Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Double-Dissociation Studies in Psychiatric Research

A Scoping Review

Kilçiksiz, Can Mişel MD; Öngür, Dost MD, PhD

doi: 10.1097/HRP.0000000000000233

Learning objectives After participating in this activity, learners should be better able to:

• Evaluate the double-dissociation approach to research in neuropsychology

• Assess research aiming to provide evidence of double dissociation between neurobiological abnormalities and clinical presentations in psychiatry

Background Psychiatric neuroscience research has grown exponentially, but it has not generated the desired breakthroughs in diagnosis, treatment development, or treatment selection. In many instances a given neurobiological abnormality is found in multiple clinical syndromes, and conversely, a clinical syndrome is associated with multiple neurobiological abnormalities. To the extent that neurobiology research is conducted to explain psychiatric manifestations, however, it should also provide insight into how certain brain abnormalities lead to one and not another specific clinical presentation—that is, “double-dissociation.” We hypothesized that most psychiatric research studies are not designed to identify such double dissociations.

Methods We selected three leading psychiatric journals (American Journal of Psychiatry, JAMA Psychiatry, and Molecular Psychiatry) that are representative of high-quality psychiatry research and that also provided a sample size that was feasible to screen. We screened all original research manuscripts published over the course of one calendar year (2017) to identify those measuring brain function or biological parameters (which, collectively, we term neurobiological measures) in psychiatric disorders. We asked whether such biological research could provide evidence for a double dissociation of any kind.

Results We found that only 7 of 403 articles published in three psychiatry journals, constituting approximately 2% of publications, examined the dissociation of neurobiological measures relating to two psychiatric disorders or symptom clusters. Of these 7 studies, 5 used imaging as research tool; 1 used genotype array; and 1 used polymerase chain reaction (PCR). Sample sizes of the 7 studies ranged from 100 to 2876.

Conclusion We report on a striking paucity of research aiming to provide evidence of double dissociation between neurobiological abnormalities and clinical presentations in psychiatry. We conclude that this paucity represents a missed opportunity for the field. Double-dissociation approaches have been used successfully in many studies in neurology and psychiatry in the past, and more widespread and explicit adoption of this design may improve the mechanistic insights obtained in psychiatry research.

From Harvard Medical School and Psychotic Disorders Division, McLean Hospital, Belmont, MA.

Original manuscript received 28 March 2019; revised manuscript received 3 July 2019, accepted for publication 16 July 2019.

Correspondence: Dost Öngür, MD, PhD, Mclean Hospital, 115 Mill St., Belmont, MA 02478. Email:

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

Harvard Review of Psychiatry offers CME for readers who complete questions about featured articles. Questions can be accessed from the Harvard Review of Psychiatry website ( by clicking the CME tab. Please read the featured article and then log into the website for this educational offering. If you are already online, click here to go directly to the CME page for further information.

© 2019 President and Fellows of Harvard College
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website