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There is growing concern about the influence of the pharmaceutical industry on psychiatric teaching and psychiatric professionalism as a whole. As a consequence, several national and international medical and psychiatric associations have issued guidelines to regulate the interactions between physicians and industry.
The EFPT-PRIRS study aims to provide the lacking data on the extent and nature of these interactions among psychiatric trainees across Europe.
Study objectives were determined by the EFPT research group (EFPT-RG), after discussion with national and international experts. A survey was then devised compiling previously published questionnaires extending them by questions with specific relevance to psychiatric trainees. The resulting questionnaire was piloted amongst members of the EFPT-RG, modified accordingly and subsequently distributed to the national study coordinators. All 24 EFPT member countries were invited to participate in the study and data collection is currently ongoing.
Preliminary analysis reveals the vast differences in industry - trainee relationships across European countries as well as major differences in personal attitudes towards these interactions.
EFPT-PRIRS will potentially have an impact on the regulation of the interactions between the pharmaceutical industry and psychiatric trainees.
Previous studies of patients with unipolar depression have shown that early decreases of prefrontal quantitative EEG (QEEG) cordance in theta band can predict clinical response to various antidepressants. We now examined whether reduction of prefrontal cordance value after 1 week of venlafaxine treatment predicts clinical response to venlafaxine in non-responders to previous antidepressant treatments.
We analyzed 25 inpatients, who finished 4-week treatment with venlafaxine. EEG data were monitored at baseline and after 1 week of treatment. QEEG cordance was computed at 3 frontal electrodes in theta frequency band. Depressive symptoms were assessed using Montgomery-Åsberg Depression Rating Scale (MADRS).
Eleven of 12 responders (reduction of MADRS ≥50%) and only 5 of 13 non-responders decreased prefrontal QEEG cordance value after the first week of treatment. The decrease of prefrontal cordance after week 1 in responders was significant (p=0.03) and there was no change in nonresponders. Positive and negative predictive value of cordance reduction for response was 0.7 and 0.9, respectively.
The reduction of prefrontal theta QEEG cordance value after first week of treatment is a useful tool in the response prediction to venlafaxine.
This study was supported by a grant from Internal Grant Agency of Ministry of Health of Czech Republic No. NR/9330-3 and a grant of Ministry of Education of Czech Republic MSMT 1M0517.
Transcranial magnetic stimulation (TMS) is a non-invasive method that induces functional changes in a relatively small area of the cerebral cortex. It is supposed that the effect of the method in therapy of neuropatic pain is based on the induction of spinothalamic tract inhibiton, which leads to the symptom withdrawal.
To prove the clinical and electrophysiological effect of rTMS in the therapy of chronic neuropatic pain.
29 patients with medication-resistant neuropatic pain were examined by Visual analog scale (VAS), McGill Pain Questionnaire (MPQ) and QST(Quantitative sensory Testing, consisted of von Frey and thermic treshold examination),then treated by high frequency rTMS in the study using double-blind randomized sham-controlled parallel design. rTMS parameters: 5 rTMS sessions (2 weeks treatment), where each session consisted of three 10 Hz rTMS series using:
1) 85%MT (motor treshold),
2) 90%MT and
Each rTMS série consisted of 20 pulses in 12 trains. Location of the active coil was administered over the contralateral motor cortex, directed specifically to facial area of homunculus (according to funcional location). Sham coil was angled 90° degrees away from the skull.
Confirmation of a significant decrease of VAS item in active group, trend to improvement in tactile sensation of severed patient faces. The changes of thermic treshold were not found. Sham rTMS did not show any trend for improvement.
Although no general recommendations can be drawn based on our result, our study is another one that suggest rTMS should be considered as an effective and safe treatment option for chronic neuropatic pain.
The previous studies have detected changes of brain electrical activity after the cerebellar hemisphere rTMS and the vermis rTMS. We supposed that right cerebellar 1Hz rTMS evokes changes in the left frontal cortex. The aim of our study was to determine if 1Hz cerebellar hemisphere and 1 Hz vermis rTMS induces different effect in frontal electrical activity.
We used 10 minutes of 1 Hz rTMS (with 600 impulses) in two sessions (first session- application over the right cerebellar hemisphere, second over the vermis). 31-channel EEG was recorded in 5 right-handed healthy volunteers before and after rTMS. The 3D distribution of the current density was revealed by a method of qEEG- Low Resolution Brain Electromagentic Tomography (LORETA, Pascual-Marqui et al. 1994; 1999).
