“The more specific we are, the more universal something can become”
As we’ve progressed through decades of exploration into mental health, psychology and neuroscience there has been a dichotomy of specificity in research to treat patients with more success whilst also creating treatments that are generalisable and can be delivered at scale across dynamic population groups.
When it comes to a patient, we know that their experience of mental illness and response to treatment is very unique. So, how do you create standardised treatments whilst also taking into account individual expressions? We sit down with Dr Ana Ganho Ávila to understand the intricacies of patient-specific research and the need to drive change for new treatment pathways, drawing from her focus on women’s mental health during the perinatal period.
Can you tell us about your background and research journey?
Dr. Ganho Ávila
Starting out my journey as a Clinical Psychologist in the early 2000s, I worked within the national health services before starting my own private practice in 2008 where I began to specialise as a Psychotherapist with a keen interest in emotional disorders such as anxiety and depression. In parallel, I was working in a community centre for women and children, and being around these women in need and the unique challenges of being a mother fuelled my passion to explore women’s mental health more closely.
Evolving in my practice, I realised that something was missing in my daily clinical work – what was happening in my patient’s brain whilst they were being treated? This sparked an idea to see their brains during therapy to understand how we produce the change that matters – so that we could be more targeted in our clinical approach.
Ultimately, this desire to bring the therapeutic and physical together led me to embark on my PhD in basic psychology. Grounding my approach in neuroscience and neuropsychophysiology, I learned the basis of human central and peripheral nervous systems before the complexity of processes that occur when someone experiences a mental illness. Working on conditioning emotional responses, I encountered practices with non-invasive brain stimulation and I have to be honest in the beginning I was resistant and thought I’d never use it.
However, as I progressed through my research, I fell in love with neuromodulation for the possibilities it offered as an alternative or complementary treatment that was medication-free providing opportunities to people, especially women who may be unable or don’t want to take antidepressants.
Whilst finishing my PhD, I created a collective network of researchers who were focused on increasing research, treatment and application of female-specific mental illness. This is now known as Riseup-PPD which includes over 29 countries and more than 160 researchers working in the field of peripartum depression disorder. Within this network, we’ve been able to discuss and prepare how we can move forward with research in perinatal mental health in general and a subgroup is focused on using non-invasive brain stimulation.
What has your experience informed you about the need for alternative pathways when it comes to treating mental health disorders?
Dr. Ganho Ávila
In women’s health and perinatal mental health, we see something very similar to what is generally seen in Psychiatry, which is that medication has limited efficacy. On top of this, many people don’t like the current treatment options they have – whether medication or psychotherapy – and the fact it can take up to 8 weeks to experience symptom remission, further impacts treatment and improvement.
For example, what I’ve seen in my experience is that if you’re a depressed woman in the peripartum period, you most probably won’t have access to psychotherapy and you will be prescribed medication that you might resist because of the potential effects on your child. Then there are the more complex layers connected to potential issues of addiction to treatment or delayed withdrawal out of fear of getting worse again. Additionally, frequently clinicians do not feel comfortable prescribing a woman in the peripartum period medication at all or prescribe sub-clinical doses. Ultimately, research in pharmacotherapy with pregnant and breastfeeding women is anecdotal and antidepressants’ prescription mostly relies on clinical trials conducted in the general population. So, in the end, it might not work out in many situations.
Therefore non-invasive brain stimulation could be a very good alternative for these situations. Now with tDCS, being remote and low cost, women can use this in their own home and combine it with what they are doing, which tackles a lot of the situational issues previously mentioned.
Can you explain further how specificity in research is needed so that these alternative treatment options can be fully adopted as part of standard care?
Dr. Ganho Ávila
We’ve known for decades that mental health disorders are expressed differently, and have seen this distinctly in men and women. There are different responses measured during testing depending on gender, for example when conducting fear condition paradigms I saw that when faced with a woman screaming in a video, the galvanic responses of men remained flat whilst in women it fluctuated. We function in a different way and our emotional responses are distinctive and we have distinct modulation of brain activity – different neuroendocrine systems, different hormones, and unique social experiences which prime our brain in different ways.
We understand the need to have generalisability for the sake of the resources we have available. One treatment that works for everyone is easier than lots of treatments for different populations. But we also see the limitations if we only strive for generalisation; we have 60% responding to pills, we have men responding differently to women – so we have a strong pull to understand the patterns of response to be able to treat people more effectively.
As the medications currently available are limited, researchers have been looking for biomarkers to understand patterns of response to better treat and diagnose. When it comes to the research the main issue lies in that there have been too small sample sizes, especially when it comes to specificity of patients, be it gender, cultural, socio-economic factors.
