Iron deficiency, depression, and fatigue in inflammatory bowel diseases.

BACKGROUND: Iron deficiency and anemia are common findings in IBD. Treatment of anemia improves quality of life. Neurological symptoms like depression or anxiety are also common in IBD; however, their relationship with ID has not been studied in detail. METHODS: Prospective, single center, non-interventional trial in an IBD cohort (n = 98), which is generally at risk for ID. Quality of sleep (using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Insomnia Severity Index) and the presence of fatigue (Piper fatigue scale), depression (Self-rating Depression Scale [SDS]) or anxiety (Self-rating Anxiety Scale [SAS]) were related to ID (ferritin, transferrin saturation), anemia (hemoglobin), and inflammatory disease activity (CRP). RESULTS: ID was present in 35 %, anemia in 16 %, and inflammation in 30 %. The overall quality of sleep in this cohort was similar to that reported for the general population. ID, anemia, or inflammation had no influence on the PSQI (median 4.0 [CI 3.0-5.0]), the ESS 5.5 (5.0-7.0), and the ISI 4.00 (2.5-5.5). Fatigue (PFS; present in 30 %), anxiety (SAS; present in 24 %), and depression (SDS; present in 33 %) were more common than in the general population. Iron deficient and anemic patients were more likely to be depressed (p = 0.02 and p < 0.01) and showed a trend towards presence of fatigue (p = 0.06 and 0.07). Systemic inflammation as measured by CRP had no effect on any of these conditions. CONCLUSION: In this IBD cohort, ID and anemia affect depression and possibly fatigue independent of the presence of inflammation.

Reduced Brain Electric Activity and Functional Connectivity in Bipolar Euthymia: An sLORETA Source Localization Study.

Bipolar disorder (BD) is a chronic illness with a relapsing and remitting time course. Relapses are manic or depressive in nature and intermitted by euthymic states. During euthymic states, patients lack the criteria for a manic or depressive diagnosis, but still suffer from impaired cognitive functioning as indicated by difficulties in executive and language-related processing. The present study investigated whether these deficits are reflected by altered intracortical activity in or functional connectivity between brain regions involved in these processes such as the prefrontal and the temporal cortices. Vigilance-controlled resting state EEG of 13 euthymic BD patients and 13 healthy age- and sex-matched controls was analyzed. Head-surface EEG was recomputed into intracortical current density values in 8 frequency bands using standardized low-resolution electromagnetic tomography. Intracortical current densities were averaged in 19 evenly distributed regions of interest (ROIs). Lagged coherences were computed between each pair of ROIs. Source activity and coherence measures between patients and controls were compared (paired t tests). Reductions in temporal cortex activity and in large-scale functional connectivity in patients compared to controls were observed. Activity reductions affected all 8 EEG frequency bands. Functional connectivity reductions affected the delta, theta, alpha-2, beta-2, and gamma band and involved but were not limited to prefrontal and temporal ROIs. The findings show reduced activation of the temporal cortex and reduced coordination between many brain regions in BD euthymia. These activation and connectivity changes may disturb the continuous frontotemporal information flow required for executive and language-related processing, which is impaired in euthymic BD patients.

Sleep and Quality of Life Under Prolonged Release Oxycodone/Naloxone for Severe Restless Legs Syndrome: An Analysis of Secondary Efficacy Variables of a Double-Blind, Randomized, Placebo-Controlled Study with an Open-Label Extension.

