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Depression has been linked to executive dysfunction and emotion recognition impairments, associated with abnormalities in fronto-temporal and subcortical brain regions. Little is known about changes of different empathy subcomponents during depression, with potential impairments being related to the interpersonal difficulties of depressed patients. Twenty patients treated for an episode of unipolar depression and 20 matched healthy controls were assessed. Measures of dispositional and behavioural empathy components were administered along with tests of cognitive flexibility, response inhibition and working memory. Relative to controls, depressed patients showed higher self-reported dispositional empathy scores, mainly driven by increased personal distress scores. Patients and controls did not differ significantly in terms of behavioural cognitive empathy, empathic concern and personal affective involvement or in their executive function performance. In the patients, cognitive flexibility and response inhibition accuracy were associated with behavioural empathy. While an increased disposition towards feeling personal distress in response to other people's suffering seems to be in generally related to depressive symptoms, behavioural empathy might depend on the functional integrity of executive control during an episode of clinical depression. Impairments in this regard could contribute to the interpersonal difficulties depressed patients are frequently faced with which might have important implications for treatment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Temporal summation of C-fiber evoked responses generates an increase in action potential discharge in second-order neurons and in perceived pain intensity (wind-up). This may be related to the central serotonergic system which modulates and partly inhibits sensory input. Aim of the study was to investigate the relationship between wind-up and serotonergic activity using loudness dependence of auditory evoked potentials (LDAEP). 18 healthy subjects were compared to 18 patients with major depression, a disease with a putative serotonin deficit. They were examined with quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain (DFNS), including the wind-up ratio (WUR), LDAEP, and psychometric measurements. We found a slight positive correlation between WUR and LDAEP both in healthy controls and depressed patients combined (r=0.340, p=0.043), indicating that WUR may be modulated by serotonergic activity. It can be concluded that inhibitory control to noxious stimuli is partly associated with the central serotonergic function as indicated by LDAEP., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Suicidality and suicide has been associated with many risk factors, while recent clinical and epidemiological studies increasingly point to a potential link between sleep loss or sleep disturbances and suicidality. This review on studies of sleep disturbances associated with suicidality, i.e., suicidal ideation, suicide attempt and completed suicide suggests a frequent association especially with insomnia and nightmares but also hypersomnia and sleep panic attacks. In suicidal insomniacs with comorbid psychiatric disorders, there is some evidence for an even independent predictive nature of sleep problems for suicidality. Considerations on the shared neurobiology, risk assessment and treatment options complement the overview. Thus, sleep disturbances may qualify as an individual treatable target of personalised medicine in the clinical routine as well as in suicide prevention programmes. A more detailed assessment of sleep problems and identification of specific risk domains in primary or secondary prevention of suicidality seem to be a future area of high importance.

Using proton magnetic resonance spectroscopy biochemical characteristics in early stages of schizophrenia were examined. N-acetylaspartate, choline and creatine were measured in hippocampus, anterior cingulate gyrus (ACC) and medial prefrontal cortex (mPFC) of 24 first episode and 30 ultra-high risk patients. Careful LCModel analyses revealed no differences between the patient groups and 31 healthy controls, casting doubt upon the idea of metabolic changes in early stages of psychosis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: High prevalence of depression has been reported in otorhinolaryngologic patients (ORL). However, studies using a semi-structured interview to determine the prevalence of depression in ORL are lacking. Therefore the present study sought to determine the depression prevalence in ORL applying a semi-structured diagnostic interview and to further characterize the pathopsychological and demographic characteristics of depression in these patients., Methods: One-hundred inpatients of the otorhinolaryngologic department of a German university hospital participated voluntarily (age M = 38.8 years, SD = 13.9; 38.0% female). Depression was assessed using a clinical interview in which the International Diagnostic Checklist for depression (IDCL) was applied. Patients completed the Brief Symptom Inventory (BSI) which constitutes three composite scores and nine symptom scales and the Beck Depression Inventory (BDI). Multivariate analyses of variance, correlations and effect sizes were conducted., Results: A prevalence of depression of 21.0% was determined, 38.0% of the depressed patients were female. Depressed patients showed higher scores on the BSI-scales "interpersonal sensitivity", "depression", "anxiety", "phobic anxiety" and "psychoticism" with medium effect sizes., Conclusions: High prevalence of depression was found which is in accordance with results of prior studies. Depressed patients showed higher psychological distress as compared to non-depressed patients. The results call for carrying on in engaging in depression research and routine depression screening in ORL.

