Incidence rate of psychiatric disorders in 2020: The pivotal role played by SARS-CoV-2 infection.

IMPORTANCE: The Coronavirus Disease (COVID-19) pandemic has significantly impacted mental health outcomes. While the frequency of anxiety and depressive symptoms has increased in the whole population, the relationship between COVID-19 and new psychiatric diagnoses remains unclear. OBJECTIVE: To compare the population incidence rate of emergence of de novo psychiatric disorders in 2020 compared to the previous years, and to compare the incidence rate of new psychiatric disorder diagnoses between people with vs without COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This study utilized administrative claims data from the Clinformatics® Data Mart database, licensed from Optum®. The study is a cross-sectional analysis that compared the incidence rate of new psychiatric disorders in 2020 vs. 2018 and 2019 in the entire insured population database. Subsequently, the incidence of new psychiatric disorders in people with vs. without COVID-19 during 2020 was analyzed. EXPOSURE: The exposures included diagnosis and severity of COVID-19 infection. MAIN OUTCOMES MEASURES: The dependent variables of interest were the incidence rates of new psychiatric disorders, specifically schizophrenia spectrum disorders, mood disorders, anxiety disorders, and obsessive-compulsive disorder. RESULTS: The population studied included 10,463,672 US adults (mean age 52.83, 52% female) who were unique people for the year of 2020. Incidence of newly diagnosed psychiatric disorders per 1,000 individuals in the 2020 whole population were 28.81 (CI: 28.71, 28.92) for anxiety disorders, 1.04 (CI: 1.02, 1.06) for schizophrenia disorders, 0.42 (CI: 0.41, 0.43) for OCD and 28.85 (CI: 28.75, 28.95) for mood disorders. These rates were not significantly higher than 2018 or 2019. When comparing incidence rates between COVID-19 vs. non-COVID-19 populations in 2020, the rates were significantly higher in the COVID-19 population: 46.89 (CI: 46.24, 47.53) for anxiety, 49.31 (CI: 48.66, 49.97) for mood disorders, 0.57 (CI: 0.50, 0.65) for OCD, and 3.52 (CI: 3.34, 3.70) for schizophrenia. COVID-19 severity was significantly associated with new diagnoses of schizophrenia, anxiety and mood disorders in multivariate analyses. CONCLUSIONS: Compared to 2018 and 2019, in 2020 there was no increased incidence of new psychiatric disorders in the general population based on insurance claims data. Importantly, people with COVID-19 were more likely to be diagnosed with a new psychiatric disorder, most notably disorders with psychosis, indicating a potential association between COVID-19 and mental/brain health.

The role of lithium treatment on comorbid anxiety symptoms in patients with bipolar depression.

BACKGROUND: Comorbid anxiety is pervasive and carries an immense psychosocial burden for patients with bipolar disorder. Despite this, trials reporting anxiety-related outcomes in this population are uncommon, particularly with regards to monotherapies. METHODS: Patients (n = 31) with both bipolar I or II disorder in current depressive episodes were enrolled in a six-week, open-label, single-center trial assessing the efficacy of lithium monotherapy in treating symptoms depression and comorbid anxiety. Patients were mostly medication-free and lithium-naïve at baseline. RESULTS: Significant improvements in depression (HAMD) and anxiety (HAM-A) were observed at the six-week endpoint, with remission and response rates greater than 50%. There was a positive correlation between endpoint HAM-A scores and HAM-D scores, r = 0.80, (p < 0.01). Improvements were realized at low serum lithium concentrations (0.49 ± 0.20 mEq/L). LIMITATIONS: Lack of placebo control and small sample size warrants validation in larger randomized studies. CONCLUSIONS: Taken in the context of prior evidence, lithium may have an important role in treating comorbid anxiety in bipolar disorder, both as adjunct and monotherapy. Lower doses of lithium may provide equivalent efficacy and enhance tolerability and compliance.

Analysis of COVID-19 Infection and Mortality Among Patients With Psychiatric Disorders, 2020.

