OBJECTIVE:A variety of diseases can cause both psychosis and myelin changes that manifest as white matter hyperintensities on T2-weighted magnetic resonance imaging of the brain. Although many of the acquired conditions relevant to this discussion are widely recognized by psychiatrists and other physicians, a number of lesser-known rare genetic disorders also deserve consideration in this context. As such, this review sought to summarize the phenotypic features, brain imaging abnormalities, and approach to diagnosing the most common leukodystrophies and other genetic leukoencephalopathies that can cause psychosis. METHODS:This is a narrative review. The most common leukodystrophies that can cause both psychosis and white matter hyperintensities are first reviewed, followed by a variety of other rarer leukodystrophies and related genetic disorders. Suggestive clinical features, workup recommendations, and potential clinical implications are subsequently discussed. RESULTS:Although the psychotic symptoms that occur in these disorders might phenomenologically resemble those typical of schizophrenia, the identification of any "red flag" neurological features, idiosyncratic medical comorbidities, additional brain imaging abnormalities, parental consanguinity, or a mendelian pattern of inheritance, should prompt consideration for an underlying genetic explanation. Making a correct diagnosis in this context is critical, given the numerous potential clinical implications, including with respect to treatment decisions. CONCLUSION:While psychiatrists are not expected to be experts in this area, at a minimum they should have a basic familiarity with the genetic disorders that are most likely to cause both psychosis and white matter hyperintensities, given the relatively frequent occurrence of this clinical scenario.
OBJECTIVE:Neurocognitive disorders (NCDs), which include delirium, major and mild NCDs such as Alzheimer's disease (AD), and other forms of dementia, constitute a significant and growing public health burden, affecting tens of millions of individuals worldwide. This systematic review aims to examine the medications approved by the United States Food and Drug Administration (FDA) for NCDs from 2008 to 2024, as well as those in the pipeline in Phase III, and to describe the mechanism of action, clinical indications, dosing, evidence for efficacy, and adverse effects. METHODS:We searched the literature using the PubMed database for studies published from January 1, 2008, to December 31, 2024, focusing on FDA-approved psychiatric medications and Phase III pipeline medications, using the keywords "neurocognitive" OR "dementia" OR "Alzheimer*" AND "psychopharm*" OR "medic*" OR "pharm*." Two reviewers performed an independent assessment of the resulting publications and reached a consensus on the eligible studies to include in the systematic review. RESULTS:From 2008 to 2024, the FDA approved eight medications for major and mild NCDs, including monoclonal antibodies, acetylcholinesterase inhibitors, N-methyl-D-aspartate (NMDA) receptor antagonists, and an atypical antipsychotic. Additionally, we identified 22 pipeline medications currently in Phase III clinical trials for NCDs as of December 31, 2024, including biologics and neuroprotective agents, among others. No medications for delirium were FDA-approved or in Phase III, although agents for a variety of encephalopathies have been developed. CONCLUSION:Significant advancements in the pharmacological management of NCDs have been made during this period, including developing disease-modifying therapies for AD. However, available medications primarily provide symptomatic relief, and challenges persist in the implementation of disease-modifying treatments due to adverse effects and high costs of care. The pipeline of Phase III clinical trials includes many emerging agents with novel mechanisms of action, and ongoing trials will prove essential to confirm the efficacy and safety of these therapies.
