Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire

OBJECTIVE: Bipolar spectrum disorders, which include bipolar I, bipolar II, and bipolar disorder not otherwise specified, frequently go unrecognized, undiagnosed, and untreated. This report describes the validation of a new brief self-report screening instrument for bipolar spectrum disorders called the Mood Disorder Questionnaire. METHOD: A total of 198 patients attending five outpatient clinics that primarily treat patients with mood disorders completed the Mood Disorder Questionnaire. A research professional, blind to the Mood Disorder Questionnaire results, conducted a telephone research diagnostic interview by means of the bipolar module of the Structured Clinical Interview for DSM-IV. RESULTS: A Mood Disorder Questionnaire screening score of 7 or more items yielded good sensitivity (0.73) and very good specificity (0.90). CONCLUSIONS: The Mood Disorder Questionnaire is a useful screening instrument for bipolar spectrum disorder in a psychiatric outpatient population.     

Expression of c-fos-like immunoreactivity in the feline brainstem in response to isometric muscle contraction and baroreceptor reflex changes in arterial pressure

This study compared whether activation of muscle ergoreceptor afferents caused by isometric muscle contraction, activation of baroreceptor afferents induced by i.v. infusion of phenylephrine, or baroreceptor afferent inactivation, caused by carotid artery occlusion, elicit similar patterns of c-Fos induction in brainstem areas. Adult cats were anesthetized with alpha-chloralose, and in each case, the experimental intervention caused an increase in the arterial blood pressure. There were two sets of control experiments: in both, animals underwent the same surgical procedures but then either remained at rest for the entire study, or the tibial nerve was stimulated, as in the contraction group, following muscle paralysis with tubocurarine. Following the procedures, animals rested for 90 min to allow neuronal expression of c-Fos. Control cats showed very little c-Fos immunoreactivity (c-Fos-ir) in the brainstem. Muscle contraction induced c-Fos-ir expression mainly in the nucleus tractus solitarius, lateral reticular nucleus, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, spinal trigeminal tract and in a lateral region of the periaqueductal grey (P 0.5-1.0). The majority of the c-Fos-ir was found in brainstem areas contralateral to the contracted muscle. In addition, muscle contraction induced c-Fos-ir in the dorsal horns of spinal segments L6-S1 on the ipsilateral side of the spinal cord. Phenylephrine infusion caused c-Fos-ir expression in the nucleus tractus solitarius, spinal trigeminal tract, solitary tract, and dorsal motor nucleus of the vagus. No c-Fos-ir was apparent in the periaqueductal grey. Carotid occlusions induced c-Fos-ir expression in the area postrema, nucleus tractus solitarius, solitary tract, and spinal trigeminal tract. Expression was bilateral. Areas that exhibited c-Fos-ir correspond to sites previously reported to release various neuropeptides in response to muscle contraction or carotid occlusions. These results indicate that the exercise pressor reflex and baroreflex activate similar, but not completely identical, sites in the brainstem.     

Proteasome inhibitor PS519 reduces infarction and attenuates leukocyte infiltration in a rat model of focal cerebral ischemia

BACKGROUND AND PURPOSE: Reperfusion brain injury after cerebral ischemia is associated with a developing inflammatory response at the site of infarction. Proteasome inhibitors block nuclear factor-kappaB activation and provide anti-inflammatory effects in several animal models of peripheral inflammation. We tested the novel proteasome inhibitor PS519 in a rat model of transient focal ischemia to establish its pharmacodynamics as a neuroprotection treatment and related effects on leukocyte infiltration. METHODS: Rats were subjected to 2 hours of focal cerebral ischemia by means of the filament method of middle cerebral artery occlusion (MCAo). After either 22 or 70 hours of reperfusion, infarct size was measured and neurological function, electroencephalographic (EEG) activity, and/or neutrophil and macrophage infiltration was quantified. PS519 was administered in a single intravenous bolus at 2 hours after MCAo. In addition, the therapeutic window for PS519 was estimated by delaying treatment for 4 or 6 hours after MCAo. RESULTS: Dose-response analysis of infarct volume at 24 hours revealed that PS519 neuroprotection approached 60%, and clinical evaluations showed significant improvements in neurological function and EEG activity. Neutrophil infiltration at 24 hours was also significantly decreased in cortical and striatal infarcted tissue of PS519-treated rats. Delaying the PS519 treatment up to 4 hours continued to result in significant neuroprotection. In the 72-hour injury model, infarction was reduced 40% by PS519, and significant improvements in neurological function and EEG recovery were again measured. Considerable reductions in both neutrophil and macrophage infiltration were evident. CONCLUSIONS: PS519 mitigates infarction and improves neurological recovery in brain-injured rats, an effect in part caused by a reduction in the leukocyte inflammatory response.     

Functional Impairment and Cognition in Bipolar Disorder

Bipolar disorder is a common, chronic and severe mental disorder, affecting approximately 2% of the adult population. Bipolar disorder causes substantial psychosocial morbidity that frequently affects the patient's marriage, children, occupation, and other aspects of the patient's life. Few studies have examined the functional impairment in patients with affective illness. Earlier outcome studies of mania reported favorable long-term outcomes. However, modern outcome studies have found that a majority of bipolar patients evidence high rates of functional impairment. These low reports of functional recovery rates are particularly surprising. The basis for such limited functional recovery is not entirely clear. Factors associated with functional dysfunction include presence of inter-episode symptoms, neuroleptic treatment, lower social economic class, and lower premorbid function. Cognitive dysfunction, a symptom domain of schizophrenia, has been identified as an important measure of outcome in the treatment of schizophrenia. Recently, there has been some suggestion that there may be impaired neuropsychological performance in euthymic patients with recurring mood disorders. Whether impaired neuropsychological performance in associated with the functional impairment in bipolar patients who have achieved syndromal recovery is an intriguing question. The literature on functional impairment and cognition in bipolar disorder is reviewed.     

