PhD students who complete their studies are encouraged to share their experiences with us.
Name: Athina Aruldass
Research group: Brain Mapping Unit
Supervisor: Professor Edward Bullmore
Advisor: Dr Sarah Morgan
Title: Functional neuroimaging studies of peripheral inflammation-related depression.
Can you give us a short background on what your PhD was about?
Thematically, my PhD was on Psychoneuroimmunology (PNI) – an interdisciplinary field linking psychiatry, neuroscience, and immunology. Despite being the leading cause of disability worldwide, depression lacks one of the typical characteristics of a disorder, disease, or disability in the traditional sense, i.e., peripheral biological markers. Recent research on the immune mechanisms of depression has reproducibly demonstrated an association between peripheral inflammation biomarkers, e.g., elevated blood levels of C-reactive protein (CRP), and depressive symptoms. However, there have been fewer brain imaging studies of inflammation-linked depression, which are critical for bridging the explanatory gap between peripheral immune states, like inflammation, and mental states, like depression, in humans. To that end, my PhD research seeks to answer if and how brain function specifically is involved in the mechanistic chain linking peripheral immune markers and fMRI-derived phenotypes in an observational depression case-control study [Wellcome Trust and industry-funded investigation – Biomarkers in Depression (BioDep)].
How would you sum up your main findings?
Broadly, the main findings from my PhD research together supported links between peripheral inflammation and depression via brain functional abnormalities. I used methods/materials including resting-state fMRI, probabilistic reinforcement learning task fMRI, peripheral blood immune markers, as well as behavioural instruments. Analytically, the series of experiments conducted were a combination of exploratory as well as “data-informed” studies. But if I may, the most exciting finding was a product of correlating resting-state fMRI-derived whole-brain functional connectivity (a measure of how well different parts of the brain “communicate” with each other) with blood concentrations of immune signalling-proteins (cytokines/chemokines) and immune cells. We found that in those with depression, dysconnectivity or abnormal functional connectivity within a network of brain regions scaled negatively against concentrations of immune markers. In other words, higher peripheral inflammation was associated with lower network functional connectivity in depression.
This was reported in my first-ever first-authored paper (Aruldass et al., 2021; Brain, Behavior & Immunity) and the article also discussed the constituents of the concerned brain network. Incidentally, these were brain regions involved in sensing and modulating peripheral bodily signals, e.g. hunger and immune signals (a process aka “interoception” – a concept I had no knowledge of prior to my PhD !). I thought this conceptual convergence between findings from my PNI-centred PhD research and reports on brain-body interactions at large was quite encouraging as we begin to think about mental health disorders and psychiatry more “monastically” (rather than “dualistic”), involving both the peripheral body and the brain. Circling back to the impetus behind this investigation, I don’t think my work has directly identified any peripheral biomarkers for depression or made any grand impact. But it’s perhaps indicating that we’re not wrong to look there, and certainly -for me at least – the findings raised more questions, e.g. is there directionality to this association we have observed, is it reliably unique to depression cases?
What made you want to do a PhD?
I’ll start by saying that I generally love learning about anything and everything – simply obsessing over understanding how things work, why things happen, and why things are the way they are. In a parallel universe, I would have been an investigative journalist! Being a scientist is a bit like that in that it involves picking things apart, making sense of evidence, bringing to the surface new insight, writing, communicating, and hoping it would all make some semblance of a difference to humanity. As I knew I wanted to continue studying a subject of interest at a higher level professionally, I needed to do a PhD as a “licensing” process to become a full-fledged researcher. As to why psychiatry/neuroscience, nothing fascinates me more than human behaviour – I want to know all about why/how humans think differently, behave differently, and process information differently! If I could ascribe a name to this, I’d pick “human behavioural biology” – a field at the confluence of physiology, the changing environment and behaviour (PopSci book recommendation: Behave; RM Sapolsky). Arguably, a lot has been figured out on the biological bases of human behaviour. But I think what is also important is unpacking them through the mental health and conversely, mental ill-health lens.
What was your best day during your PhD?
Academically speaking, I think the single best day was when I finally passed (second try) my upgrade viva / first-year exam held to confirm one’s PhD candidacy. I perhaps could have said say it was when I published my first-authored journal paper or when I submitted my thesis, but it truly was my candidacy re-examination day because it came after an initial failure. So, succeeding the second time was a personal milestone – a very meaningful one – as in retrospect, I think the learning curve was steepest for me in Year 1. The day brought with it a renewed sense of ambition/motivation that I think shifted my outlook for my remaining years.
What was your worst day during your PhD?
There is no one specific day, rather a “dark period,” i.e. the second half of my first year where I really struggled to make progress, failed to deliver, and even had thoughts about quitting. A series of problems coupled with a profound sense of inadequacy, in many ways presaged my unsuccessful first attempt at the PhD upgrade exam (see above). But the experience certainly galvanized me to pause, take a hard look at my situation and make changes where relevant / adapt. I am especially grateful to my Supervisor and Advisor for supporting me then. I think having a safe space to be vulnerable – a “panic room” so to speak – is crucial when one is trying to navigate turbulent times.
Do you have any words of advice for future PhD/MPhil students in Psychiatry?
Some corny/sappy ones,
- Honor your ambition(s). If you wish to pursue a PhD for whatever reason – go for it, don’t let anyone or anything stop you from at least trying.
- Don’t compare yourself to others. Your PhD and your PhD experience are unique to you. Till the very end, the cycle of self-doubt is never fully broken – but the key is to manage it by practicing self-compassion and focusing on your own growth.
- If your ultimate goal is to be an academic / scientist, a PhD is fundamentally a training program – don’t see it as a series of checkboxes e.g. make novel discoveries, get p-values, publish papers etc. Rather, make it a good learning experience. In the words of my Supervisor – “make all the mistakes now!”.
- Pace yourself and diversify your hours. For example, I enjoy writing very much and “making pictures” (designing figures to present data). So, on my (unauthorized) midweek “mental health day(s)” aka my midweek holiday because I don’t want to stare at my data, I work on a side writing project or scour the internet to figure out how I could level up my figures/tables. Doing something perhaps a bit more creative (in the traditional sense) not only helps me decompress but often times have gotten me unstuck from analyses-related problems!
- Engineer your PhD years judiciously. I was quite set on an academic scientist career from the get-go. As such, most, if not all of my PhD technical skills especially, could be readily exported to a postdoctoral scientist role. However, if you are considering non-academia positions be it in industry, publishing, policy-making etc. – think about how your PhD journey can equip you with relevant transferrable skills e.g. project/people management, event organizing, and evidence of leadership. Consider inserting yourself in activities and roles that would help give you that edge.
What do you hope to do next?
I will be putting my new “license” to the test! After some time of anticipation, come Nov, I will be taking up a Research Fellow post at McLean Hospital, Harvard Medical School, US with the NeuroGenomics and Translational Bioinformatics Lab led by A/Prof Nikos Daskalakis. I will continue to build my research portfolio on brain-body-behaviour interaction with some old friends (psychiatry/mental health disorders) and new friends (genetics and systems biology).