Background: Concerning diagnostics of mental disorders, increasing time and cost pressure in the clinical practice often requires an ad hoc and intuitive holistic examination of the patient's clinical presentation instead of the application of standardized diagnostic instruments. This study examined whether attributes of mental healthcare professionals (professional training, clinical experience, socio-demographic variables) affect their implicit weighing of symptoms they encounter in such unstandardized diagnostic situations., Methods: Twenty psychiatrists and 28 clinical psychologists rated the relevance of 241 items for the diagnosis of a depressive episode. Items referred to the nine A-criteria of DSM-IV and associated features. Intraclass correlations (ICC), regression analysis and t-tests were calculated., Results: Clinicians agreed largely in their relevance judgements on the different items ( ICC = 0.97, F (183,8784) = 44.29, p < 0.001). Stepwise regression analyses with profession, clinical experience, age and gender as predictors for each DSM-IV A-criterion revealed no significant β-coefficient except for one: 'profession' was a significant predictor for the mean relevance judgement on items that could not be assigned to an A-criterion. This effect turned out to be caused by only one item (obsessive-compulsive behaviour)., Conclusions: Clinical experts agree highly in their implicit weighing of depression symptoms regardless of their age, gender, clinical experience and professional training.

Background: Transcranial sonography (TCS) has become a new diagnostic tool in the evaluation of extrapyramidal disorders. Studies of TCS report alterations of the mesencephalic raphe in patients with depression. The aim of this study was to evaluate TCS findings in patients with Huntington disease in correlation with their neurologic and psychiatric status., Methods: We recruited patients with genetically confirmed Huntington disease. The neurological and psychiatric status of participants was assessed by independent physicians. Echogenicities were investigated according to examination protocol for extrapyramidal disorders using a Siemens Sonoline Elegra system. The sonography examiner was blinded for clinical data., Results: We included 39 patients in our study; 21 patients (53.8%) showed symptoms of depression at the time of evaluation and, of those, 15 (71.4%) had hypoechogenic raphe structures. Thirty patients (76.9%) had a history of depressive episodes, 19 (63.3%) of them with hypoechogenic raphe structures. All 9 patients without a history of depressive episodes showed normal echogenicity of raphe structures (sensitivity 63.3%, specificity 100%). Twelve (70.6%) of the 17 patients with Huntington disease who showed psychiatric disturbances prior to the occurrence of motor symptoms exhibited pathological raphe echogenicity (sensitivity 70.6%, specificity 68.2%)., Limitations: Most of the patients were taking antichoreatic medication, which particularly influences neurologic status. Thus, a meaningful interpretation of the correlation between TCS findings and neurologic features was limited., Conclusion: As a novel finding, a relation between mesencephalic raphe echogenicity and depressive state could be identified in patients with Huntington disease. An alteration of the serotonergic brain stem raphe might be involved in the pathogenesis of depression in these patients.

Mismatch negativity (MMN) is an auditory event-related potential indicating auditory sensory memory and information processing. The present study tested the hypothesis that chronic cannabis use is associated with deficient MMN generation. MMN was investigated in age- and gender-matched chronic cannabis users (n = 30) and nonuser controls (n = 30). The cannabis users were divided into two groups according to duration and quantity of cannabis consumption. The MMNs resulting from a pseudorandomized sequence of 2 × 900 auditory stimuli were recorded by 32-channel EEG. The standard stimuli were 1,000 Hz, 80 dB SPL and 90 ms duration. The deviant stimuli differed in duration (50 ms) or frequency (1,200 Hz). There were no significant differences in MMN values between cannabis users and nonuser controls in both deviance conditions. With regard to subgroups, reduced amplitudes of frequency MMN at frontal electrodes were found in long-term (≥8 years of use) and heavy (≥15 joints/week) users compared to short-term and light users. The results indicate that chronic cannabis use may cause a specific impairment of auditory information processing. In particular, duration and quantity of cannabis use could be identified as important factors of deficient MMN generation.

