Antipsychotics and Medical Comorbidity: A Retrospective Study in an Urban Outpatient Psychiatry Clinic.

Patients with psychotic disorders have increased rates of medical comorbidities. In this cross-sectional study, we investigated the relationship between antipsychotics and medical comorbidities among patients with psychotic disorders in an urban psychiatry clinic in Atlanta, Georgia (n = 860). Each antipsychotic group was compared to a group of patients from the same sample who were not on any antipsychotic, and logistic regression models were constructed for each comorbidity. Ziprasidone was associated with diabetes (aOR 2.56, 95% CI 1.03-6.38) and obesity (aOR 3.19, 95% CI 1.37-7.41). Aripiprazole was associated with obesity (aOR 2.39, 95% CI 1.27-4.51). Clozapine was associated with GERD (aOR 3.59, 95% CI 1.11-11.61), movement disorders (aOR 4.44, 95% CI 1.02-19.32), and arrythmias (4.89, 95% CI 1.44-16.64). Two antipsychotics that are considered weight neutral, ziprasidone and aripiprazole, were associated with cardiometabolic comorbidities. This study suggests that research is warranted to study the association between antipsychotics, medical comorbidity, and psychotic symptom burden.

Confabulation, amnesia and motor memory loss as a presentation of apparent ITPR1 antibody autoimmune encephalitis.

A 59-year-old woman presented to the hospital with acute, hypoactive altered mental status. Her symptoms had begun 3 days prior when she developed hallucinations, urinary and faecal incontinence, and somnolence. She also exhibited confabulations, amnesia, motor memory loss and a wide-based gait. Medical, psychiatric and neurological evaluations including imaging and laboratory workup were unrevealing. Treatment for possible Wernicke encephalopathy and psychosis with high-dose intravenous thiamine and antipsychotic medications did not lead to improvement. After discharge, a send-out cerebrospinal fluid autoimmune encephalitis panel resulted positive for the newly identified neuronal inositol triphosphate receptor one (ITPR1) antibody. This prompted readmission for intravenous steroids, plasmapheresis and intravenous immunoglobulin, which yielded mild clinical improvement. Here, we describe confabulations and psychiatric symptoms as novel manifestations of the primary presentation of anti-ITPR1 encephalitis in an effort to promote faster recognition of this disease and early initiation of treatment in suspected cases.

Splenic injury following endoscopic drainage of a large pancreatic pseudocyst: a case report.

BACKGROUND: Many pancreatic pseudocysts spontaneously resolve, but larger or symptomatic pseudocysts may require procedural management. Though endoscopic ultrasound guided approaches are standard of care and have high success rates, complications can include bleeding, infection, and splenic perforation. This patient case report details an unusual series of complications of endoscopic cystogastrostomy that should encourage clinicians to evaluate for anatomic disruptions caused by mass effects of pancreatic pseudocysts prior to endoscopic pseudocyst drainage. CASE PRESENTATION: A 53-year-old African American male with a past medical history notable for alcohol use disorder, chronic pancreatitis, and insulin dependent diabetes presented with a 4-day history of left upper quadrant abdominal pain. Computed tomography imaging with contrast revealed enlargement of a known pancreatic pseudocyst to 15.9 × 10.4 cm. Due to pseudocyst size and the patient's symptoms, endoscopic cystogastrostomy stent placement was performed. However, postprocedurally, he developed leukocytosis to 19,800 cells/m3 (from 14,100 cells/m3 preoperatively) as well as acute hypoxemic respiratory failure with a large left pleural effusion. Postprocedural computed tomography with contrast demonstrated a new large subcapsular splenic hematoma in communication with a new subdiaphragmatic fluid collection. Due to suspicion of endoscopic procedural complication, he underwent open laparotomy which revealed grade 4 splenic laceration, septic splenic hematoma, and a subdiaphragmatic abscess. CONCLUSIONS: While endoscopic drainage of pancreatic pseudocyst was technically successful, this case demonstrates complications from mass effect of a large pancreatic pseudocyst which putatively tore the splenorenal ligament, leading to excessive separation of the left kidney and spleen. If anatomic disruptions caused by mass effect from a pancreatic pseudocyst are recognized through preprocedural abdominal imaging, such cases may be considered for early open repair versus cystogastrostomy.

A Gene-Based Analysis of Acoustic Startle Latency.

Latency of the acoustic startle response is the time required from the presentation of startling auditory stimulus until the startle response is elicited and provides an index of neural processing speed. Latency is prolonged in subjects with schizophrenia compared to controls in some but not all studies and is 68-90% heritable in baseline startle trials. In order to determine the genetic association with latency as a potential inroad into genetically based vulnerability to psychosis, we conducted a gene-based study of latency followed by an independent replication study of significant gene findings with a single-nucleotide polymorphism (SNP)-based analysis of schizophrenia and control subjects. 313 subjects from an urban population of low socioeconomic status with mixed psychiatric diagnoses were included in the gene-based study. Startle testing was conducted using a Biopac M150 system according to our published methods. Genotyping was performed with the Omni-Quad 1M or the Omni Express BeadChip. The replication study was conducted on 154 schizophrenia subjects and 123 psychiatric controls. Genetic analyses were conducted with Illumina Human Omni1-Quad and OmniExpress BeadChips. Twenty-nine SNPs were selected from four genes that were significant in the gene-based analysis and also associated with startle and/or schizophrenia in the literature. Linear regressions on latency were conducted, controlling for age, race, and diagnosis as a dichotomous variable. In the gene-based study, 2,870 genes demonstrated the evidence of association after correction for multiple comparisons (false discovery rate < 0.05). Pathway analysis of these genes revealed enrichment for relevant biological processes including neural transmission (p = 0.0029), synaptic transmission (p = 0.0032), and neuronal development (p = 0.024). The subsequent SNP-based replication analysis revealed a strong association of onset latency with the SNP rs901561 on the neuregulin gene (NRG1) in an additive model (beta = 0.21, p = 0.001), indicating that subjects with the AA and AG genotypes had slower mean latency than subjects with GG genotype. In conclusion, startle latency, a highly heritable measure that is slowed in schizophrenia, may be a useful biological probe for genetic contributions to psychotic disorders. Our analyses in two independent populations point to a significant prediction of startle latency by genetic variation in NRG1.

Relationship between Toxoplasma gondii seropositivity and acoustic startle response in an inner-city population.

Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (SCZ), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p=0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F=7.41, p=0.0068; F=10.05, p=0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease.