Psychiatry Practice Changers 2014

Bret S. Stetka, MD; Cristoph U. Correll, MD


December 08, 2014

In This Article


As in many fields of medicine, in 2014, genomics inched its way further into psychiatry. However, how much these advancements in knowledge will enable the field to change diagnostic and treatment approaches in the near future still remains to be seen.

One of the major genetics breakthroughs of the year in mental health was the publication of results of a multistage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. Findings were published in July in Nature[2] and Psychiatric Genetics.[3] With this largest sample size in schizophrenia genetics studies to date, 128 independent associations spanning 108 conservatively defined loci were identified that meet genome-wide significance, including 83 new genes. Associations included the dopamine DRD2 gene and several genes involved in glutamatergic neurotransmission and immune response. The same study indicated that a variant in the metabotropic glutamate receptor 3 (GRM3) gene results in a two- to threefold increased risk of developing schizophrenia or alcohol dependence, as well as a threefold increased risk of developing bipolar disorder. Work[4] published earlier this year in Nature reported that mutations in genes involved in synaptic function are overexpressed in patients with schizophrenia, and perhaps treatment approaches that modulate the strength of synaptic connections are worth pursuing.

As a paper[5] published this year in Current Opinion in Psychiatry discussed, while at the moment the "genetic architecture" of schizophrenia is not yet elucidated, numerous genetic variants have been associated with the disease, opening the possibility of developing a polygenic schizophrenia risk calculator.

Work[6] presented at the American Society of Human Genetics 2014 Annual Meeting suggests that whole genome sequencing can now be used to identify a genetic cause for most severe intellectual disabilities. As lead investigator Christian Gilissen, PhD, told Medscape Medical News, "Based on clinical diagnostic criteria, we can provide a genetic diagnosis for the majority of severe intellectual disability cases."

Finally, a study[7] published in October in Translational Psychiatry linked genetic markers with significantly longer abstinence in alcohol-dependent patients treated with acamprosate (Campral®).

These genetic research advancements are noteworthy and relevant. With sample sizes surpassing 100,000 cases, a multitude of genes can be identified as being associated with a given disorder. However, associations with other disorders and questions of relevance of findings from small subgroups of patients pose difficulties. The hope is that individual findings converge on pathways and circuits that have more generalizable relevance for the understanding of the pathophysiology of complex phenotypes, such as mental disorders, and for treatment options for the disorders, including biologically informed individualized care.


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