Importance: People with major psychiatric disorders are more likely to have comorbidities associated with worse outcomes of COVID-19. This fact alone could determine greater vulnerability of people with major psychiatric disorders to COVID-19. Objective: To assess the odds of testing positive for and mortality from COVID-19 among and between patients with schizophrenia, mood disorders, anxiety disorders and a reference group in a large national database. Design, Setting, and Participants: This cross-sectional study used an electronic health record data set aggregated from many national sources in the United States and licensed from Optum with current and historical data on patients tested for COVID-19 in 2020. Three psychiatric cohorts (patients with schizophrenia, mood disorders, or anxiety disorders) were compared with a reference group with no major psychiatric conditions. Statistical analysis was performed from March to April 2021. Exposure: The exposures observed include lab-confirmed positivity for COVID-19 and mortality. Main Outcomes and Measures: The odds of testing positive for COVID-19 in 2020 and the odds of death from COVID-19 were measured. Results: The population studied included 2 535 098 unique persons, 3350 with schizophrenia, 26 610 with mood disorders, and 18 550 with anxiety disorders. The mean (SD) age was 44 (23) years; 233 519 were non-Hispanic African American, 1 583 440 were non-Hispanic Caucasian; and 1 580 703 (62%) were female. The schizophrenia cohort (positivity rate: 9.86%; adjusted OR, 0.90 [95% CI, 0.84-0.97]) and the mood disorder cohort (positivity rate: 9.86%; adjusted OR, 0.93 [95% CI, 0.87-0.99]) had a significantly lower rate of positivity than the anxiety disorder cohort (positivity rate: 11.17%; adjusted OR, 1.05 [95% CI, 0.98-1.12) which was closer to the reference group (11.91%). After fully adjusting for demographic factors and comorbid conditions, patients with schizophrenia were nearly 4 times more likely to die from the disease than the reference group (OR, 3.74; 95% CI, 2.66-5.24). The mood disorders COVID-19 cohort had a 2.76 times greater odds of mortality than the reference group (OR, 2.76; 95% CI, 2.00-3.81), and the anxiety disorders cohort had a 2.39 times greater odds of mortality than the reference group (OR, 2.39; 95% CI, 1.68-3.27). Conclusions and Relevance: By examining a large database while controlling for multiple confounding factors such as age, race and ethnicity, and comorbid medical conditions, the present study found that patients with schizophrenia had much increased odds of mortality by COVID-19.

Apathy is not associated with a panel of biomarkers in older adults with HIV disease.

OBJECTIVE: Apathy is prevalent in HIV disease and can significantly impact personal well-being; however, little is known about its neurobiological substrates in persons with HIV (PWH) disease. METHODS: This cross-sectional, correlational study examined the association between apathy and several plasma biomarkers (tumor necrosis factor alpha, kynurenine, tryptophan, quinolinic acid, brain-derived neurotrophic factor, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau at position threonine 181) in 109 PWH and 30 seronegative participants ages 50 and older. Apathy was measured with a composite score derived from subscales of the Frontal Systems Behavior Scale and the Profile of Mood States. RESULTS: Multiple regressions showed that PWH had significantly greater severity of apathy symptoms, independent of both data-driven and conceptually-based covariates. Pairwise correlations in the PWH sample indicated that apathy was not significantly associated with any of the measured biomarkers and all of the effect sizes were small. CONCLUSION: Findings suggest that apathy is not strongly associated with peripheral biomarkers of inflammation, neurotrophic support, or neurodegeneration in older PWH. Limitations of this study include the cross-sectional design, the use of self-report measures of apathy, and low rates of viremia. Longitudinal studies in more representative samples of PWH that include a more comprehensive panel of fluid biomarkers, informant and behavioral indicators of apathy, and relevant psychosocial factors might help to further clarify the neurobiological substrates of this complex neuropsychiatric phenomenon.

Evaluating the Efficacy of Automated Smoking Treatment for People With HIV: Protocol for a Randomized Controlled Trial.

