Antidepressants as add-on treatment to antipsychotics for people with schizophrenia and pronounced negative symptoms: a systematic review of randomized trials

The aim of our meta-analysis was to review the evidence base for the efficacy and safety of antipsychotic and antidepressant combinations in the treatment of the negative symptoms of schizophrenia and schizophrenia-like psychoses. Randomized controlled trials comparing the combination of antidepressants and antipsychotics with antipsychotics alone for patients with pronounced negative symptoms in schizophrenia were searched for by accessing the register of randomized controlled trials of the Cochrane Schizophrenia group. The studies identified were independently inspected and their quality assessed by two reviewers. The principal outcome of interest was the reduction of negative symptoms. Dichotomous data were analyzed using the relative risk and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. It was possible to include seven trials (n = 202) examining antidepressants as add-on to antipsychotics in this review. Except for one study, all included studies used first generation antipsychotics. While there was often merely a trend in favour of augmentation of antipsychotics with antidepressants in the small single studies, the meta-analytic combination resulted in a statistically significant superiority in the outcome reduction of negative symptoms as a whole. Statistically significant differences between groups in terms of specific subscores of the SANS were found, but the results were inconsistent. The combination of antipsychotics and antidepressants may be more effective in treating negative symptoms of schizophrenia than antipsychotics alone, but this finding needs to be corroborated by further large trials.     

Semantic processing of unattended meaning is modulated by additional task load: evidence from electrophysiology

Recently, we observed that the perception of word meaning, as measured with the N400 component of the event-related brain potential, is delayed but unimpaired by various additional tasks when the language task requires the processing of semantic properties of the word stimuli. In the present study, we assessed whether similar effects would be observed when the language task relates to acoustic rather than to semantic properties of the word stimuli. The N400 was elicited by synonymous and non-synonymous spoken noun pairs that were to be classified according to tone pitch. In a single task experiment, there was a small but clear synonymity effect in ERPs (N400), indicating the availability of word meaning to the semantic system. Additional processing load, imposed by an overlapping task, abolished N400 for all SOAs when stimulus-response assignments were incompatible. For compatible assignments, N400 amplitude was present but much attenuated at the longest SOA. We conclude that the availability of task-irrelevant meaning is modulated by additional task load and decay in short-term memory.     

Cortical oscillatory activity during spatial echoic memory

In human magnetoencephalogram, we have found gamma-band activity (GBA), a putative measure of cortical network synchronization, during both bottom-up and top-down auditory processing. When sound positions had to be retained in short-term memory for 800 ms, enhanced GBA was detected over posterior parietal cortex, possibly reflecting the activation of higher sensory storage systems along the hypothesized auditory dorsal space processing stream. Additional prefrontal GBA increases suggested an involvement of central executive networks in stimulus maintenance. The present study assessed spatial echoic memory with the same stimuli but a shorter memorization interval of 200 ms. Statistical probability mapping revealed posterior parietal GBA increases at 80 Hz near the end of the memory phase and both gamma and theta enhancements in response to the test stimulus. In contrast to the previous short-term memory study, no prefrontal gamma or theta enhancements were detected. This suggests that spatial echoic memory is performed by networks along the putative auditory dorsal stream, without requiring an involvement of prefrontal executive regions.     

Human gamma-band activity: a window to cognitive processing

This review highlights recent developments in research on human cortical oscillations in the gamma-band range (30-100 Hz). Electroencephalography has demonstrated a role of these signals for cognitive functions including visual perception, attention, learning and memory. During auditory processing, magnetoencephalogram has identified oscillatory activity in higher frequency ranges and with a more discrete localization than electroencephalogram. Gamma-band activity increases have been observed in the putative auditory dorsal and ventral processing streams during the processing of auditory spatial and pattern information, respectively. Additional gamma-band activity has been found over the frontal cortex during top-down tasks. Oscillatory activity in the gamma range may serve to assess the temporal dynamics of cortical networks and their interactions.     

A multicenter study about Neurobiology of Suicidal Behavior: design, development, and preliminary results.

The subproject 1.5 "Neurobiology of Suicidal Behavior" is a multicenter study assessing peripheral parameters of the serotonergic, noradrenergic, and dopaminergic transmitter systems. Additionally, stress hormones and the lipid system as well as inhibitory and excitatory amino acids will be investigated. The different parameters are collected in cerebral spinal fluid (CSF), blood, and saliva. Patients with a depressive spectrum disorder with and without a suicide attempt (during the last three weeks) and being medication free for two weeks are included in the study. So far, 103 patients and controls have been recruited. The design and development of this project as well as interconnections with the others subprojects are described. Preliminary results about the stress hormone system and suicidality are presented.     