Motor response suppression and the prepotent tendency to respond: a parametric fMRI study

In the present study we utilised functional magnetic resonance imaging (fMRI) to examine cerebral activation during performance of a classic motor task in which response suppression load was parametrically varied. Linear increases in activity were observed in a distributed network of regions across both cerebral hemispheres, although with more extensive involvement of the right prefrontal cortex. Activated regions included prefrontal, parietal and occipitotemporal cortices. Decreasing activation was similarly observed in a distributed network of regions. These response forms are discussed in terms of an increasing requirement for visual cue discrimination and suppression/selection of motor responses, and a decreasing probability of the occurrence of non-target stimuli and attenuation of a prepotent tendency to respond. The results support recent proposals for a dominant role for the right-hemisphere in performance of motor response suppression tasks that emphasise the importance of the right prefrontal cortex.     

GABAA receptor mediated elevation of Ca2+ and modulation of gonadotrophin-releasing hormone action in alphaT3-1 gonadotropes

gamma-amino butyric acid (GABA) is the major inhibitory neurotransmitter in the CNS, mediating fast inhibitory synaptic transmission, by activating GABAA receptors. However, these GABA-gated Cl- channels can also be excitatory, causing depolarization, and increasing Ca2+ entry via voltage-operated Ca2+ channels (VOCCs). Evidence exists for excitatory ionotropic GABA receptors in anterior pituitary cells, including gonadotropes, but these have not been directly characterized and their pharmacology remains controversial. Here we have measured the cytosolic Ca2+ concentration ([Ca2+]i) in alphaT3-1 gonadotropes, to test for expression of excitatory GABA receptors. The GABAA agonists, GABA and muscimol, both caused rapid, robust and dose-dependent increases in [Ca2+]i (EC50 values 2.7 and 1 microM), whereas the GABAB agonist, baclofen, did not. The GABAA antagonist, bicuculline, inhibited muscimol's effect, whereas the GABAB antagonist, phaclofen, did not. The neuroactive steroid 5alpha-pregnan-3alpha-ol-11,20-dione (an allosteric activator of GABAA receptors) increased [Ca2+]i, and this effect, like that of muscimol, was inhibited by picrotoxin. The muscimol effect on [Ca2+]i was blocked by the VOCC antagonist, nifedipine, or by Ca2+-free medium. When cells were pretreated with muscimol this increased the spike phase of the [Ca2+]i response to subsequent stimulation with gonadotropin-releasing hormone (GnRH). Similar amplification was seen in muscimol-pretreated cells stimulated with GnRH in Ca2+-free medium, but not when cells were pretreated with muscimol in Ca2+-free medium. The amplification was not, however, GnRH receptor-specific, because the spike response to ionomycin was also increased by muscimol pretreatment. These data provide the first direct evidence for expression of excitatory GABAA receptors, and the first demonstration of acute steroid effects, on GnRH-responsive pituitary cells. They also reveal a novel mechanism by which GABAA activation modulates GnRH action, raising the possibility that this may also influence gonadotrophin secretion from non-immortalized gonadotropes.     

Measurement of dose in panoramic dental radiology

The National Radiological Protection Board (NRPB) has recommended the introduction of dose-width product (DWP) for the measurement of patient dose in panoramic dental radiology and has proposed a reference level of 65 mGy mm for adult exposures. This paper describes a method for measuring DWP and dose-area product (DAP) using thermoluminescent dosemeters (TLDs). The technique was used on 16 sets with a range of exposure settings. The mean value of DWP was 14% higher than the mean value reported from a survey by the NRPB. This difference is most likely to be caused by systematic variations due to measurement method. The average DAP for a standard adult examination was shown to be 11.3 cGy cm2. Data are presented so that the DAP can be derived from the exposure factors (tube current and operating potential) and beam area. Based on published data for effective dose, it is estimated that the DAP to effective dose conversion factor is approximately 0.06 mSv(Gy cm2)-1. The average DAP value (11.3 cGy cm2) can be compared with the average value for intraoral radiography (9.3 cGy cm2) based on the NRPB survey of entrance surface doses assuming 6 cm circular collimation.     

The somatizing patient

The authors discuss the significance of identifying primary care patients with dramatic and persistent unexplained physical (medical) symptoms, especially given the concerns about containing health care costs. Such patients are a cause of frustration to the clinician, because the clinician may experience a sense of failure after using the state of the art and still being eluded by a diagnosis. We focus on the methods for understanding somatic worry or preoccupation, which is the essential process in a variety of somatoform disorders. The second half of the article focuses on evaluation and treatment considerations and includes a discussion of both psychotherapeutic and psychopharmacologic treatment strategies for the somatizing patient.     

Birth prevalence of Prader-Willi syndrome in Australia.

This is the first population based study to estimate the birth prevalence of DNA proven Prader-Willi syndrome. Thirty infants were reported to the Australian Paediatric Surveillance Unit between 1998 and 2000, a prevalence of 4 per 100,000 live births or approximately 1/25,000 live births per annum.