OBJECTIVE: The aim was to assess the effects of prolonged release oxycodone/naloxone (OXN PR) on sleep and quality of life (QoL) in patients with severe restless legs syndrome (RLS) refractory to first-line dopaminergic RLS treatment. METHODS: Sleep and QoL data from a 12-week, randomized, double-blind, placebo-controlled study with subsequent 40-week, open-label extension were analyzed. Instruments included the Medical Outcomes Study (MOS) sleep scale, RLS-6 rating scale, and RLS-QoL questionnaire. RESULTS: The full analysis population included 132 OXN PR and 144 placebo patients. After 12 treatment weeks, improvements in the MOS domains 'sleep disturbance' [-18.6; 95 % confidence interval (CI) -24.4 to -12.9; p < 0.0001], 'sleep adequacy' (14.9; 95 % CI 7.9-21.9; p < 0.0001), and 'sleep quantity' (0.77 h; 95 % CI 0.43-1.11; p < 0.0001) were significantly greater under OXN PR than under placebo. OXN PR also reduced symptom severity (when falling asleep and during the night) and daytime tiredness, and increased sleep satisfaction to a significantly greater extent than placebo (all p < 0.001; RLS-6). QoL improved in both treatment arms, with a significant difference of -9.02 (95 % CI -12.85 to -5.19; p < 0.001) in the mean sum score in favor of OXN PR. All sleep and QoL aspects also improved under 40 weeks of open-label OXN PR treatment. CONCLUSIONS: OXN PR improved RLS symptom severity and sleep quantity and adequacy, resulting in greater sleep satisfaction, less daytime tiredness, and improved QoL. In appropriate patients, OXN PR should be considered as an alternative treatment option for severe RLS that cannot be controlled by first-line dopaminergic medications. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01112644) and EudraCT (2009-011107-23).

Recent advances in sleep research.

The past two decades have witnessed substantial progress in methodology and knowledge in sleep research all over the world. The paper at hand will present some recent local contributions to this field. The first is a European project (SIESTA) focusing on the creation of an automatic sleep classification system and a normative database, including polysomnographic (PSG) and psychometric measures, in order to make it possible to diagnose sleep-disordered patients as compared with and age- and sex-matched healthy controls between 20 and 95 years of age. Subsequently, two trials on nonorganic sleep disorders in generalized anxiety disorder (GAD) and bruxism, as well as two trials on organic sleep disorders, i.e. snoring/sleep-disordered breathing treated with a mandibular advancement device (I.S.T.) and restless legs syndrome treated with ropinirole and gabapentin, will be discussed.

[Sleep disorders in psychiatry and their treatment]. / Schlafstörungen In Der Psychiatrieund Therapeutische Maßnahmen.

Sleep disturbances are frequent and multifaceted and have serious consequences. They play an important role within psychiatric symptoms and disorders. On the one hand they may appear as a symptom of a disorder, which may also be a diagnostic criterion, as for example in affective disorders, on the other hand they may be independent disorders or last but not least sequelae of psychiatric disorders or their pharmacological therapy, as with antidepressants or neuroleptics, which may cause or deteriorate nocturnal movement disorders. They may aggravate psychiatric disorders, perpetuate them or predict a disease onset, like in depressive or manic episodes. Also in organic sleep disorders, such as sleep-related breathing disorders or nocturnal movement disorders, increased anxiety or depression scores may be observed. Patients suffering from sleep disorders do not only experience impaired well-being, but also show deteriorations in cognition and performance, have a higher risk of accidents, are generally more prone to health problems, have a higher sickness absence rate, seek medical help more often and thus are also an important socioeconomic factor. This is why sleep disorders should be taken seriously and treated adequately.

Dysfunctional pain modulation in somatoform pain disorder patients.

To date, pain perception is thought to be a creative process of modulation carried out by an interplay of pro- and anti-nociceptive mechanisms. Recent research demonstrates that pain experience constitutes the result of top-down processes represented in cortical descending pain modulation. Cortical, mainly medial and frontal areas, as well as subcortical structures such as the brain stem, medulla and thalamus seem to be key players in pain modulation. An imbalance of pro- and anti-nociceptive mechanisms are assumed to cause chronic pain disorders, which are associated with spontaneous pain perception without physiologic scaffolding or exaggerated cortical activation in response to pain exposure. In contrast to recent investigations, the aim of the present study was to elucidate cortical activation of somatoform pain disorder patients during baseline condition. Scalp EEG, quantitative Fourier-spectral analyses and LORETA were employed to compare patient group (N = 15) to age- and sex-matched controls (N = 15) at rest. SI, SII, ACC, SMA, PFC, PPC, insular, amygdale and hippocampus displayed significant spectral power reductions within the beta band range (12-30 Hz). These results suggest decreased cortical baseline arousal in somatoform pain disorder patients. We finally conclude that obtained results may point to an altered baseline activity, maybe characteristic for chronic somatoform pain disorder.

EEG low-resolution brain electromagnetic tomography (LORETA) in Huntington's disease.

