Depressed Patients with Earlier and More Severe Symptoms Have High Genetic Risk for Major Psychiatric Disorders

Reports new study in Biological Psychiatry

Philadelphia, PA, February 7, 2017

Clinical features of major depressive disorder (MDD) may help identify specific subgroups of depressed patients based on associations with genetic risk for major psychiatric disorders, reports a study in Biological Psychiatry. Led by Brenda Penninx, PhD, of the VU University Medical Center in Amsterdam, the Netherlands, the study found that patients with an early age at onset and higher symptom severity have an increased genetic risk for MDD, bipolar disorder and schizophrenia.

The findings highlight genetic similarities between subgroups of MDD patients based on their clinical characteristics. Although researchers know that genetics play a role in the development of MDD, the heterogeneous nature of MDD patients has hindered the search for risk genes. The new findings suggest a way to stratify the wide range of patients with MDD, which may boost the likelihood of identifying culpable genes.

“This is of importance as it suggests that it is useful to create phenotypically more homogenous groups of depressed patients when searching for genes associated with MDD,” said co-first author Dr. Judith Verduijn.

In the study, Dr. Verduijn and Dr. Yuri Milaneschi, along with their colleagues, analyzed genome-wide data of 3331 people, 1539 of whom were diagnosed with MDD, from the Netherlands Study of Depression and Anxiety. For each patient, they calculated genomic risk profile scores for MDD, bipolar disorder and schizophrenia.

Only characteristics associated with a more severe form of depression, including an early age at onset, high symptom severity score and a high number of specific symptoms from the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, were associated with higher genetic load for the three psychiatric disorders. The analysis did not reveal any associations between genetic risk profile scores and duration of symptoms, family history of depression, recurring MDD episodes, or stage of MDD.

“This study supports the idea that psychiatric disorders are heterogeneous and that the early onset and more severe forms of depression are the ones with greater heritability,” said Dr. John Krystal, Editor of Biological Psychiatry.

Using an independent group of 1602 MDD patients and 1390 control participants from the RADIANT-UK study, the researchers also replicated their finding that patients with a high number of DSM symptoms have increased genetic risk for schizophrenia.

---

Notes for editors
The article is "Using Clinical Characteristics to Identify Which Patients With Major Depressive Disorder Have a Higher Genetic Load for Three Psychiatric Disorders," by Judith Verduijn, Yuri Milaneschi, Wouter J. Peyrot, Jouke Jan Hottenga, Abdel Abdellaoui, Eco J.C. de Geus, Johannes H. Smit, Gerome Breen, Cathryn M. Lewis, Dorret I. Boomsma, Aartjan T.F. Beekman, and Brenda W.J.H. Penninx (http://dx.doi.org/10.1016/j.biopsych.2016.05.024). It appears in Biological Psychiatry, volume 81, issue 4 (2017), published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at +1 214 648 0880 or biol.psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Judith Verduijn, M.D., at j.verduijn@ggzingeest.nl.

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

John H. Krystal, M.D., 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 5th out of 140 Psychiatry titles and 11th out of 256 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2015 Impact Factor score for Biological Psychiatry is 11.212.

About Elsevier
Elsevier is a global information analytics company that helps institutions and professionals progress science, advance healthcare and improve performance for the benefit of humanity. 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, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, more than 35,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. www.elsevier.com

Media contact
Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880
biol.psych@utsouthwestern.edu