BACKGROUND: Smoking prevalence rates among people with HIV are nearly 3 times higher than those in the general population. Nevertheless, few smoking cessation trials targeting smokers with HIV have been reported in the literature. Efforts to develop and evaluate sustainable, low-cost, and evidence-based cessation interventions for people with HIV are needed. Given the widespread proliferation of mobile phones, the potential of using mobile health apps to improve the reach and efficacy of cessation interventions is promising, but evidence of efficacy is lacking, particularly among people with HIV. OBJECTIVE: This study will consist of a 2-group randomized controlled trial to evaluate a fully automated smartphone intervention for people with HIV seeking cessation treatment. METHODS: Participants (N=500) will be randomized to receive either standard treatment (ST; 250/500, 50%) or automated treatment (AT; 250/500, 50%). ST participants will be connected to the Florida Quitline and will receive nicotine replacement therapy in the form of transdermal patches and lozenges. This approach, referred to as Ask Advise Connect, was developed by our team and has been implemented in numerous health systems. ST will be compared with AT, a fully automated behavioral treatment approach. AT participants will receive nicotine replacement therapy and an interactive smartphone-based intervention that comprises individually tailored audiovisual and text content. The major goal is to determine whether AT performs better in terms of facilitating long-term smoking abstinence than the more resource-intensive ST approach. Our primary aim is to evaluate the efficacy of AT in facilitating smoking cessation among people with HIV. As a secondary aim, we will explore potential mediators and moderators and conduct economic evaluations to assess the cost and cost-effectiveness of AT compared with ST. RESULTS: The intervention content has been developed and finalized. Recruitment and enrollment will begin in the fall of 2021. CONCLUSIONS: There is a critical need for efficacious, cost-effective, and sustainable cessation treatments for people with HIV who smoke. The AT intervention was designed to help fill this need. If efficacy is established, the AT approach will be readily adoptable by HIV clinics and community-based organizations, and it will offer an efficient way to allocate limited public health resources to tobacco control interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05014282; https://clinicaltrials.gov/ct2/show/NCT05014282. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33183.

Pharmacogenomics of Lithium Response in Bipolar Disorder.

Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium's therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium's exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.

Brain-derived neurotrophic factor (BDNF) is associated with depressive symptoms in older adults with HIV disease.

Symptoms of depression are common among persons with HIV (PWH) and can have a significant impact on socioeconomic and personal well-being, but little is known about their neurobiological substrates in the context of HIV disease. This study examined the possible role of brain-derived neurotrophic factor (BDNF) in symptoms of depression and other aspects of mood in 109 PWH and 43 seronegative participants aged 50 and older. Participants completed the Profile of Mood States (POMS) which measured six dimensions of mood and was normatively adjusted for sex. A model controlling for medical comorbidities and substance use diagnoses among PWH showed a significant interaction between BDNF and POMS subscales. Planned post hoc analyses revealed that lower BDNF was only associated with higher scores on Depression-Dejection and Confusion-Bewilderment POMS subscales among PWH and at small-to-medium effect sizes. Lower levels of BDNF were associated with AIDS diagnoses and CD4 count, but not with viremia or duration of infection. BDNF levels did not differ between the PWH and HIV - samples, and there were no significant correlations between BDNF and any POMS variable in the HIV - group. Findings implicate BDNF in the neuropathophysiology of specific depressive symptoms in the context of HIV disease. Future studies may examine whether BDNF levels change over time, are sensitive to other aspects of mood disorders in HIV, and are associated with markers of HIV-associated neural injury.

Olanzapine-Induced Hyponatremia Presenting with Seizure Requiring Intensive Care Unit Admission.

Rapid-onset hyponatremia is a rare, but potential, complication of olanzapine treatment. Hyponatremia, secondary to atypical antipsychotic use, has been reported in many case reports and is thought to be associated with a syndrome of inappropriate anti-diuretic hormone secretion (SIADH). Psychogenic polydipsia is a separate cause of hyponatremia, which is also seen in the psychiatric population, particularly in schizophrenia, and must be differentiated from SIADH. We report a case of sudden-onset hyponatremia resulting in seizure onset necessitating intensive care unit admission in a patient taking olanzapine during hospitalization in a psychiatric unit. Clinicians should be aware of the association between olanzapine and hyponatremia secondary to SIADH or psychogenic polydipsia. As in our case, the patient status may decline rapidly, resulting in seizure onset. Physicians should actively monitor patients taking antipsychotics for changes in serum sodium levels.

