Despite the advice of two of the most successful pop anthems of the last two decades, when it comes to depression, no one can just “shake it off” or “let it go.” If we jump back to 1988, we’ll find the advice “don’t worry, be happy” to be just as worthless. People can’t simply “think their way” out of depression, and hectoring them to do so probably makes them feel worse, which can lead to terrible results.
That’s because depression isn’t simply the natural experience of mourning a tragic event, such as a divorce or a death in the family. It’s profoundly disordered thinking that makes experiencing happiness difficult or impossible, and by sabotaging concentration, memory, and decision-making, makes it far easier to feel worthlessness, guilt, and the yearning to stop existing. It’s a massive problem – the World Health Organization estimates that globally, around 5.7% of adults, or 332 million people, endure depression.
So, could there be a secret weapon to fight this terrible curse, especially for people who, until now, have experienced the double-damnation of “drug-resistant” depression?
According to researchers at Columbia and McGill universities, the answer is yes. Their discovery of the powerful role of the stress-responsive protein SGK1 is key, as lead author Christoph Anacker, assistant professor of clinical neurobiology in the Department of Psychiatry at Columbia, and his co-authors explore in their Molecular Psychiatry paper, “Hippocampal SGK1 promotes vulnerability to depression: the role of early life adversity, stress, and genetic risk.”
As Anacker explains, his team’s research is especially promising because “it raises the prospect of quickly developing new treatments, as SGK1 inhibitors are in development for other conditions,” which provides “a screening tool to identify people at greatest risk."
About a decade ago, Anacker and his co-researchers discovered strangely high levels of SGK1 in blood samples from people experiencing depression who were not receiving medication for it. His team eventually also found SGK1 at high levels in the brain tissue of people who ended their own lives, and the highest levels of all in people who had reported childhood trauma. In the US, about 60% of people with diagnoses for major depression, and around two-thirds of people who attempt to take their own lives, faced trauma in childhood.
As Anacker explains, because some people carry genetic variants that increase SGK1 production, the interaction between SGK1 and trauma causes them to be at far greater risk of depression as teens and adults than those with “less stressful childhoods."
Experiments injecting SGK1 inhibitors into the blood of mice have successfully inhibited the mice from demonstrating depressive-like behaviour during prolonged stress. Therefore, SGK1-blocking drugs offer tremendous hope, especially with patients for whom selective serotonin reuptake inhibitors (SSRIs) don’t work.
If combined with genetic screening, SGK1 inhibitors would be a powerful deliverance for people who survived early childhood trauma including neglect, verbal abuse, sexual assault, degradation, exploitation, and war. As Anacker says, "There's an urgent need to identify and treat people with the greatest risk of depression and suicide after exposure to early life adversity, and SGK1 is a promising avenue to explore."
Source: Columbia University
