Is there an anatomical endophenotype for neurodevelopmental disorders? A review of dual disorder anatomical likelihood estimation (ALE) meta-analyses of grey matter volumes

Abstract

The term "neurodevelopmental disorder" broadly encompasses conditions thought to arise early in development and includes schizophrenia, bipolar disorder and autism among others. These conditions share a number of genetic and environmental risk factors postulated to lead to common difficulties in socio-emotional processing, communication and cognitive function. The alternative position is that, while the same traits are affected across these conditions, the nature or direction in which they are modified may be distinct. MRI studies provide a rapidly expanding and rich database which we propose can be used to contribute to this debate. Anatomical likelihood estimation (ALE) is a method of meta-analysis applied to voxel-based MRI studies. We have adapted this method to explore the extent to which schizophrenia and bipolar disorder and schizophrenia and autism share a common brain structural phenotype. We will review this work here and discuss whether there is sufficient other evidence to justify a common framework for further research into the inter-relatedness of such conditions. The endophenotype approach to schizophrenia and related disorders considers traits associated with the condition also observable in individuals who do not meet diagnostic criteria. The strategy relies upon assuming a dimensional perspective. It allows the size of samples studied to be greatly expanded as unaffected individuals or relatives who show similar traits to individuals with the illness can be included. In this way the impact of confounds such as medication and illness chronicity are reduced. In this paper we exploit the endophenotype approach in a rather different manner. Symptoms in psychiatry are never pathognomonic. Individuals with similar clusters of symptoms, response to treatment and outcome are categorized into discrete diagnostic groupings, but often the distinctions between diagnostic groups are blurred. This challenge in defining the target condition can be considered to be a disadvantage. However, an alternative is to examine similarities across different conditions from an intermediate or endophenotype perspective and determine whether common causal mechanisms may be at work across diagnostic categories.

Gray Matter Abnormalities in Type 1 and Type 2 Diabetes: A Dual Disorder ALE Quantification

“…The imaging technique used was clearly described so that it could be reproduced 10 Measurements were clearly described so that they could be reproduced In the present study, we adopted the "Dual Disorder ALE Quantification." We have previously applied this method to study similarities across different disorders such as schizophrenia and bipolar disorder, and schizophrenia and autism (Cheung et al, 2010;Yu et al, 2010;McAlonan et al, 2011). In brief, a map of gray matter difference compared to controls was generated for each study.…”

Endophenotype strategies for the study of neuropsychiatric disorders: A quest

“…In particular, this special issue comprises 9 papers-which were presented at the Symposium. The first 4 papers [7][8][9][10] are mainly focus on neuroanatomical and neuroimaging issues of endophenotypes for schizophrenia and related disorders. Two papers [11,12] are working on the development of a battery specifically capturing neuropsychological endophenotypes for schizophrenia, and how it may help develop a research-oriented programme for studying endophenotypes for neuropsychiatric disorders.…”