After 1 Hz right cerebellar hemisphere rTMS the current density decreased in the alfa2, beta1, beta2 and beta3 band over the frontal cortex including medial frontal cortex and the anterior cingulate (p<0.01). After 1 Hz vermis rTMS we found no significant changes.
Our results suggest the possibility to influence the frontal cortical activity by means of the cerebellar hemisphere rTMS. No significant changes after 1Hz vermis rTMS may suggest either large distance between the rTMS coil and the vermis or our sample is too small to make definitive conclusions.
Previous studies demonstrated predictive effect of reduction of prefrontal cordance for non-resistant outpatients or resistant inpatients treated by various antidepressants or venlafaxine. The aim of the present study was to examine whether the reduction of theta prefrontal QEEG cordance value after 1 week of bupropion administration is associated with response to 4 weeks treatment in patients with resistant depressive disorder. We extended our previous pilot data.
We analyzed 18 inpatients, who finished 4-week treatment with venlafaxine. EEG data were monitored at baseline and after 1 week of treatment. QEEG cordance was computed at 3 frontal electrodes in theta frequency band. Depressive symptoms were assessed using Montgomery-Åsberg Depression Rating Scale (MADRS).
Nine of 11 responders (reduction of MADRS ≥50%) and no one of 7 non-responders decreased prefrontal QEEG cordance value after the first week of treatment. Positive and negative predictive value (PPV, NPV) of cordance reduction for response to treatment was 1.0 (95% CI, 0.8-1.0) and 0.78 (95% CI, 0.57-0.78), respectively.
Based on our results, the prefrontal QEEG cordance might be helpful in the prediction of the response to bupropion treatment in resistant patients.
This study was supported by a grant from Internal Grant Agency of Ministry of Health of Czech Republic No. NR/9330-3 and a grant from Ministry of Health of Czech Republic MZ0PCP2005.
The previous studies have detected changes of brain electrical activity (current density) after cerebellar rTMS. We suppose that right cerebellar rTMS evokes changes in the left frontal cortex. The aim of our study was to determine if 1Hz and 10Hz cerebellar rTMS induces antagonistic effect in frontal electrical activity.
We used 10 minutes of 10 Hz and 10 minutes of 1 Hz rTMS (both with 600 impulses, application over the right cerebellar hemisphere) in two sessions. 31-channel EEG was recorded in 10 right-handed healthy volunteers before and after rTMS. The 3D distribution of the current density was revealed by a method of qEEG- Low Resolution Brain Electromagentic Tomography (LORETA, Pascual-Marqui et al. 1994; 1999).
After right cerebellar 1 Hz rTMS the current density decreased in the alfa2, beta1, beta2 and beta3 band over the frontal cortex including medial frontal cortex and anterior cingulate. After 10 Hz rTMS we found a decrease over the frontal cortex in the delta, theta and alfa1 band bilaterally, more on the left side (p<0.01).
Our results suggest the possibility to influence the frontal cortical activity by means of the cerebellar 1Hz and 10 Hz rTMS (antagonistic effect in the frontal cortex- decrease in slow frequencies after 1 Hz and in fast frequencies after 10 Hz rTMS).
A series of clinical studies demonstrated that QEEG prefrontal theta cordance value decreases after one week of treatment in responders to antidepressants and precedes clinical improvement. Ketamine, a non-competitive antagonist of NMDA receptors, has a unique rapid antidepressant effect but its influence on theta cordance is still unknown.
In a double-blind, cross-over, placebo-controlled experiment we studied the influence of ketamine (0.54 mg/kg) on theta cordance in a group of 20 right-handed healthy volunteers. Participants were evaluated with the Brief Psychiatric Rating Scale before infusion and after 10 and 30 min. Three EEG segments obtained at baseline and prior to BPRS examinations at 10 and 30 min after dosing were entered into spectral analyses and QEEG cordance values in theta frequency band were calculated for four regions (prefrontal, central, left and right temporal).
Ketamine infusion induced a decrease in prefrontal theta cordance at 10 (p=0.04) and 30 min (p=0.02) and a significant increase of theta cordance in central region at both time points (p=0.01). We observed no significant effect on cordance values in the left and right temporal regions.
