Authors Info & Affiliations November 27, 2023
“The Second Pandemic
“Over the past few years, the perceived level of psychological stress has risen dramatically across the globe due to a combination of events including the long-lasting Covid-19 pandemic, civil unrest, escalation of political instability across the globe, and climate change that has triggered major environmental and economic perturbations. The consequences of this broad-scale increase in stress are only beginning to be appreciated, but evidence suggests that we are facing a second pandemic of mood and anxiety disorders, including major depression, anxiety, and posttraumatic stress disorder (PTSD). This Special Issue entitled “The Neurobiology of Stress: Vulnerability, Resilience, and Major Depression” is intended to ask “How can science help?” Our hope is to initiate a broad discussion on the power of basic and clinical scientific tools to confront these challenges and to offer strategies for treatment and prevention.
“Unlike the case of a virus triggering a pandemic where the biomedical scientific strategy for combatting it is relatively clear, brain disorders present significant, complex challenges and involve many unknowns. While depression and related disorders have a strong neurobiological basis (1), our biological insights are not yet sufficiently complete to be fully translated into clinical practice. This starts with their classification—mood and anxiety disorders are clearly heterogeneous and highly interrelated but are currently diagnosed solely on the basis of behavioral abnormalities, with no biological measures to assist diagnosis (2). Yet, the magnitude and impact of these ill-defined mood and anxiety disorders are staggering and the recent increase in their incidence is truly alarming.
“Prior to the 2019 Covid-19 pandemic, it was already established that Major Depressive Disorder (MDD) and anxiety disorders are among the leading health burdens globally (3). Within the first year, the pandemic triggered a dramatic rise in these disorders, adding an estimated 53 million cases of MDD and 76 million cases of anxiety disorders globally, representing an approximately 25% increase in the incidence of these disorders (4). The magnitude of increase in mood and anxiety disorders in any given country was highly correlated with the magnitude of the impact of the Covid-10 pandemic on that country. Moreover, younger people and females in particular have been more profoundly impacted by the pandemic than other groups (4). Individuals in certain professions, such as healthcare workers (5), and those confronting economic and social challenges or experiencing racial discrimination were especially affected as well (6).
Hidden behind these statistics are additional sobering facts: Mood and anxiety disorders are typically chronic relapsing disorders that alter the brain in complex ways (1). Their rising incidence in children, adolescents, and young adults is particularly concerning because, if left untreated, they will have consequences for decades. They also increase the risk for other illnesses such as cardiovascular disease and inflammation (7, 8) and have a profound impact on the individual, their family, and society more broadly. It is therefore no exaggeration to conceive of the current mental health crisis as a pandemic—i.e., an instance wherein a disease with significant consequences has spread rapidly across the globe. In addition, while not contagious in the strict viral sense, mood and anxiety disorders are contagious in the societal sense, as evidenced by their dramatic rise in certain communities and specific populations. It is therefore essential to work toward limiting not only the spread but also the duration of this wave of severe distress that so many are experiencing.
“What Can Science Do?
“While the scope and nature of the challenge of this second pandemic are daunting, there is much that science can offer to alleviate it. This requires a clear vision of what can be achieved in the immediate term, coupled with a thoughtful, strategic, and well-integrated plan for the longer term.
“During the last few decades, we have made major strides in our understanding of the biological underpinnings of mood and emotions ranging from genetic to societal factors, with a wealth of knowledge at the molecular, cellular, neurocircuit, and behavioral levels. As importantly, science has reframed the discourse around these illnesses and has debunked many overly simplified ideas about the biology of mood and anxiety disorders—the notion that it is a “chemical imbalance” of a single neurotransmitter system (e.g., serotonin); the notion that a handful of genes will emerge as the cause of these disorders and allow ready treatment targets; and even the idea that the name of any of these disorders—depression, anxiety, PTSD—signifies a single entity. We have begun to confront the complexity and heterogeneity of these disorders and herein lies the hope for dealing with them in a clear-eyed and strategic manner.
“A good analogy might be the trajectory of cancer research over the last few decades. While “cancer” is an important umbrella term, key to the progress has been fundamental research in cell signaling, growth, and death, and the innumerable ways these mechanisms can become dysregulated. But equally important is the reliance on clinical insights about the nature, heterogeneity, and complexity of multiple types and subtypes of cancer as a framework within which fundamental research questions are articulated. Indeed, it is this marriage of confronting complexity and uncovering fundamental biological mechanisms that has inspired the precision approaches to certain types of cancers and their treatment. However, it is notable that even for cancers, which are far simpler than mental illness—where a tumor can be detected, characterized at the molecular level, excised, and monitored regularly, the journey has been long and arduous. We are more than half a century since the creation of the National Cancer Institute and the “war on cancer,” yet are only now beginning to see advances in precision cancer treatment reach the clinic.
“The challenge is much greater for depression and other related disorders where the illness itself is enormously harder to capture. But, as in the case for cancer where cell signaling, growth, and death represent a shared biological framework, mood and anxiety disorders have a common biological underpinning that serves as a starting place for understanding these disorders at a mechanistic level: the stress system, which will be briefly described below. Stress biology also forms a nexus for both immediate action to combat the current mental health crisis and for advancing our fundamental understanding of these disorders in the longer term and arriving at novel, targeted treatment approaches. The partnership between fundamental and clinical research, the recognition of complexity and need for greater specificity and precision, the importance of removing stigma, and forging a strong alliance with the public are all key lessons that must be adapted from cancer research and other fields of medicine to help meet the current mental health challenge…”
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