Early Chronic Fluoxetine Treatment of Ts65Dn Mice Rescues Synaptic Vesicular Deficits and Prevents Aberrant Proteomic Alterations.

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS.

The Proposal Preparation Program: A Group Mentoring, Faculty Development Model to Facilitate the Submission and Funding of NIH Grant Applications.

This article describes the University of Minnesota Medical School Proposal Preparation Program (P3). P3 is designed to develop grant-writing skills for assistant professors preparing their first K- or R-series application to the National Institutes of Health (NIH). Three 4-month P3 cycles are conducted annually. For each cycle, a cohort of around 10 assistant professor participants and 5 regular faculty mentors meet for ten ~2-hour group sessions. Participants receive iterative oral and written feedback on their proposals in development within a small, interdisciplinary, group mentoring setting providing structure, accountability, guidance, and support. Between sessions, 1 peer and 1 mentor are assigned (on a rotating basis) to critique each participant's developing application. The sessions include a brief mentor-led presentation on a particular grant section followed by discussion of each participant's application conducted by the assigned reviewers. The cycle concludes with a mock NIH review session, in which each participant is matched with a University of Minnesota faculty content expert who critiques their completed application using NIH guidelines. In a survey sent to all past P3 participants as of 2018 (n = 194), 88% of respondents reported having submitted their P3-developed NIH grant, and 35% of these submitters reported funding success. A separate analysis of institutional data for all past P3 participants as of 2016 (n = 165) showed that 73% submitted at least 1 NIH proposal since completing P3 and that 43% of these had acquired NIH funding, for a combined total of $193 million in funding awarded. The estimated rate at which participants obtained funding for their P3-developed grant application (~35%) exceeds the national annual NIH grant funding rates (~20%) by approximately 50%. This article provides the practical information needed for other institutions to implement a P3-like program and presents a cost-benefit analysis showing the advantages of doing so.

Corrigendum: Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder.

[This corrects the article DOI: 10.3389/fpsyt.2018.00418.].

Activity of ceftazidime-avibactam against Escherichia coli isolates from U.S. veterans (2011) in relation to co-resistance and sequence type 131 (ST131) H30 and H30Rx status.

Escherichia coli ST131, with its multidrug-resistance-associated H30R1 and H30Rx clonal subsets within the H30R subclone, causes most antimicrobial-resistant E. coli infections. The activity of ceftazidime-avibactam (CZA) against ST131 strains is undefined. We determined CZA MICs for 595 E. coli clinical isolates from 24 Veterans Affairs Medical Centers (2010-2011). Resistance status and MICs were compared with study resistance category (fluoroquinolone-susceptible, fluoroquinolone-resistant, and extended-spectrum beta-lactamase (ESBL)-producing); ST131, H30R1, and H30Rx status; blaCTX-M-15-like genotype; and MICs for piperacillin-tazobactam, levofloxacin, gentamicin, ceftazidime, and meropenem. Proportion resistant ranged from zero (CZA, meropenem) to 61% (levofloxacin). MICs generally increased by resistance category (from fluoroquinolone-susceptible through fluoroquinolone-resistant to ESBL), clonal subgroup (from non-ST131-H30 through H30R1 to H30Rx), and blaCTX-M-15-like status. CZA MICs were slightly but significantly greater in association with resistance (or elevated MICs) to each comparator yet remained in the susceptible range. CZA was reliably active and outperformed noncarbapenem comparators, so it should prove useful as a carbapenem-sparing alternative.

Using consumer-wearable technology for remote assessment of physiological response to stress in the naturalistic environment.

Psychosocial stress is a major risk factor for morbidity and mortality related to a wide range of health conditions and has a significant negative impact on public health. Quantifying exposure to stress in the naturalistic environment can help to better understand its health effects and identify strategies for timely intervention. The objective of the current project was to develop and test the infrastructure and methods necessary for using wearable technology to quantify individual response to stressful situations and to determine if popular and accessible fitness trackers such as Fitbit® equipped with an optical heart rate (HR) monitor could be used to detect physiological response to psychosocial stress in everyday life. The participants in this study were University of Minnesota students (n = 18) that owned a Fitbit® tracker and had at least one upcoming examination. Continuous HR and activity measurements were obtained during a 7-day observation period containing examinations self-reported by the participants. Participants responded to six ecological momentary assessment surveys per day (~ 2 hour intervals) to indicate occurrence of stressful events. We compared HR during stressful events (e.g., exams) to baseline HR during periods indicated as non-stressful using mixed effects modeling. Our results show that HR was elevated by 8.9 beats per minute during exams and by 3.2 beats per minute during non-exam stressors. These results are consistent with prior laboratory findings and indicate that consumer wearable fitness trackers could serve as a valuable source of information on exposure to psychosocial stressors encountered in the naturalistic environment.