Our data indicate that ketamine infusion immediately induces similar changes as monoaminergic-based antidepressants do gradually after a series of downstream signaling steps. The reduction in theta prefrontal cordance could serve as a marker of fast antidepressant effect of ketamine, a hypothesis that should be tested in antidepressants-refractory patients.
This study was supported by a grant of IGA MHCR NR/9330-3 and by a project of MEYS CR VZ0021620816.
Hundreds of QEEG-related papers brought new information about the temporal dynamics of complex neuronal interactions that underlie impaired processing in many psychiatric diagnoses. Besides this fact, many researchers, clinical psychiatrists and neuroscientists prefer new imaging techniques (Positron Emission Tomography, PET; and functional Magnetic Resonance, fMRI) even if they are based on an indirect index of brain computing as metabolic or hemodynamic measurements which are blind to millisecond phenomena. We present the results of our studies provided with QEEG techniques (Low Resolution Electromagnetic Tomography, LORETA; EEG coherence, EEG cordance) in: 1) more than 60 patients with schizophrenia examined by means of QEEG and PET. We found significantly lower EEG coherence values, mainly from the left frontotemporal derivations in patients group and there was also significant correlation between the decrease of frontotemporal EEG coherence and elevated glucose metabolic uptake in the limbic structures (posterior cingulate and hippocampus). LORETA analysis showed almost the same results as analysis of PET images, not only in basal disease process, but also after successful application of rTMS in the subgroup of patients with treatment-resistant auditory hallucination. 2) in more than 30 patients with resistant depressive disorder we computed the new EEG indicator value (EEG cordance), and we showed, that the decrease in prefrontal EEG cordance in theta frequency band may indicate early changes of prefrontal activity and can become a useful tool in the prediction of response to antidepressants.
The aim of our study was detection of brain electrical activity changes in panic disorder (PD) patients by means of the electromagnetic tomography. Several observations suggest the panic disorder should be characterized by right frontal hyperactivation (Wiedemann et al., 1999).
Electroencephalograms of 33 panic disorder patients (9 men and 24 women) were compared with the same number of age and gender matched control subjects. EEG was recorded in the resting state with a 19-channel amplifier. 3-dimensional distribution of the current density was revealed by a method of quantitative electroencephalography - Low Resolution Brain Electromagentic Tomography (LORETA, Pascual-Marqui et al. 1994)
There was increase in the beta1 and beta2 frequency band over the frontal cortex including the insula and orbitofrontal cortex (p<0.01) with right side maximum in panic disorder patients. Also bilateral decrease in the alpha band over the occipital cortex including precuneus and posterior cingulate (p<0.02) was found.
The findings of our study confirmed hypothesis of frontal brain asymmetry with higher level of right hemisphere activation in panic disorder patients. These data are the first evidence of applying LORETA method to panic disorder studying.
This study was supported by the project MZ0PCP2005
QEEG almost consistently reports an abnormal excess of delta/theta activity, reduced alpha activity and posterior excess of beta activities in schizophrenics. LORETA allows more precise localization of these findings (excess of delta in bilateral anterior cingulate, increase of beta in parietal gyrus).All antipsychotic drugs induce significant changes in QEEG reflecting differential effects on inhibitory and excitatory activities. Two QEEG profiles of first-generation antipsychotics may be differentiated: a)chlorpromazine-type profile, characterized by an increase in delta/theta and a decrease in alpha and beta power spectra, and b)haloperidol-type profile, which exhibits no significant change in delta/theta frequency band but increase of alpha and alfa adjacent beta activity. The second generation antipsychotics have different QEEG and LORETA profiles probably reflecting their different mechanism of action. Clozapine produces an increase of delta, theta and alpha1 and decrease of alpha2 and fast beta activities. Comparing to antipsychotic-naïve schizophrenics, clozapine-treated patients showed an excess of delta and theta activities in anterior cingulate and medial frontal cortex. QEEG profile of olanzapine is similar to clozapine, whereas tomography show slightly different pattern (decrease of alpha1-beta activities in the occipital cortex and posterior limbic structures and decrease of beta3 sources in the fronto-temporal cortex and anterior cingulum). Risperidone increased current density in frontal regions for delta, theta and alpha1 in healthy subjects, whereas we found no changes in LORETA between risperidone-treated and antipsychotic-naïve patients. According to‘key–lock principle'the pharmaco-EEG topography and tomography could be helpful in the optimization of antipsychotic therapy.