Decision-making capacity (DMC) is a core element of ethical and effective clinical care, ensuring that patients can understand, appreciate, reason through, and communicate informed choices about treatment. Accurate assessment of DMC is essential in psychiatric settings, where serious mental illness (SMI) may affect cognition, insight, or judgment, yet does not inherently imply incapacity. This paper examines how implicit, racial, and cognitive biases can influence DMC evaluations and contribute to disparities, particularly for Black and Hispanic patients with SMI. Diagnostic overshadowing, assumptions about insight, and misinterpretation of culturally influenced communication may lead to incorrect determinations of incapacity and undermine patient autonomy. Evidence indicates that while cognitive impairment is a significant contributor to reduced DMC, many individuals with SMI retain the ability to make reasoned treatment decisions. Standardized tools-such as the MacArthur Competence Assessment Tool and related instruments-can improve reliability and mitigate subjective judgment, though current measures lack explicit integration of cultural and racial considerations. This paper highlights strategies to reduce bias in DMC assessments, including clinician education, development of culturally informed protocols, interdisciplinary decision-making, and expanded access to advocacy resources. These efforts support equitable, accurate, and ethically grounded evaluation of patient capacity across diverse clinical populations.
BACKGROUND:Cognitive Assessment Tool for Pediatric Clinical Research (CAT-PCR) is a new brief nonverbal test battery validated in a Zambian school-aged population. CAT-PCR involves the standardized administration of two tests, WAVES and SYMBOLS. CAT-PCR provides measures of visuomotor processing (VMP) and visuographomotor constructional processing (VGCP). The psychometric properties of CAT-PCR were evaluated in a field trial complemented with an ancillary test-retest study. RESULTS:Four-hundred-twenty children, aged 5 to 17 years, 51.2 percent female, speaking Bemba (81.1%), English (72.6 %), Nyanja (22.8%), Tonga (1.9%), and Lozi (1.2%), were recruited at multiple Zambian clinical sites and schools. Children able to speak one, two, and three or more languages composed 23.5, 10.0, and 66.5 percent of participants, respectively. CAT-PCR detected differences in cognitive performance between two comparable subgroups of children with or without conditions associated with increased risk for cognitive impairment. The poorer health group composition reflected a spectrum of conditions such as chronic neurologic or medical diseases (ie, epilepsy, human immunodeficiency virus/acquired immunodeficiency syndrome [HIV/AIDS], recurrent malaria, sickle cell disease, and other cardiac and metabolic conditions) or prolonged exposure to psychosocial stress and deprivation. The reliability was satisfactory. The intraclass correlation coefficient (95% confidence interval) at test-retest at 48 hours (n=86) was 0.85 (0.78, 0.91) for VGCP Index and 0.84 (0.76, 0.90) for VMP Index. CONCLUSION:Study findings support the reliability, validity, and utility of CAT-PCR measures in evaluating the effect of health-related risks on the child's cognitive functioning and development. Further research should address the validity of CAT-PCR in response prediction, monitoring, and evaluation of health-promoting interventions.
OBJECTIVE:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a wide range of neurological symptoms and neuropsychiatric conditions. SARS-CoV-2 shows various degrees of neurotropism. SARS-CoV-2 primarily targets respiratory and gastrointestinal tracts; however, it can affect other organs. Neurological and neuropsychological manifestations of COVID-19 have been reported. Several mechanisms are involved in these manifestations in COVID-19. Therefore, the present narrative review will take account of mechanisms underlying the neurological and neuropsychological manifestations in COVID-19. METHODS:A literature search for relevant articles in different databases was made with a focus on recent publications for this narrative review. RESULTS:Inflammation and thrombosis have been suggested to be mechanisms contributing to these manifestations. Also, renin-angiotensin system (RAS), transmembrane serine protease 2 (TMPRSS2), cathepsin B and L, furin, neuropilin-1 (NRP1), and sterile alpha motif and HD domain-containing protein 1 (SAMHD1) have been proposed to be involved in pathogenesis of SARS-CoV-2. Moreover, cluster of differentiation 147 (CD147) and dipeptidyl peptidase 4 (DPP4) have been suggested to have a role in SARS-CoV-2 entry into the central nervous system (CNS). CONCLUSION:Further investigation on the underlying mechanisms leading to SARS-CoV-2-associated neurological and neuropsychological manifestations is pivotal. Insights into these mechanisms will help the treatment strategies for patients with COVID-19 and such manifestations.
