Depression is the leading cause of disability in the world. In the United States, close to 10% of adults struggle with depression. But because it's a mental illness, it can be a lot harder to understand than, say, high cholesterol. One major source of confusion is the difference between having depression and just feeling depressed. Almost everyone feels down from time to time. Getting a bad grade, losing a job, having an argument, even a rainy day can bring on feelings of sadness. Sometimes there's no trigger at all. It just pops up out of the blue. Then circumstances change, and those sad feelings disappear. Clinical depression is different. It's a medical disorder, and it won't go away just because you want it to. It lingers for at least two consecutive weeks, and significantly interferes with one's ability to work, play, or love. Depression can have a lot of different symptoms: a low mood, loss of interest in things you'd normally enjoy, changes in appetite, feeling worthless or excessively guilty, sleeping either too much or too little, poor concentration, restlessness or slowness, loss of energy, or recurrent thoughts of suicide. If you have at least five of those symptoms, according to psychiatric guidelines, you qualify for a diagnosis of depression. And it's not just behavioral symptoms. Depression has physical manifestations inside the brain. First of all, there are changes that could be seen with the naked eye and X-ray vision. These include smaller frontal lobes and hippocampal volumes. On a more microscale, depression is associated with a few things: the abnormal transmission or depletion of certain neurotransmitters, especially serotonin, norepinephrine, and dopamine, blunted circadian rhythms, or specific changes in the REM and slow-wave parts of your sleep cycle, and hormone abnormalities, such as high cortisol and deregulation of thyroid hormones. But neuroscientists still don't have a complete picture of what causes depression. It seems to have to do with a complex interaction between genes and environment, but we don't have a diagnostic tool that can accurately predict where or when it will show up. And because depression symptoms are intangible, it's hard to know who might look fine but is actually struggling. According to the National Institute of Mental Health, it takes the average person suffering with a mental illness over ten years to ask for help. But there are very effective treatments. Medications and therapy complement each other to boost brain chemicals. In extreme cases, electroconvulsive therapy, which is like a controlled seizure in the patient's brain, is also very helpful. Other promising treatments, like transcranial magnetic stimulation, are being investigated, too. So, if you know someone struggling with depression, encourage them, gently, to seek out some of these options. You might even offer to help with specific tasks, like looking up therapists in the area, or making a list of questions to ask a doctor. To someone with depression, these first steps can seem insurmountable. If they feel guilty or ashamed, point out that depression is a medical condition, just like asthma or diabetes. It's not a weakness or a personality trait, and they shouldn't expect themselves to just get over it anymore than they could will themselves to get over a broken arm. If you haven't experienced depression yourself, avoid comparing it to times you've felt down. Comparing what they're experiencing to normal, temporary feelings of sadness can make them feel guilty for struggling. Even just talking about depression openly can help. For example, research shows that asking someone about suicidal thoughts actually reduces their suicide risk. Open conversations about mental illness help erode stigma and make it easier for people to ask for help. And the more patients seek treatment, the more scientists will learn about depression, and the better the treatments will get.