Molecular and immunological origins of catatonia.

Catatonia occurs secondary to both primary psychiatric and neuromedical etiologies. Emerging evidence suggests possible linkages between causes of catatonia and neuroinflammation. These include obvious infectious and inflammatory etiologies, common neuromedical illnesses such as delirium, and psychiatric entities such as depression and autism-spectrum disorders. Symptoms of sickness behavior, thought to be a downstream effect of the cytokine response, are common in many of these etiologies and overlap significantly with symptoms of catatonia. Furthermore, there are syndromes that overlap with catatonia that some would consider variants, including neuroleptic malignant syndrome (NMS) and akinetic mutism, which may also have neuroinflammatory underpinnings. Low serum iron, a common finding in NMS and malignant catatonia, may be caused by the acute phase response. Cellular hits involving either pathogen-associated molecular patterns (PAMP) danger signals or the damage-associated molecular patterns (DAMP) danger signals of severe psychosocial stress may set the stage for a common pathway immunoactivation state that could lower the threshold for a catatonic state in susceptible individuals. Immunoactivation leading to dysfunction in the anterior cingulate cortex (ACC)/mid-cingulate cortex (MCC)/medial prefrontal cortex (mPFC)/paralimbic cortico-striato-thalamo-cortical (CSTC) circuit, involved in motivation and movement, may be particularly important in generating the motor and behavioral symptoms of catatonia.

Neurocircuitry Hypothesis and Clinical Experience in Treating Neuropsychiatric Symptoms of Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2.

Persistent symptoms following COVID-19 infection have been termed postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. Many of these symptoms are neuropsychiatric, such as inattention, impaired memory, and executive dysfunction; these are often colloquially termed "brain fog". These symptoms are common and often persist long after the acute phase. The pattern of these deficits combined with laboratory, neuroimaging, electroencephalographic, and neuropsychological data suggest that these symptoms may be driven by direct and indirect damage to the frontal-subcortical neural networks. Here, we review this evidence, share our clinical experience at an academic medical center, and discuss potential treatment implications. While the exact etiology remains unknown, a neurocircuit-informed understanding of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection can help guide pharmacology, neuromodulation, and physical and psychological therapeutic approaches.

Post-Acute Sequelae of SARS-CoV-2 Infection: A Descriptive Clinical Study.

OBJECTIVE: The investigators aimed to describe the clinical experience of a single center reporting on neuropsychiatric findings among patients experiencing persistent symptoms as part of post-acute sequelae of SARS-CoV-2 (PASC) infection. METHODS: Data were collected retrospectively (between February 2020 and May 2021) from a cohort (N=100) within a COVID-19 survivors study of patients with persistent symptoms enrolled after a short inpatient stay or who had been outpatients never hospitalized. Patients without confirmatory positive PCR or antibody diagnostic test results were grouped separately as presumptive cases (N=13). RESULTS: Of the 87 patients with confirmed SARS-CoV-2, 63 (72.4%) were female, and 65 (74.7%) were White. The mean age was 49.2 years (SD=14.9). The most prevalent symptoms after COVID-19 infection were fatigue, "brain fog," headache, anxiety, and sleep issues. Attention and executive function were frequently impaired. The mean Montreal Cognitive Assessment score was 26.0 (SD=2.8). Concentration and attention as well as memory issues were both significantly correlated with the complaint of brain fog. CONCLUSIONS: These preliminary findings suggest that post-acute sequelae of SARS-CoV-2 vary in frequency and duration with relation to premorbid history and that these conditions affect functional domains and patients' ability to return to work. Longitudinal research with larger cohorts is needed to characterize PASC and to optimize care, especially for vulnerable populations.

Akinetic Mutism and Coronavirus Disease 2019: A Narrative Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with neuropsychiatric complications ranging from new-onset psychosis to delirium, dysexecutive syndromes, catatonia, and akinetic mutism (AM). AM can be conceptualized as a disorder of motivation wherein patients exhibit a loss of speech and spontaneous movement, owing to disruption of underlying frontal-subcortical circuits. OBJECTIVES: The objectives of this study were to review the concept and differential diagnosis of AM, as well as the clinical literature on AM in COVID-19 and discuss potential implications for underlying functional neuroanatomy and mechanistic pathways, as well as clinical management. METHODS: A narrative literature review was performed using PubMed querying published articles for topics associated with AM and its occurrence in COVID-19. RESULTS: AM has been described in case reports and a prospective cohort study of patients with COVID with neurological complaints. Three COVID-19 AM subgroups can be distinguished, including individuals with severe respiratory illness, those with meningoencephalitis, and those with delirium and pre-existing neuropsychiatric illness. Electrophysiology and functional imaging suggest COVID-19 AM may result from underlying frontal lobe dysfunction and disruption of associated distributed circuits subserving goal-directed behavior. Distinctive combinations of pathophysiological mechanisms may be at play in the different subgroups of COVID-19 AM cases. CONCLUSION: AM has been described in association with COVID-19 and may manifest in clinically heterogenous subgroups with distinct underlying mechanisms. The diagnosis of AM and evaluation of potential etiologies can be complex. The occurrence of AM contributes evidence to the hypothesis of frontal lobe dysfunction in COVID-19.

What Counts As 'Safe?': Exposure To Trauma And Violence Among Asylum Seekers From The Northern Triangle.