Objectives: To provide a first evaluation of the Rasch-Based Depression Screening (DESC) in consecutive patients with neurologic disorders., Design: Cross-sectional study., Setting: Hospital specializing in neurologic disorders., Participants: Eligible patients (N=323; mean age +/- SD, 53.4+/-17.2y; 49.3% women) age 18 years and older., Interventions: Not applicable., Main Outcome Measures: DESC with 2 parallel versions., Results: Both versions of the DESC showed good item separation (DESC-I=4.96; DESC-II=4.94) and person separation (DESC-I=2.01; DESC-II=2.14) as well as item separation reliability (DESC-I=.96; DESC-II=.96) and person separation reliability (DESC-I=.80; DESC-II=.82). All items fit the Rasch model (infit and outfit mean squares < or =1.3). There were no signs of violation of unidimensionality. One item of DESC-I showed differential item functioning because of age and 1 item because of sex. Parallel test reliability of the 2 DESC forms was r equal to .92., Conclusions: The DESC shows good psychometric characteristics that suggest high psychometric quality of the instrument in patients with neurologic disorders. Differential item functioning on single items needs further examination but should not substantially interfere with the valid interpretation of DESC sum scores.

Lithium occurs naturally in food and water. Low environmental concentrations in drinking water are associated with mental illnesses and behavioural offences, and at therapeutic dosages it is used to treat psychiatric (especially affective) disorders, partly by facilitating serotonergic (5-HT) neurotransmission. As little is known about the psychophysiological role of nutritional lithium in the general population, endogenous lithium concentrations were hypothesised to be associated with measurable effects on emotional liability and the loudness dependence (LD) that is proposed as one of the most valid indicators of 5-HT neurotransmission. Auditory evoked potentials of healthy volunteers [N=36] with high (>2.5 microg/l) or low (<1.5 microg/l) lithium serum concentrations were recorded. Emotional liability was assessed using the Brief Symptom Inventory (BSI). Low-lithium levels correlated with Somatisation while correlations between lithium and LD were not significant. Still, LD correlated positively with Paranoid Ideation, negatively with Anxiety and, in the high-lithium group, inversely with further aspects of emotional liability (Depression, Psychological Distress). In conclusion, the effects of low levels of endogenous lithium are associated with emotional liability, and high levels with some protective effects, although findings remain inconclusive regarding LD. Potential benefits of endogenous lithium on neurobehavioural functioning, especially in high-risk individuals, would have public health implications.

Objectives: The serotonergic system plays an important pathophysiological role in various psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is involved in the differentiation and survival of serotonergic neurons. A previous study showed that low serum BDNF levels were associated with strong loudness dependence of auditory evoked potentials (LDAEP) as a reflection of low central serotonergic activity. To evaluate the genetic basis of this relationship, we studied whether the LDAEP is correlated with genetic variants within the BDNF gene., Methods: Ninety five healthy subjects (41 males, 54 females) received electrophysiological recording of LDAEP and blood drawing for BDNF genotyping. Three BDNF markers (including the single nucleotide polymorphism rs6265(Val66Met)) were analyzed., Results: Haplotype analysis revealed stronger LDAEP values in carriers of the G(Val)-C-T [rs6265(Val66Met)-rs2030324-rs1491850] haplotype within the BDNF gene in comparison to other haplotype carriers. These findings were demonstrated for the LDAEP of both left and right primary auditory cortices as well as for the vertex electrode (Cz)., Conclusion: Subjects with the BDNF haplotype G(Val)-C-T seem to be characterized by low serotonergic activity as well as possibly by low serum BDNF levels. These findings need replication in independent samples., ((c) 2009 Elsevier Ltd. All rights reserved.)

In verbal communication, prosodic codes may be phylogenetically older than lexical ones. Little is known, however, about early, automatic encoding of emotional prosody. This study investigated the neuromagnetic analogue of mismatch negativity (MMN) as an index of early stimulus processing of emotional prosody using whole-head magnetoencephalography (MEG). We applied two different paradigms to study MMN; in addition to the traditional oddball paradigm, the so-called optimum design was adapted to emotion detection. In a sequence of randomly changing disyllabic pseudo-words produced by one male speaker in neutral intonation, a traditional oddball design with emotional deviants (10% happy and angry each) and an optimum design with emotional (17% happy and sad each) and nonemotional gender deviants (17% female) elicited the mismatch responses. The emotional category changes demonstrated early responses (<200 ms) at both auditory cortices with larger amplitudes at the right hemisphere. Responses to the nonemotional change from male to female voices emerged later ( approximately 300 ms). Source analysis pointed at bilateral auditory cortex sources without robust contribution from other such as frontal sources. Conceivably, both auditory cortices encode categorical representations of emotional prosodic. Processing of cognitive feature extraction and automatic emotion appraisal may overlap at this level enabling rapid attentional shifts to important social cues., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

