New insights into depression

 

New insights into depression

(Posted 24 March 2015)
Depression is a complex condition - men and women may manifest different behaviours when depressed, and people with inflammatory diseases such as rheumatoid arthritis, cancer and cardiovascular disease often experience depression alongside their ailment.

Dr Jana Haase has been getting glimpses into the molecular underpinnings that could help explain some of these more ‘personalised’ aspects of depression. Her main focus is on a protein called the serotonin transporter, or SERT, which regulates how efficient the neurotransmitter serotonin gets recycled back into brain cells after triggering signals in neighbouring cells.

“By regulating how much serotonin lingers in the space between brain cells and for how long, the transporter has quite an important function in mood,” says Dr Haase, a Lecturer at UCD School of Biomolecular and Biomedical Sciences. “SERT is also a target for the most common antidepressants, the selective serotonin re-uptake inhibitors, and also MDMA, better known as ecstasy.”

We have much yet to learn about SERT and its role in depression, and this has clinical implications, as Dr Haase explains. “Only about 30-40 per cent of people respond successfully to first-line treatment with the anti-depressants that target SERT, and it can take weeks for them to have an effect,” she says.

To get a deeper insight into SERT and its function and regulation in the brain, Dr Haase has been looking at the proteins that interact with the transporter. Through a screening process, she identified some interesting proteins, and has brought those through to in vivo studies.

While working with a model that lacks one of these key proteins, Dr Haase noticed a remarkable difference between the effects in male and females. “It was surprising, but it was striking,” she recalls. “It looks like the genders have different mechanisms to reach the same levels of SERT activity.”

While the research is at an early stage, the observation could tie in with gender-related differences in depression, she notes. “About twice as many women develop depression as do men, and we also know that symptoms of depression are different in women than men - women tend to have more feelings of guilt and worthlessness, while men tend to be more irritable. I think we may have uncovered something that could be a molecular contributor to the basis of this gender difference.”

The observations add to a growing body of evidence that pre-clinical and clinical trials of depression treatments in humans need look at the effects of gender, according to Haase, who also suggests that males and females might even need different types of drugs to target depression.

She is now exploring links between depression, SERT and the chronic inflammation that underpins diseases such as cardiovascular disease, diabetes, rheumatoid arthritis and cancer. “We know that these inflammatory diseases are associated with a higher incidence of depression, and we are looking at how SERT is regulated in models of inflammation,” she explains.

Dr Haase would like to see her research feed into a wider conversation about depression in inflammatory illness. “We need to be looking more actively at depression in these diseases, as it can have such an impact on quality of life.”

Dr Jana Haase, Lecturer at UCD School of Biomolecular and Biomedical Science, was interviewed by freelance journalist Dr Claire O'Connell.