Topographical distribution of corticotropin-releasing factor type 2 receptor-like immunoreactivity in the rat dorsal raphe nucleus: co-localization with tryptophan hydroxylase.

Corticotropin-releasing factor (CRF) and CRF-related neuropeptides are involved in the regulation of stress-related physiology and behavior. Members of the CRF family of neuropeptides bind to two known receptors, the CRF type 1 (CRF₁) receptor, and the CRF type 2 (CRF₂) receptor. Although the distribution of CRF₂ receptor mRNA expression has been extensively studied, the distribution of CRF₂ receptor protein has not been characterized.

Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms.

Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers.

Hemodynamic patterning of the avian atrioventricular valve.

In this study, we develop an innovative approach to rigorously quantify the evolving hemodynamic environment of the atrioventricular (AV) canal of avian embryos. Ultrasound generated velocity profiles were imported into Micro-Computed Tomography generated anatomically precise cardiac geometries between Hamburger-Hamilton (HH) stages 17 and 30. Computational fluid dynamic simulations were then conducted and iterated until results mimicked in vivo observations.

Auditory steady state response in bipolar disorder: relation to clinical state, cognitive performance, medication status, and substance disorders.

Objectives:   Abnormalities in auditory steady state response (ASSR) at gamma range frequencies have been found in bipolar disorder, but the relationship of these neurophysiological disturbances to clinical factors has not been well characterized. We therefore evaluated the ASSR in bipolar disorder and examined its sensitivity to clinical symptoms, cognitive function, and pharmacological treatment.

Methods:   A total of 68 patients with bipolar disorder and 77 control participants were evaluated.

A selective, non-peptide CRF receptor 1 antagonist prevents sodium lactate-induced acute panic-like responses.

Corticotropin releasing factor (CRF) is implicated in a variety of stress-related disorders such as depression and anxiety, and blocking CRF receptors is a putative strategy for treating such disorders. Using a well-studied animal model of panic, we tested the efficacy of JNJ19567470/CRA5626, a selective, non-peptidergic CRF type 1 receptor (CRF1) antagonist (3, 10 and 40 mg/kg intraperitoneal injection), in preventing the sodium lactate (NaLac)-induced panic-like behavioural and cardiovascular responses. Adult male rats with chronic reduction of GABA levels (by inhibition of GABA synthesis with l-allyglycine, a glutamic acid decarboxylase inhibitor) in the dorsomedial/perifornical hypothalamus are highly anxious and exhibit physiological and behavioural responses to intravenous NaLac infusions similar to patients with panic disorder.

An ex-ovo chicken embryo culture system suitable for imaging and microsurgery applications.

Understanding the relationships between genetic and microenvironmental factors that drive normal and malformed embryonic development is fundamental for discovering new therapeutic strategies. Advancements in imaging technology have enabled quantitative investigation of the organization and maturing of the body plan, but later stage embryonic morphogenesis is less clear. Chicken embryos are an attractive vertebrate animal model system for this application because of its ease of culture and surgical manipulation.

Increased temporal variability of auditory event-related potentials in schizophrenia and Schizotypal Personality Disorder.

Previous studies suggest that deficits in neural synchronization and temporal integration are characteristic of schizophrenia. These phenomena have been rarely studied in SPD, which shares phenomenological and genetic similarities with schizophrenia. Event-related potentials (ERPs) were obtained using an auditory oddball task from 21 patients with schizophrenia, 19 subjects with SPD and 19 healthy control subjects.

Two-photon microscopy-guided femtosecond-laser photoablation of avian cardiogenesis: noninvasive creation of localized heart defects.

Embryonic heart formation is driven by complex feedback between genetic and hemodynamic stimuli. Clinical congenital heart defects (CHD), however, often manifest as localized microtissue malformations with no underlying genetic mutation, suggesting that altered hemodynamics during embryonic development may play a role. An investigation of this relationship has been impaired by a lack of experimental tools that can create locally targeted cardiac perturbations.

Multiple anxiogenic drugs recruit a parvalbumin-containing subpopulation of GABAergic interneurons in the basolateral amygdala.

The basolateral amygdala is a nodal structure within a distributed and interconnected network that regulates anxiety states and anxiety-related behavior. Administration of multiple anxiogenic drugs increases cellular responses (i.e.

Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder.

Background: Antagonism of corticotropin-releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF-1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD).

Method: This was a multicenter, randomized, double-blind, placebo-controlled and active comparator trial.

Scale-up and coverage of Avahan: a large-scale HIV-prevention programme among female sex workers and men who have sex with men in four Indian states.

Objective: Documenting the implementation of a public health programme as per its design is critical to interpretation of results from survey-led outcome and impact evaluation activities, the authors describe the scale-up and coverage of large-scale HIV-prevention services provided to female sex workers (FSWs) and high-risk men who have sex with men (HR-MSM) during the first 5 years of the Avahan programme in India.

Methods: Implementing NGO partner-generated denominator estimates from 70 districts were used to estimate the programme's intended coverage. Routine programme-monitoring data until December 2008 were used to describe the service and commodity availability, service utilisation to generate internal estimates of coverage.

Changes in central sodium and not osmolarity or lactate induce panic-like responses in a model of panic disorder.

Panic disorder is a severe anxiety disorder characterized by recurrent panic attacks that can be consistently provoked with intravenous (i.v.) infusions of hypertonic (0.

Induction of c-Fos in 'panic/defence'-related brain circuits following brief hypercarbic gas exposure.