Chronic cannabis use has been found to be associated with major depression. It is suggested that cannabis use induces changes in neurotransmitter systems involved in the pathogenesis of depressive disorders, particularly in the serotonergic system. The analysis of the loudness dependence of auditory evoked potentials (LDAEP) is a valid non-invasive indicator of central serotonergic activity in animals and humans. In the present study, we investigated the effects of chronic cannabis use on LDAEP in 30 psychiatrically unaffected users compared to 30 non-user controls. Users were required to abstain from cannabis for at least 24 h before testing. Putative depressive symptoms were assessed by using the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for Depression (HAMD-21). LDAEP as well as BDI and HAMD-21 scores did not differ between cannabis users and controls. Moreover, LDAEP neither correlate with duration and quantity of cannabis use nor with psychometric assessments. These results indicate that chronic cannabis use had no influence on the LDAEP in this study sample. It can be suggested that significant alterations in serotonergic systems may rather be related to acute activation of the endogenous cannabinoid system or to cannabis dependence accompanied by manifest depressive symptoms.

Objective: The Beck Depression Inventory (BDI) is widely used for depression screening in various patient populations. However, there are still insufficient data about its sensitivity and specificity in nonpsychiatric patients. Furthermore, some research suggests that somatic BDI items heighten its sum score artificially in physically ill patients. The aim of the present study was to validate the conventional BDI cut-off score by examination of its sensitivity and specificity in a mixed sample of cardiac inpatients and compare it to a modified "cognitive-emotional" BDI (BDI(c/e)) after exclusion of somatic items., Methods: A total of 126 cardiologic inpatients were assessed. Receiver operating characteristic curves (ROC) were calculated for total BDI (BDI(t)) and BDI(c/e). Screening performance of cut-off scores was evaluated using the Youden Index (Y)., Results: With the application of the conventional BDI cut-off score, ROC analysis revealed a moderate overall screening performance with Y=52.6 and an area under the curve (AUC) of 0.83. In contrast, Y improved to 57.5 at a cut-off score of >9, but screening performance was still not optimal. BDI(c/e) showed also a moderate screening performance (AUC=.82); Y was maximized at a cut-off score of >8 (Y=0.53.5). Again, no cut-off score provided optimal screening performance., Conclusion: The BDI cannot be recommended as a formal screening instrument in cardiac inpatients since no cut-off score for either BDI(t) or BDI(c/e) combined both sufficiently high sensitivity and specificity. However, the shorter BDI(c/e) could be used as alternative to BDI(t) which may be confounded in physically ill patients. Generally, researchers should consider using alternative screening instruments (e.g., the Hospital Anxiety and Depression Scale) instead.

Questionnaires for the assessment of depression benefit from modern test construction like item-response-modelling. We developed two parallel 10 item depression questionnaires, the Rasch-based Depression Screening version 1 (DESC-I) and 2 (DESC-II), by combining Rasch analysis and structural equation modelling on patient samples suffering primarily from a mental disorder or from somatic diseases. Both scales base upon a Rasch homogeneous item bank and proved unidimensionality and good model fit. Cut-off scores with good sensitivity and specificity were developed using ROC analyses. Results suggest that DESC may be appropriately used to screen for depression and may be beneficial for repeated measurements.

Objective: The calibration of item banks provides the basis for computerized adaptive testing that ensures high diagnostic precision and minimizes participants' test burden. The present study aimed at developing a new item bank that allows for assessing depression in persons with mental and persons with somatic diseases., Method: The sample consisted of 161 participants treated for a depressive syndrome, and 206 participants with somatic illnesses (103 cardiologic, 103 otorhinolaryngologic; overall mean age = 44.1 years, SD =14.0; 44.7% women) to allow for validation of the item bank in both groups. Persons answered a pool of 182 depression items on a 5-point Likert scale., Results: Evaluation of Rasch model fit (infit < 1.3), differential item functioning, dimensionality, local independence, item spread, item and person separation (>2.0), and reliability (>.80) resulted in a bank of 79 items with good psychometric properties., Conclusions: The bank provides items with a wide range of content coverage and may serve as a sound basis for computerized adaptive testing applications. It might also be useful for researchers who wish to develop new fixed-length scales for the assessment of depression in specific rehabilitation settings., ((PsycINFO Database Record (c) 2009 APA, all rights reserved).)

