[Electroconvulsive Therapy - A beneficial and well tolerated therapy in children and adolescents with schizophrenia]. / Elektrokonvulsionstherapie ­ bei Kindern und Jugendlichen mit Schizophrenie wirksam und gut verträglich.

We report four cases of 12- to 17-year-old patients with schizophrenia, two of them suffering from catatonia, which were treated by ECT. Under a combined treatment with either ziprasidone or clozapine, and electroconvulsive therapy (ECT), they improved markedly. Severity and course of acute schizophrenia were evaluated by the Brief Psychiatric rating Scale (BPRS), severity and course of catatonia were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This article underlines the benefit, the safety and the tolerability of ECT in younger patients with schizophrenic disorders.

1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

BACKGROUND: Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. OBJECTIVE: This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. METHODS: Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. RESULTS: A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. CONCLUSION: Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. TRIAL REGISTRATION: Controlled Trials: http://www.isrctn.com/ISRCTN89848288.

Living in the Fast Lane: Evidence for a Global Perceptual Timing Deficit in Childhood ADHD Caused by Distinct but Partially Overlapping Task-Dependent Cognitive Mechanisms.

Dysfunctions in perceptual timing have been reported in children with ADHD, but so far only from studies that have not used the whole set of timing paradigms available from the literature, with the diversity of findings complicating the development of a unified model of timing dysfunctions and its determinants in ADHD. Therefore, we employed a comprehensive set of paradigms (time discrimination, time estimation, time production, and time reproduction) in order to explore the perceptual timing deficit profile in our ADHD sample. Moreover, we aimed to detect predictors responsible for timing task performance deficits in children with ADHD and how the timing deficits might be positively affected by methylphenidate. Male children with ADHD and healthy control children, all aged between 8 and 13 years, participated in this longitudinal study with three experimental sessions, where children with ADHD were medicated with methylphenidate at the second session but discontinued their medication at the remaining sessions. The results of our study reveal that children with ADHD were impaired in all timing tasks, arguing for a general perceptual timing deficit in ADHD. In doing so, our predictor analyses support the notion that distinct but partially overlapping cognitive mechanisms might exist for discriminating, estimating/producing, and reproducing time intervals. In this sense, working memory deficits in terms of an abnormally fast internal counting process might be common to dysfunctions in the time estimation/time production tasks and in the time reproduction task, with attention deficits (e.g., in terms of disruptions of the counting process) additionally contributing to time estimation/time production deficits and motivational alterations additionally contributing to time reproduction deficits. Methylphenidate did not significantly alter performance of the ADHD sample, presumably due to limited statistical power of our study. The findings of our study demonstrate a pivotal role of disturbed working memory processes in perceptual timing task performance in childhood ADHD, at the same time broadening the view for additional attentional and motivational determinants of impaired task performance.

Effects of prefrontal rTMS on autonomic reactions to affective pictures.

Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of stimulated cortical areas, such as prefrontal areas involved in emotion regulation. Low frequency (LF) rTMS is expected to have inhibitory effects on prefrontal regions, and thereby should disinhibit limbic activity, resulting in enhanced emotional and autonomic reactions. For high frequency (HF) rTMS, the opposite pattern might be assumed. The objective of this study was to determine the effects of different rTMS frequencies applied to the right dlPFC on autonomic functions and on emotional perception. In a crossover design, two groups of 20 healthy young women were either stimulated with one session of LF rTMS (1 Hz) or one session of HF rTMS (10 Hz), compared to sham stimulation. We assessed phasic cardiac responses (PCR), skin conductance reactions (SCR), and emotional appraisal of emotional pictures as well as recognition memory after each rTMS application. After LF rTMS, PCR (heart rate deceleration) during presentation of pictures with negative and neutral valence was significantly increased compared to the presentation of positive pictures. In contrast, the modulatory effect of picture valence and arousal on the cardiac orienting response was absent after HF rTMS. Our results suggest that frontal LF rTMS indirectly activates the ANS via inhibition of the right dlPFC activity, likely by enhancing the sensory processing or attention to aversive and neutral stimuli.

Prediction of Parkinson's disease subsequent to severe depression: a ten-year follow-up study.

Major depressive disorder (MDD) has been associated with an increased risk of subsequent Parkinson's disease (PD) in case-control and cohort studies. However, depression alone is unlikely to be a useful marker of prodromal PD due to its low specificity. In this longitudinal observational study, we assessed whether the presence of other potential markers of prodromal PD predicts the subsequent development of PD in MDD patients. Of 57 patients with severe MDD but no diagnosis of PD who underwent a structured interview, olfactory and motor investigation and transcranial sonography at baseline, 46 (36 women; mean age 54.9 ± 11.7 years) could be followed for up to 11 (median, 10) years. Three patients (2 women; age 64, 65 and 70 years) developed definite PD after 1, 7, and 9 years, respectively. The combined finding of mild asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity predicted subsequent PD in all patients who could be followed for longer than 1 year. Out of the whole study cohort, only the subjects with subsequent PD presented with the triad of asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity in combination with at least two out of four reportable risk factors (family history of PD, current non-smoker, non-coffee drinker, constipation) at baseline investigation. Post-hoc analysis revealed that additional rating of eye and eye-lid motor abnormalities might further improve the prediction of PD in larger cohorts. Findings of this pilot-study suggest that MDD patients at risk of subsequent PD can be identified using an inexpensive non-invasive diagnostic battery.

A case of catatonia in a 14-year-old girl with schizophrenia treated with electroconvulsive therapy.

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

Structural and functional cortical disconnection in Alzheimer's disease: a combined study using diffusion tensor imaging and transcranial magnetic stimulation.

We investigated the functional consequences of compromised white matter integrity in Alzheimer's disease by combining Diffusion Tensor Imaging (DTI) and Transcranial Magnetic Stimulation (TMS) in 19 patients with AD (Alzheimer's disease) and 19 healthy controls. We used a region of interest approach and correlated the ipsilateral silent period (iSP) and the resting motor threshold (RMT) from TMS with fractional anisotropy (FA) and mean diffusivity (MD) values of the corpus callosum and corticospinal tract. AD patients showed significant reductions of FA in intracortical projecting fibre tracts compared to controls and widespread increases in MD. TMS data showed increased latency of iSP in AD patients and a decreased RMT, indicating decreased motor cortical inhibition. Although both TMS and DTI metrics were prominently altered in AD patients, impaired white matter integrity was not associated with increased iSP latency or reduced RMT, as correlation of TMS parameters with FA and MD values in the a priori defined regions showed no significant effects. Therefore, we argue that beside the direct degeneration of the underlying fibre tracts, other pathophysiological mechanisms may account for the observation of decreased transcallosal inhibition and increased motor excitability in AD.

Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson's disease.

OBJECTIVE: Characteristic features of Parkinson's disease (PD) are asymmetric parkinsonian motor signs, hyposmia and substantia nigra (SN) hyperechogenicity on transcranial ultrasound. However, each of these features has limited diagnostic value as they may be present, albeit less frequently, in other parkinsonian disorders. Here, the diagnostic sensitivity and specificity of combined assessment of these three features are evaluated. METHODS: 632 patients with parkinsonism (PD, vascular parkinsonism, atypical parkinsonian syndromes, essential tremor and major depressive disorder with motor slowing) were assessed on the Unified Parkinson's disease Rating Scale for motor asymmetry (right-left score difference ≥2), the 12 item Sniffin' Sticks test (SS-12) and transcranial ultrasound. The derivation (validation) cohort consisted of 517 (115) subjects (193 (35) women; age 65.4±9.6 (62.3±10.3) years) of whom 385 (68) had PD and 132 (47) non-PD parkinsonism; another 21 (6) subjects were not included due to missing transcranial insonability. Of the validation cohort, all patients had a disease duration ≤2 years and observers were blind to diagnoses. RESULTS: The optimum cut-off values for discrimination of PD were SS-12 score <8 (hyposmia) and SN echogenic size ≥0.24 cm(2) (SN hyperechogenicity). Sensitivity, specificity and positive predictive values for the diagnosis of PD were as follows, for the derivation cohort: motor asymmetry 88%, 54% and 85%; hyposmia 75%, 70% and 88%; SN hyperechogenicity 90%, 63% and 88%; two features present 96%, 72% and 91%; three features present 57%, 94% and 97%; and for the validation cohort: two features present 91%, 77% and 85%; three features present 49%, 98% and 97%. CONCLUSION: The combined assessment of motor asymmetry, hyposmia and SN hyperechogenicity improves diagnostic specificity and allows early diagnosis of PD.

