HPC NewsScience

Forward looking review of the genetics of heterogeneity in depression

Sources of heterogeneity that impact depression research in terms of operationalization (phenotype, measurement), manifestation (symptoms, time course, group characteristics, endophenotypes, comorbidities), and etiology.

Dr. Na Cai’s review on the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies is now published in Human Molecular Genetics!

 

Na Cai from the Helmholtz Pioneer Campus, Eiko Fried from Leiden University, and Karmel Choi from Harvard T.H. Chan School of Public Health just published a review on hetereogeneity in depression. 


Want to know have in-depth view from the authors?
Read the tweetorial! 


In this interview, Dr. Cai shares insights on the topic.

 

What is the current definition of Depression? How is the current definition of depression impacting research and medicine outcomes?

The currently used standard for diagnosis of Major Depressive Disorder is specified by the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) or International Statistical Classification of Diseases (ICD-10), and consist of a 9-item symptom criteria (see below) with further criteria over duration, severity, impairment, exclusion of history of mania, and exclusion of other potential causes (substance abuse, other chronic medical conditions, schizophrenia or other psychotic disorders) 

Symptom criteria (≥5 symptoms most of the day nearly every day during the same two week period that are a change from previous functioning; depressed mood and/or loss of interest/pleasure must be present; exclude symptoms clearly attributable to another medical condition)
S1. Depressed mood
S2. Loss of interest/pleasure
S3. Weight/appetite loss or gain 
S4. Insomnia or hypersomnia
S5. Psychomotor retardation or agitation 
S6. Fatigue
S7. Feeling worthless or excessive/inappropriate guilt
S8. Decreased concentration 
S9. Thoughts of suicide/death (not just fear of dying) 

Yes the definition of MDD definitely affects research and clinical practice and outcomes. One one hand, researchers have criticised the DSM for not encompassing all aspects of clinical depression, so using it consistently could mean disregarding aspects of MDD. On the other hand, not using the same criteria between studies have resulted in huge discrepancies in definitions of depression across studies, and we’ve previously shown that these different definitions reflect different conditions with different epidemiology and genetic contributions. 

2. You have mentioned that depression is a very heterogenic disease, why? 

Even if we use one definition of MDD, based on DSM-5, there could be more than 10,000 symptom profiles that fulfil the diagnostic criteria. Further, patients experience episodes at different points in their lives (early adolescent onset, peri-partum etc), with different severity, for different durations, and with different incidence of recurrence. Some genetic studies have also shown genetic factors specific to particular symptom profiles or age of onset of disease, suggesting there are different genetic factors contributing to different subtypes.  

3. How could research and medicine handle this heterogeneity better in order to improve diagnostic and target treatments?

We can begin by collecting data in a way that allow us to assess this heterogeneity. As we advocate in the paper, we need to measure more and measure consistently across studies. Only with this data are we able to dissect the heterogeneity in depression. 

 

Read the full review here:
https://academic.oup.com/hmg/article/doi/10.1093/hmg/ddaa115/5860824#205700377