Depressive disorders are highly prevalent, under-diagnosed and under-treated, causing high direct and socioeconomic costs. So far, the role of pharmacists in counselling and supervision of patients with depression has hardly been investigated. However, as pharmaceutical experts for doctor's prescriptions as well as self-medication, they represent an important multiplicator group in health care systems. The aim of nationwide seminars for pharmacists was to improve attitudes and knowledge of the spectrum of depressive disorders. The evaluation (n=102) which was performed within the seminars shows that personal beliefs of pharmacists regarding depression depend on their own age and years of professional experience. The study points out that specific training programmes (e. g., communication techniques), especially in a subgroup of younger and less experienced staff members in the pharmacy, may improve the care of depressive individuals. This should--in close cooperation with general practitioners, mental health specialists and health care systems--also substantially contribute to enhance effectiveness of treatment of depressive disorders and to reduce healthcare costs.

Rationale: Many studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-D-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model)., Objectives: The aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design., Materials and Methods: Fifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation., Results: Nine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN., Conclusions: The NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis.

Depressive syndromes in chronic heart failure (CHF) are common and are associated with a poorer prognosis, particularly with increased morbidity and mortality. CHF as a severe physical disorder may increase the risk of developing depressive syndromes or vice-versa as an interaction of possible common psycho-organic etiological aspects. Depression in CHF is associated with impaired NYHA status and daily activities, resulting in enhanced hospitalisation rates and medical costs with a great impact on long-term health. Only a fraction of comorbid patients receives antidepressants. Therefore, identification of risk factors and prevention by optimizing cardiological and psychiatric therapeutic strategies appear essential for these patients. Early diagnosis and treatment of both CHF and depression may prevent further pathophysiological effects on the heart and brain. This review gives a comprehensive overview of the occurrence, risk factors and shared pathophysiology of depression in CHF, and focuses on improving insufficient diagnosis and therapy of depression. Special attention is given on the cardiac effects of psychopharmacological and alternate non-pharmacological antidepressant therapy in CHF. Recommendations are made for treating depression in CHF patients for a better prevention of this disabling physical and psychosocial condition.

Previous studies suggest an important role for serotonergic (5-HT) modulation of the acoustic startle reflex (ASR) and prepulse inhibition (PPI). Acute challenge of brain serotonin by means of tryptophan depletion test (TDT) represents an established human challenge tool for temporary reduction of tryptophan (-TRP) levels and central nervous serotonin. Under these experimental conditions, PPI was found attenuated in males, but greater biochemical effects of TDT in the central nervous system of females are known. Therefore, in order to explore influence of 5-HT on various standard startle parameters in females, 16 young healthy females participated in a double-blind, cross-over TDT study. Acoustic stimuli were presented in 15 pulse-alone trials (100 dB, 40 ms) randomly followed by 25 pulse-alone or prepulse (70 dB, 30 ms; 120 ms interval) trials alongside electromyographic eyeblink recordings and mood state assessments. During 81% depletion of free plasma TRP, mean ASR magnitudes were significantly reduced compared to control (+TRP) condition while there were no differences in habituation or PPI nor did startle parameters correlate with mood states. Changes of plasma TRP and mood states correlated in tendency negatively in (-TRP) for depression and positively in (+TRP) for fatigue. In conclusion, this first study of startle parameters after TDT in a homogenous female population demonstrates that depletion of brain 5-HT in women only influences ASR.

