How does OCD show up in the brain? A Q&A with Dr. Christine Lochner

Post-mortem research entails examining the tissues of the deceased, offering unique insights into the conditions they lived with. This approach has the potential to provide valuable information that cannot be obtained through other methods, filling crucial knowledge gaps and improving outcomes for millions, even billions of people, over time. 

In her recently published paper, Dr. Christine Lochner—of the SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Stellenbosch, South Africa—conducted a systematic review of post-mortem research on the brains of people who’d been diagnosed with Obsessive-Compulsive Disorder (OCD). We spoke with Dr. Lochner about her work and its implications for treating the condition in the years ahead. 

Q: First off, what led you to want to perform this research? 

As we noted in the paper, there is a growing body of post-mortem work on mental disorders such as schizophrenia, but there seems to have been less attention to conditions like OCD. 

Q: Could you explain how the systematic review was conducted? What specific criteria were used to select the studies included in the review? 

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines provide a framework for systematic reviews and meta-analyses. They’re aimed at improving the quality and reliability of systematic reviews. The guidelines provide advice on the formulation of the study title, the abstract structure, the rationale of the review, eligibility criteria of the studies that are included, how the search and selection of studies were done, detail on the risk of bias, summary measures, synthesis of results, the discussion, and conclusions.

Concerning the inclusion criteria, studies examining post-mortem brains of people of any sex or gender and of all ages who had OCD or who presented with obsessive-compulsive symptoms during their lifetime were considered for inclusion in the review. This review considered the inclusion of studies that were conducted in any setting. Publications were only included if they were in English. Papers were eligible only if the studies included suitably matched healthy controls. Quantitative, qualitative, or mixed methods primary research studies reporting on post-mortem findings in OCD or obsessive-compulsive symptoms were considered for inclusion in the review.

Q: The chosen studies provided data on DNA methylation, cellular and molecular alterations, and gene expression profiling in brain areas associated with OCD. Can you discuss some of the key findings or trends that emerged from these studies? 

We’d like to argue that post-mortem investigations, supported by reliable diagnostic procedures and information on comorbid psychiatric and neurological conditions and risk factors (e.g., environmental factors), may be a useful strategy to address the gaps in our understanding of the underpinnings of OCD—or any psychiatric disorder, for that matter. 

Researching the post-mortem brains of people with OCD or any of these other conditions can potentially contribute to our conceptualization of psychiatric conditions by determining, for example, whether behaviors that overlap across disorders have similar underpinnings. 

In the paper, we noted that post-mortem research on fresh glial cells (collected soon after brain dissection) can be used to investigate the impact of environmental risk factors in vitro, for example. Ultimately, post-mortem studies may facilitate the discovery of novel targets for therapeutic interventions. This is a longer-term endeavor.

Q: How do these findings contribute to our understanding of the neurobiological underpinnings of OCD? Are there any particular discoveries that stood out in terms of their potential implications for OCD research and treatment? 

It’s really too soon to draw firm conclusions from this on the implications for treatment. There are too small samples in these papers, too few articles on the topic, etc. However, to me, the three most important messages were:

1. That research on post-mortem brains from well-characterized individuals with OCD has potential value in increasing our understanding of the neurobiology of OCD.
2. More post-mortem research is needed in this area.
3. Brain donation for neurobiological research is something to consider (and is a possibility in some countries).  

Q: The study suggests that there is potential value in studying post-mortem brains of well-characterized individuals with OCD. Could you explain why this approach is particularly valuable in advancing our knowledge of OCD? 

Post-mortem brain data allow researchers to address questions that other techniques cannot answer. See, for example,  the paper by De Lange that highlighted several questions about psychiatric disorders that have not yet been addressed by OCD literature (e.g., are the numbers of neuronal or microglial cells altered in specific brain regions?).

In any of these conditions, including OCD, answers to these questions would be of benefit, contributing knowledge and insight into their underpinnings. 

Q: Based on the results of this systematic review, are there any specific recommendations or directions for future research in the field of post-mortem studies related to OCD? 

I think the field of post-mortem work in OCD is still in its infancy. Potential directions for future research may include—but are certainly not limited to—examining the correlations between post-mortem findings and clinical characteristics of patients with OCD. This could potentially enhance the clinical relevance of this type of research. As a psychologist, I would be particularly keen on comparing post-mortem data with detailed OCD symptom profiles and treatment responses. 

Other avenues where post-mortem data may be of value (but which are not my field of expertise) are in the exploration of gene expression patterns in brain tissue, or on the potential role of immune system abnormalities or signs of neuroinflammation in the brain of people with OCD. Exploration of a broader range of brain regions and circuits would also be of interest going forward. 

Q: In light of the findings, do you believe there are potential avenues for collaboration or interdisciplinary research that could further enhance our understanding of the neurobiology of OCD? 

I agree that collaboration is crucial in advancing our understanding of the neurobiology of OCD. This has been the focus of many research endeavors in recent years (see, for example, the efforts of the ENIGMA consortium. Indeed, interdisciplinary efforts can bring together experts from various fields who can contribute their unique skills to a particular research question/s. 

Key role players in post-mortem research in psychiatry may include neuropathologists, neuroscientists (including specialists in molecular and cellular biology and geneticists), psychiatrists, psychologists, and many others.

You can access effective treatment for OCD and related conditions

Promising scientific research about OCD continues to be published, but one thing researchers have known for decades is just how treatable the condition is with exposure and response prevention (ERP) therapy. 

This evidence-based form of treatment is now more accessible than ever, through live, face-to-face video therapy sessions with NOCD Therapy. Research has shown that NOCD’s virtual ERP is just as effective as in-person OCD treatment, and leads to results in half the time.

If you or someone you love may be struggling with OCD, we encourage you to learn more about NOCD’s accessible approach to OCD and related conditions.