Lab Talk

The Difficulty of Diagnosing Depression

Should we really be diagnosing depression based on a questionnaire?


Depression is terrible. With symptoms like overwhelming persistent sadness, feelings of worthlessness, and fatigue, it can turn your life upside down, put you out of work, break up your marriage, and at its worst, drive you to suicide.  With an estimated 350 million people suffering from depression worldwide, it is so common that even if you haven’t suffered from it yourself, you probably know someone who has, and have some sense for what it is…except not exactly.

That’s because, as common as it is, diagnosing it is immensely challenging.

Diagnosing depression

Depression comes in many flavors that can be very different among people. Some people might be anxious and angry, and others withdrawn or unable to make decisions. Two depressed people are never the same. This makes the diagnosis very, very complicated.

Lab tests are used to screen for other diseases and rule them out. However, depression is essentially diagnosed based on a standardized questionnaire that tries to determine how many symptoms of depression you have, how long you have had them, and how much they interfere with your ability to live life normally. Its really not so different from a quiz in Cosmopolitan magazine that will give you a score telling you, for example, how emotionally healthy your relationship is.  As in all questionnaires of this nature, it is subjective and there are many ways to arrive at the same score. The commonly used DSM-5 scale, for instance, diagnoses depression based on a set of 9 questions where up to 256 combinations of answers can give you a positive diagnosis! HAM-D is also a commonly used questionnaire for evaluating the severity of depression, where the physician will ask 17 questions with rating scales for the severity of your symptoms. In the end, you total up the score for your diagnosis. A diagnosis of moderate depression can be arrived at with over 25,000 combinations of selections! That’s a lot of different combinations for people to be diagnosed with exactly the same disease.

This leads us to our next problem. How to treat something that we don’t really know how to diagnose?

Treating Depression

Treating depression usually involves one type of antidepressant medication or combinations of multiple antidepressant medications – sometimes associated with other treatment options such as psychotherapy. Medication used to treat depression can have serious side effects such as addiction, which can lead to withdrawal symptoms and cause setbacks in the patient’s mental health. If you have depression, it’s a real challenge is to find the right medication for your particular mental state, leave alone deal with the side-effects of changing medication until you find the right one. Finding the right medication usually takes time or may never truly be successful.

The lack of success in the treatment of depression is obvious. However, the real problem may lie in the diagnosis. To have a whole disease spectrum diagnosed solely on questionnaires seems a bit of an underachievement.  If it is necessary to physiologically define any other disease before we can treat it effectively, why shouldn’t the same apply to depression?

Brain activity: a tool for diagnostics?

Recently, there has been an increase in published papers that try to define and categorize different types of depression based on physiologic parameters instead of subjective answers. These studies are beginning to give us a view into the behavior of our brain when we experience symptoms of depression. Indeed there are differences between a healthy brain and the brain of a depressed subject – not only morphological changes, as depression may cause shrinkage of some important brain structures, but also changes in brain activity.  

In fact, recent research is beginning to show promising results that link depression with changes in brain activity that can be measured by the EEG – from differences in the spectral properties of the signal to differences in connectivity across regions.  This may be only the beginning, but more precise views of a physiology of depression – or, really, the many types – of depression may be not far in the future.  Perhaps it will lead to complete overhaul of our disease definitions, or at the very least, will help to optimize medication and personalize therapy.

Cindy Duarte Castelão has a degree in Human Biology and Health and a personal interest in mental health issues.