Veterans Aging Cohort Study Index as a Marker of Bone Disease in HIV-Infected Patients.

People living with human immunodeficiency virus (HIV) infection have higher risk of low bone mineral density (BMD) and fragility fracture than general population. The aim of our retrospective study was to explore if HIV-specific Veterans Aging Cohort Study (VACS) Index and its specific components could help identify patients at risk for low BMD. A total of 195 HIV-infected patients with dual-energy X-ray absorptiometry (DXA) scan between 2007 and 2014 were included and DXA scan results were used to classify patients with osteopenia. VACS Index was calculated for all patients using laboratory values closest to the date of DXA scan. Logistic regression was used to assess the association between VACS Index score or individual components of VACS Index with the presence of low BMD after adjusting for confounding variables. A total of 109 (56%) patients were diagnosed with low BMD. VACS Index score was significantly associated with low BMD, with the odds of low BMD increasing 1.21 times for each 10 unit increase in VACS Index score [confidence interval (95% CI) 1.03-1.42; p = .02]. The two groups differed significantly on patient weights, proportion of white patients, and hepatitis C-coinfected patients. After adjusting for white race and weight, hepatitis C coinfection was significantly associated with increased risk of low BMD (odds ratio 24.4; 95% CI 7.45-80.16). VACS Index score, previously demonstrated to be a marker of frailty in HIV-infected patients, is significantly associated with risk of low BMD and could be used to develop a prediction tool to screen for low BMD in resource-limited setting where DXA scans are not easily available.

Impact of surgical intervention on seizure and psychiatric symptoms in patients with temporal lobe epilepsy.

Temporal lobe epilepsy (TLE), a common form of localisation-related epilepsy, is characterised by focal seizures and accompanied by variety of neuropsychiatric symptoms. This form of epilepsy proves difficult to manage as many anticonvulsant and psychotropic medications have little to no effect on controlling the seizure and neuropsychiatric symptoms respectively. The authors, report a patient with TLE and recurrent seizures that were refractory to multiple classes of antiepileptic therapy. Additionally, she exhibited psychosis, depression and irritability that required antipsychotic medication. After several years of poorly controlled seizure disorder, the patient underwent anterior temporal lobectomy and amygdalohippocampectomy, which proved beneficial for seizure control, as well as her neuropsychiatric symptoms. While it is common to treat refractory temporal lobe epilepsy with surgical interventions, there is little literature about it also treating the neuropsychiatric symptoms. This case underscores both the neurological and psychiatric benefits following surgical intervention for patients with TLE.

Disseminated histoplasmosis mimicking relapsed chronic lymphocytic leukaemia.

Histoplasma microconidia when inhaled are presented in antigenic form to T cells, limiting the extent of infection; however, defects in cellular immunity results in disseminated disease. Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disorder resulting in functionally impaired lymphocytes, predisposing patients to various opportunistic infections. The author reports a recently treated patient with CLL presenting with constitutional symptoms accompanied by hepatosplenomegaly and diffuse adenopathy. Considering the recent diagnosis and treatment of CLL, initial suspicion was relapsed disease. However, considering the immune deficiency associated with CLL and its treatment, infectious aetiologies were strongly considered. Further investigation revealed a case of disseminated histoplasmosis mimicking CLL in this reported patient. Considering appropriate diagnosis and timely therapy, the reported patient had good prognosis despite being diagnosed with disseminated histoplasmosis. This case highlights consideration of disseminated histoplasmosis in patients presenting with diffuse adenopathy along with hepatomegaly and/or splenomegaly in the right clinical setting.

Delay of alternative antiviral therapy and poor outcomes of acyclovir-resistant herpes simplex virus infections in recipients of allogeneic stem cell transplant - a retrospective study.

