Development of Schizophrenia in a Genetically Predisposed Individual Following COVID-19

We present a patient who is a 56-year-old female with a psychiatric history of anxiety disorder and a medical history of hypercholesterolemia and hyperthyroidism, who was admitted to the hospital after a witnessed seizure at an inpatient psychiatric facility. This patient’s family history is significant for her mother experiencing unspecified psychotic disorder that required psychiatric hospitalization. Our patient was first admitted to the psychiatric hospital after exhibiting worsening paranoid delusions and hallucinations that began several months prior. The patient had reportedly begun locking herself in the restroom and screaming “get out, they’re spying on me”, referring to her next-door neighbors whom she began exhibiting paranoia towards upon discharge from her hospital stay for COVID-19. At first, the patient believed her neighbors were “too noisy” during their home renovations, and more recently believed they were infiltrating her mind with “radio waves”. While in the hospital, we increased the dosage of Quetiapine that she was receiving at the inpatient psychiatric facility. To enhance a supportive environment at home, psychoeducation regarding her presentation and management was provided to her nephew. After stabilizing her medical conditions, the patient was discharged back to the inpatient psychiatric facility where she was originally admitted involuntarily. The dual hit hypothesis denotes the significance of genetic vulnerability compounded by environmental factors in the pathogenesis of schizophrenia. Our patient has a genetic predisposition to psychotic disorders based on her mother’s psychiatric history. She later developed a severe case of COVID-19 infection that required ICU-level of care, which has likely served as the environmental insult that instigated the development of a psychotic syndrome. COVID-19 has been shown in recent studies to trigger an inflammatory response and alter the biochemical profile in the nervous system. The long-term and downstream effects of COVID infection, which may include long COVID and psychosis, remain a topic of intense research interest. In the case of our patient, her genetic predisposition to psychosis, coupled with COVID-19 infection, has led to the development of schizophrenia in accordance with the dual hit hypothesis. We are hopeful that further investigation into the relationship between COVID-19 infection and the development of primary psychotic disorders will yield further insights into the pathogenesis of psychosis and post-COVID psychiatric symptoms

Case Series: Continued Remission of PTSD Symptoms After Discontinuation of Prazosin

Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which is prescribed off-label for flashbacks and nightmares due to trauma, is often continued indefinitely due to reports of symptoms returning upon discontinuation. There is no standard guidance for a trial of discontinuation of prazosin due to intolerance or side effects. In this case series, three patients are started on prazosin leading to remission of trauma-related symptoms, and symptoms continue to remit after treatment for an average of about 2 years followed by discontinuation of the medication. There are many similarities in these case reports which serve to provide guidance as to when a trial of prazosin discontinuation may be warranted

Multi-institution analysis of racial disparity among African- American men eligible for prostate cancer active surveillance

There is a significant controversy on whether race should be a factor in considering active surveillance for low-risk prostate cancer. To address this question, we analyzed a multi-institution database to assess racial disparity between African-American and White-American men with low risk prostate cancer who were eligible for active surveillance but underwent radical prostatectomy. A retrospective analysis of prospectively collected clinical, pathologic and oncologic outcomes of men with low-risk prostate cancer from seven tertiary care institutions that underwent radical prostatectomy from 2003–2014 were used to assess potential racial disparity. Of the 333 (14.8%) African-American and 1923 (85.2%) White-American men meeting active surveillance criteria, African-American men were found to be slightly younger (57.5 vs 58.5 years old; p = 0.01) and have higher BMI (29.3 v 27.9; p \u3c 0.01), pre-op PSA (5.2 v 4.7; p \u3c 0.01), and maximum percentage cancer on biopsy (15.1% v 13.6%; p \u3c 0.01) compared to White-American men. Univariate and multivariate analysis demonstrated similar rates of upgrading, upstaging, positive surgical margin, and biochemical recurrence between races. These results suggest that single institution studies recommending more stringent AS enrollment criteria for AA men with a low-risk prostate cancer may not capture the complete oncologic landscape due to institutional variability in cancer outcomes. Since all seven institutions demonstrated no significant racial disparity, current active surveillance eligibility should not be modified based upon race until a prospective study has been completed. © Dinizo et al

Research Article

Background. Elucidation of a pathogen's antimicrobial susceptibility requires subculture after the organism is first isolated. This takes several days, requiring patients to be treated with broad-spectrum antibiotics. This approach contributes to the development of bacterial resistance. Methods. Microtiter wells were coated with a polyclonal antibody targeting the pathogen of interest. Bacterial suspensions were added in the presence/absence of selected antibiotics. After washing, captured bacteria were detected. Findings. Group B streptococcus (GBS), Enterococcus faecalis, and Neisseria gonorrhoeae were each detected at 10 5 bacteria/mL following a 20-minute incubation period. Susceptibility to select antibiotics was discernable following a 6-hour incubation period (GBS and Enterococcus). Sensitivity was increased to 10 −2 bacteria/mL for GBS, 10 −1 bacteria/mL for E. faecalis, and 10 1 bacteria/mL for N. gonorrhoeae following 18-24-hour culture. Conclusion. This novel assay allows for the highly sensitive and specific identification of a pathogen and simultaneous determination of its antimicrobial susceptibility in a reduced time

Immune-modulation by polyclonal IgM treatment reduces atherosclerosis in hypercholesterolemic apoE−/− mice

AbstractObjectiveGamma-globulin treatment reduces experimental atherosclerosis by modulating immune function; however the effect of IgM on atherosclerosis is not known. We investigated the effect of serum-derived, non-immune polyclonal IgM (Poly-IgM) on atherosclerosis in mice with advanced disease and also assessed its immune-modulatory effects.Methods and resultsAortic atherosclerosis was assessed in apoE−/− mice fed atherogenic diet starting at 6 weeks of age. In addition, mice were also subjected to perivascular cuff injury to the carotid artery at 25 weeks of age to induce accelerated atherosclerosis. At the time of injury, the mice were treated weekly with a commercially available Poly-IgM (0.4mg/mouse) or PBS for 4 weeks and euthanized at 29 weeks of age. Poly-IgM reduced aortic atherosclerosis, and reduced lesion size in the aortic sinus and injured carotid artery, without significant changes in serum cholesterol levels. Poly-IgM treatment was associated with increased anti-oxLDL IgG titers and a reduction in the % splenic CD4+ T cells compared to controls. The splenic CD4+ T cell cultured from the Poly-IgM treated mice had reduced proliferation in vitro compared with controls.ConclusionPoly-IgM treatment reduced aortic and accelerated carotid atherosclerosis in apoE−/− mice in association with increased anti-oxLDL IgG titers, and reduced number and proliferative function of splenic CD4+ T cells. Our study identifies a novel athero-protective and immunomodulatory role for non-immune polyclonal IgM

DRD2 C957T polymorphism is associated with improved 6-month verbal learning following traumatic brain injury

Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1-5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI

DRD2 C957T polymorphism is associated with improved 6-month verbal learning following traumatic brain injury

Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1-5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI

COMT Val 158 Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury

Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val158Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met158 allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09-0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20-6.86]) 6-months following injury. The COMT Val158Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03-0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69-4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings