619 · Source: PubMed
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.
    • "The extent of shared pathophysiology can then be estimated by comparing the occurrence of the comorbid disorder in relatives of individuals with only the index disorder and not the comorbidity, versus in unaffected relatives to matched comparison individuals without the index disorder. (Szatmari, White & Merikangas, 2007). The rationale for the use of the family study method in study III was based on the fact that if the occurrence of the comorbid disorder (i.e., schizophrenia or bipolar disorder) is increased only when coupled with the index disorder (Darier disease), this would suggest that the index disorder promotes the comorbid disorder (Merikangas, 1990). "
    [Show abstract] [Hide abstract] ABSTRACT: Psychotic disorders such as schizophrenia entail substantial suffering for the affected individuals and their networks. Traditionally, these disorders come as diagnosable entities that you either have or have not. However, recent epidemiological research has shown that symptoms of psychotic disorder, i.e., psychotic experiences, are common in the general population, especially during adolescence, and that these experiences are correlated with the development of psychosis. Thus, the traditionally binary psychosis phenotype can be extended to also include psychotic experiences. Despite efforts, little is known about the causes, correlates and consequences of the “extended psychosis phenotype”. Therefore, this thesis aimed to shed new light on these aspects of this broadly defined psychosis phenomenon. In studies I and II, data from the Child and Adolescent Twin Study in Sweden (CATSS) were used to examine childhood neuropsychiatric problems (here language and mathematical problems, autistic traits, and general neuropsychiatric problems) as risk factors of adolescent psychotic experience (and juvenile mania symptoms). When possible, twin models were additionally used to disentangle the relative contributions of genetic and environmental influences in the observed associations. Results showed that childhood problems with communication, reading and mathematics, but not speech, predicted adolescent psychotic experiences. Further, it was found that the association between childhood autistic traits was explained by general neuropsychiatric problems. The twin models revealed that the same set of genes produce susceptibility for the studied childhood neuropsychiatric problems and adolescent psychotic experiences. In study III, data from the National Patient Register was used to determine if Darier disease, a rare skin disease, would correlate with schizophrenia or bipolar disorder in the general population. The hypothesis was based on the shared common ectodermal origin of skin and brain. We found that individuals with Darier disease had a 2-fold elevated risk of being diagnosed with schizophrenia, and a 4-fold excess risk of being diagnosed with bipolar disorder, compared with matched comparison subjects. In study IV, CATSS data was linked to the National Patient Register to examine consequences of adolescent psychotic experiences. Results revealed that adolescents reporting psychotic experiences had elevated risks of being diagnosed with alcohol or substance misuse, or suicide attempt. In sum, we found that adolescent psychotic experiences are neurodevelopmental phenomena that share genetic etiological factors with childhood neuropsychiatric problems. Further, we demonstrated population associations between Darier disease and schizophrenia, and bipolar disorder. Lastly, we observed that adolescent psychotic experiences are associated with adverse consequences. These results confirm the neurodevelopmental origin of the extended psychosis phenotype, including psychotic experiences, and highlight the need for cross-professional monitoring of adolescents reporting psychotic experiences.
    Full-text · Thesis · Feb 2016 · PLoS ONE
    • "Multiple animal models of prenatal infection have found evidence of diverse neurobehavioral abnormalities, whether through direct exposure of pregnant mice or rodents to influenza virus, or through non-infectious activation of the maternal immune system (e.g., using RNA poly(I:C) to stimulate an antiviral inflammatory response or lipopolysaccharide to stimulate a bacterial inflammatory response) (Brown and Derkits, 2010; Deverman and Patterson, 2009; Meyer et al., 2011; Miller et al., 2013; Patterson, 2011). The different pattern of associations observed for ASD with and without comorbid intellectual disability reinforces the possibility that higher-functioning and lowerfunctioning ASD may have different etiologies (Szatmari et al., 2007). For example, in an earlier study, we found that maternal use of antidepressants during pregnancy was associated with ASD without intellectual disability, but not with ASD with intellectual disability (Rai et al., 2013). "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Sep 2014
    • "Since information on DSM or ICD subcategories was not readily available in all registers, we could not ASD according to these classifications. However, as boundaries between subcategories are not clearly supported in literature [43], we instead defined ASD according to DSM-V work group recommendations [43], and used an empirically supported division based on co-morbid intellectual disability [44]. Another limitation is that our case validation was based on case-note review rather than direct clinical assessment. "
    [Show abstract] [Hide abstract] ABSTRACT: Reports of rising prevalence of autism spectrum disorders (ASD), along with their profound personal and societal burden, emphasize the need of methodologically sound studies to explore their causes and consequences. We here present the design of a large intergenerational resource for ASD research, along with population-based prevalence estimates of ASD and their diagnostic validity. The Stockholm Youth Cohort is a record-linkage study comprising all individuals aged 0-17 years, ever resident in Stockholm County in 2001-2007 (N = 589,114). ASD cases (N = 5,100) were identified using a multisource approach, involving registers covering all pathways to ASD diagnosis and care, and categorized according to co-morbid intellectual disability. Prospectively recorded information on potential determinants and consequences of ASD were retrieved from national and regional health and administrative registers. Case ascertainment was validated through case-note review, and cross validation with co-existing cases in a national twin study. The 2007 year prevalence of ASD in all children and young people was 11.5 per 1,000 (95% confidence interval 11.2-11.8), with a co-morbid intellectual disability recorded in 42.6% (41.0-44.2) of cases. We found 96.0% (92.0-98.4) of reviewed case-notes being consistent with a diagnosis of ASD, and confirmed ASD in 85.2% (66.2-95.8) of affected twins. Findings from this contemporary study accords with recently reported prevalence estimates from Western countries at around 1%, based on valid case ascertainment. The Stockholm Youth Cohort, in light of the availability of extensive information from Sweden's registers, constitutes an important resource for ASD research. On-going work, including collection of biological samples, will enrich the study further.
    Full-text · Article · Jul 2012
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