Pleiotropic effects on psychopathology (Lancet 2013)

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
Lancet. 2013 Apr 20;381(9875):1371-9.
Cross-Disorder Group of the Psychiatric Genomics Consortium.
Erratum in: Lancet. 2013 Apr 20;381(9875):1360.

Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories.
We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.

We analyzed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders

SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2.
Model selection analysis supported effects of these loci for several disorders.
Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity.
Pathway analysis supported a role for calcium channel signalling genes for all five disorders.

Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology.
These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.

cited by:
Genes and the Human Condition (From Behavior to Biotechnology)
Coursera 2014

Mental health: On the spectrum

Mental health: On the spectrum
Nature 496, 416–418 (25 April 2013)
David Adam
Research suggests that mental illnesses lie along a spectrum — but the field’s latest diagnostic manual still splits them apart.

diagnosed with several disorders, or co-morbidities: About one-fifth of people who fulfil criteria for one DSM-IV disorder meet the criteria for at least two more.
These are patients “who have not read the textbook”

Psychiatrists see so many people with co-morbidities that they have even created new categories to account for some of them.
The classic Kraepelian theoretical division between schizophrenia and bipolar disorder, for example, has long been bridged by a pragmatic hybrid called schizoaffective disorder, which describes those with symptoms of both disorders and was recognized in DSM–IV.

Ironically, the ingrained category approach is actually inhibiting the scientific research that could refine diagnoses, in part because funding agencies have often favoured studies that fit the standard diagnostic groups.
“Until a few years ago we simply would not have been able to get a gra nt to study psychoses,” says Nick Craddock, who works at the Medical Research Council Centre for Neuropsychiatric Genetics and Genomics at Cardiff University, UK.
“Researchers studied bipolar disorder or they studied schizophrenia. It was unthinkable to study them together.”

“Introducing a botched dimensional system prematurely into DSM-5 may have the negative effect of poisoning the well for their future acceptance by clinicians,” wrote Allen Frances, emeritus professor of psychiatry at Duke University in Durham, North Carolina, in an article in the British Journal of Psychiatry

The controversial personality-disorder dimensions were voted down by the APA’s board of trustees at the final planning meeting in December 2012.

The APA claims that the final version of DSM-5 is a significant advance on the previous edition and that it uses a combination of category and dimensional diagnoses.
The previously separate categories of substance abuse and substance dependence are merged into the new diagnosis of substance-use disorder.

Bodurka’s group is studying the idea that dysfunctional brain circuits trigger the release of inflammatory cytokines and that these drive anhedonia by suppressing motivation and pleasure.
The scientists plan to probe these links using analyses of gene expression and brain scans. In theory, if this or other mechanisms of anhedonia could be identified, patients could be tested for them and treated, whether they have a DSM diagnosis or not.

On the question of dimensionality, most outsiders see it as largely the same as DSM-IV. Kupfer and Regier say that much of the work on dimensionality that did not make the final cut is included in the section of the manual intended to provoke further discussion and research.

All involved agree on one thing.
Their role model now is not Freud or Kraepelin, but the genetic revolution taking place in oncology.
Here, researchers and physicians are starting to classify and treat cancers on the basis of a tumour’s detailed genetic profile rather than the part of the body in which it grows.
Those in the psychiatric field say that genetics and brain imaging could do the same for diagnoses in mental health.