GazeAlyze: a MATLAB toolbox for the analysis of eye movement data.

This article presents GazeAlyze, a software package, written as a MATLAB (MathWorks Inc., Natick, MA) toolbox developed for the analysis of eye movement data. GazeAlyze was developed for the batch processing of multiple data files and was designed as a framework with extendable modules. GazeAlyze encompasses the main functions of the entire processing queue of eye movement data to static visual stimuli. This includes detecting and filtering artifacts, detecting events, generating regions of interest, generating spread sheets for further statistical analysis, and providing methods for the visualization of results, such as path plots and fixation heat maps. All functions can be controlled through graphical user interfaces. GazeAlyze includes functions for correcting eye movement data for the displacement of the head relative to the camera after calibration in fixed head mounts. The preprocessing and event detection methods in GazeAlyze are based on the software ILAB 3.6.8 Gitelman (Behav Res Methods Instrum Comput 34(4), 605-612, 2002). GazeAlyze is distributed free of charge under the terms of the GNU public license and allows code modifications to be made so that the program's performance can be adjusted according to a user's scientific requirements.

Availability of psychiatric medication in an urban area of The Gambia/West Africa.

The use of a wide and differentiated arsenal of psychopharmacological substances is integral part of modern psychiatric treatment in addition to non-pharmacological interventions (e.g., psychotherapy). However, worldwide the access to such medication can vary considerably. In this study, access to a wide range of psychiatric medication including antidepressants, antipsychotics, tranquilisers, mood stabilisers and ADHD medication was analysed for the Western African country of The Gambia by surveying private pharmacies within the urban and sub-urban areas of Banjul, the country's capital. The results show that most of these pharmacies tend to keep a very limited range of psychiatric drugs in stock. In many instances only a tricyclic antidepressant (e.g., amitriptyline), the neuroleptic haloperidol and the benzodiazepine diazepam were readily available. None of the pharmacies kept ADHD medication in stock, and only very few had mood stabilisers. However, several pharmacies reported to be able to obtain at request most of the drugs from international sources, including atypical antipsychotics, SSRIs, and dual-acting antidepressants. Therefore, it can be concluded that in rapidly growing urban centres of developing countries exemplified by Banjul, the infrastructure for modern psychopharmacotherapy is well established, and that the lack of immediate access to modern psychopharmacological compounds represents not so much a genuine lack of availability, but rather a lack of demand which may be associated with the considerable cost-implications of such treatment and the absence of prescribers (i.e. psychiatrists and other doctors with an expertise in modern psychopharmacotherapy). To our knowledge this is the first such study for The Gambia and results might be representative for the wider Western African region. It also exemplifies the challenges psychiatry is facing in developing countries worldwide. It is essential that government-sponsored so-called "essential medication lists" are continuously updated in order to reflect the progress in medical research including psychopharmacology. Further research into how to facilitate psychopharmacotherapy is urgently needed in order to further improve psychiatric services.

Repetitive transcranial magnetic stimulation (rTMS) for treatment of alcohol dependence.

