Other designs

A probable future trend in psychiatric MRI research over the next few years is that the hypotheses under investigation will become more concerned with aetiological mechanisms and pathogenetic models and less concerned with the basic question of whether a given group of patients has abnormal brain structure. This shift in hypothetical interest will dictate a shift in design away from case-control or cross-sectional studies.

Longitudinal designs, in which a cohort of patients are scanned repeatedly over a period of months or years, are a powerful way of demonstrating degenerative or developmental changes in brain structure.(3) They have the obvious disadvantage that they are time consuming to complete and subjects may not attend for multiply repeated examination. Mixed longitudinal designs, in which each subject is scanned just a few times but the sample as a whole includes subjects over a wide range of ages, are a pragmatic alternative for studies of normal and abnormal brain development.

Genetic designs involve subjects that are defined genotypically, rather than phenotypically as in the standard case-control design. Imaging studies of monozygotic twins discordant for a disorder, (4> and of families multiply affected by a disorder, are examples of genetic designs in which there may be complete knowledge about the proportion of genetic information that is shared between subjects but incomplete knowledge about the genetic constitution of each subject. As the human genome becomes better characterized and genetic risk factors for psychiatric disorder are more precisely identified, it is likely that genetic imaging designs will increasingly be focused on the anatomical expression of one or more specific genes.

Overall, there is no single perfect design for an imaging study. Often designing a study will entail finding pragmatic and arguably justifiable solutions to problems for which there is not an absolutely correct answer. Furthermore, the 'goodness' of a design can really only be judged in relation to the hypothesis under investigation and the methods of analysis applied to the data. The best imaging studies will convey a sense that the design is both ingenious and inevitable, given the hypothesis and available methods, and will probably also include a frank discussion of the limitations or implications of the particular design adopted.

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