Objectives: Direct challenge of cortical serotonergic (5-hydroxytryptamine, 5-HT) availability by tryptophan depletion test (TDT) was used to assess the hypothesized inverse relationship between central 5-HT function and loudness dependence of auditory evoked potentials (LDAEPs). Gender must be taken into particular account here, since there are gender differences in 5-HT brain synthesis, with women reacting more strongly to TDT., Methods: In a double-blind, controlled cross-over study, 16 healthy females were ingested two highly concentrated amino acid mixtures with (+TRP) or without TRP (-TRP). While monitoring TRP levels and mood states, the AEP of different loudness stimuli were recorded, followed by dipole source analysis., Results: Under the -TRP condition, free plasma TRP levels decreased by 81.10% (+/-5.14). Most of the loudness change rates of the relevant N1/P2 tangential dipole activities were significantly increased under -TRP, but calculated LDAEP did not differ significantly between treatments. LDAEP and states of mood were not correlated., Conclusions: Despite strong TRP depletion, the results did not reach sufficient evidence that LDAEP is a valid biological marker of central 5-HT activity in females when using TDT. This agrees with the literature and supports the view that LDAEP indicates predominantly biological vulnerability in predisposed individuals., ((c) 2007 John Wiley & Sons, Ltd.)

The neurodegenerative aspects of chronic progressive multiple sclerosis (MS) have received increasing attention in recent years, since anti-inflammatory and immunosuppressive treatment strategies have largely failed. However, successful neuroprotection and/or neuroregeneration in MS have not been demonstrated yet. Encouraged by the multifaceted neuroprotective effects of recombinant human erythropoietin (rhEPO) in experimental models, we performed an investigator-driven, exploratory open label study (phase I/IIa) in patients with chronic progressive MS. Main study objectives were (i) evaluating safety of long-term high-dose intravenous rhEPO treatment in MS, and (ii) collecting first evidence of potential efficacy on clinical outcome parameters. Eight MS patients, five randomly assigned to high-dose (48,000 IU), three to low-dose (8000 IU) rhEPO treatment, and, as disease controls, two drug-naïve Parkinson patients (receiving 48,000 IU) were followed over up to 48 weeks: A 6-week lead-in phase, a 12-week treatment phase with weekly EPO, another 12-week treatment phase with bi-weekly EPO, and a 24-week post-treatment phase. Clinical and electrophysiological improvement of motor function, reflected by a reduction in expanded disability status scale (EDSS), and of cognitive performance was found upon high-dose EPO treatment in MS patients, persisting for three to six months after cessation of EPO application. In contrast, low-dose EPO MS patients and drug-naïve Parkinson patients did not improve in any of the parameters tested. There were no adverse events, no safety concerns and a surprisingly low need of blood-lettings. This first pilot study demonstrates the necessity and feasibility of controlled trials using high-dose rhEPO in chronic progressive MS.

Monoaminergic challenge tests allow investigating central nervous changes in humans under acute depletion of specific neurotransmitters (5-HT, DA, NE). Along with studies using alpha-methyl-para-tyrosine test (AMPT) and phenylalanine/tyrosine depletion test (APTD), the tryptophan depletion test (ATDT) represents the currently most established human challenge tool for the assessment of brain serotonin functioning. Neurophysiological studies in healthy and clinical samples may contribute to the search for a non-invasive and reliable biological marker of monoaminergic vulnerability or dysfunction. In the design of these studies, various biochemical and methodological aspects have to be taken into account. This article focuses on electrophysiological methodology and results of monoamine depletion studies (i.e., electroencephalography, magnetoencephalography, polysomnography, auditory evoked potentials and startle response).

Brain monoaminergic neurotransmission is involved in the pathophysiology of various psychiatric disorders including depression. Reliable indicators of central monoaminergic activity might be helpful to specifically identify and differentiate dysfunctions in individual patients in order to selectively adjust medication and predict clinical response. In patients with depression, predictors of treatment response to serotonergic versus non-serotonergic (e.g., noradrenergic) antidepressants could be of considerable clinical relevance by avoiding unfavorable factors such as a prolonged duration of the disorder, risk of suicidality and therapy-resistance. Consequently, these tools might help to decrease direct and indirect costs of treatment. The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been proposed as a noninvasive neurophysiological indicator of central serotonergic function. This review focuses on recent studies providing evidence for the validity of LD as an indirect serotonergic marker and highlights data on the clinical application in terms of prediction of treatment response in patients with depression.

Delusional syndromes can occur in a number of psychiatric, neurological or other disorders. They can also be caused by neurotoxic agents (e.g., heavy metals) as well as substance addiction. There are several hypotheses on the underlying cognitive or emotional processes associated with organic factors of delusional disorders, depending on the patient groups examined and the methods used. The aim of this paper is to provide a comprehensive review and critical assessment of the various, rather heterogeneous theories in this field.

