Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment.

Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption). Proper assessment and management is critical, as individuals with TRLLD often present in medical settings and suffer from cognitive decline and other marks of accelerated aging. This article serves as an evidence-based guide for medical practitioners who encounter TRLLD in their practice.

From Mourning and Melancholia to Neurobiology in an Era of Global Warming, Pandemic Disease, and Social Chasms: Grief as a Requisite for Change.

We find ourselves in a unique time in history with the confluence of a pandemic, global warming, and social chasms felt throughout the world. In this article, it is suggested that the grieving process is necessary for progress. The article addresses grief from a psychodynamic lens and progresses through the neurobiological changes that occur in the grieving process. The article discusses grief as both a result of and a necessary response to COVID-19, global warming, and social unrest. It is argued that grief is a vital process in order to fully change as a society and move forward. The role of psychiatry, and specifically psychodynamic psychiatry, is integral in paving the way to this new understanding and a new future.

Invisible wounds: Suturing the gap between the neurobiology, conventional and emerging therapies for posttraumatic stress disorder.

A sharp increase in the prevalence of neuropsychiatric disorders, including major depression, anxiety, substance use disorders and posttraumatic stress disorder (PTSD) has occurred due to the traumatic nature of the persisting COVID-19 global pandemic. PTSD is estimated to occur in up to 25% of individuals following exposure to acute or chronic trauma, and the pandemic has inflicted both forms of trauma on much of the population through both direct physiological attack as well as an inherent upheaval to our sense of safety. However, despite significant advances in our ability to define and apprehend the effects of traumatic events, the neurobiology and neuroanatomical circuitry of PTSD, one of the most severe consequences of traumatic exposure, remains poorly understood. Furthermore, the current psychotherapies or pharmacological options for treatment have limited efficacy, durability, and low adherence rates. Consequently, there is a great need to better understand the neurobiology and neuroanatomy of PTSD and develop novel therapies that extend beyond the current limited treatments. This review summarizes the neurobiological and neuroanatomical underpinnings of PTSD and discusses the conventional and emerging psychotherapies, pharmacological and combined psychopharmacological therapies, including the use of psychedelic-assisted psychotherapies and neuromodulatory interventions, for the improved treatment of PTSD and the potential for their wider applications in other neuropsychiatric disorders resulting from traumatic exposure.

Early experience unpredictability in child development as a model for understanding the impact of the COVID-19 pandemic: A translational neuroscience perspective.

Extensive evidence links adverse experiences during childhood to a wide range of negative consequences in biological, socioemotional, and cognitive development. Unpredictability is a core element underlying most forms of early adversity; it has been a focus of developmental research for many years and has been receiving increasing attention recently. In this article, we propose a conceptual model to describe how unpredictable and adverse early experiences affect children's neurobiological, behavioral, and psychological development in the context of the COVID-19 pandemic. We first highlight the critical role of unpredictability in child development by reviewing existing conceptual models of early adversity as they relate to subsequent development across the lifespan. Then, we employ a translational neuroscience framework to summarize the current animal- and human-based evidence on the neurobiological alterations induced by early experience unpredictability. We further argue that the COVID-19 pandemic serves as a global "natural experiment" that provides rare insight to the investigation of the negative developmental consequences of widespread, clustered, and unpredictable adverse events among children. We discuss how the pandemic helps advance the science of unpredictable early adverse experiences. As unpredictability research continues to grow, we highlight several directions for future studies and implications for policymaking and intervention practices.

Emerging Knowledge of the Neurobiology of COVID-19.

Many patients with COVID-19 will experience acute or longer-term neuropsychiatric complications. The neurobiological mechanisms behind these are beginning to emerge; however, the neurotropic hypothesis is not strongly supported by clinical data. The inflammatory response to SARS-CoV-2 is likely to be responsible for delirium and other common acute neuropsychiatric manifestations. Vascular abnormalities such as endotheliopathies contribute to stroke and cerebral microbleeds, with their attendant neuropsychiatric sequelae. Longer-term neuropsychiatric syndromes fall into 2 broad categories: neuropsychiatric deficits occurring after severe (hospitalized) COVID-19 and "long COVID," which occurs in many patients with a milder acute COVID-19 illness.

Real-time individual benefit from social interactions before and during the lockdown: the crucial role of personality, neurobiology and genes.

Social integration is a major resilience factor for staying healthy. However, the COVID-19-pandemic led to unprecedented restrictions in social life. The consequences of these social lockdowns on momentary well-being are yet not fully understood. We investigated the affective benefit from social interactions in a longitudinal birth cohort. We used two real-time, real-life ecological momentary assessments once before and once during the initial lockdown of the pandemic (N = 70 participants; n~6800 observations) capturing the protective role of social interactions on well-being. Moreover, we used a multimethod approach to analyze ecological assessment data with individual risk and resilience factors, which are promising moderators in the relationship of social behavior, stress reactivity, and affective states (i.e., amygdala volume, neuroticism, polygenic risk for schizophrenia). Social contacts were linked to higher positive affect both during normal times and during the COVID-19-pandemic (beta coefficient = 0.1035), highlighting the beneficial role of social embedding. Interestingly, this relationship was differentially moderated by individual risk and resilience factors. In detail, participants with a larger left amygdala volume (beta coefficient = -0.0793) and higher neuroticism (beta coefficient = -0.0958) exhibited an affective benefit from more social interactions prior to the pandemic. This pattern changed during the pandemic with participants with smaller amygdala volumes and lower neurotic traits showing an affective gain during the pandemic. Moreover, participants with low genetic risk for schizophrenia showed an affective benefit (beta coefficient = -0.0528) from social interactions irrespective of the time point. Our results highlight the protective role of social integration on momentary well-being. Thereby, we offer new insights into how this relationship is differently affected by a person's neurobiology, personality, and genes under adverse circumstances.

SnapShot: Neurobiology of opioid use disorder.

The use of opioid drugs and related overdose deaths, which rose to epidemic proportions over the past decade, have been exacerbated by the COVID pandemic, a time of great uncertainty and isolation. Much is known about opioid pharmacology and related neural circuits that, combined with novel emerging neurobiological insights, can help guide new treatment strategies. To view this SnapShot, open or download the PDF.

Gone with the Wind.

OBJECTIVE: If the narrative of "coronavirus" has an underlying theme, it may perhaps for some be one of survival, whilst for others, the theme might be suffering. The recurring motif of survival has continued throughout history, yet for the first time the sum of all fears has amounted to a run on the bare essentials. This paper seeks to offer an alternative formulation of "panic buying," with references to literature, philosophy, and contemporary neurobiology. CONCLUSION: The bare essentials disappeared perhaps as part of some self-fulfilling prophecy: the supermarkets became bare because others inadvertently lead us to believe they would become bare. The contagion model of emotional propagation provides a psychological model of how "panic buying" by an individual might lead to the replication of panic in an observer. The Polyvagal Theory further informs us of how the threat posed by the pandemic primes our limbic system to perceive danger, and explains how witnessing others engaging in fight-flight responses might evoke a fearful affect in an observer. In the end, it is perhaps through Nietzsche's study of classical tragedy that we may find some meaning to the pandemic, allowing our collective lived experience to serve as a template for growth.