OBJECTIVES: Neuroimaging studies have found that alcohol dependent patients display dopaminergic dysfunction in the ventral striatum, which is associated with alcohol craving. Repetitive transcranial magnetic stimulation (rTMS) was introduced as a promising new treatment option for depression, and among other neurobiological mechanisms, it is able to stimulate the striatal dopaminergic system. The aim of our study was to investigate the effect of high frequency rTMS of the left dorsolateral prefrontal cortex compared to sham stimulation on craving and mood in alcohol dependent women. Furthermore, the impact on an attentional blink (AB) paradigm to pictures with neutral, emotional and alcohol-related contents was proofed. METHODS: Nineteen female detoxified patients were randomized either to a high frequency rTMS (20 Hz) over the left DLPFC (n = 10) or a sham stimulations (n = 9) at 10 days. Alcohol craving was determined with the Obsessive Compulsive Drinking Scale, depressive symptoms were registered by means of Hamilton Depression Rating Scale and Beck' Depression Inventory. For the AB paradigm an age-matched control group was investigated. RESULTS: There were no significantly differences between both groups regarding alcohol craving or mood. In the AB paradigm, real stimulated patients detected alcohol related T2 targets incorrectly in comparison to the sham stimulated and control subjects. SUMMARY: Although there were no differences in clinical parameters such as craving or mood after real high frequency rTMS compared to sham stimulation, we found an interesting difference between the real and the sham stimulated group and controls in the AB paradigm indicating an increase of the AB effect to alcohol-related pictures after real stimulation. Further studies are needed to replicate these findings and correlate them to clinical and neurophysiological data.

Influence of repetitive transcranial magnetic stimulation on special symptoms in depressed patients.

Since various studies, including multi-centre studies, investigating the effect of repetitive transcranial magnetic stimulation (rTMS) in depression have shown different results, it is now important to research, which symptoms of depression are most responsive to this kind of non-invasive brain stimulation. Furthermore, an increasing interest of rTMS as a potential tool for treatment of neurological and psychiatric disorders should be recorded. Therefore, it is critical to investigate dopaminergic functional interactions in the prefrontal cortex, and in particular, the effect of dorsolateral prefrontal cortex stimulation on clinical symptoms depending on dopaminergic concentrations in various brain regions. This short review summarizes important preliminary data, which focus on the symptom-oriented effects of rTMS in depression.

The effects of 10 Hz repetitive transcranial magnetic stimulation on resting EEG power spectrum in healthy subjects.

10 Hz rTMS over the left prefrontal cortex may be useful in the treatment of depressive disorders. However, the effects of 10 Hz rTMS applied in potentially effective doses on electroencephalographic activity are not well studied. Using EEG, we aimed to investigate the neurobiological effects of the 10 Hz rTMS set of parameters currently used for depression treatment in a sample of healthy subjects. In 18 healthy subjects, either 10 Hz real rTMS or sham stimulation were given in a crossover design. Real rTMS stimulation was carried out with an intensity of 110% of motor threshold (MT) over the left dorsolateral prefrontal cortex. For the sham condition, the coil was angled over a parietotemporal position and the intensity was reduced to 90% of MT. EEG recordings were taken before and after a single rTMS session. EEG power spectrum was extracted using the complex demodulation method and changes in power were evaluated statistically. Real 10 Hz rTMS induced an overall increase in delta power. This increase prevailed throughout the sample, whereas effects on the power of the alpha, beta and theta EEG bands were highly variable. Sham stimulation had no substantial effects on the EEG power spectrum. Furthermore, no changes in EEG asymmetry were detected. Real 10 Hz rTMS applied at 2000 stimuli and 110% intensity may induce significant changes in resting EEG in healthy subjects.

Maternal nerve growth factor serum levels in the perinatal period.

Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are potent modulators of neuronal and immune function, and have been implicated recently in diseases associated with pregnancy. In contrast to serum BDNF, which is reportedly suppressed in the perinatal period, regulation of NGF in the perinatal period is unknown. In this study, serum NGF concentrations were measured in 40 pregnant (follow-up: 30th and 37th week of gestation, 1 week and 8 weeks after childbirth) and 40 non-pregnant women. Maternal NGF serum levels did not differ significantly from controls (median: 7.6 pg NGF/ml serum) neither before nor after childbirth, although there was a trend towards increased NGF concentrations at the 37th week of gestation (median: 12.5 pg NGF/ml serum) and 1 week after childbirth (median: 11.6 pg NGF/ml serum). There was no association of maternal NGF with 17beta-estradiol, progesterone, dehydroepiandrosterone sulfate (DHEAS) and cortisol concentrations in maternal serum, or maternal depression, as measured by the Edinburgh Postnatal Depression Scale (EPDS). In the non-pregnant control group, NGF serum concentrations were negatively correlated with the number of days since the first day of the menstrual cycle (r=-0.32, p<0.05). In conclusion, NGF is not altered during normal pregnancy on a systemic level. In addition, NGF displays a different regulation compared with BDNF during the menstrual cycle.