Previous studies have shown abnormal electroencephalography (EEG) in Huntington's disease (HD). The aim of the present investigation was to compare quantitatively analyzed EEGs of HD patients and controls by means of low-resolution brain electromagnetic tomography (LORETA). Further aims were to delineate the sensitivity and utility of EEG LORETA in the progression of HD, and to correlate parameters of cognitive and motor impairment with neurophysiological variables. In 55 HD patients and 55 controls a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Power spectra and intracortical tomography were computed by LORETA in seven frequency bands and compared between groups. Spearman rank correlations were based on V-EEG and psychometric data. Statistical overall analysis by means of the omnibus significance test demonstrated significant (p < 0.01) differences between HD patients and controls. LORETA theta, alpha and beta power were decreased from early to late stages of the disease. Only advanced disease stages showed a significant increase in delta power, mainly in the right orbitofrontal cortex. Correlation analyses revealed that a decrease of alpha and theta power correlated significantly with increasing cognitive and motor decline. LORETA proved to be a sensitive instrument for detecting progressive electrophysiological changes in HD. Reduced alpha power seems to be a trait marker of HD, whereas increased prefrontal delta power seems to reflect worsening of the disease. Motor function and cognitive function deteriorate together with a decrease in alpha and theta power. This data set, so far the largest in HD research, helps to elucidate remaining uncertainties about electrophysiological abnormalities in HD.

Comparative EEG mapping studies in Huntington's disease patients and controls.

Huntington's disease (HD) is a devastating neurodegenerative disorder with prominent motor and cognitive decline. Previous studies with small sample sizes and methodological limitations have described abnormal electroencephalograms (EEG) in this cohort. The aim of the present study was to investigate objectively and quantitatively the neurophysiological basis of the disease in HD patients as compared to normal controls, utilizing EEG mapping. In 55 HD patients and 55 healthy controls, a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Evaluation of 36 EEG variables was carried out by spectral analysis and visualized by EEG mapping techniques. To elucidate drug interference, the analysis was performed for the total group, unmedicated patients only and between treated and untreated patients. Statistical overall analysis by the omnibus significance test demonstrated significant (p < 0.01 and p < 0.05) EEG differences between HD patients and controls. Subsequent univariate analysis revealed a general decrease in total power and absolute alpha and beta power, an increase in delta/theta power, and a slowing of the centroids of delta/theta, beta and total power. The slowing of the EEG in HD reflects a disturbed brain function in the sense of a vigilance decrement, electrophysiologically characterized by inhibited cortical areas (increased delta/theta power) and a lack of normal routine and excitatory activity (decreased alpha and beta power). The results are similar to those found in other dementing disorders. Medication did not affect the overall interpretation of the quantitative EEG analysis, but certain differences might be due to drug interaction, predominantly with antipsychotics. Spearman rank correlations revealed significant correlations between EEG mapping and cognitive and motor impairment in HD patients.

Computer-assisted sleep classification according to the standard of the American Academy of Sleep Medicine: validation study of the AASM version of the Somnolyzer 24 × 7.

BACKGROUND: In 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine (AASM). Concerning the visual classification of sleep stages, these new rules are intended to replace the rules by Rechtschaffen and Kales (R&K). METHODS: We adapted the automatic R&K sleep scoring system Somnolyzer 24 × 7 to comply with the AASM rules and subsequently performed a validation study based on 72 polysomnographies from the Siesta database (56 healthy subjects, 16 patients, 38 females, 34 males, aged 21-86 years). Scorings according to the AASM rules were performed manually by experienced sleep scorers and semi-automatically by the AASM version of the Somnolyzer. Manual scorings and Somnolyzer reviews were performed independently by at least 2 out of 8 experts from 4 sleep centers. RESULTS: In the quality control process, sleep experts corrected 4.8 and 3.7% of the automatically assigned epochs, resulting in a reliability between 2 Somnolyzer-assisted scorings of 99% (Cohen's kappa: 0.99). In contrast, the reliability between the 2 manual scorings was 82% (kappa: 0.76). The agreement between the 2 Somnolyzer-assisted and the 2 visual scorings was between 81% (kappa: 0.75) and 82% (kappa: 0.76). CONCLUSION: The AASM version of the Somnolyzer revealed an agreement between semi-automated and human expert scoring comparable to that published for the R&K version with a validity comparable to that of human experts, but with a reliability close to 1, thereby reducing interrater variability as well as scoring time to a minimum.

