Neuropsychiatric Manifestations of Antiphospholipid Syndrome—A Narrative Review

Antiphospholipid syndrome (APS) is a common autoimmune pro-thrombotic condition characterised by thrombosis and pregnancy morbidity. There are a broad range of neuropsychiatric manifestations associated with APS, from focal symptoms to more global dysfunction. Patients commonly present with transient ischaemic attacks and ischaemic strokes, with identifiable lesions on brain imaging. However, the underlying pathogenesis remains uncertain in other manifestations, such as cognitive dysfunction, seizures, headache and chorea. The aim is to provide a comprehensive review of the various neuropsychiatric manifestations associated with APS. A detailed literature search was applied to PubMed, including citations from 1983 to December 2021.

Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

Thyroid hormones (TH) have a cardinal role in the development of the central nervous system during embryogenesis and early infancy. However, the TH responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems. Cognitive decline, dysphoria and depression are common manifestations of overt hypothyroidism while hyperthyroidism can cause agitation, acute psychosis and apathy especially in older people. Whereas levothyroxine treatment can reverse dementia in the setting of hypothyroidism, the effect of levothyroxine on depressive symptoms in subjects with subclinical hypothyroidism is controversial. The use of supraphysiologic doses of TH to treat depression refractory to antidepressant remains a viable therapeutic tool with the caveat that excessive doses of thyroid hormone to treat depression may have potentially damaging effects on other organ systems. The present communication describes the pathophysiology of neuropsychiatric manifestations of thyroid disease including changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier dysfunction, increased risk of cerebrovascular disease and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease. Elucidating the molecular mechanisms of TH effect on cerebral tissue will help identify novel therapeutic targets for managing people with neuropsychiatric disorders.

Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19

: The incidence of infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for coronavirus disease 2019 (COVID-19), has dramatically escalated following the initial outbreak in China in late 2019, resulting in a global pandemic with millions of deaths. Although the majority of infected patients survive, and the rapid advent and deployment of vaccines have afforded increased immunity against SARS-CoV-2, long term sequelae of SARS-CoV-2 infection have become increasingly recognized. These include, but are not limited to, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurological dysfunction that may lead to psychological and neurocognitive impairment. A major component of cognitive dysfunction is operationally categorized as “brain fog” which comprises difficulty with concentration, forgetfulness, confusion, depression, and fatigue. Multiple parameters associated with long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinical studies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations of COVID-19 are by nature complex, but broad based working models have focused on mitochondrial dysregulation leading to systemic reductions of metabolic activity and cellular bioenergetics within CNS structures. Multiple factors underlying the expression of brain fog may facilitate future pathogenic insults leading to repetitive cycles of viral and bacterial propagation. Interestingly, diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observed in other historical pandemics, thereby providing a broad and integrative perspective on potential common mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health status may be reciprocally linked to compromised immune processes and enhanced susceptibility to infection by diverse pathogens. By extrapolation, we contend that COVID-19 may potentiate the severity of neurological/neurocognitive deficits in patients afflicted by well-studied neurodegenerative disorders such as Alzheimer's disease and Parkinson’s disease. Accordingly, the prevention, diagnosis, and management of sustained neuropsychiatric manifestations of COVID-19 are pivotal health care directives and provide a compelling rationale for careful monitoring of infected patients, as early mitigation efforts may reduce short- and long-term complications.

Anabolic-Androgenic Steroid Misuse: Mechanisms, Patterns of Misuse, User Typology, and Adverse Effects

Anabolic-androgenic steroids (AAS) encompass a broad group of natural and synthetic androgens. AAS misuse is highly prevalent on a global scale, with the lifetime prevalence of AAS misuse in males being estimated to be around 6%, with 15 to 25% of male gym attendees using it at any one time. AAS are associated with sudden cardiac death, neuropsychiatric manifestations, and infertility. The average AAS user is unlikely to voluntarily declare their usage to a physician, with around 1 in 10 actively engaging in unsafe injection techniques. The aim of this paper is to review the current evidence base on AAS with emphasis on mechanisms of action, adverse effects, and user profiles that are most likely to engage in AAS misuse. This paper also reviews terminologies and uses methods specific to the AAS user community.

