Post-genomic outlooks on neuropsychiatric disease

1


Two forward-looking views of research into
neuropsychiatric disease and its treatment are published today in BMC BiologyAiden Corvin predicts how the identification of susceptibility
genes may transform the diagnosis and treatment of patients who are today
classified as suffering from schizophrenia on the basis of purely clinical
criteria. Kevin Mitchell, Josh Huang, Bita Moghaddam and Akira Sawa assert that it is time to discard behavioral approaches to
modeling psychiatric disorders in animals, and lay out a framework for using
causal genetic variants, together with the latest neurogenetic tools, instead.

Both articles consider recent genetic
advances, and how the identification of rare structural variants that have a
large effect in predisposing people to one or more of these disorders has
challenged previous thinking.  Disorders such as schizophrenia, bipolar
disorder and autism are common, and for much of the last 60 years a consensus
has held sway that common diseases, unlike rare Mendelian diseases, are caused
not by mutations of large effect, but by the combined effect of numerous common
variants. Corvin explains how, in the case of schizophrenia, this model was
first assailed by two rare cytogenetic mutations found in the pre-genome era,
followed, in the post-genomic era, by rare copy number variants (short
deletions or duplications) that together account for about 5% of schizophrenia
cases.  Both he and Mitchell and colleagues also predict that sequencing
studies are likely to uncover many more rare variants associated with
disease.  The two articles take a different view, however, on whether
previous thinking has been completely overturned. Corvin summarizes the recent
findings from genome-wide association studies  reflecting the ongoing debate in the
field.   

Penelope Austin

View the latest posts on the On Biology homepage

One Comment

By commenting, you’re agreeing to follow our community guidelines.

Your email address will not be published. Required fields are marked *

paul whiteley

The link between neuropsychiatric conditions and the various SNPs and CNVs reported is no doubt an area of great importance for future work and does much to finally move away from the rather simplistic models of genes and psychiatry of old.
Alongside being pretty heterogeneous labels, there is the added complication of comorbidity and instability in symptom presentation over time in many of these conditions. Cumulatively these factors make for a very complicated mix particularly when trying to ascertain ‘what might do what’.
One area that perhaps also needs to be included in this brave new world of genomic investigation is that of epigenetics – changes to gene activity without changes to the genetic code. Realising the interaction between genes and environment represents perhaps the most fruitful approach to elucidating commonalities in the pathways of these puzzling conditions.

Reply