Comparative placebo-controlled polysomnographic and psychometric studies on the acute effects of gabapentin versus ropinirole in restless legs syndrome.

The aim of the present placebo-controlled sleep laboratory study was to compare the acute effects of gabapentin (GBT) and ropinirole (ROP) in restless legs syndrome (RLS). In a parallel-group design, 40 RLS patients received 300 mg GBT and another 40 patients 0.5 mg ROP as compared with placebo. Polysomnographic and psychometric measures were obtained in three sleep laboratory nights (screening/placebo/drug). Statistics included a Wilcoxon test for differences between drug and placebo and a U test for inter-group differences. Sleep efficiency and latency were found significantly improved after GBT, while they remained unchanged after ROP, with significant inter-drug differences. Sleep architecture showed oppositional changes after the two drugs: While GBT decreased S1, increased slow-wave sleep and SREM and shortened REM latency, ROP increased S2, decreased slow-wave sleep and SREM and increased REM latency. Periodic leg movements (PLM) showed a significantly greater decrease after ROP (-73%) than after GBT (-35%). Subjective sleep quality improved significantly only after GBT; mental performance improved after both drugs with no inter-drug differences. In conclusion, the dopamine agonist ROP showed acute therapeutic efficacy with regard to PLM measures only, whereas GBT had a less pronounced effect on these measures, but improved objective and subjective sleep and awakening quality as compared with both placebo and ROP. Differential acute drug effects may serve as prognostic indicators of therapeutic response of individual patients.

Modafinil improves information processing speed and increases energetic resources for orientation of attention in narcoleptics: double-blind, placebo-controlled ERP studies with low-resolution brain electromagnetic tomography (LORETA).

BACKGROUND AND PURPOSE: Recent neuroimaging studies in narcolepsy discovered significant gray matter loss in the right prefrontal and frontomesial cortex, a critical region for executive processing. In the present study, event-related potential (ERP) low-resolution brain electromagnetic tomography (LORETA) was used to investigate cognition before and after modafinil as compared with placebo. PATIENTS AND METHODS: In a double-blind, placebo-controlled cross-over design, 15 patients were treated with a 3-week fixed titration scheme of modafinil and placebo. The Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT) and auditory ERPs (odd-ball paradigm) were obtained before and after the 3 weeks of therapy. Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. RESULTS: The ESS score improved significantly from 15.4 (+/- 4.0) under placebo to 10.2 (+/- 4.1) under 400mg modafinil (p=0.004). In the MWT, latency to sleep increased nonsignificantly after modafinil treatment (11.9+/-6.9 versus 13.3+/-7.1 min). In the ERP, N2 and P300 latencies were shortened significantly. While ERP amplitudes showed only minor changes, LORETA revealed increased source strengths: for N1 in the left auditory cortex and for P300 in the medial and right dorsolateral prefrontal cortex. CONCLUSION: LORETA revealed that modafinil improved information processing speed and increased energetic resources in prefrontal cortical regions, which is in agreement with other neuroimaging studies.

Double-blind, placebo-controlled, multiple-ascending-dose study on the pharmacodynamics of ABIO-08/01, a new CNS drug with potential anxiolytic activity. 1. EEG mapping, psychometric and tolerability findings.

In a double-blind, placebo-controlled, multiple-ascending-dose study, the encephalotropic and psychotropic properties of ABIO-08/01, a new potentially anxiolytic and nootropic isoxazoline, were studied in 16 young healthy males. In a randomized nonbalanced phase 1 study, they received 3 oral drug doses (10, 20, 40 mg) and placebo for 7 days (washout period 8 days). EEG mapping and psychometry were carried out at hours 0, 1, 6 of day 1 (acute effect) and day 5 (subacute and superimposed effects). MANOVA/ Hotelling T(2) test demonstrated significant central effects of ABIO-08/01 versus placebo after acute, subacute and superimposed administration of all doses in the resting, vigilance-controlled and eyes-open EEG. Univariate analysis revealed activating patterns in the resting EEG (40 mg > 20 mg > 10 mg), and sedative patterns in the eyes-open EEG (10 mg > 20 mg > 40 mg). In the vigilance-controlled EEG, 40 mg of ABIO-08/01 induced activating patterns, whereas 10 mg induced sedative patterns. Concerning psychometry, ABIO-08/01 improved concentration (40 mg > 20 mg > 10 mg; activating effect) and deteriorated well-being (10 mg > 20 mg > 40 mg; sedative effect). Ten milligrams also improved reaction time performance and psychomotor activity. ABIO-08/01 is well-tolerated and is of interest in anxiety disorders.