Vascular Brain Disease in Geriatric Neuropsychiatry

Vascular brain diseases are a significant cause of dementia, and their presence, alone or associated with degenerative conditions, increases the risk of conversion to progressive cognitive decline. Neuropsychiatric manifestations vary according to the affected brain territory and disrupted neuronal circuits. In the current chapter, epidemiological prevalence, the harmonization of the diagnostic criteria of vascular subtypes, and the impact of age and socio-demographic aspects are critically reviewed. Another explored topic refers to the diagnostic and therapeutic approach. Structural imaging, including magnetic resonance (MRI) and computer tomography (CT), and a thorough neuropsychological and clinical exam, may help establish the differential diagnosis and substantially impact clinical evolution. Treatment involves various strategies, including controlling cardiovascular and metabolic risk factors, such as hypertension, atrial fibrillation, cardiopathies, and adopting a healthy lifestyle. Treatment relies on preventive and health promotion strategies related to the timely control of vascular risk factors and symptomatic approaches. The use of acetylcholinesterase inhibitors aims at stabilizing symptoms and is recommended in all stages of dementia.

Delirium and other neuropsychiatric manifestations of COVID-19 infection in people with preexisting psychiatric disorders: a systematic review

Background Psychiatric disorders increase risk of neuropsychiatric disease and poor outcomes, yet little is known about the neuropsychiatric manifestations of COVID-19 in the psychiatric population. The primary objective is to synthesize neuropsychiatric outcomes of COVID-19 in people with preexisting psychiatric disorders. Methods Data were collected during an ongoing review of the impact of pandemics on people with existing psychiatric disorders. All study designs and gray literature were included. Medline, PsychInfo, CINAHL, EMBASE, and MedRx were searched from inception to September 1 2020. Risk of bias was assessed using a published tool that can accommodate all study types. Two independent authors screened the studies and extracted data. Data were narratively synthesized, as there were insufficient data to meta-analyze. Evidence was appraised according to GRADE. Results Four case reports were included, comprising 13 participants from three countries. Many large-sample, relevant papers were omitted for not reporting psychiatric history, despite reporting other comorbidities. Included participants (n = 13) were hospitalized with COVID-19 and appeared to meet criteria for delirium. Myoclonus, rigidity, and alogia were also reported. The most commonly reported preexisting psychiatric diagnoses were mood disorders, schizophrenia, and alcohol use disorder. Conclusions People with preexisting psychiatric disorders may experience delirium, rigidity, myoclonus, and alogia during COVID-19 infection; although higher quality and longitudinal data are needed to better understand these phenomena. Relevant COVID-19 literature does not always report psychiatric history, despite heightened neuropsychiatric vulnerability within this population. Trial Registration: PROSPERO (CRD42020179611).

A CASE OF NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS (NPSLE) PRESENTED WITH NEGATIVE SYMPTOMS OF SCHIZOPHRENIA

Systemic lupus erythematosus is an autoimmune chronic inflammatory disorder affecting connective tissues of body organs. It is more common in female. Neuropsychiatric manifestations like headache, cerebrovascular events like stroke, seizures, psychosis, cognitive impairment, which is termed as neuropsychiatric systemic lupus erythematosus 1,2,3 (NPSLE)

CXCL13 Neutralization Attenuates Neuropsychiatric Manifestations in Lupus-Prone Mice

Neuropsychiatric lupus (NPSLE), the nervous system presentation of systemic lupus erythematosus (SLE), remains challenging to treat due to its unclear pathogenesis and lack of available targeted therapies. A potential contributor to disease progression is brain tertiary lymphoid structures (TLS); these ectopic lymphoid follicles that can develop tissue-targeted antibodies have recently been described in the MRL/lpr lupus mouse strain, a classic model for studying NPSLE. The brains of MRL/lpr mice show a significant increase of CXCL13, an important chemokine in lymphoid follicle formation and retention that may also play a role in the disease progression of NPSLE. The aim of the present study was to inhibit CXCL13 and examine the effect of this intervention on lymphoid formation and the development of neurobehavioral manifestations in lupus mice. Female MRL/lpr mice were injected with an anti-CXCL13 antibody, an IgG1 isotype-matched antibody, or PBS either three times a week for 12 weeks intraperitoneally (IP) starting at 6-8 weeks of age, or continuously intracerebroventricularly (ICV) with an osmotic pump over a two-week period starting at 15 weeks of age. Cognitive dysfunction and depression-like behavior were assessed at the end of treatment. When treatment was delivered IP, anti-CXCL13 treated mice showed significant improvement in cognitive function when compared to control treated mice. Depression-like behavior was attenuated as well. Furthermore, mice that received anti-CXCL13 by the ICV route showed similar beneficial effects. However, the extent of lymphocyte infiltration into the brain and the general composition of the aggregates were not substantively changed by anti-CXCL13 irrespective of the mode of administration. Nevertheless, analysis of brain gene expression in anti-CXCL13 treated mice showed significant differences in key immunological and neuro-inflammatory pathways that most likely explained the improvement in the behavioral phenotype. Our results indicate that CXCL13 affects the behavioral manifestations in the MRL/lpr strain and is important to the pathogenesis of murine NPSLE, suggesting it as a potential therapeutic target.