As much as we’d like to shush about it, the fact remains that mental health is an imperative component of one’s overall well-being that encompasses a wide range of emotional, psychological, and social factors. One key area of research in mental health sciences is the study of neurobiology, which focuses on the biological and physiological processes that, when gone awry, are responsible for various mental health conditions. This research has led to a greater understanding of the complex interactions between genetic, epigenetic, and environmental factors that contribute to the development of mental health conditions.
The winner of the Infosys award 2022 in biological sciences, Professor Vidita Vaidya, is a neurobiologist. She has devoted her scientific career to the pursuit of understanding how factors that cause stress, especially in early life, can lead to mood disorders such as anxiety and depression. Vidita and her team study the molecular and cellular mechanisms that contribute to such disorders, with a special focus on the function of serotonin.
You may know of serotonin from the headlines last year, where one of our most widely held beliefs about depression was turned topsy-turvy by scientists from the UK. The study claimed that, contrary to popular belief, depression is not simply caused by a lowering of serotonin levels. The finding came as a shock to many patients and caregivers worldwide, but most researchers in the field already knew it to be true.
Serotonin is a molecule working in our bodies prominently as a neuro-messenger. It carries messages between nerve cells that instruct the body how to work. It affects memory and learning and has many functions in our body, such as regulating body temperature, sleep, hunger, and so on.
Vidita’s lab has discovered that serotonin increases energy production in brain cells and aids in their ability to withstand stress. The neuro-messenger was shown to do this by generating new mitochondria in neurons. Mitochondria are known as the powerhouses of the cell as they release energy required for cellular activities. Vidita and team’s work, which shows that serotonin improves mitochondrial function in neurons, establishes a cardinal link between neurotransmitter activity, cellular energy regulation, and brain function.
Vidita’s lab has shown that an imbalance in serotonin mechanisms in nerve cells caused by different signalling receptors with different G protein-based signalling pathways is an important contributor to stress-induced mental dysfunction.
Serotonin2A receptor is a receptor found widely distributed on nerve cells in the brain and spinal cord to which serotonin binds. It plays an active role in memory, learning and cognition. Vidita’s research group has determined that the serotonin2A receptor plays a critical role in the long-term effects of early stress on the programming of anxiety- and depression-like behaviours in adulthood in mouse models.
Clinical research had already indicated that depressed individuals with a history of early life stress have altered function and expression of this serotonin receptor. What Vidita and her team have demonstrated is that early life stress enhances the function of the serotonin2A receptors in the forebrain. Increased signalling through these receptors in excitatory neurons in the forebrain during early-life can induce enhanced anxiety — and depression-like behaviours as well as disrupt sensorimotor responses — a defining characteristic observed in schizophrenic patients that are observed well into adulthood. Vidita’s research indicates how early life stress, a critical risk factor for several neurological and psychiatric disorders, may develop into these disorders due to increased serotonin2A receptor signalling throughout early life.
Early life adversity
While early life adversity is a major risk factor for the development of psychiatric disorders, it is certainly not a guarantee, argues Prof. Vaidya.
She explains, “We are surrounded by numerous stories of individuals who have overcome significant obstacles in their lives. Even people with the same genetic makeup and similar circumstances do not react to life experiences in the same way.”
It starts in the womb itself, where the epigenetic marks that the in-womb experience can leave on even identical twins can differ. Epigenetics literally means beyond the genetic code. It refers to environmental, behavioural, or other non-genetically coded factors that can affect how your genes work. Early life adversity is an epigenetic factor that can, you guessed it right, make permanent changes in our genetic material.
Each experience we go through can leave epigenetic alterations on our genome that change how genes are expressed. Also, life experiences, particularly those in early life, can sculpt brain circuits quite distinctly, driving differences in behaviour and stress responses. We see this even in genetically inbred rodent models, where despite limited genetic variation behavioural responses do show changes from individual to individual, highlighting the profound impact of life experience on the brain.
Nurture and care
Vidita studies neurobiology with mice models. Here is one of her experiments — She took a mouse family and separated the mother and babies for short durations daily. This changes the mother’s behavior as she is not actively choosing to leave the pups for example to find food, but has them taken away, which ends up resulting in deteriorated maternal care. The pups end up with poor quality of care as a consequence. Then Vidita and team studied the molecules and signalling, taking samples from the babies as they grew. This was compared to samples taken from mice pups who were not separated from their mother and had normal nurture. The early life stress experienced by the pups without enough nurture time evidently displayed enhanced anxiety- and depression-like behaviours as adults.
An advocate for providing care and nurturing to growing children, Vidita talks of how the early windows of life are profoundly important for shaping stress responses across the entire lifespan. This itself should tell us how important these early windows of life are, she emphasises. In this window, the brain is most plastic (capable of substantial change) and has a profound capacity to learn and grow, which is much more restricted in adulthood or aged life. So, this window matters as it sets the stage for the rest of your life.
“Nurture is vital in this window, and adults can provide this for children in so many different roles as parents, grandparents, foster parents, aunts and uncles, caregivers, teachers, and also as policymakers who shape the experiences children go through in the first decade or so of their life. Getting this right is the biggest investment we can make for the future”, Vidita asserts.
To young researchers
The beauty of this research is that all the insights about nurture and caring come in from molecular insights. From mice! By understanding how the brain works at a molecular level, we are gaining enlightenment into what triggers certain behaviours and why neurotransmitters affect mood and decision-making, as well as how this could lead us to understand human behaviour. Not only does Vidita’s research give us an understanding of the molecular mechanisms surrounding mood disorders, but it also gives us the hopes of drugs that could be designed following her research.
When asked what advice she has for the youth who are interested in studying in her field, Vidita replies, “If you enjoy asking challenging questions about this little 1.5 kg, jelly-like wrinkled structure that does all kinds of fascinating things like write poetry, build space stations, solve mathematical conundrums, score the perfect goals and produce the most exquisite musical compositions - as well as give you the ability to appreciate them, then neurobiology is the field for you.”
This article has been run past the researcher, whose work is covered, to ensure accuracy.