A new method for analysing transition to psychosis: Joint modelling of time‐to‐event outcome with time‐dependent predictors

An active area in psychosis research is the identification of predictors of transition to a psychotic state among those who are assessed as being at high risk of psychosis. Many of the potential predictors are time dependent in the sense that they may change over time and are measured at a number of assessment time points. Examples are various psychopathological measures such as negative symptoms, positive symptoms, depression, and anxiety. Most research in transition to psychosis has not made use of the dynamic nature of these measures, probably because suitable statistical methods and software have not been easily available. However, a relatively new statistical methodology is well suited to include such time‐dependent predictors in transition to psychosis analysis. This methodology is called joint modelling and has recently been incorporated in mainstream statistical software. This paper describes this methodology and demonstrates its usefulness using data from one of the pioneering studies on transition to psychosis.     

Stress‐coping strategies of patients with gender identity disorder

Aims: Previous research has not addressed gender differences in coping strategies among patients with gender identity disorder (GID). Nor has the relationship of coping strategies to other demographic characteristics ever been clarified in GID. In this study, we tried to clarify the relationship between stress‐coping strategies and demographic characteristics among patients with GID. Methods: The coping strategies of 344 patients with GID [227 female‐to‐male (FTM) and 117 male‐to‐female (MTF)] were assessed using the Japanese version of the Ways of Coping Questionnaires, Lazarus Stress‐coping Inventory. Results: Comparison of the stress‐coping inventory between MTF and FTM GID patients revealed that FTM GID patients were significantly more reliant on positive reappraisal strategies in stressful situations than MTF GID patients (P = 0.007). Conclusions: The difference in the usage of positive reappraisal strategies between MTF and FTM type GID patients was not explained by other demographic characteristics, and we suppose that the gender difference in GID patients might influence the usage of positive reappraisal strategies. The ratio of FTM GID patients might be higher at our center because MTF GID patients can obtain vaginoplasty easily, whereas phalloplasty surgery for FTM GID patients is performed at only a few centers, including our clinic, in Japan. As a result, more FTM GID patients come to our clinic with a clear intention to undergo sexual rearrangement surgery, which might influence the gender difference in using positive reappraisal.     

Psychiatric comorbidity among patients with gender identity disorder

Aims: Psychiatric comorbidity and mental instability seem to be important unfavorable prognostic factors for long‐term psychosocial adjustment in gender identity disorder (GID). However, psychiatric comorbidity in patients with GID has rarely been assessed. In this study, we investigated the psychiatric comorbidity and life events of patients with GID in Japan. Methods: A total of 603 consecutive patients were evaluated independently by at least two senior psychiatrists at the GID clinic using clinical information and results of examinations. Results: Using DSM‐IV criteria, 579 patients (96.0%) were diagnosed with GID. Among the GID patients, 349 (60.3%) were the female‐to‐male (FTM) type, and 230 (39.7%) were the male‐to‐female (MTF) type. Current psychiatric comorbidity was 19.1% (44/230) among MTF patients and 12.0% (42/349) among FTM patients. The lifetime positive history of suicidal ideation and self mutilation was 76.1% and 31.7% among MTF patients, and 71.9% and 32.7% among FTM patients. Among current psychiatric diagnoses, adjustment disorder (6.7%, 38/579) and anxiety disorder (3.6%, 21/579) were relatively frequent. Mood disorder was the third most frequent (1.4%, 8/579). Conclusions: Comparison with previous reports on the psychiatric comorbidity among GID patients revealed that the majority of GID patients had no psychiatric comorbidity. GID is a diagnostic entity in its own right, not necessarily associated with severe comorbid psychological findings.     

Field validation of a method for population screening of parkinsonism.

We sought to validate an instrument and two application procedures for screening for prevalence of parkinsonism in conjunction with a door-to-door survey in Cantalejo, Spain. Residents in Cantalejo aged 40 years or older were assigned to three groups specifically designed to optimise case-finding and cost/efficiency. A nine-item questionnaire aimed at identifying parkinsonism-related symptoms was administered and collected door-to-door by laymen and repeated by specialists at a medical facility before neurological examination. Diagnoses were then established and confirmed after a 3-year follow-up. Different indices for and concordance of answers were studied for both applications in groups of 25 individuals with parkinsonism. The scoring procedure was updated using the prevalence community sample of parkinsonism. Whereas the application administered by laymen showed, using the same cut-off scores, a higher sensitivity for parkinsonism than that administered by trained personnel, it yielded a lower positive predictive value for parkinsonism diagnosed during the study, i.e., at a 30-point cut-off (96% vs. 80% and 15% vs. 76%, respectively). Concordance was > or =64% with kappa >or=0.316 and P 相似文献   

Pre‐hospital notification reduced the door‐to‐needle time for iv t‐PA in acute ischaemic stroke

