Skip to main content Accessibility help
×
Home

Contents:

Information:

  • Access

Actions:

      • Send article to Kindle

        To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Authors' reply
        Available formats
        ×

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Authors' reply
        Available formats
        ×

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Authors' reply
        Available formats
        ×
Export citation

Dr Crow is concerned that the publication of our recent study on BDNF endangers the field of psychiatric genetics. We would suggest that this concern may be overstated for the following reasons.

First, Dr Crow claims that the two meta-analyses and two cohort studies invalidate our results. We find this conclusion to be puzzling, given that none of these studies assessed the phenotype of schizoaffective disorder. Notably, the cohort studies relied on a single self-report item as the primary assessment of psychopathology. We addressed limitations of the meta-analyses in our original paper. We suggest that careful and comprehensive examination of the diverse phenotypes associated with neuropsychiatric illness may be a more fruitful approach.

Second, Dr Crow cites his own review of the linkage literature to suggest that most of the candidate genes reported by our group, and many others, are not supported by linkage studies and thus should be discounted. This reasoning is based on a flawed understanding of the role of linkage in complex disorders and is inconsistent with a large body of recent empirical evidence in complex genetics. In other complex disorders, a majority of susceptibility loci that have been unambiguously replicated in association studies fall outside of previously identified areas of even suggestive linkage (e.g. Barrett et al 1 ). Therefore, an argument utilising non-significant linkage data to invalidate a subsequent candidate gene association is erroneous.

Third, Dr Crow notes the productivity of our lab over the past several years as a source of concern for him. In so doing he mischaracterises our papers. First, he is simply incorrect in stating that only one paper reports strictly negative results (see Fubke et al 2 and Hodgkinson et al 3 ). Moreover, many of our papers report complex relationships that are not so simplistically reduced to ‘positive’ v. ‘negative’. More importantly, Dr Crow fails to mention that most of our papers are not simply analyses of association to schizophrenia diagnosis, but instead examine alternative phenotypes. For example, our study of DRD2 assessed the relationship between a functional promoter region polymorphism and clinical response to olanzapine and risperidone in the context of a randomised controlled clinical trial in first-episode schizophrenia. 4 Therefore, it is not surprising that our DRD2 results were not ‘replicated’ in either linkage studies or the association study of Sanders et al, 5 as these papers were restricted to mere association to diagnosis.

Although Dr Crow is entitled to his opinions, the field of psychiatric genetics may be better served by more constructive discussion leading towards a better understanding of the complexities of these devastating disorders.

1 Barrett, JC, Hansoul, S, Nicolae, DL, Cho, JH, Duerr, RH, Rioux, JD, et al. Genomewide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008; 40: 955–62.
2 Funke, BH, Lencz, T, Finn, CT, DeRosse, P, Poznik, GD, Plocik, AM, et al. Analysis of TBX1 variation in patients with psychotic and affective disorders. Mol Med 2007; 13: 407–14.
3 Hodgkinson, CA, Goldman, D, Ducci, F, DeRosse, P, Caycedo, DA, Newman, ER, et al. The FEZ1 gene shows no association to schizophrenia in Caucasian or African American populations. Neuropsychopharmacology 2007; 32: 190–6.
4 Lencz, T, Robinson, DG, Xu, K, Ekholm, J, Sevy, S, Gunduz-Bruce, H, et al. DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am J Psychiatry 2006; 163: 529–31.
5 Sanders, AR, Duan, J, Levinson, DF, Shi, J, He, D, Hou, C, et al. No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. Am J Psychiatry 2008; 165: 497506.