In 2019 the United States signed Asylum Cooperative Agreements with the Northern Triangle countries of El Salvador, Guatemala, and Honduras, in Central America. In November 2019 the Trump administration announced that these agreements would be used to permit the expedited removal of asylum seekers from the US, claiming that these countries provided comprehensive legal procedures for adjudicating asylum claims and protection against further persecution. To assess the presence of dangerous conditions in the three countries, we examined forensic medical evaluations of asylum seekers from the Northern Triangle who are in the US and who presented to an academic medical center asylum clinic in Boston, Massachusetts, from 2017 to 2020. Northern Triangle asylum seekers reported high rates of exposure to trauma and violence, including gender-based violence and violence perpetrated by gangs, and they also exhibited a high prevalence of trauma-related psychiatric disorders. Asylum seekers also reported state actors in Northern Triangle countries as perpetrators of violence and described denial of protection from the state when it was solicited. These findings cast doubt on key tenets underpinning the legal basis for the Asylum Cooperative Agreements. The agreements should be formally terminated and investigations undertaken to determine the impact on people who were subject to removal from the US during preliminary implementation.

Neurocovid: Pharmacological Recommendations for Delirium Associated With COVID-19.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified. OBJECTIVE: In this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. METHODS: We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. RESULTS: Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. CONCLUSIONS: COVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.

Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement.

INTRODUCTION: Neuropsychiatric manifestations of the coronavirus disease 2019 (COVID-19) have been described, including anosmia, ageusia, headache, paresthesia, encephalitis and encephalopathy. Little is known about the mechanisms by which the virus causes central nervous system (CNS) symptoms, and therefore little guidance is available regarding potential workup or management options. CASES: We present a series of four consecutive cases, seen by our psychiatry consultation service over a one-week period, each of which manifested delirium as a result of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). DISCUSSION: The four cases highlighted here all occurred in older patients with premorbid evidence of cognitive decline. Unique features seen in multiple cases included rigidity, alogia, abulia, and elevated inflammatory markers. In all four cases, a change in mental status was the presenting symptom, and three of the four cases lacked significant respiratory symptoms. In addition to discussing unique features of the cases, we discuss possible pathophysiologic explanations for COVID-19 delirium. CONCLUSIONS: Delirium should be recognized as a potential feature of infection with SARS-CoV-2 and may be the only presenting symptom. Based on the high rates of delirium demonstrated in prior studies, hospitals should consider adding mental status changes to the list of testing criteria. Further research is needed to determine if delirium in COVID-19 represents a primary encephalopathy heralding invasion of the CNS by the virus, or a secondary encephalopathy related to systemic inflammatory response or other factors.

Stigma, Partners, Providers and Costs: Potential Barriers to PrEP Uptake among US Women.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) use has remained low among US women while significantly increasing among men who have sex with men. Besides lack of awareness, women face several social and structural barriers in gaining access to and using PrEP. METHODS: Four focus group discussions with 20 HIV-negative women who live in the Washington DC metropolitan area. RESULTS: The women expressed concerns about social and structural barriers to PrEP use. They were afraid that stigma related to using "HIV medicines" could affect PrEP use as well. They are worried that family and friends may question their reasons for taking anti-retrovirals and suspect that they were HIV-positive. They expected hostile reactions from male partners, including accusations of infidelity and introducing mistrust in their relationships. Communicating with health care providers about sexual matters in general and their need for PrEP in particular were identified as further barriers. Women reported that providers rarely ask about risk behaviors related to HIV acquisition; that short visits hinder establishing a trusting relationship to discuss sensitive matters. They were concerned that disclosure of risk behaviors may result in judgmental responses and harsh treatment from providers. Lastly, women were concerned that PrEP costs, including insurance coverage and copays, would keep PrEP out of their reach. While cognizant of the potential barriers, women were unwavering in their determination to find ways to circumvent challenges to PrEP access. CONCLUSION: Social and structural barriers may impede women's access to PrEP despite their own reported interest. Continued efforts to reduce HIV stigma, improve patient-provider relationships and ensure affordability of PrEP may increase the likelihood that women will use this important prevention modality.

Women want Pre-Exposure Prophylaxis but are Advised Against it by Their HIV-positive Counterparts.

OBJECTIVES: The latest advancement in HIV prevention, Pre-Exposure Prophylaxis (PrEP), could reduce incidence among women. However, PrEP uptake has remained low among US women since its approval in 2012, while use has increased among men who have sex with men. This study addresses women's knowledge, attitudes and potential behaviors regarding PrEP. While HIV-negative women are the potential users of antiretroviral (ARV) medications for PrEP, HIV-positive women who have used ARVs could contribute immensely to our understanding of the complexities related to taking such medications. This study is the first to synthesize the opinions of both groups of women. METHODS: We conducted eight focus group discussions, segregated by sero-status; four with at-risk HIV-negative (20) and four with HIV-positive (19) women in Washington DC during 2014. Topics discussed include PrEP awareness, likelihood of use, barriers and target populations. RESULTS: PrEP awareness was almost non-existent and the HIV-negative women urged publicity. They expressed much enthusiasm about PrEP and wanted to use and recommend it to others despite recognizing potential complexities related to taking PrEP, such as side effects, access, duration and frequency of use. HIV-positive women were less supportive of PrEP for those same reasons based on their experience with taking ARVs. They preferred condoms over PrEP given relative efficacy, affordability, accessibility, and prevention of other STIs. CONCLUSIONS: There is an urgent need for PrEP public health campaigns catered to the needs and concerns of women, most importantly bolster their awareness of PrEP.