Mood disorders on genetic spectrum

Researchers quantify similarities and differences between depression and bipolar disorder in a genetic meta-analysis in Biological Psychiatry


Philadelphia, February 4, 2020

Researchers shed new light on the genetic relationship between three mood disorders associated with depression—major depression and bipolar disorder types 1 and 2, in a new study in the journal Biological Psychiatry, published by Elsevier.

“The clearest findings are a genetic distinction between type 1 bipolar and type 2 bipolar, and the greater similarity of type 2 bipolar to major depressive disorder,” said first author Jonathan Coleman, PhD, a statistical geneticist and postdoctoral fellow in the lab of senior author Gerome Breen, PhD at the Institute of Psychiatry, Neuroscience, and Psychology at Kings College London, UK.

Both types of bipolar disorder used to be referred to as ‘manic-depressive disorder’. Mania is a behavioral state associated with behavioral activation, euphoric or irritable mood, reduced need for sleep, impulsive behavior, impaired judgement, racing disorganized thoughts, impulsive behaviors, and frequently strongly held false beliefs (delusions) or hallucinations. Bipolar disorder type 1 is associated with mania and depression, while bipolar 2 is predominately associated with depression marked by mild symptoms reminiscent of mania, called hypomania.

The insights came from several extremely large datasets analyzed together. For their meta-analysis, Coleman, Breen and their co-authors combined genome-wide association studies from three large datasets of people with major depression and bipolar disorder to evaluate shared and distinct molecular genetic associations. Most of the data came from the large international Psychiatric Genomics Consortium. Additional data came from the UK Biobank, a major health resource established by the Wellcome Trust, and the online genetic service platform, 23andMe.

There are significant racial and ethnic differences in the findings from genome-wide association studies (GWAS). The findings of this study pertain only to people of European ancestry and findings might be different in other groups.

The authors also report that the genetic risk for these disorders was predictive of other traits as well. For example, the genetic risk for bipolar disorder was correlated with more educational attainment, while the heritable risk for major depressive disorder was associated with less education.

In the mouse brain, the authors also mapped the genetic risk for these disorders on to particular brain cell types using a sophisticated analytic strategy building on the pattern of genes expressed. They implicated serotonin neurons in the risk for both depression and bipolar disorder, while bipolar disorder distinctively involved GABA and glutamate neurons (nerve cell types also implicated in schizophrenia).

“We have long known that mood disorders are highly heterogeneous and the boundaries between types of mood disorders are often difficult to define clinically,” said John Krystal, MD, editor of Biological Psychiatry. “This new study suggests that there are aspects of genetic risk, and presumably brain function, that link forms of mood disorders, but there are also distinctions that may shed light on subtypes of depression that may have important implications for treatment.”

Ultimately, the researchers want to develop clinical tools to help predict if a first episode of depression is likely to persist as a disorder or progress into bipolar disorder. “Genetic data won’t ever replace clinical insight, but it might be a useful addition to clinical models,” said Coleman.

---

Notes for editors
The article is "The genetics of the mood disorder spectrum: genome-wide association analyses of over 185,000 cases and 439,000 controls ," by Jonathan R.I. Coleman, Héléna A. Gaspar, Julien Bryois, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Gerome Breen. (https://doi.org/10.1016/j.biopsych.2019.10.015). It appears inBiological Psychiatry, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at Biol.Psych@sobp.org. Journalists wishing to interview the authors may contact Gerome Breen at gerome.breen@gmail.com or +44 20 784 804 09 or Jonathan Coleman at jonathan.coleman@kcl.ac.uk, or +44 20 784 808 56.

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry
Biological Psychiatry
is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 7th out of 146 Psychiatry titles and 12th out of 267 Neurosciences titles in the Journal Citations Reports® published by Clarivate Analytics. The 2018 Impact Factor score for Biological Psychiatry is 11.501. www.sobp.org/journal

About Elsevier
Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we’re committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers. www.elsevier.com

Media contact
Rhiannon Bugno, Editorial Office
Biological Psychiatry
+1 214 648 0880
Biol.Psych@sobp.org