Background and purpose: Intrahospital delay is the most serious obstacle in thrombolysis in acute ischaemic stroke (AIS). We implemented the pre‐hospital notification system from the emergency medical information system in our metropolitan area to reduce intrahospital delay. Methods: From October 2007, we implemented a 24‐h hotline system between our stroke center and the Korean Emergency Medical Information System in Busan. We compared processing times and clinical outcomes amongst patients after using intravenous tissue type plasminogen activator (iv t‐PA) with and without the hotline system. Results: After the pre‐hospital notification system was implemented, the rate of iv t‐PA use increased from 6.5% to 14.3%. Time of onset in patients with pre‐hospital notification was much longer than in patients without (121.5 ± 34.8 min vs. 74.7 ± 38.5 min, P < 0.01) notification but door‐to‐needle time was significantly reduced (28.9 ± 11.4 min vs. 47.7 ± 22.8 min, P < 0.01). However, there were no significant differences in 90‐day clinical outcomes between the two groups. Conclusions: The pre‐hospital notification system reduced intrahospital processing times which led to increased iv t‐PA use after AIS. However, the improvement of clinical outcomes in thrombolysis might require organization of not only intrahospital processes but of outside processes such as the early recognition and rapid dispatch of patients with suspected AIS.     

Threat modulates neural responses to looming visual stimuli

Objects on a collision course with an observer produce a specific pattern of optical expansion on the retina known as looming, which in theory exactly specifies the time‐to‐collision (TTC) of approaching objects. It was recently demonstrated that the affective content of looming stimuli influences perceived TTC, with threatening objects judged as approaching sooner than non‐threatening objects. Here, the neural mechanisms by which perceived threat modulates spatiotemporal perception were investigated. Participants judged the TTC of threatening (snakes, spiders) or non‐threatening (butterflies, rabbits) stimuli, which expanded in size at a rate indicating one of five TTCs. Visual‐evoked potentials (VEPs) and oscillatory neural responses measured with electroencephalography were analysed. The arrival time of threatening stimuli was underestimated compared with non‐threatening stimuli, though an interaction suggested that this underestimation was not constant across TTCs. Further, both speed of approach and threat modulated both VEPs and oscillatory responses. Speed of approach modulated the N1 parietal and oscillations in the beta band. Threat modulated several VEP components (P1, N1 frontal, N1 occipital, early posterior negativity and late positive potential) and oscillations in the alpha and high gamma band. The results for the high gamma band suggest an interaction between these two factors. Previous evidence suggests that looming stimuli activate sensorimotor areas, even in the absence of an intended action. The current results show that threat disrupts the synchronization over the sensorimotor areas that are likely activated by the presentation of a looming stimulus.     

Fetal brain activity and hemodynamic response to a vibroacoustic stimulus

Previous studies have demonstrated the practicality of using functional magnetic resonance imaging (fMRI) techniques to assess fetal brain activity. The purpose of this study was to compare the fetal hemodynamic response to that of the adult. Seventeen pregnant subjects, all of whom were at more than 36 weeks gestation were scanned while the fetus was exposed to a vibroacoustic stimulus. Thirteen adult subjects were scanned with an equivalent acoustic stimulus. Of the fetal subjects, two could not be analyzed due to technical problems, eight did not show significant activation, and seven showed significant activation. In all cases, activation was localized within the temporal region. Measures of fetal hemodynamic responses revealed an average time to peak (ttp) of 7.36 +/- 0.94 sec and an average percentage change of 2.67 +/- 0.93%. In contrast, activation was detected in 5 of 13 adults with an average ttp of 6.54 +/- 0.54 sec and an average percentage change of 1.02 +/- 0.40%. The measurement of changes in the fetal hemodynamic response may be important in assessing compromised pregnancies.     

Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli

Interleukin-1 beta (IL-1 beta) is thought to act on the brain to induce fever, neuroendocrine activation, and behavioral changes during disease through induction of prostaglandins at the blood-brain barrier (BBB). However, despite the fact that IL-1 beta induces the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in brain vascular cells, no study has established the presence of IL-1 receptor type 1 (IL-1R1) protein in these cells. Furthermore, although COX inhibitors attenuate expression of the activation marker c-Fos in the preoptic and paraventricular hypothalamus after administration of IL-1 beta or bacterial lipopolysaccharide (LPS), they do not alter c-Fos induction in other structures known to express prostaglandin receptors. The present study thus sought to establish whether IL-1R1 protein is present and functional in the rat cerebral vasculature. In addition, the distribution of IL-1R1 protein was compared to IL-1 beta- and LPS-induced COX-2 expression. IL-1R1-immunoreactive perivascular cells were mostly found in choroid plexus and meninges. IL-1R1-immunoreactive vessels were seen throughout the brain, but concentrated in the preoptic area, subfornical organ, supraoptic hypothalamus, and to a lesser extent in the paraventricular hypothalamus, cortex, nucleus of the solitary tract, and ventrolateral medulla. Vascular IL-1R1-ir was associated with an endothelial cell marker, not found in arterioles, and corresponded to the induction patterns of phosphorylated c-Jun and inhibitory-factor kappa B mRNA upon IL-1 beta stimulation, and colocalized with peripheral IL-1 beta- or LPS-induced COX-2 expression. These observations indicate that functional IL-1R1s are expressed in endothelial cells of brain venules and suggest that vascular IL-1R1 distribution is an important factor determining BBB prostaglandin-dependent activation of brain structures during infection.     