Supported by the projects IGA MZCR NR9330-3/2007 and MSMTCR1M0517.
The aim of our study was to examine whether the change of current density detected by standardized low resolution brain electromagnetic tomography (sLORETA) is different between responders and non-responders to prefrontal repetitive transcranial magnetic stimulation (rTMS).
A total of 25 inpatients with depressive disorder (DSM-IV criteria), who previously did not respond to at least one antidepressant treatment underwent 4 weeks of rTMS treatment (1 Hz, 100% of motor threshold, 600 pulses/session, 20 session) applied over the right dorsolateral prefrontal cortex. 19-channel EEG was recorded before treatment and 3 days after rTMS treatment. The effect of rTMS on brain electrical activity (revealed by the use of sLORETA, Pascual-Marqui RD, 2002) was measured separately in responders (reduction of MADRS≥50%) and non-responders.
The significant current density increase in alpha 1 band was detected in prefrontal and limbic cortex (Brodman areas 6, 8, 9, 32) bilaterally (p < 0.05, corrected) in a group of nine responders. No significant changes were detected in non-responders.
Our findings implicate that the antidepressant effect of 1 Hz rTMS is connected with a current density increase in alfa 1 band in the prefrontal cortex. Supported by 1M0517 and MZ0PCP2005.
Cordance is a QEEG method that incorporates both absolute and relative power and has been shown to have a strong association with cerebral perfusion or metabolism. Cordance accurately characterizes brain function on the cortical convexities and has demonstrated usefulness for characterizing antidepressant response. The aim of this study was to evaluate the efficacy of QEEG cordance in the prediction of response to various antidepressants in patients with resistant depression.
A total of 81 inpatients with depressive disorder (MADRS≥20) who previously did not respond to at least one antidepressant treatment were treated with various antidepressants for 4 weeks. QEEG cordance was computed at 3 frontal electrodes in theta frequency band (4–8 Hz). Depressive symptoms were assessed using Montgomery-Åsberg Depression Rating Scale.
29 from 33 responders and 14 from 48 non-responders decreased prefrontal QEEG cordance value after the first week of treatment (p = 0,0001). There was a difference between responders and nonresponders in the change of cordance value after first week of treatment (p = 0.002). Positive and negative predictive value of cordance reduction for response to treatment was 0.67 (0.58–0.73) and 0.90 (0.79–0.96), respectively. The overall accuracy of the test was 0.78 and the effect size (w = 0.59) was in large range.
Early change in prefrontal theta band cordance probably reflects a common underlying mechanism of antidepressant effect, regardless of the type of treatment. Prefrontal cordance may provide a useful biomarker for the early detection of response to antidepressant therapy.
A series of clinical studies demonstrated that QEEG (quantitative electroencephalography) prefrontal theta cordance value decreases after one week of treatment in responders to antidepressants and precedes clinical improvement. Ketamine, a non-competitive antagonist of NMDA receptors, has a unique rapid antidepressant effect but its influence on QEEG measures is still unknown. To date wasn’t studied predictive value of cordance in response to single infusion of ketamine in depressive subjects.
In a double-blind, cross-over, randomized, placebo-controlled experiment we studied the influence of ketamine (0.54 mg/kg) on theta cordance in a group of 27 right-handed hospitalized depressive patients on stable antidepressant medication. QEEG cordance values in theta frequency band were calculated according to UCLA algorithm.
Responders (n=11) to ketamine in compare to non-responders (n=16) showed significant difference in cordance values at the end of ketamine infusion (Spearman, p= 0.039). The cordance decrease, measured between the end of infusion and next day, positively correlated with ketamine antidepressant response (MADRS decrease) fourth day after infusion (two-tailed Fisher's Exact test, df=1, p=0.0076) with NPV 90.9% (95% CI 64.3%-99.5%) and PPV 62.5% (95% CI 44.2%-68.4%).
Our data indicate that ketamine infusion immediately induces similar changes as monoaminergic-based antidepressants do gradually after a series of downstream signalling steps. The reduction in theta prefrontal cordance could serve as a biomarker of sustained antidepressant response, a hypothesis that should be tested in larger depressive population.
Experiences of depression and anxiety are common among patients with persecutory delusions. It has been theorized that emotional disturbances affect the formation and appraisal of persecutory delusions directly and possibly via increasing the sense of aberrant salience.