Acyclovir is commonly used to prevent and treat herpes simplex virus (HSV) reactivation after hematopoietic cell transplant (HCT), and only few reports have been published on acyclovir-resistant HSV in HCT recipients. We reviewed the medical records of patients with a microbiologic diagnosis of acyclovir-resistant HSV by plaque reduction test who received an HCT from 2002 through 2014. A total of 4 028 HCTs were performed during the study period, and 18 of the recipients met the diagnostic criteria for acyclovir-resistant HSV. All cases had undergone allogeneic HCTs. Most patients were in the pre-engraftment period or on systemic corticosteroid therapy for graft-versus-host disease (GVHD). The median time between diagnosis and susceptibility testing was 15 days, and antiviral therapy was changed at a median of 27 days. Patients required prolonged therapy (~80 days), and many had serious complications including renal failure and hospitalization. In conclusion, acyclovir-resistant HSV infection is more likely during the period of profound deficit in T-cell-mediated immunity and is associated with significant morbidities. Higher doses of acyclovir prophylaxis might be needed for patients with history of HSV during pre-engraftment or GVHD treatment. In patients who do not respond or progress after 1 week of acyclovir therapy, testing for drug-resistant HSV, and early switch to an alternative antiviral should be considered.

Baseline Neurocognitive Functioning Predicts Viral Load Suppression at 1-Year Follow-Up Among Newly Diagnosed HIV Infected Patients.

The current prospective observational study evaluated the impact of baseline neurocognitive impairment on future viral load suppression among antiretroviral medication naive persons newly diagnosed with HIV infection. We used the Montreal Cognitive Assessment (MoCA) score less than 26, to identify patients with neurocognitive deficits. Of the 138 patients enrolled; virologic suppression was seen in 61% of the participants, while 72% of the participants had a MoCA score less than 26 at baseline. Variables significantly associated with low MoCA score included higher age (p < 0.01) and presence of depression (p < 0.01). After adjusting for these variables, MoCA score less than 26 was significantly associated with a higher risk of failing achieve viral load suppression (adjusted OR 2.7; 95% CI 1.09-6.69). Baseline neurocognitive deficit as measured by MoCA was associated with a higher risk for failing to achieve viral load suppression at one-year follow-up.

Diagnostic approach in persistent Staphylococcus aureus bacteraemia.

Staphylococcus aureus is the leading cause of bacteraemia and can lead to complicated infections that may be difficult to diagnose and hence lead to higher morbidity. Failure to identify such could lead to severe complications or relapsing bacteraemia due to inadequate treatment. The authors report a patient presenting with methicillin-resistant S. aureus (MRSA) bacteraemia and septic arthritis, who developed a complicated infection with multiple metastasis and persistent bacteraemia despite adequate treatment. A fluorodeoxyglucose (FDG)-positron emission tomography scan 2 weeks after the initial presentation identified a linear area of intense FDG uptake within the right upper extremity which raised suspicion for an infected thrombus within the right cephalic vein. Adequate treatment of the infected thrombus helped resolve the patient's persistent MRSA bacteraemia and complicated infection. This case highlights the importance of considering suppurative thrombophlebitis in the setting of persistent bacteraemia and metastatic infections due to MRSA.

Antiviral therapy for respiratory viral infections in immunocompromised patients.

INTRODUCTION: Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed.

Fulminant hepatic failure secondary to acyclovir-resistant herpes simplex virus.

Liver failure is a frequent and serious complication that causes morbidity and mortality in haematopoietic stem cell transplantation (HCT) recipients. Liver dysfunction in these patients can be related to infectious causes, most common viral hepatitis. We report a case of disseminated acyclovir-resistant herpes simplex virus (HSV) infection following HCT that led to acute liver failure and death. Although rare, HSV hepatitis leads to high morbidity and mortality and should be considered in the differential diagnosis of HCT recipients with marked elevation of hepatic transaminase. Acyclovir is a first-line therapy for HSV infection; however, acyclovir-resistant viral strains should be considered and alternative HSV therapies given in HCT recipients whose HSV infection does not improve on acyclovir therapy.