Inspiration of air containing high concentrations of carbon dioxide (CO(2); hypercarbic gas exposure) mobilizes respiratory, sympathetic and hypothalamic-pituitary-adrenal axis responses and increases anxiety-like behaviour in rats and humans. Meanwhile the same stimulus induces panic attacks in the majority of panic disorder patients. However, little is known about the neural circuits that regulate these acute effects.

A key role for orexin in panic anxiety.

Panic disorder is a severe anxiety disorder with recurrent, debilitating panic attacks. In individuals with panic disorder there is evidence of decreased central gamma-aminobutyric acid (GABA) activity as well as marked increases in autonomic and respiratory responses after intravenous infusions of hypertonic sodium lactate. In a rat model of panic disorder, chronic inhibition of GABA synthesis in the dorsomedial-perifornical hypothalamus of rats produces anxiety-like states and a similar vulnerability to sodium lactate-induced cardioexcitatory responses.

Current perspectives of the roles of the central norepinephrine system in anxiety and depression.

Norepinephrine (NE) is a major monoamine neurotransmitter that has widespread effects across multiple brain areas to regulate arousal and stress responses. The underlying function of the NE cortical system is to balance vigilance/scanning behavior with focused attention on novel environmental stimuli and the state of arousal. The central NE system is involved intrinsically with the stress response system, and dysregulation within the NE system has been implicated in the pathogenesis of anxiety and depressive disorders.

Relationships between auditory event-related potentials and mood state, medication, and comorbid psychiatric illness in patients with bipolar disorder.

Background: Patients with bipolar disorder (BD) exhibit aberrations in auditory event-related potentials (ERPs), although the relationships between these measures and mood state at testing, comorbid psychiatric illness, presence of psychotic features, and medication usage are unclear. The purpose of this study was to investigate the relationships between these factors and auditory ERP measures in BD patients.

Methods: An auditory 'oddball' discrimination task was used to elicit ERPs from 69 patients with type I BD and 52 healthy controls.

Cortical-striatal integration of cocaine history and prefrontal dysfunction in animal modeling of dual diagnosis.

Background: High rates of substance disorders in schizophrenia and other mental illnesses may reflect biological vulnerabilities to the addiction process. Interactions between addictive drug effects and mental illness involving circuits that generate motivated behavior may underpin this vulnerability.

Methods: We examined separate and combined effects of neonatal ventral hippocampal lesions (NVHLs)-a neurodevelopmental model of schizophrenia (vs.

Timing dysfunctions in schizophrenia as measured by a repetitive finger tapping task.

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. Although a variety of behavioral studies have provided strong evidence for perceptual timing deficits in schizophrenia, no study to date has directly examined overt temporal performance in schizophrenia using a task that differentially engages perceptual and motor-based timing processes. The present study aimed to isolate perceptual and motor-based temporal performance in individuals diagnosed with schizophrenia using a repetitive finger-tapping task that has previously been shown to differentially engage brain regions associated with perceptual and motor-related timing behavior.

From QTL to candidate gene: a genetic approach to alcoholism research.

A major focus of research in alcohol-related disorders is to identify the genes and pathways that modulate alcohol-seeking behavior. In light of this, animal models have been established to study various aspects of alcohol dependence. The selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines were developed from Wistar rats to model high and low voluntary alcohol consumption, respectively.

Event-related potential abnormalities in schizophrenia: a failure to "gate in" salient information?

Sensory gating refers to the central nervous system's ability to filter sensory inputs, and can be measured by comparing the suppression of event-related brain potential (ERP) amplitudes in a paired auditory stimulus procedure. Poor gating scores in schizophrenia may be caused by abnormal responses to the first (S1), the second (S2) or both of the paired stimuli. However, since S1 and S2 responses may index separate psychological phenomenon, corresponding to the ability to "gate in" and "gate out" sensory stimuli respectively, the precise mechanism affected in schizophrenia remains unclear.

Steady state and induced auditory gamma deficits in schizophrenia.

Steady state auditory evoked potentials (SSAEPs) in the electroencephalogram (EEG) and magnetoencephalogram (MEG) have been reported to be reduced in schizophrenia, most consistently to frequencies in the gamma range (40 Hz and greater). The current study evaluated the specificity of this deficit over a broad range of stimulus frequencies and harmonics, the relationship between phase locking and signal power, and whether induced 40 Hz activity was also affected. SSAEPs to amplitude modulated tones from 5 to 50 Hz were obtained from subjects with schizophrenia (SZ) and healthy control subjects in 5 Hz steps.

Timing dysfunctions in schizophrenia span from millisecond to several-second durations.

Schizophrenia may be associated with a fundamental disturbance in the temporal coordination of information processing in the brain, leading to classic symptoms of schizophrenia such as thought disorder and disorganized and contextually inappropriate behavior. However, the majority of studies that have examined timing behavior in schizophrenia have employed temporal durations in the range of several seconds, which requires higher cognitive processes beyond initial sensory registration for temporal encoding. Accordingly, the present study assessed both millisecond and several-second duration estimates in schizophrenia using a well-established task of time perception.

Anxiety-like behavior is modulated by a discrete subpopulation of interneurons in the basolateral amygdala.

The basolateral amygdala (BL) is a putative site for regulating anxiety, where inhibition and excitation respectively lead to decreases and increases in anxiety-like behaviors. The BL contains local networks of GABAergic interneurons that are subdivided into classes based on neurochemical content, and are hypothesized to regulate unique functional responses of local glutamatergic projection neurons. Recently it was demonstrated that lesioning a portion of the BL interneuronal population, those interneurons that express neurokinin1 receptors (NK(1r)), resulted in anxiety-like behavior.