Congratulations Professor Vidita Vaidya for being awarded the Infosys Prize 2022 in the lifesciences category. The award is for your contributions to understand brain mechanisms that underlie mood disorders such as anxiety and depression. Has the increased focus on mental health during COVID helped or harmed diagnosis and treatment of mood disorders?
Many thanks for your wishes. COVID-19 brought with it lockdowns, social isolation, a crumbling of social support structures and highlighted the fissures in healthcare infrastructure. WHO estimates about a 25 per cent increase in anxiety and depression during this period, accompanied by substantial disruption and breakdown of mental health treatment services and support. COVID-19 was a source of major global stress and stress-associated psychopathology was certainly heightened as a consequence.
Can you explain how your work on the function of serotonin, the neurotransmitter associated most closely with regulation of mood, will add to the understanding and treatment of mood disorders?
We have identified a key role for the serotonin2A receptor in contributing to the long-term impact of early stress in programming anxio-depressive behaviours in adulthood in rodent models. Clinical studies had suggested that the function and expression of this serotonin receptor is altered in depressed patients with a history of early life stress. What we have shown is that early stress enhances forebrain serotonin2A receptor function and enhanced signalling via the serotonin2A receptors in the forebrain, in particular, in excitatory neurons in the forebrain, during early life, can actually programme enhanced anxiety and depression-like behaviours and also disrupt sensorimotor responses, a hallmark feature noted in schizophrenic patients that are seen well into adulthood. This suggests that some of the impact of early life stress that is such a critical risk factor for several neuropsychiatric disorders may arise due to enhanced serotonin2A receptor signalling during early life.
We also showed that serotonin itself is a key regulator of mitochondria, boosting mitochondrial production, function and efficiency. This matters because neurons are highly energetically demanding. Impaired function of mitochondria can contribute to both neuropsychiatric and neurodegenerative disorders. Identifying serotonin and the key pathways downstream that can boost neuronal power plants has broad implications of therapeutic strategies.
How can we track the effectiveness of antidepressants, especially in arresting such disorders, if diagnosed and treated early enough in individuals? Are such patients going to be dependent lifelong on such medication or can they manage their conditions with other interventions like counselling on nutrition, lifestyle changes, triggers, etc? How does your research contribute to our understanding of these aspects?
Our work does not directly speak to this, as our findings are preclinical and open up new leads via which to understand how early stress may change risk. Further, our work identifies mechanisms that may be important to the mechanisms targetted by antidepressants, particularly those that modulate serotonin. There are exciting new leads emerging where low-dose and controlled exposure to serotonergic psychedelics may be used for treatment refractory depression and post-traumatic disorder. Our work does speak to the mechanisms targetted by such compounds, particularly the impact on how serotonergic psychedelics directly impact bioenergetics in the brain.
What impact will the government’s recent decision to rationalise and reduce the awards for scientific and health research have on the morale of scientists and researchers in lifesciences?
The recognition of science and technology as key drivers of a knowledge economy is obvious. There are also multiple levels at which society and government bodies can recognise the efforts of individuals, teams and institutions that contribute to both fundamental and applied research. While review of award processes, their effectiveness and impact is something that awarding bodies and reviewing mechanisms should do on a regular basis, a statement suggestive of a shutdown may have the unintended impact of sending a message that the very drivers of a knowledge economy are not a priority. This is something that would not be a good idea when India has the ambition to catapult itself into a leadership position in science and technology.
Are there enough alternative awards and recognition from corporate/non-government sources like the Infosys Science Foundation to nurture researchers, especially who may choose moon-shot projects which may be off the beaten paths?
It has been good to see the growth of non-government sources of funding that have either instituted extramural support for science via philanthropic grants or via the establishment of endowed chairs, awards or funding of research centres. However, we are still at the nascent stages when it comes to seeing strong philanthropic support for STEM disciplines in the country. This needs to grow, and public-private partnerships are certainly the call of the hour. The pandemic period has exposed several vulnerabilities, but also gave us the chance to see how effective public-private initiatives can be, if facilitated. This space needs to grow at all levels from private endowments, established of research units, joint ventures, joint grant funding and awards/recognition. We need the full spectrum — it is vital for the STEM spaces in India to become fully vibrant.