The old hospital at UCLA is a sprawling brick complex built in the 1950s. Its rambling hallways stretch out longer than any non-military building in the US. Only the Pentagon has more hallways. Lost somewhere up on the third floor, in a corner by myself, is where I spent most of grad school – sitting at a computer, running statistical models for research on .

The lab studied biomarkers of antidepressant treatment response. That is, we aimed to see if there was something we could measure about brain activity that would predict who would get better on which and when. If worked the same on everybody, this wouldn’t be necessary, but they don’t. We know that a given antidepressant will work great on about a third of people, do an ok job on another third, and not do much for the rest. But before actually giving the medication to the person for three months, it’s hard to say who will respond and who won’t.

On one of my first days there I heard my colleagues whispering about a patient. One mumbled something about “empty” that I couldn’t quite hear. I jumped into the conversation and asked what they were talking about. She replied, “I said he has ‘Empty-man syndrome’.” Intrigued, I asked her what that was. It was a term she came up with to describe certain men with depression. It applies to guys in their 40s and up who were single or , and don’t have any friends, are unemployed or stuck in a job they don’t like, and have no real hobbies. I asked why she came up with a term for this, and she sighed, “Because they don’t ever seem to get better.”

This sent a jolt through me, thinking about these men suffering through their joyless lives. Her description of empty-man syndrome led me to realize the simplicity of current treatments for depression. The medications used in our studies might enhance their serotonin signaling, or alter norepinephrine activity, but a simple pill could not address these complex influences that life has on the brain, and which were conspiring against them.

For both sexes, social support is extremely powerful in fighting depression, particularly support from a loving spouse. A study out of Cornell looked at the effect of on recovery from depression (Meyers 2002). When controlling for other factors, being married more than doubled the odds of a speedy recovery (2.4 times to be precise).

Obviously marriage is not the only way to receive social support, but women may have an easier time getting social support from places other than their significant other. In one huge study of depression, conducted across 23 countries, being single or widowed was a much stronger risk factor for depression for men than for women (Van de Velde 2010).

In addition to social support, feeling like you have a purpose in life is an important aspect of . This is one reason that having a job can be protective against depression, and why losing your job can be devastating. One German study (Warnke 2014) looked at patients hospitalized for depression – so they were in pretty bad shape. The researchers wanted to see what factors predicted whether they would be hospitalized again in the future. It turns out that having a job helps. Patients who had a job at the time of their first hospitalization reduced their risk of being hospitalized again by 32%. Importantly, a huge study from Spain – of over 15,000 people – showed that unemployment has a larger effect on men, causing a greater risk than women of developing depression (Artazcoz 2004).

So certain aspects of social support along with unemployment contribute more to depression in men than women. Unfortunately, these factors can interact and create an even more difficult situation for men. An older study from Massachusetts looked at depression in 100 men who were all blue-collar workers that had just been laid off (Gore 1978). They were also all married, but had varying degrees of social support. The study found that men with low social support were affected much more by unemployment than men with higher social support. So if a man lost his job, but he had good social support, he could turn out fine. But without that social support, the loss of a job significantly increased his risk of getting depressed.

This is not to say that the causes of depression are rooted simply in life circumstances. That’s far from the truth. But , early experiences, and coping strategies all combine with life circumstances and random luck to get the brain stuck in depression. Depression robs your brain’s ability to access joy. But sometimes, even if it were capable, there may be no joy to experience.

This brief comment about empty man syndrome has stuck with me for almost 10 years. And I think it’s because at the time I saw in it the faint reflection of my own life. Sitting by myself day after day, uncertain of whether I should really be in grad school, I didn’t have a girlfriend and I worried I would never find the right one. What if I just didn’t show up to work and lay in bed all day feeling sorry for myself? Would anybody notice? I could see how these empty men might never recover. Once you start falling through the cracks, it’s hard to stop falling.

I’m not writing about this to convince people that men have it worse than women. In fact, women are more than twice as likely as men to be depressed. I’m writing about this to highlight the complexity of depression as a disorder. There is still so much we don’t understand. But people don’t generally want to hear complex answers, so we don’t give them. Medical professionals also fuel the simplifying of depression, not intentionally, but because they have a limited set of medical interventions and we don’t understand why they work.

The important thing is that we are always gaining a better understanding of how all the different variables interact. As I described above, numerous studies have highlighted the interacting contributions of social support, employment and . Biomarkers to predict treatment response are slowly being refined. For example, we know that people with higher activity in the anterior cingulate are more likely to respond to antidepressants (Korb 2009). Yes, we don’t understand why, and we don't understand how this relates to and interacts with the other factors, but we’re progressing.

People often complain about the effectiveness of antidepressants – how they don’t work on everyone, or they take too long to work. But I like to think of it the other way. Given the complexity of depression, how intricate the human mind, how little we understand, and the myriad ways we get stuck in suffering, even then sometimes a little pill is all it takes to get better. And things will only go up from here.

If you liked this article then check out my new book - The Upward Spiral: Using Neuroscience to Reverse the Course of Depression, One Small Change at a Time

References:

Artazcoz L et al (2004). Unemployment and Mental Health: Understanding the Interactions Among Gender, Family Roles, and Social Class. Am J Public Health.

Gore S (1978). The Effect of Social Support in Moderating The Health Consequences of Unemployment. J Health and Social Behavior.

Korb A et al (2009). Rostral anterior cingulate cortex theta current density and response to antidepressants and in major depression. Clinical Neurophys.

Meyers B et al (2002). Predictors of Early Recovery From Major Depression Among Persons Admitted to Community-Based Clinics. Arch Gen Psych

Van de Velde S et al (2010). Gender differences in depression in 23 European countries. Cross-national variation in the gender gap in depression. Social Science and Medicine.

Warnke I et al (2014) Antidepressants: relationship to the time to readmission and probability of being in hospital in depressive patients. Frontiers in pub health.