Double-blind, placebo-controlled, multiple-ascending-dose study on the pharmacodynamics of ABIO-08/01, a new CNS drug with potential anxiolytic activity. 2. EEG-tomography findings based on LORETA (low-resolution brain electromagnetic tomography).

Effects of ABIO-08/01, a new potentially anxiolytic isoxazoline, on regional electrical brain generators were investigated by 3-dimensional EEG tomography. In a double- blind, placebo-controlled, multiple-ascending-dose study, 16 healthy males (30.2 +/- 5.7 years) received 3 oral drug doses (10, 20, 40 mg) and placebo for 7 days (8-day wash-out) in a randomized non-balanced design for phase-1 studies. A 3-min vigilance-controlled (V) EEG, a 4-min resting (R) EEG with eyes closed, a 1-min eyes-open (EO) EEG and psychometric tests were performed 0, 1 and 6 h after taking the drug on days 1 and 5. Low-resolution brain electromagnetic tomography (LORETA) was computed from the spectrally analyzed EEG data, and differences between drug and placebo were displayed as statistical parametric maps. Data were registered to the Talairach-Tournoux Human Brain Atlas available as a digitized MRI. An overall omnibus significance test followed by a voxel-by-voxel t test demonstrated significant regional EEG changes after ABIO-08/01 versus placebo, dependent on recording condition, dose and time. While in the EO-EEG specifically the lowest dose of ABIO-08/01 induced pronounced sedative effects (delta/theta and beta increase) 1 h after acute and slightly less so after superimposed administration, in the 6th hour a decrease in alpha and beta activity signaled less sedative and more relaxant action. In the V-EEG these changes were less pronounced, in the R-EEG partly opposite. Hemisphere-specific changes were observed, suggesting increases in LORETA power over the left temporal, parietal, superior frontal regions and decreases over the right prefrontal, temporal pole and occipital regions. These LORETA changes are discussed in the light of neuroimaging findings on anxiety and anxiolytics.

Event-related-potential low-resolution brain electromagnetic tomography (ERP-LORETA) suggests decreased energetic resources for cognitive processing in narcolepsy.

OBJECTIVE: Event-related potentials (ERPs) are sensitive measures of both perceptual and cognitive processes. The aim of the present study was to identify brain regions involved in the processes of cognitive dysfunction in narcolepsy by means of ERP tomography. METHODS: In 17 drug-free patients with narcolepsy and 17 controls, ERPs were recorded (auditory odd-ball paradigm). Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. Psychometry included measures of mental performance, affect and critical flicker fusion frequency (CFF). RESULTS: In the ERPs patients demonstrated delayed cognitive N2 and P300 components and reduced amplitudes in midline regions, while N1 and P2 components did not differ from controls. LORETA suggested reduced P300 sources bilaterally in the precuneus, the anterior and posterior cingulate gyri, the ventrolateral prefrontal cortex and the parahippocampal gyrus. In psychometry, patients demonstrated deteriorated mood, increased trait anxiety, decreased CFF and a trend toward reduced general verbal memory and psychomotor activity. CONCLUSIONS: Narcoleptic patients showed prolonged information processing, as indexed by N2 and P300 latencies and decreased energetic resources for cognitive processing. SIGNIFICANCE: Electrophysiological aberrations in brain areas related to the 'executive attention network' and the 'limbic system' may contribute to a deterioration in mental performance and mood at the behavioral level.

Double-blind, placebo-controlled, multiple-ascending-dose study on the effects of ABIO-08/01, a novel anxiolytic drug, on perception and cognition, utilizing event-related potential mapping and low-resolution brain electromagnetic tomography.

