The heterogeneous nature of depression

New study questions efficacy of ‘one-size-fits-all’ treatment

24 October 2016

Depression is generally considered to be a specific and consistent disorder characterised by a fixed set of symptoms and often treated with a combination of psychotherapy and medication. However, the standard rating scales used by healthcare professionals and researchers to diagnose this disease often differ in the symptoms they list, perhaps explaining why a one-size-fits-all treatment has to date been so ineffective. This is the finding of research conducted by psychologist Eiko Fried from the University of Amsterdam (UvA). His results are published in the latest edition of the Journal of Affective Disorders.

Depression is often viewed as a common medical disorder like measles – one either has it or one doesn’t. As a result, diagnosis is generally followed by assigning specific treatment options. But unlike physical disorders where blood tests or other objective tests enable a reliable diagnosis, there are no such measures to determine whether someone is depressed. Instead, researchers and clinicians query patients about symptoms that are indicative of depression, such as sadness, suicidal ideation and sleep problems. If a person has many depression symptoms, she is considered depressed.


In his study, Fried used a content analysis to investigate the symptom overlap of 7 rating scales of symptoms that are commonly used in depression research. One of the scales is the Hamilton Rating Scale of Depression, which contains 17 predominantly physical depression symptoms like paralysis, weight loss and psychomotor retardation. Another is the Beck Depression Inventory, which includes 21 mostly cognitive-affective symptoms such as feelings like worthlessness, guilt, crying and self-dislike.

What he found was that these and other rating scales show surprisingly little symptom overlap. Moreover, together they feature a total of 52 different depression symptoms ranging from sadness, lack of interest and suicidal ideation to genital problems, irritability and anxiety. These findings underline the striking heterogeneity of depression, a disorder mostly viewed as one consistent syndrome, says Fried. ‘Patients diagnosed with depression are often thought to have similar kinds of problems and therefore receive very similar treatment. However, the fact that 7 common rating scales of depression contain over 50 different symptoms shows how strikingly different depressed patients can be in terms of the problems they experience. This seems to indicate the need for more personalized treatment and might explain why current “one-size-fits-all” solutions like antidepressants show so little efficacy.’

Predetermined outcome

Fried believes his findings could also pose a major problem for depression research because the type of scale used by researchers might determine the outcome of a scientific study. Fried: ‘For example, imagine you are a researcher and want to study the brain structure of depressed patients. This is usually done by giving a large group of people one specific depression scale, and if these people have a certain number of symptoms they are enrolled into the study as depressed.’ According to Fried, his findings suggest that the type of scale a researcher uses might dictate the kind of people who are enrolled in the study. ‘For instance, if a researcher uses Hamilton’s scale, which is focused on physical symptoms, the kinds of participants she examines in her brain study will differ dramatically from those who would be enrolled if she were to use Beck’s cognitive-affective scale. And these different groups of people will likely differ in their brain structures. As this and prior studies show, depressed people differ considerably in the problems they experience and symptoms they exhibit. This likely explains why so many different depression studies come to very different conclusions.’

Publication details

Fried, E. I. (in press): The 52 symptoms of major depression: lack of content overlap among seven common depression scales. Journal of Affective Disorders. DOI: 10.1016/j.jad.2016.10.019

Published by  UvA Persvoorlichting