Genetics Leading to Better Bipolar Disorder Diagnosis

I wanted to alert Brain Posts readers to an important new review of genetics and diagnosis in brain disorders including bipolar disorder.

One hope for the emerging genetics research in mental disorders is a better diagnostic classification system.

The current psychiatric diagnostic system is hampered by use of a primary symptoms and signs approach leading to messy heterogeneous groups of clinical conditions.

Elliot Gerson has been a giant in neuroscience genetics for quite some time and recently published an important manuscript titled: "Genetic and genomic analyses as a basis for new diagnostic nosologies" in the journal Dialogues in Clinical Neuroscience.

Gershon notes current clinical diagnostic categories in psychiatry fail three of five tests for diagnostic validity described by Feigher in 1972:

• family study clustering
• course of illness 
• laboratory tests

There is promise for using genetic and genomic findings to improve diagnostic validity in psychiatric disorders. Gershon goes on to outline what is currently known in psychiatric genetics and how future genetic research can lead to "biologically coherent diagnostic entities".

Here is my summary on what I see as the key points in the review:

• The number of common gene single-neucleotide polymorphisms (SNPs) linked to brain disorders is growing (from 10 to over 100 for schizophrenia an example)
• Summing risk across known schizophrenia SNPs using risk profile scores accounts for 7% of genetic variance in schizophrenia (this increases to up to 23% of variance when broader phenotypic systems are used)
• A similar SNP risk profile approach separates bipolar disorder groups from controls
• Larger sample sizes may increase this SNP genetic variance understanding in schizophrenia and bipolar disorder
• Some SNPs contribute to risk for more than one disorder i.e. schizophrenia, bipolar disorder and major depression showing weakness of current classification system
• Common genome-wide SNP data may be a promising path to defining better diagnostic categories
• Rare variants such as copy number variations (CNVs) may also be promising for improved psychiatric diagnosis
• Chromosome 22q11 deletion (DiGeorge syndrome or velocardiofacial syndrome) occurs in 1/4000 births and has high penetrance for psychiatric diagnosis although nonspecific (23% autism sprectrum, 68% schizophrenia, 26% bipolar disorder)
• Brain molecular network modeling also holds promise as a basis for diagnosis
• Many known risk genes for psychiatric illness have been linked to key brain network nodes
• Genetic variants could be mapped to human molecular networks and this map may lead to predictable "therapeutic targets"
• Brain connectivity networks (fMRI) may be a promising alternate approach to psychiatric diagnosis

The validity criteria for psychiatric diagnosis described by Feighner in 1972 continue to be a gold standard. Emerging genetic, genomic and brain connectivity research may be part of the tool set that has been missing. Applying these tools to better diagnosis holds promise for new and better treatment and the reduction in pain and suffering for many brain disorders.

Interested readers can access the free full-text manuscript of the Gerson and Grennan review by clicking on the PMID link in the citation below.

Photo of brown pelican and ruddy turnstone is from the author's files.

Follow the author on Twitter WRY999

Gershon ES, & Grennan KS (2015). Genetic and genomic analyses as a basis for new diagnostic nosologies. Dialogues in clinical neuroscience, 17 (1), 69-78 PMID: 25987865