The phenotype of short stature homeobox gene (SHOX) deficiency in childhood: contrasting children with Leri-Weill dyschondrosteosis and Turner syndrome

OBJECTIVE: To evaluate the growth disorder and phenotype in prepubertal children with Leri-Weill dyschondrosteosis (LWD), a dominantly inherited skeletal dysplasia, and to compare the findings from girls with Turner syndrome (TS). STUDY DESIGN: We studied the auxologic and phenotypic characteristics in 34 prepubertal LWD subjects (ages 1 to 10 years; 20 girls, 14 boys) with confirmed short stature homeobox-containing gene (SHOX) abnormalities. For comparative purposes, we evaluated similar physical and growth parameters in 76 girls with TS (ages 1 to 19 years) and 24 girls with LWD (ages 1 to 15 years) by using data collected from the postmarketing observational study, GeNeSIS. RESULTS: In the clinic sample LWD subjects, height standard deviation score ranged from -5.5 to +0.1 (-2.3 +/- 1.3, girls and -1.8 +/- 0.6, boys). Wrist changes related to Madelung deformity were present in 18 of 34 (53%) LWD subjects. In comparing the LWD and TS populations in the GeNeSIS sample, Madelung deformity, increased carrying angle, and scoliosis were more prevalent in the LWD population, whereas high arched palate was similarly prevalent in the two populations. CONCLUSIONS: Short stature is common in both LWD (girls and boys) and TS (girls). Clinical clues to the diagnosis of SHOX haploinsufficiency in childhood include short stature, short limbs, wrist changes, and tibial bowing.     

Tick-borne encephalitis in children in Styria and Slovenia between 1980 and 2003

BACKGROUND: To describe the effect of the Austrian vaccination program against tick-borne encephalitis (TBE) on the incidence of this disease in children from Styria, an Austrian federal state, and to compare it with that in Slovenia, the neighboring country with a risk to acquire TBE similar to that of Styria. METHODS: A retrospective population-based cohort study was performed with the use of discharge data from all Styrian pediatric hospitals and data from the Center for Communicable Diseases at the National Institute of Public Health in Ljubljana, Slovenia. RESULTS: From January 1980 to December 2003, 139 cases of TBE in children younger than 16 years were observed in Styria. The annual incidence of TBE/100,000 Styrian children declined from 2.5-9.3 cases between 1980 and 1986 to 0-2.2 between 1987 and 1993 and to 0-1 between 1994 and 2003. Extrapolating the incidence of 6.3 cases/100,000 children between 1980 and 1986 to the time from 1994 to 2003, 124 pediatric TBE cases had been prevented in Styria in the past 10 years. CONCLUSIONS: Our data show that the Austrian vaccination program against TBE can lead to the nearly complete disappearance of TBE in children living in areas highly endemic for TBE.     

Pharmacokinetics of enteric-coated mycophenolate sodium in stable pediatric renal transplant recipients

This study aims to characterize the pharmacokinetics of mycophenolic acid (MPA) and its glucuronide metabolite (mycophenolic acid 7-O-glucuronide, MPAG) following single oral administration of enteric-coated mycophenolate sodium (EC-MPS, myfortic) at an approximate dose level of 450 mg/m(2) body surface area (BSA) to 25 stable renal transplant recipients (aged 5-16 yr), and to evaluate the safety and tolerability of EC-MPS in this pediatric population. Patients had been maintained on a cyclosporine emulsion, Neoral-based immunosuppressive regimen for at least 3 months and had received their first or second renal transplant more than 6 months prior to entry into the study. After a brief lag phase (t(lag) 0.75 h), MPA was rapidly absorbed (t(max) 2.5 h) and rapidly converted to MPAG (t(max) 3.25 h), with relatively high plasma concentrations of MPAG (C(max) 67.7 microg/mL) compared with MPA (C(max) 36.3 microg/mL). The elimination half-life for MPAG was slightly longer than for MPA (approximately 13 h vs. 8.5 h), and the apparent oral clearance of MPA was approximately 0.2 L/h/kg. The pharmacokinetics of MPA or MPAG were not affected by age, body weight or BSA, within the study population. The pharmacokinetic results for pediatric patients are comparable with those obtained previously in adults, although exposure based on AUC(0-infinity) was approximately 23% higher, and this finding may be a result of dosing on the basis of BSA, rather than body weight. The recommended dose of EC-MPS in pediatric patients is 400-450 mg/m(2) twice daily or, alternatively, approximately 10-14 mg/kg twice daily when used in combination with cyclosporine microemulsion.     

Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses

Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.     

Animal models of multiple system atrophy

Multiple system atrophy (MSA) is a fatal neurodegenerative disorder presenting with autonomic failure and motor impairment, primarily comprising L-dopa-resistant parkinsonism but occasionally involving cerebellar ataxia. These features result from progressive multisystem neuronal loss that is associated with oligodendroglial alpha-synuclein inclusions. The growing number of animal models for MSA reflects the search for a preclinical test-bed for elucidating MSA pathogenesis and for developing novel therapeutic interventions. Here, the currently available MSA animal models will be reviewed and leads for future research will be identified.