Early pharmacological studies in animals demonstrated that ABIO-08/01, a new isoxazoline, exerted anxiolytic and anticonvulsant, but also cognition-enhancing properties. Thus, the aim of the present double-blind, placebo-controlled multiple-ascending-dose study was to investigate the effect of the new compound on event-related potentials (ERPs). In a randomized ascending-dose design for phase-1 studies, 16 young healthy male subjects aged 30.2 +/- 5.7 years received three ascending drug doses (10, 20, and 40 mg) and placebo for 7 days, with a washout period of 8 days in between. Auditory ERPs were recorded pre-dose and 2 h post-dose on days 1 (acute effect) and 5 (subacute and absolute superimposed effect). Descriptive statistics with one confirmatory statement on P300 latency demonstrated a significant shortening after acute, subacute, and superimposed administration of 40 mg ABIO-08/01. While ERP amplitudes showed only minor effects, low-resolution brain electromagnetic tomography (LORETA) demonstrated that ABIO-08/01 promotes more efficient information processing by reallocating perceptual and cognitive ERP resources. Thus, our ERP studies confirm early pharmacological findings in animals of a cognition-enhancing effect of ABIO-08/01, which is interesting in the context of the anxiolytic mode of action of the compound as its CNS effects are quite different from those of anxiolytic sedatives, such as benzodiazepines.

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.

Low-resolution brain electromagnetic tomography (LORETA) identifies brain regions linked to psychometric performance under modafinil in narcolepsy.

Low-resolution brain electromagnetic tomography (LORETA) showed a functional deterioration of the fronto-temporo-parietal network of the right hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of this study was to determine the effects of modafinil on cognitive and thymopsychic variables in patients with narcolepsy and investigate whether neurophysiological vigilance changes correlate with cognitive and subjective vigilance alterations at the behavioral level. In a double-blind, placebo-controlled crossover design, EEG-LORETA and psychometric data were obtained during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or 400 mg modafinil. Cognitive investigations included the Pauli Test and complex reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood, affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli Test) was significantly better after modafinil than after placebo. Concerning reaction time and thymopsychic variables, no significant differences were observed. Correlation analyses revealed that a decrease in prefrontal delta, theta and alpha-1 power correlated with an improvement in cognitive performance. Moreover, drowsiness was positively correlated with theta power in parietal and medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A less significant correlation was observed between midmorning EEG LORETA and the MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but it significantly improved cognitive performance, which may be related to medial prefrontal activity processes identified by LORETA.

EEG topography and tomography (LORETA) in the classification and evaluation of the pharmacodynamics of psychotropic drugs.

By multi-lead computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (QEEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping or topography), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ, the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects and therapeutic efficacy will be discussed. Imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be shown for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently. By considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. Thus, pharmaco-EEG topography and tomography are valuable methods in human neuropsychopharmacology, clinical psychiatry and neurology.

Craving and other characteristics of the comorbidity of alcohol and nicotine dependence.

PURPOSE: In this cross-sectional study we compared alcohol-dependent smokers and non-alcohol-dependent smokers with respect to intensity of nicotine dependence, craving conditions, sleep disturbances, comorbidity with major depression, reasons for smoking, accompanying somatic diseases and patients' prolonged abstinence from smoking during the 3 years preceding the study. SUBJECTS AND METHODS: Fifty-one alcohol-dependent smokers and 327 non-alcohol-dependent smokers diagnosed as ICD-10 and DSM-IV-nicotine dependent, were investigated by means of the Fagerström Test for Nicotine Dependence, the Lübeck Craving-Recurrence Risk Questionnaire and the Lesch Alcohol Dependence Typology (both adapted to smoking). RESULTS: The intensity of nicotine dependence was more enhanced in alcohol-dependent smokers compared to non-alcohol-dependent smokers. Several variables of all factors of craving ("depressive mood", "stimulation", "relaxation", "socially triggered tension") were significantly increased in alcohol-dependent patients (P<0.05). Alcohol-dependent smokers showed depressive symptoms and sleep disturbances, whilst non-alcohol-dependent individuals mainly smoked for stress release and weight control. DISCUSSION: Our study demonstrates that the intensity of nicotine dependence, several conditions of craving for nicotine, sleep disturbances and symptoms of depression appear to be enhanced in alcohol-dependent smokers compared with non-alcohol-dependent smokers. Conclusions. - It is hoped that the factors of craving and reasons for smoking identified in this study will contribute to a better understanding of smoking temptation in alcohol-dependent smokers and non-alcohol-dependent smokers in future.

EEG mapping and low-resolution brain electromagnetic tomography (LORETA) in diagnosis and therapy of psychiatric disorders: evidence for a key-lock principle.

Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by 3-dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.