Mental Health Diagnoses in Veterans Referred for Outpatient Geriatric Psychiatric Care at a Veterans Affairs Medical Center.

INTRODUCTION: Nearly half of the U.S. veterans are over 65 years of age. Older veterans are at higher risk for mental health (MH) conditions, which are associated with increased mortality and health care costs. Given the deficit of specialty-trained geriatric providers, we are conducting a Quality Improvement initiative to improve MH services for older veterans at Minneapolis Veterans Affairs Health Care System. Our first step is to understand the demographic and diagnostic characteristics of veterans referred for geriatric MH specialty treatment. MATERIALS AND METHOD: We conducted a retrospective chart review of demographics and psychiatric diagnoses in veterans seen for outpatient geriatric MH intake between May 1, 2011 and April 30, 2016. We used chi-square and Spearman's rho tests to examine age, diagnoses, and service-time era variables. RESULTS: 1,059 veterans were evaluated, average age of 73.5 years. Depressive (47%), neurocognitive (42%), and anxiety disorders (22%) were the most common MH conditions. Vietnam veterans showed higher prevalence of depressive (56%), post-traumatic stress (11%), and alcohol use (10%) disorders. World War II veterans showed higher prevalence of neurocognitive disorders (71%). Neurocognitive disorder prevalence was significantly correlated with age. CONCLUSIONS: Prevalence and comorbidity of major MH conditions is high in veterans referred for geriatric MH services. Future work will examine challenges faced by non-specialty providers in caring for older veterans, with the goal of developing targeted educational and clinical interventions to better address aging veterans' MH needs.

Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder.

Mindfulness Based Stress Reduction (MBSR) is an effective non-pharmacologic treatment for veterans with PTSD. Extensive work has identified epigenetic factors related to PTSD disease risk and pathophysiology, but how these factors influence treatment response is unclear. Serotonin signaling and hypothalamic-pituitary-adrenal (HPA) axis functioning may be perturbed in PTSD and are molecular pathways targeted by PTSD treatments. To identify potential biomarkers for treatment response, we utilized genomic DNA isolated from peripheral blood samples from veterans with PTSD who were responders (n = 11) or non-responders (n = 11) to MBSR as part of a clinical trial. We assessed methylation levels at CpG sites in regions of the serotonin transporter (SLC6A4) previously associated with expression and depression outcomes, as well as the Intron 7 region of the FK506 binding protein 5 (FKBP5) containing known glucocorticoid response elements suggested to regulate this gene. Selected subjects were matched across MBSR responder status by baseline symptoms, age, sex, current smoking status, and current antidepressant use. Percent methylation was compared between responders and non-responders at baseline (pre-MBSR treatment). Additionally, percent change in methylation from baseline to post-treatment was compared between responders and non-responders. There was a significant time x responder group interaction for methylation in FKBP5 intron 7 bin 2 [F (1, 19) = 7.492, p = 0.013] whereby responders had a decrease in methylation and non-responders had an increase in methylation from before to after treatment in this region. Analyses of the three CpG sites within bin 2 revealed a significant time x responder group interaction for CpG_35558513 [F (1, 19) = 5.551, p = 0.029] which resides in a known glucocorticoid response element (GRE). Decreases in FKBP5 methylation after treatment in responders as compared to increases in non-responders suggest that effective meditation intervention may be associated with stress-related pathways at the molecular level. These preliminary findings suggest that DNA methylation signatures within FKBP5 are potential indicators of response to meditation treatment in PTSD and require validation in larger cohorts.

Patterns of conventional and complementary non-pharmacological health practice use by US military veterans: a cross-sectional latent class analysis.

