Interview with a Researcher: The science behind depression.

Image Credit: Unsplash: Josh Riemer

As a tribute to World Mental Health Day, Jana Joha sits down with Dr. Jana Haase to discuss her research on depression.

Dr Jana Haase is a researcher and lecturer in the School of Biomolecular and Biomedical Science at UCD. Her research focuses on the serotonin transporter and particularly its function and regulation in rheumatoid arthritis and depression. Serotonin is a molecule (neurotransmitter) present in our brains that is responsible for complex signalling that affects our behaviour. It is also referred to as the ‘happy’ neurotransmitter as it can modulate our mood and feeling of well-being. The serotonin transporter's role is to regulate serotonin levels and signalling in the brain and it"s the main target of most antidepressants. Dr Haase explained that the "treatment of depression is tricky, antidepressants don’t work as well as they should… so we aim to contribute to finding some answers by focussing on understanding serotonin transporter regulation at a molecular level, but also in models of depression". 

In an interview with the University Observer, Dr Haase discussed how she started in this field. Originally, she did her PhD on how transport occurs across cell membranes particularly in bacteria. However, after starting her Post-doctorate at Trinity College Dublin, she "found the serotonin transporter a fascinating protein" as "very little was known about it, yet it seemed to play such a critical role in depression and antidepressant action". While already at UCD, she became "interested in the causes of depression, specifically how systemic inflammation triggers or contributes to the precipitation of depression." This led her and her team to hypothesise "that serotonin transporters might play a key role in inflammation-induced depression". 

The way that inflammation can cause depression is through something called "sickness behaviour" which "is essentially… a behavioural response… the brain realises that the body is sick" and "it tells the brain you have to change your behaviour. So you preserve energy… protect yourself, so stay away from danger because you’re weak, you are vulnerable". This sickness behaviour caused by inflammation also makes you "restrict social interactions that reduce the spreading of infections". Dr Haase explained that "behaviour adaptation is very similar to what people experience when they"re depressed and 20-30 years ago people have made the connection between sickness behaviour and depression, which started a new line of research in this field". Normally, "once infection is gone [the sickness behaviour] dissipates" but it was proposed that "depression is perhaps a maladaptation to prolonged inflammation that isn"t resolved or is very intense".

Dr Haase explained that chronic inflammatory diseases like multiple sclerosis, rheumatoid arthritis and even diabetes are often associated with depression symptoms - "many of these diseases that have this chronic inflammation… we know that the patients that have these diseases are more prone to depression or anxiety type diseases". Dr Haase also noted that unfortunately up until recently, the depression symptoms experienced by patients with these diseases has not been readily recognised by health professionals; "they don't take it seriously and it’s as if these symptoms… they have to be dismissed". In fact, it has been recently shown that inflammation may be the root cause for certain types of depression. For example, when patients with rheumatoid arthritis or psoriasis are treated with novel anti-inflammatory treatments, "not only does the treatment suppress the inflammation in joints or on their skin but it also reduces depression symptoms, sometimes even independently of the improvement in the physical symptoms, suggesting that there may be a clear connection between inflammation and depression".   

Antidepressants are another issue that Dr Haase discussed. She explained that certain neurotransmitters, particularly serotonin, norepinephrine and dopamine for example "are thought to be reduced in the brain and then you have a reduction in the signalling because there is a lack of neurotransmitter that can be released and so the idea behind antidepressants… [is] that they block the serotonin transporter and so they prolong the availability of serotonin" in the brain which allows for increased signalling to take place. However, even though this process "happens within hours, most people have to wait for at least 4-6 weeks before they get better". This prompted doctors and researchers to "understand or believe that the actual reason for depression is not so much the acute signalling but more the adaptive changes that happen down the road. Essentially, the whole system may be out of sync and it may take a while to repair or restart the system and normalise everything". Dr Haase highlighted the issue of the ineffectiveness of antidepressants and the urgency of finding alternatives for these treatments with fewer harmful side effects as she noted that "certain antidepressants are dangerous for teenagers… it has been reported that the incidence of suicide increases after they start antidepressants."

Research in her group currently focuses on understanding the regulation of the serotonin transporter and how it differs between sexes. "We stumbled across some molecular underpinnings of these sex differences and that’s one of the things that we focus on at the moment". She and her team have found that the regulation of the serotonin transporter differs between males and females. She explained that "even when the activity of the serotonin transporter is the same in males and females, the underlying regulation appears to differ considerably". Dr Haase notes that upon stumbling across this discovery she was initially "shocked," "didn't believe it" and "thought that there must have been a mistake in the experiment!". She also mentioned that this was one of the highlights of her career. This realisation prompted her group to consistently include both males and females in their experiments. Her findings have shed a light on just how complex illnesses like depression can be as she explained that "when you see that there is clear differences in terms of how certain things work… that tells you that the causes of depression or anything else… could have very different causes in males and females". This also highlights current limitations on how we treat many diseases as most therapies and drugs do not take into account these sex differences. Dr Haase believes that more needs to be done "especially in psychiatric diseases… there"s very little done even though it’s very clear that there is a difference… so I don"t think you can treat them the same".  

Dr Haase’s incredible research may help us better understand how diseases such as depression are triggered and caused which may perhaps open the avenue for treatments that take on a more personalised approach which take into account sex differences. Dr Haase remarked that even though she doesn't "have the answers" and that "we don't have the drugs yet" she believes that "what [they] are doing might contribute to at least understanding what the differences are between males and females which can maybe precipitate new research or drug development down the road". She also noted that having "the awareness" and "knowing that there's a neurobiological reason for “depression and that "it's not a choice" is important especially for "young people [as they] are particularly vulnerable". Unfortunately "there is still a stigma associated with depression and mental health in general" and we must raise more awareness about it because "we don’t fully understand the aetiology of depression". We have come a long way but more still needs to be done to get rid of the "stigma" that exists around depression and Dr Haase"s research may just help us achieve that.