"Surveys indicate that more than 80% of the public blames a “chemical imbalance” in the brain."

"For decades, it has also been touted as the pharmaceutical MVP for fighting depression."

"Yet the causes of depression go far beyond serotonin deficiency. Clinical studies have repeatedly concluded that the role of serotonin in depression has been overstated."

"They found no convincing evidence that lower levels of serotonin caused or were even associated with depression."

"People with depression didn’t reliably seem to have less serotonin activity than people without the disorder."

"“Their lung function and everything wasn’t getting much better, but their mood tended to improve,” said Gerard Sanacora"

"They discovered that the drugs blocked the animals’ body from absorbing compounds called amines — which include serotonin, a chemical that carries messages between nerve cells in the brain."

"“Just because aspirin relieves a headache, [it] doesn’t mean that aspirin deficits in the body are causing headaches,”"

"Some clinical psychiatrists believe that one of the other compounds may be the true force inducing or relieving depression."

"“There’s quite good evidence from tryptophan depletion studies,” said Michael Browning, a clinical psychiatrist at the University of Oxford."

"A number of tryptophan depletion studies found that about two-thirds of people who have recently recovered from a depressive episode will relapse when given diets artificially low in tryptophan."

"And tryptophan has a secondary effect of raising serotonin levels in the brain."

"Recent evidence also suggests that both tryptophan and serotonin may contribute to the regulation of bacteria and other microbes growing in the gut, and chemical signals from these microbiota could affect mood."

"Not all theories of depression hinge on neurotransmitter deficiencies. Some look for culprits at the genetic level."

"“It’s really important that people understand that there is a genetics of depression,” Krystal said"

"“For most common traits of interest, both genetic and environmental factors play a critical role.”"

"Different genetic variations can affect whether individuals respond to certain types of stress, such as sleep deprivation, physical or emotional abuse, and lack of social contact, by becoming depressed."

"Research suggests that in the brains of people with chronic depression, the “white matter” areas that are rich in nerve fibers have fewer connections. The cause for this difference is uncertain, however."

"Differences in a person’s genes may predispose them to depression; so, too, may differences in the neural wiring and structure of their brain."

"Numerous studies have shown that individuals differ in how the neurons in their brains interconnect to form functional pathways, and that those pathways influence mental health."

"In a recent conference presentation, a team led by Jonathan Repple, a psychiatry researcher at Goethe University in Frankfurt, Germany, described how they scanned the brains of acutely depressed volunteers and found that they differed structurally from those of a non-depressed control group."

"For example, people experiencing depression showed fewer connections within the “white matter” of the nerve fibers in their brains."

"After the depressed group underwent six weeks of treatment, Repple’s team ran another round of brain scans. This time, they found that the general level of neural connectivity in the depressed patients’ brains had increased as their symptoms lessened."

"A possible explanation for this change is the phenomenon of neuroplasticity. “Neuroplasticity means that the brain actually is able to create new connections, to change its wiring,” Repple said."

"If depression occurs when a brain has too few interconnections or loses some, then harnessing neuroplastic effects to increase interconnectedness might help lift a person’s mood."

"Perhaps the depressed patients’ brain connections were impaired by inflammation."

"Chronic inflammation impedes the body’s ability to heal, and in neural tissue it can gradually degrade synaptic connections."

"When psychiatrists have evaluated populations of patients who have chronic inflammatory diseases like lupus and rheumatoid arthritis, they’ve found that “all of them have higher-than-average rates of depression,” said Charles Nemeroff, a neuropsychiatrist at the University of Texas, Austin."

"The sudden influx of inflammatory cytokines leads to appetite loss, fatigue and a slowdown in mental and physical activity — all symptoms of major depression."

"Viral inflammation can extend directly to tissues in the brain. Devising an effective anti-inflammatory treatment for depression may depend on knowing which of these causes is at work."

"Increasingly, some scientists are pushing to reframe “depression” as an umbrella term for a suite of related conditions, much as oncologists now think of “cancer” as referring to a legion of distinct but similar malignancies."

"But “appreciating the true, real complexity of depression takes us down a path that is ultimately going to be most impactful,”"