For example, when it comes to neuromodulation we find that there are many clinicians prescribing ECT for severe cases of depression because in general it has been studied across large sample sizes to show a positive effect in treating depression. However, since 1984 only 39 women have been included in ECT studies, yet this treatment is indicated to be effective at treating depressive disorders during pregnancy or even postpartum depression.
Within Riseup-PPD, we have recently conducted a systematic review and found that 136 women across the perinatal period were studied using TMS & tDCS in depression, which has shown positive results. However, TMS and tDCS are still considered as a last line of treatment as the current standard indicates the samples are too small.
What do we need right now? Multi-centred large sample trials to get meaningful data across different groups of people. This is what we’ve been pursuing with Riseup PPD, to get funding and gain more understanding, with trials across countries that will help us to understand the biomarkers that are linked to treatment response.
On the other extreme away from the specificity of genes, genders, ages and cultural differentiators is the approach of the RDoC system, which tells us that everything which happens in the brain, happens in the same material.
We have the same cognitive functions, the same regions; you have attention, memory, executive functions and all of these are the basis for how we respond to our daily lives – from stress to parenthood. One same object (the brain), with the same regions, the same components and physiology – so for sure there are processes that happen equally between people in general and are transdiagnostic.
For several years, psychiatry has been struggling with diagnoses and labels. It is very hard to get people to fit perfectly into specific labels and this is why you have primary diagnoses and secondary diagnoses, such as primary depression, secondary anxiety and maybe there is a personality disorder that brings all of this together. This leads to mixed diagnoses all within the same person – so instead of looking at diagnoses, it’s interesting to look at processes. Flipping the way in which we diagnose to be based purely on symptomatology as opposed to population grouping.
Therefore, we’ve ended up with different levels of analysis – you can look at genes, at brain networks, at self-report measures but in the end, these are only different levels of analysis of the same object. We need to do more to balance the when and the why, moving from basic science to application – the first step was the RDoC framework and now we need to move to the population we wish to treat.
How do you see this division between the healthcare system and the need for more specific treatments coming together?
Dr. Ganho Ávila
In the next ten years, we will see a lot of positive changes in regards to this due to the current pressure for more patients, women-centred research and novelty in treatment programmes. What this might enable us to do in the future when treating mental health disorders is collect a sample of saliva and in a few days, along with the clinician’s reports, we will know the genes and the genetic expression of the patient. From this, we will be able to say that this particular patient has an increased or decreased chance of response to a specific treatment according to the presence or absence of a specific polymorphism. We will then be able to propose the treatment option to which a particular patient most probably will respond best, amongst the different ones available
Is there anything else you’d like to add?
Dr. Ganho Ávila
When it comes to new patient-specific research and creating change within alternative treatment pathways, the people’s choices are ultimately the clinician’s choices at this point.
From a clinician’s perspective, there is not enough time to read everything about new treatments and promising research. To understand the efficacy of a new potential treatment in comparison to the ones they use most of the time (regardless of the robustness of the research behind it), they’ll rely mostly on meta-analysis reviews and they don’t always have the resources or the willingness to embrace practices based on small sample sizes or case-reports. And this brings a problem: publication biases towards large samples and positive results are informing daily practice.
For example, with non-invasive brain stimulation, journals might not publish research results if the quality of the study is deemed low (i.e. small samples), which is great if we drive for high-quality research. However, old habits might prevail without the proper research. This is what we wanted to highlight in our work, ECT is used as a practice in severe cases despite it being barely studied in the case of pregnant women. Whereas there is a lot of research that has been done on women, that won’t pass into reviews even though it is more than what our current treatment offers are based on.
For patients, they are pushing for different options, especially if they have chronic mental health disorders. We need to support the patient and clinicians by disseminating science in a way that shows that it is worthwhile taking a new option even if for a clinic it can seem to be a more difficult road. In the end, it is worth it to reach more people and treat more people effectively and if there are alternative non-pharmaceutical options these should be brought to the discussion and treatment decision.
We want to thank Dr Ana Ganho Ávila for sharing her expert insight and highlighting the importance of moving towards more patient-specific research. If you want to hear more from Dr Ganho Ávila, follow her on LinkedIn.
Stay tuned for our next Expert Spotlight!
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Favourite: At home. Do not get me wrong, I love to be among people but academia can be very stressful.
With the best resources, team and amenities: Faculty of Social and Behavioural Sciences University of Amsterdam
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