Transcranial magnetic stimulation: the method and application.

Transcranial magnetic stimulation is a noninvasive method for stimulation of brain that is based on the ability of magnetic field to penetrate skull and brain meninges, subsequently inducing electric current in the brain tissues that produces neuronal depolarization and generation of action potentials. Moreover, transcranial magnetic stimulation has effects on neurochemical and synaptic processes in neurons. Due to its easy use and relatively fair side effects, nowadays, transcranial magnetic stimulation is widely used in neurosciences and medicine. The main areas of transcranial magnetic stimulation application are: 1) the investigation of cortical and spinal excitability, 2) the investigation of neuronal plasticity, 3) the investigation of neuronal connectivity, 4) functional mapping, and 5) the treatment of some neurological and psychiatric disorders. Transcranial magnetic stimulation alone or in combination with other noninvasive neuroimaging (PET--positron emission topography, MRI--magnetic resonance imaging) and neurofunctional (EEG--electroencephalography, ERP--event-related potentials, fMRI--functional magnetic resonance imaging) methods allows conducting research on brain functions. Thus, transcranial magnetic stimulation is suitable as a diagnostic tool in neurologic and neuropsychiatric brain research.

Maternal serum concentrations of BDNF and depression in the perinatal period.

There is accumulating evidence that a deficiency in brain-derived neurotrophic factor (BDNF) plays a critical role in the pathophysiology of depression. This is in line with the postulate that low BDNF levels in serum are associated with depression. However, the regulation of maternal BDNF serum levels in the perinatal period, and its relationship to maternal depression is unknown. In this study, serum BDNF concentrations were measured in 40 pregnant (follow-up: 30th and 37th week of gestation, 1 week and 8 weeks after childbirth) and 40 non-pregnant women (20-40 years old). The Edinburgh Postnatal Depression Scale (EPDS) was assessed in all subjects at all time points. Maternal serum levels of BDNF were markedly decreased, both before and after childbirth (median: <30% of non-pregnant controls). BDNF correlated with decreased Serotonin (5-HT) levels in serum (r>0.6 and p<0.001 at all time points). In contrast, there was no association with altered estrogen, progesterone, dehydroepiandrosterone or cortisol concentrations in serum. There were significantly higher cortisol levels in cases of maternal depression (EPDS scores>9 points) than in cases without depression. There was a trend to a decrease of BDNF and 5-HT levels in cases of maternal depression (as compared to cases without depression), but this was not significant. In conclusion, we demonstrate that women display markedly decreased BDNF serum levels before and after childbirth. This phenomenon might reflect an increased risk for the development of mood disorders in the perinatal period. However, the individual serum concentration of BDNF alone did not predict maternal depression in our study.

Antidepressant efficacy of two different rTMS procedures. High frequency over left versus low frequency over right prefrontal cortex compared with sham stimulation.

BACKGROUND: This placebo-controlled study was designed to investigate the influence of two different stimulation procedures of repetitive transcranial magnetic stimulation (rTMS) on depressive symptoms in patients with depressive disorders. Furthermore, effects on cognitive functions and psychomotor functioning were tested. METHODS: Thirty patients with depression (22 females and 8 males; mean age of 56.4 years) were included. They were treated with a stable dosage of antidepressant medication. They received either high frequency rTMS (20 Hz) over the left dorsolateral prefrontal cortex (LDLPFC), low frequency rTMS (1 Hz) over the right dorsolateral prefrontal cortex (RDLPFC) or sham stimulations (10 patients in each group) as add on treatment at 10 days within 2 weeks. Depressive symptoms were registered by means of observer ratings (Hamilton Depression Rating Scale - HDRS) and self reports (Beck Depression Inventory - BDI). Psychomotor retardation was investigated by the Motor Agitation and Retardation Scale and cognitive function by d2 test. RESULTS AND CONCLUSIONS: Differences between the rTMS procedures regarding depressive symptoms could not be found. Motor abnormalities, however, significantly improved exclusively after real stimulation procedures. Patients with less severe deficits in psychomotor speed and concentration responded more intensively than patients with severe deficits.