Time‐varying synchronous cell ensembles during consummatory periods correlate with variable numbers of place cell spikes

Spike rates of a hippocampal place cell are not constant and vary even when an animal visits an identical place field with nearly identical behavior. As one potential neurophysiological source underlying place cell spiking variability, we focused on the temporally fluctuating activity states of neuronal ensembles. Spike patterns of hippocampal neurons were recorded from rats performing a linear track task. Within a single consummatory period, similar sets of neurons were more frequently recruited in synchronous firing events, whereas different synchronized firing patterns of neuronal populations tended to be identified in different consummatory periods. A linear regression analysis indicated that the time‐varying activation patterns of neuronal populations during consummatory periods are correlated with the spike rates of a place cell within its place field during running. These findings suggest that place cell in‐field spiking is not only triggered by static inputs that represent external environments but also strongly depends on the time‐varying internal states of neuronal populations.     

Four cases of panic disorder successfully treated with Kampo (Japanese herbal) medicines: Kami-shoyo-san and Hange-koboku-to

Kampo medicines have been used to treat patients with psychogenic disorders from ancient times. In the present report the cases are described of four patients with panic disorder successfully treated with Kampo medicines. These four patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for panic disorder with agoraphobia. The Kampo medicine Kami-shoyo-san (TJ-24) relieved panic attacks, anticipatory anxiety and agoraphobia in two patients, and Hange-koboku-to (TJ-16) relieved these symptoms in the other two patients. The patients in whom Kami-shoyo-san was effective were older and complained of more symptoms than those in whom Hange-koboku-to was effective. These Kampo medicines may be useful as additional or alternative treatments for panic disorder.     

The comparison of mouse full metallothionein‐1 versus α and β domains and metallothionein‐1‐to‐3 mutation following traumatic brain injury reveals different biological motifs

Traumatic injury to the brain is one of the leading causes of injury‐related death or disability, but current therapies are limited. Previously it has been shown that the antioxidant proteins metallothioneins (MTs) are potent neuroprotective factors in animal models of brain injury. The exogenous administration of MTs causes effects consistent with the roles proposed from studies in knock‐out mice. We herewith report the results comparing full mouse MT‐1 with the independent α and β domains, alone or together, in a cryoinjury model. The lesion of the cortex caused the mice to perform worse in the horizontal ladder beam and the rota‐rod tests; all the proteins showed a modest effect in the former test, while only full MT‐1 improved the performance of animals in the rota‐rod, and the α domain showed a rather detrimental effect. Gene expression analysis by RNA protection assay demonstrated that all proteins may alter the expression of host‐response genes such as GFAP, Mac1 and ICAM, in some cases being the β domain more effective than the α domain or even the full MT‐1. A MT‐1‐to‐MT‐3 mutation blunted some but not all the effects caused by the normal MT‐1, and in some cases increased its potency. Thus, splitting the two MT‐1 domains do not seem to eliminate all MT functions but certainly modifies them, and different motifs seem to be present in the protein underlying such functions. © 2010 Wiley‐Liss, Inc.     

Hickam's dictum: Angiosarcoma‐to‐meningioma metastasis

Tumor‐to‐tumor metastasis is a seldom reported phenomenon whereby a neoplasm seeds within another histologically distinct tumor, with only 84 cases documented in the literature. We hereby describe the case of a 95‐year‐old woman who died of widespread metastases identified as a primary hepatic angiosarcoma on autopsy, and the interesting finding of a seeding foci within a dural meningioma. Although meningiomas are the most common intracranial neoplasms to harbor such a phenomenon, this is to our knowledge the first case where an angiosarcoma was identified as the donor tumor.     

Trunk movement in Parkinson's disease during rising from seated position.

Parkinson's disease (PD) is associated with particular difficulties rising from a seated position. Little is known about the mechanisms of sit-to-stand in this condition. We sought to define trunk movement during sit-to-stand in a group of patients with PD. Six patients and seven normal volunteers were studied using a six camera ELITE motion analysis system (BTS, Milan, Italy), which permitted data collection in the coronal, sagittal, and transverse planes. Retroreflective markers were positioned along the spine at C7, T3, T6, T9, T12, L3, and the sacrum. Whole-trunk kinematics and the movement at the six different trunk markers were recorded during rising. PD patients have a significantly greater degree of trunk flexion than controls, showing a significant increase in angular velocity of the trunk in the sagittal plane. The total range of movement of trunk rotation was significantly smaller in the PD group, but lateral movement in the trunk was greater than normal. These data suggest that patients with early PD compensate for their difficulties rising from a chair by generating greater trunk flexion at higher angular velocity, thus developing greater forward momentum. This process results in a decrease in the duration of the unstable transitional phase of sit-to-stand, allowing PD patients to reach the upright position as easily and safely as possible. Small rotational movements are an effective way to maintain the centre of mass within the base of support during sit-to-stand. This mechanism appears to be denied to the PD patients who may use increased movements in the coronal plane as an alternative strategy.