Functional imaging in humans and anatomical data in monkeys have implicated the insula as a multimodal sensory integrative brain region. The topography of insular connections is organized by its cytoarchitectonic regions. Previous attempts to measure the insula have utilized either indirect or automated methods. This study was designed to develop a reliable method for obtaining volumetric magnetic resonance imaging (MRI) measurements of the human insular cortex, and to validate that method by examining the anatomy of insular cortex in adults with Williams syndrome (WS) and healthy age-matched controls. Statistical reliability was obtained among three raters for this method, supporting its reproducibility not only across raters, but within different software packages. The procedure described here utilizes native-space morphometry as well as a method for dividing the insula into connectivity-based sub-regions estimated from cytoarchitectonics. Reliability was calculated in both ANALYZE (n=3) and BrainImageJava (N=10) where brain scans were measured once in each hemisphere by each rater. This highly reliable method revealed total, anterior, and posterior insular volume reduction bilaterally (all p’s < .002) in WS, after accounting for reduced total brain volumes in these participants. Although speculative, the reduced insular volumes in WS may represent a neural risk for the development of hyperaffiliative social behavior with increased specific phobias, and implicate the insula as a critical limbic integrative region. Native-space quantification of the insula may be valuable in the study of neurodevelopmental or neuropsychiatric disorders related to anxiety and social behavior.

IntroductionLimited evidence exists evaluating the impact of gabapentin in conjunction with benzodiazepines for the management of alcohol withdrawal. A review of outcomes associated with combination gabapentin and benzodiazepine therapy may illuminate new therapeutic uses in clinical practice.MethodsThis retrospective study evaluated the impact of gabapentin on as-needed use of benzodiazepines in inpatients being treated for acute alcohol withdrawal. The treatment cohort consisted of patients prescribed gabapentin while on a symptom-triggered alcohol withdrawal protocol. The control cohort consisted of patients on symptom-triggered alcohol withdrawal protocol without concurrent gabapentin use. Secondary objectives included length of hospital stay, duration on alcohol withdrawal protocol, frequency of complicated withdrawal, and use of additionally prescribed as-needed or scheduled benzodiazepines.ResultsThe gabapentin cohort was on the alcohol withdrawal protocol for a similar duration, compared with the control cohort (median of 4 [interquartile range: 2,6] days vs 3 [2,4] days, P = .09, respectively). Similarly, the gabapentin cohort required a median of 1 [1,2] benzodiazepine dose for alcohol withdrawal symptoms compared with a median of 1 [1,2] dose in the control cohort, P = .89. No significant difference was found between cohorts for as-needed and scheduled benzodiazepine use. Length of stay in hospital was similar between groups.DiscussionThese results suggest that gabapentin use, in conjunction with benzodiazepines, impacts neither the time on alcohol withdrawal protocol or the number of benzodiazepine doses required for withdrawal. Larger, prospective studies are needed to detect if gabapentin alters benzodiazepine usage and to better elucidate gabapentin's role in acute alcohol withdrawal.

Fragile X Syndrome (FraX) is the most common form of inherited mental deficit and is caused by mutations of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome. While males and females with the full FMR1 mutation are affected differently because the disorder is Xlinked, both suffer from varying degrees of cognitive impairment, attention deficits and social anxiety. The insula is a sensory integrative region that has been increasingly suggested as a critical area involved in anxiety manifestation.The current study was designed to examine possible changes in insular volume in FraX compared to age-and gender-matched typically developing healthy controls (HC) as well as age, gender-, and intelligence-matched developmentally delayed controls (DD). An established native-space, manual morphometry method was utilized to quantify total and regional insular volumes using structural magnetic resonance imaging.Total, anterior and posterior insular volumes were found to be reduced in FraX compared to both HC and DD. The current data add to a growing literature concerning brain abnormalities in FraX and suggests that significant volume reduction of the insula is a component of the FraX neuroanatomical phenotype. This finding also provides an intriguing potential neural correlate for hyperarousal and gaze aversion, which are prominent behavioral symptoms of FraX.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a new diagnosis, as recent as 2007, that develops as a result of autoantibodies to the NMDA receptor. The clinical manifestations of the disorder include complex psychiatric symptoms, seizures, movement disorders, cognitive dysfunction, and autonomic instability. Tumor resection, if present, and immunotherapy are the mainstays of therapy. Treatment should be initiated early and aggressively as it has been associated with better patient outcomes. A significant proportion of patients with anti-NMDA receptor encephalitis initially seek the help of a psychiatrist, highlighting the importance of its recognition within the mental health community. In an effort to promote disease awareness, this article will review a patient case and the pathophysiology, clinical presentation, diagnosis, and management of anti-NMDA receptor encephalitis.

Recent data suggests that psychotic major depression (PMD) may be a discrete disorder distinguishable from nonpsychotic major depression (NPMD), and that patients with PMD may be more similar to individuals with schizophrenia than individuals with NPMD. The insula is a brain region in which morphometric changes have been associated with psychotic symptom severity in schizophrenia and affective psychosis. It was hypothesized that insular volumes would be reduced in PMD compared to NPMD and controls, and insular volumes would correlate with psychosis but not depression severity. Insular gray matter volumes were measured in PMD and NPMD patients and matched healthy controls using magnetic resonance images and manual morphometry. Clinical measures of illness severity were obtained to determine their relationship with insular volume. Posterior insular volumes were significantly reduced in PMD compared to HC. There were also significant group-by-gender interactions for total, anterior and posterior insular volumes. Using Pearson product-moment correlations, anterior insular volumes did not correlate with depression severity. Left anterior insular volume was significantly correlated with total and positive symptom psychosis severity in the PMD group. Atypical insular morphometry may be related to the inability to distinguish between internally- and externally-generated sensory inputs characteristic of psychosis.