If thousands of variants confer susceptibility to MD, then this could explain a genetic correlation with other psychiatric disorders. We have no reason to expect the genetic architecture of anxiety, BP, or schizophrenia to be very different from MD: they are all likely to involve many loci of small Forskolin order effect, and they

are all, at some level, brain disorders. Indeed, Ripke and colleagues estimate that 8,300 independent SNPs contribute to the genetic basis of schizophrenia, accounting for 50% of the variance in liability to schizophrenia (Ripke et al., 2013a). With 18,000 genes expressed in the brain (Lein et al., 2007), and each disorder influenced by variants in thousands of genes, genetic correlation may be inevitable. The second point to note about the correlation between MD

and other disorders concerns how well selleck the phenotypic distinctions have been drawn. For example, no one has been able to identify features that distinguish with high accuracy episodes of MD in unipolar cases from episodes of MD in cases with bipolar illness. Furthermore, there is evidence that MD and BP share more characteristics than is sometimes appreciated: several authors have claimed that a large number of patients diagnosed with unipolar disorder have features of bipolar illness (Angst et al., 2010, Angst et al., 2011, Cassano et al., 2004 and Zimmermann et al., 2009). When symptoms of subthreshold mania are sought (elevated mood, irritable mood, or increased activity), a large proportion of unipolar cases are found to qualify: up

to half of all cases with unipolar illness (Angst et al., 2010, Angst et al., 2011 and Zimmermann et al., 2009). However, subthreshold diagnoses depend critically on the quality of the assessments and the exact interpretation of what constitutes subclinical mania (it is easy to confuse a state of hypomania with elation from “normal” causes like falling in love, or getting a grant funded in grim times, or hyperactivity from the agitation that occurs in some depressive subtypes). We can conclude that genetic and phenotypic classifications concur in identifying Phosphoprotein phosphatase considerable overlap between anxiety and MD, with mixed support for a distinction between MD and bipolar disorder. The genetic data point to genetic overlap, but this may be, to some extent, a consequence of the polygenicity of complex traits. We turn next to the question of whether there exists a pure MD, rarer and harder to distinguish from bipolar than currently acknowledged, which has at least partly distinct genetic roots. Or more generally, we ask, are there genetically homogenous subtypes of MD? Those unfamiliar with the literature debating the division of MD into subtypes may be surprised not only at the diversity of the proposed classificatory systems employed (e.g.