BACKGROUND: Non-pharmacological therapies and practices are commonly used for both health maintenance and management of chronic disease. Patterns and reasons for use of health practices may identify clinically meaningful subgroups of users. The objectives of this study were to identify classes of self-reported use of conventional and complementary non-pharmacological health practices using latent class analysis and estimate associations of participant characteristics with class membership. METHODS: A mailed survey (October 2015 to September 2016) of Minnesota National Guard Veterans from a longitudinal cohort (n = 1850) assessed current pain, self-reported overall health, mental health, substance use, personality traits, and health practice use. We developed the Health Practices Inventory, a self-report instrument assessing use of 19 common conventional and complementary non-pharmacological health-related practices. Latent class analysis was used to identify subgroups of health practice users, based on responses to the HPI. Participants were assigned to their maximum-likelihood class, which was used as the outcome in multinomial logistic regression to examine associations of participant characteristics with latent class membership. RESULTS: Half of the sample used non-pharmacological health practices. Six classes of users were identified. "Low use" (50%) had low rates of health practice use. "Exercise" (23%) had high exercise use. "Psychotherapy" (6%) had high use of psychotherapy and support groups. "Manual therapies" (12%) had high use of chiropractic, physical therapy, and massage. "Mindfulness" (5%) had high use of mindfulness and relaxation practice. "Multimodal" (4%) had high use of most practices. Use of manual therapies (chiropractic, acupuncture, physical therapy, massage) was associated with chronic pain and female sex. Characteristics that predict use patterns varied by class. Use of self-directed practices (e.g., aerobic exercise, yoga) was associated with the personality trait of absorption (openness to experience). Use of psychotherapy was associated with higher rates of psychological distress. CONCLUSIONS: These observed patterns of use of non-pharmacological health practices show that functionally similar practices are being used together and suggest a meaningful classification of health practices based on self-directed/active and practitioner-delivered. Notably, there is considerable overlap in users of complementary and conventional practices.

The State of Sleep Medicine Education in North American Psychiatry Residency Training Programs in 2013: Chief Resident's Perspective.

OBJECTIVE: To assess the current state of sleep medicine educational resources and training offered by North American psychiatry residency programs. METHODS: In June 2013, a 9-item peer-reviewed Sleep Medicine Training Survey was administered to 39 chief residents of psychiatry residency training programs during a meeting in New York. RESULTS: Thirty-four percent of the participating programs offered an elective rotation in sleep medicine. A variety of innovative approaches for teaching sleep medicine were noted. The majority of the chief residents felt comfortable screening patients for obstructive sleep apnea (72%), half felt comfortable screening for restless legs syndrome (53%), and fewer than half were comfortable screening for other sleep disorders (47%). CONCLUSIONS: This is the first report in the last decade to provide any analysis of current sleep medicine training in North American psychiatry residency training programs. These data indicate that sleep medicine education in psychiatry residency programs is possibly in decline.

Altered subcellular localization of fragile X mental retardation signaling partners and targets in superior frontal cortex of individuals with schizophrenia.

Schizophrenia is a severe, debilitating, neurodevelopmental disorder that affects 1% of the world's population. Recent findings from our laboratory have identified reduced levels of fragile X mental retardation protein (FMRP) and several downstream FMRP targets in superior frontal cortex of individuals with schizophrenia. We hypothesized that altered subcellular expression of FMRP and its signaling partners may explain these changes. In the current study we employed subcellular fractionation and western blotting to determine levels of FMRP, phosphorylated-FMRP as well as selected signaling partners [protein phosphatase 2A catalytic subunit (PP2AC), p70 S6 kinase (p70 S6K), and amyloid-ß A4 precursor protein (APP)] in the total homogenate, nuclear, and rough endoplasmic reticulum fractions in superior frontal cortex of individuals with schizophrenia versus controls (N=12/group). In total homogenate of individuals with schizophrenia, we identified significantly lower levels of FMRP, phosphorylated-FMRP, and PP2AC. In the nuclear fraction of individuals with schizophrenia we found significantly higher levels of PP2AC, p70 S6K, APP 120 kDa, and APP 88 kDa proteins. Finally, in rough endoplasmic reticulum of individuals with schizophrenia, we identified significantly lower protein levels of p70 S6K and APP 120 kDa. These results provide evidence for a potential mechanism to explain altered FMRP expression in schizophrenia.

Examining Burnout, Depression, and Self-Compassion in Veterans Affairs Mental Health Staff.

