Two New Perspectives on Depression

In the last week or tow, there were two new articles on depression that offer a new way into the understanding and treatment of this challenging state experience. I think each of these findings can offer possibilities for new treatments - and with depression becoming more and more common (we're talking clinical depression here, not sadness or situational melancholy), new approaches are welcome.

Gene therapy helps depressed mice

Revving up expression of a single gene in the brain reverses depression symptoms

Alla Katsnelson

Gene therapy might one day be used to treat neuropsychiatric diseases - if it can be translated from mice to humans.Punchstock

Gene therapy delivered to a specific part of the brain reverses symptoms of depression in a mouse model of the disease — potentially laying the groundwork for a new approach to treating severe cases of human depression in which drugs are ineffective. But the invasive nature of the treatment, and the notorious difficulty in translating neuropsychiatric research from animal models to humans, could complicate its path to the clinic.

Many researchers believe that poor signalling of the neurotransmitter serotonin is responsible for causing depression, and common antidepressants act by increasing serotonin's concentration. Research published today in Science Translational Medicine¹ uses a virus to deliver an extra dose of the gene p11 to the adult mouse brain. The protein expressed by the gene is thought to bind to serotonin receptor molecules and ferry them to the cell surface, positioning them to receive serotonin's signals from neighbouring cells.

"I think it awakens the possibility of gene therapy for neuropsychiatric diseases," says Husseini Manji, a senior investigator at Johnson & Johnson Pharmaceutical Research & Development in Titusville, New Jersey, who was not involved in the study. But, he adds, "thinking about delivering a gene to the brain poses all sorts of challenges".

The p11 gene was only recently linked to depression. In 2006, Paul Greengard, a neuroscientist at the Rockefeller University in New York, and his colleagues created mutant mice lacking the gene, and found that the animals developed depression-like behaviours².

Read the whole article.

New Theory Links Depression To Chronic Brain Inflammation

Chronic depression is an adaptive, reparative neurobiological process gone wrong, say two University of California, San Diego School of Medicine researchers, positing in a new theory that the debilitating mental state originates from more ancient mechanisms used by the body to deal with physical injury, such as pain, tissue repair and convalescent behavior.

In a paper published in the September online edition of Neuroscience and Biobehavioral Review, Athina Markou, PhD, professor of psychiatry, and Karen Wager-Smith, a post-doctoral researcher, integrate evidence from diverse clinical, biological and behavioral studies to create a novel theory they hope will lead to a shift in thinking about depression.

"In contrast to other biological theories of depression, we started with a slightly different question," said Wager-Smith. "Other theories address the question: 'What is malfunctioning in depression?' We took a step back and asked the question: 'What is the biology of the proper function of the depressive response?' Once we had a theoretical model for the biology of a well-functioning depressive response, it helped make sense of all the myriad differences between depressed and non-depressed subjects that the biomedical approach has painstakingly amassed."

According to the new theory, severe stress and adverse life events, such as losing a job or family member, prompt neurobiological processes that physically alter the brain. Neurons change shape and connections. Some die, but others sprout as the brain rewires itself. This neural remodeling employs basic wound-healing mechanisms, which means it can be painful and occasionally incapacitating, even when it's going well.

"It's necessary and normal so that an individual can adapt, change behavior and deal with altered circumstances," Markou said. Real problems occur only "when these restructuring processes go into overdrive, beyond what is necessary and adaptive, and for longer periods of time than needed. Then depression becomes pathological."

The theory extends findings made by other researchers that the neurobiological substrates of physical and emotional pain overlap. Just as the body's repair mechanisms for physical injury can sometimes result in chronic pain and inflammation, so too can the response to psychological trauma, resulting in chronic depression.

Read the whole article.

Tags: Gene therapy helps depressed mice, gene expression, single gene, reverses depression symptoms, Alla Katsnelson, Chronic Brain inflammation, depression, brain, genetics, Psychology, neuroscience, neurobiology, Athina Markou, research, treatment