Using a time-lagged analysis of experience sampling data, this study modelled the role of momentary levels of negative emotions and aberrant salience in maintaining persecutory delusions in patients with active delusions.
Clinically acute participants with at least a mild level of persecutory delusions were assessed using experience sampling method (ESM; 7 entries per day for 14 days) and clinical rating scales. ESM data of participants who completed at least 30 ESM entries were analysed by using multilevel regression modelling.
The final sample consisted of 14 participants, with a total of 1161 momentary observations. Time-lagged analysis revealed that both negative emotions (B = 0.125, P = .009) and aberrant salience (B = 0.267, P< .001) predicted an increase in persecutory delusions in the next moment. Conversely, persecutory delusions did not predict change in negative emotions or change in aberrant salience in the next moment (ps> .05). Negative emotions also predicted an increase in aberrant salience in the next moment (B = 0.087, P = .009).
Our results supported the hypothesis that both negative emotions and aberrant salience exacerbate persecutory delusions, rather than being merely the sequelae of the symptoms. Our results suggested both direct and indirect (via aberrant salience) pathways from negative emotions to persecutory delusions.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present a new class of bioinspired nanomaterials that are stabilized by a combination of covalent and hydrogen bonds. Prior work by others has shown that cyclic peptides can self-assemble to form supramolecular assemblies through backbone-backbone hydrogen bonding. To improve upon this molecular architecture, we develop a synthesis route to polymerize cyclic peptides and form a linear polymer chain that can transition between a rigid nanorod and an unfolded conformation. For a cyclic peptide polymer containing amine-terminated side chains on each ring, we demonstrate self-assembly can be triggered in aqueous solutions by varying the pH. We measure the elastic modulus of the rigid nanorods to be ca. 50 GPa, which is comparable to our molecular dynamics (MD) prediction (ca. 64 GPa). Our results highlight the uniqueness of our molecular architecture, namely their exemplary toughness (up to 3 GJ m-3), in comparison to other cyclic peptide-based assemblies. Finally, we demonstrate amphiphilic cyclic β-peptides are capable of inhibiting the growth of gram-negative and gram-positive bacteria.
Problem behavior of young children is generally not assessed with structured child interviews. This paper examined how information about problem behavior, obtained by structured interviews with six-year-old children, relates to DSM-disorders obtained from parents and to treatment referral.
In a population-based cohort, caregivers of 1084 young children (mean age 6.7 years) were interviewed with the DSM-based Diagnostic Interview Schedule-Young Child version (DISC-YC), and they scored the Child Behavior Checklist (CBCL). Children themselves were interviewed about problem behavior using the semi-structured Berkeley Puppet Interview (BPI). Information regarding treatment referral to mental health services was obtained by parent-reported questionnaire when children were on average eight years old.
DSM-disorders and CBCL problems in the clinical range were cross-sectionally associated with higher levels of child self-reported problems. Associations were strongest in the externalizing domain (e.g. DISC-YC externalizing disorders with BPI externalizing scores: F(1, 416) = 19.39, P < 0.001; DISC-YC internalizing disorders with BPI internalizing scores: F(1, 312) = 3.75, P = 0.054). Moreover, higher BPI internalizing and externalizing problem scores predicted treatment referral two years later.
We conclude that systematically interviewing preschool and young elementary school-aged children should be an integral part of child assessment. This approach may contribute to a better understanding of child development and may predict future problems.
Carbapenem-resistant Acinetobacter baumannii (CRAB) with diverse multilocus sequence typing emerged among our nursing home residents (6.5%) with a high background rate of MRSA (32.2%). Rectal swabs yielded a higher rate of CRAB detection than axillary or nasal swabs. Bed-bound status, use of adult diapers, and nasogastric tube were risk factors for CRAB colonization.
Observations have been suggested that star clusters could form from the rapid collapse and violent relaxation of substructured distributions. We investigate the collapse of fractal stellar distributions in no, weak, and very strong tidal fields. We find that the rapid collapse of substructure into spherical clusters happens quickly with no or a weak tidal field, but very strong tidal fields prevent a cluster forming. However, we also find that dense Plummer spheres are also rapidly destroyed in strong tidal fields. We suggest that this is why the low-mass star clusters cannot survive near the galactic centre which has strong tidal field.