OBJECTIVES: Burnout, a state of emotional exhaustion associated with negative personal and occupational outcomes, is prevalent among healthcare providers. A better understanding of the psychological factors that may be associated with resilience to burnout is essential to develop effective interventions. Self-compassion, which includes kindness toward oneself, recognition of suffering as part of shared human experience, mindfulness, and nonjudgment toward inadequacies and failures, may be one such factor. The purpose of this study was to examine the relationships between burnout, depression, and self-compassion in Veterans Affairs (VA) mental health staff. DESIGN: Cross-sectional study. SETTING: VA medical center and affiliated community-based clinics. PARTICIPANTS: VA mental health staff. OUTCOME MEASURES: The 19-item Copenhagen Burnout Inventory, the 26-item Self-Compassion Scale, and the Patient Health Questionnaire 2-item depression screen. Demographic information included age, sex, years worked in current position, and number of staff supervised. RESULTS: One hundred and twenty-eight of a potential 379 individuals (33.8%) responded. Clerical support, nursing, social work, psychology, and psychiatry were the major professions represented. Self-compassion was inversely correlated with burnout (r = -0.41, p < 0.001), and inversely correlated with depression (rpb = -0.39, p < 0.001). The inverse relationship between self-compassion and burnout remained significant even after accounting for depressive symptoms and demographic variables in a multiple linear regression model. Of all the variables examined, self-compassion was the strongest predictor of burnout. CONCLUSIONS: The results of this study support the hypothesis that self-compassion may be associated with resilience to burnout. Alternatively, decreased self-compassion may be a downstream effect of increased burnout. Prospective, longitudinal studies are needed to determine the directional relationship between these factors, and whether interventions that cultivate self-compassion may decrease burnout and/or protect against its negative personal and professional outcomes.

GABAA and GABAB receptor dysregulation in superior frontal cortex of subjects with schizophrenia and bipolar disorder.

Schizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma-aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABAA and two GABAB receptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls. Analyses of Variance (ANOVAs) identified significant group effects for protein levels for the α1, α6, ß1, ß3, δ, ɛ, and π GABAA receptor subunits and R1 and R2 GABAB receptor subunits. Follow-up t tests confirmed changes for these subunits in subjects with schizophrenia, subjects with bipolar disorder, or both groups. Alterations in stoichiometry of GABA receptor subunits could result in altered ligand binding, transmission, and pharmacology of GABA receptors in superior frontal cortex. Thus, impaired GABAergic transmission may negatively contribute to symptoms such as anxiety or panic as well as impaired learning and information processing, all of which are disrupted in schizophrenia and bipolar disorder. Taken together, these results provide additional evidence of GABAergic receptor abnormalities in these disorders.

The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum.

Prenatal viral infection has been identified as a potential risk factor for the development of neurodevelopmental disorders such as schizophrenia and autism. Additionally, dysfunction in gamma-aminobutyric acid, Reelin, and fragile X mental retardation protein (FMRP)-metabotropic glutamate receptor 5 signaling systems has also been demonstrated in these two disorders. In the current report, we have characterized the developmental profiles of selected markers for these systems in cerebella of mice born to pregnant mice infected with human influenza (H1N1) virus on embryonic day 16 or sham-infected controls using SDS-PAGE and Western blotting techniques and evaluated the presence of abnormalities in the above-mentioned markers during brain development. The cerebellum was selected in light of emerging evidence that it plays roles in learning, memory, and emotional processing-all of which are disrupted in autism and schizophrenia. We identified unique patterns of gene and protein expression at birth (postnatal day 0 [P0]), childhood (P14), adolescence (P35), and young adulthood (P56) in both exposed and control mouse progeny. We also identified significant differences in protein expression for FMRP, very-low-density lipoprotein receptor, and glutamic acid decarboxylase 65 and 67 kDa proteins at specific postnatal time points in cerebella of the offspring of exposed mice. Our results provide evidence of disrupted FMRP, glutamatergic, and Reelin signaling in the exposed mouse offspring that explains the multiple brain abnormalities observed in this animal model. © 2016 Wiley Periodicals, Inc.

The class-dimensional structure of PTSD before and after deployment to Iraq: Evidence from direct comparison of dimensional, categorical, and hybrid models.

The assumption of specific etiology in posttraumatic stress disorder (PTSD) differentiates the disorder from most other psychiatric conditions. A 'risky test' of the assumption of specific etiology and resultant trauma-related symptom dimensions was conducted through structural modeling of PTSD symptoms in soldiers before (N=522) and after (n=423) a combat deployment to Iraq. If PTSD represents a discrete diagnostic entity that emerges after trauma exposure, we hypothesized either the number of latent classes should increase from pre- to post-deployment or symptom dimensions should qualitatively distinguish affected from unaffected classes following trauma exposure. Comparison of latent structural models revealed best fitting hybrid models for PTSD and depression with strong invariance of symptom dimensions across classes both before and after deployment and only quantitative (i.e., severity) differences between classes. These findings suggest PTSD is generally well-conceptualized as a dimensional syndrome worsened but not necessarily elicited by trauma exposure.

Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders.

Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa and 33k Da forms of STEP in subjects with schizophrenia; 3) reduced expression of 88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders.

Downregulation of GABAA receptor protein subunits α6, ß2, δ, ε, γ2, θ, and ρ2 in superior frontal cortex of subjects with autism.

We measured protein and mRNA levels for nine gamma-aminobutyric acid A (GABAA) receptor subunits in three brain regions (cerebellum, superior frontal cortex, and parietal cortex) in subjects with autism versus matched controls. We observed changes in mRNA for a number of GABAA and GABAB subunits and overall reduced protein expression for GABAA receptor alpha 6 (GABRα6), GABAA receptor beta 2 (GABRß2), GABAA receptor delta (GABRδ), GABAA receptor epsilon (GABRε), GABAA receptor gamma 2 (GABRγ2), GABAA receptor theta (GABRθ), and GABAA receptor rho 2 (GABRρ2) in superior frontal cortex from subjects with autism. Our data demonstrate systematic changes in GABAA&B subunit expression in brains of subjects with autism, which may help explain the presence of cognitive abnormalities in subjects with autism.

Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex.

BACKGROUND: Candidate genes associated with idiopathic forms of autism overlap with other disorders including fragile X syndrome. Our laboratory has previously shown reduction in fragile X mental retardation protein (FMRP) and increase in metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and superior frontal cortex (BA9) of individuals with autism. METHODS: In the current study we have investigated expression of four targets of FMRP and mGluR5 signaling - homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP) - in the cerebellar vermis and superior frontal cortex (BA9) via SDS-PAGE and western blotting. Data were analyzed based on stratification with respect to age (children and adolescents vs. adults), anatomic region of the brain (BA9 vs. cerebellar vermis), and impact of medications (children and adolescents on medications (n = 4) vs. total children and adolescents (n = 12); adults on medications (n = 6) vs. total adults (n = 12)). RESULTS: There were significant increases in RAC1, APP 120 kDa and APP 80 kDa proteins in BA9 of children with autism vs. healthy controls. None of the same proteins were significantly affected in cerebellar vermis of children with autism. In BA9 of adults with autism there were significant increases in RAC1 and STEP 46 kDa and a significant decrease in homer 1 vs. controls. In the vermis of adult subjects with autism, RAC1 was significantly increased while APP 120, STEP 66 kDa, STEP 27 kDa, and homer 1 were significantly decreased when compared with healthy controls. No changes were observed in vermis of children with autism. There was a significant effect of anticonvulsant use on STEP 46 kDa/ß-actin and a potential effect on homer 1/NSE, in BA9 of adults with autism. However, no other significant confound effects were observed in this study. CONCLUSIONS: Our findings provide further evidence of abnormalities in FMRP and mGluR5 signaling partners in brains of individuals with autism and open the door to potential targeted treatments which could help ameliorate the symptoms of autism.

An exploratory examination of risk-taking behavior and PTSD symptom severity in a veteran sample.

The present study conducted an exploratory examination of the relationship between self-reported symptoms of post-traumatic stress disorder and an expanded definition of risk-taking behaviors among 395 veterans at a large Midwestern Veterans Affairs Medical Center. Post-traumatic stress disorder symptoms were associated with elevated rates of substance use, thrill seeking, aggression, risky sexual practices, and firearm possession. Results indicated that suicidal ideation and aggressive driving behavior were among the most frequently reported. The present findings hold significant public health implications and highlight the need to attend to risk-taking behaviors in treatment planning.

Deficits in GABA(B) receptor system in schizophrenia and mood disorders: a postmortem study.

Postmortem and genetic studies have clearly demonstrated changes in GABA(B) receptors in neuropsychiatric disorders such as autism, bipolar disorder, major depression, and schizophrenia. Moreover, a number of recent studies have stressed the importance of cerebellar dysfunction in these same disorders. In the current study, we examined protein levels of the two GABA(B) receptor subunits GABBR1 and GABBR2 in lateral cerebella from a well-characterized cohort of subjects with schizophrenia (n=15), bipolar disorder (n=14), major depression (n=13) and healthy controls (n=12). We found significant reductions in protein for both GABBR1 and GABBR2 in lateral cerebella from subjects with schizophrenia, bipolar disorder and major depression when compared with controls. These results provide further evidence of GABAergic dysfunction in these three disorders as well as identify potential targets for therapeutic intervention.