Patients with heart failure (HF) often suffer from sleep-related breathing disorders (SRBD) like Cheyne-Stokes respiration (CSR). Cardiac resynchronization therapy (CRT) improves myocardial function and exercise capacity in patients with HF and conduction disturbances. As CRT has been shown to reduce CSR in patients with HF, it is not clear whether CRT improves quality of life and symptomatic depression by improvement of apnea/hypopnea index (AHI) and sleep quality. Forty-two HF patients with conduction disturbance before CRT were screened for CSR and evaluated for sleep quality [Pittsburgh Sleep Quality Index (PSQI)], quality of life score [36-item short form (SF-36)], depression, and exercise capacity (VO2 peak) and ejection fraction (EF). Eighteen patients (three females, age 61+/-10, body mass index 24+/-4 kg m(-2), EF 24+/-4%, QRS complex duration 156+/-32 ms) presented CSR with an AHI of 18+/-8 (11 CSR, 7 mixed). Fourteen patients showed no SRBD (PSQI<5,AHI<5). All patients received CRT and were reevaluated after 18+/-7 weeks. CSR worsen quality of life in seven of eight terms compared to patients without SRBD. Symptomatic depressive symptoms (Beck Depression Inventory>10) were only present in patients with CSR. CRT results in improvement of peak VO2 and EF. There was no difference between patients with CSR and without SRBD on exercise capacity or EF under CRT, whereas CRT led to a significant decrease in AHI (18+/-8 to 3+/-2, p<0.0001), PSQI (18+/-4 to 6+/-3, p=0.0007), with reduction of depression score (12+/-3 to 4.8+/-3, p=0.004). In patients with HF, CSR is associated with symptomatic depressive syndromes and impaired quality of life. CRT reduced CSR with improvement of sleep quality and symptomatic depression.

Mood disorders in patients with epilepsy are not frequently diagnosed and not treated. Because of the high prevalence of depression and the resulting high suicide rate, precise diagnosis and effective therapy are very important. Frequently, the clinical pictures of depressive syndromes in epileptics do not correspond with those described in operationalized classification systems such as ICD-10 or DSM-IV. The incidence of depressive disorders in epileptics is estimated in the literature to be 30%-70%. Multifactorial pathogenetic models include the type of seizures, the location of the epileptic focus, and neurotransmitter dysfunctions, as well as hereditary and psychosocial influences, and negative psychotropic effects of antiepileptic drugs. Despite an insufficient number of available controlled studies, based on the current data, treatment with the newer serotonergic antidepressants can be recommended for patients with epilepsy.

Background: Quality of life in patients with chronic heart failure (HF) is often severely compromised. Sleep-related breathing disorders (SRBD) like Cheyne-Stokes Respiration (CSR) or obstructive sleep apnea (OSAS) are often observed in patients with severe HF resulting in fragmentation of sleep, excessive daytime sleepiness and an increased mortality. While an apnea/hypopnea-index (AHI) >30/h represents an independent predictor of poor prognosis, clinical relevance of even minor SRBD with an AHI <30/h remains unclear with respect to quality of life, exercise capacity or depression rate., Methods: Sixty-nine consecutive ambulatory patients with stable HF (NYHA II-III, EF 25%) underwent two night polygraphies with a six-channel ambulatory recording. Spiroergometry was performed, and patients were examined for sleep quality (PSQI), depressed mood (BDI) and health-related quality of life (SF-36). The data were compared to 10 age-matched healthy controls and 11 patients with OSAS (AHI 14-29/h) not suffering from HF., Results: Fifty-one patients completed follow up. 52% were positively diagnosed for SRBD (AHI 16-30/h: 12 patients CSR, 5 patients OSAS, 9 patients mixed); 25 patients (48%) showed no relevant SRBD. Patients with HF and SRBD had lower quality of life than patients without SRBD and HF. The severity of SRBD as indicated by the AHI significantly correlated with quality of life measures: Bodily pain, physical functioning and social functioning showed largest impairment in patients with HF and SRBD. Furthermore, elevated depression rates in correlation to the AHI were only observed in patients with SRBD similar to patients with OSAS without HF., Conclusion: Even minor SRBD in patients with HF independently influence quality of life and correlate with estimation of depression and sleep disturbances.

Synthetic glucocorticosteroids can induce various severe mental disorders. Persisting cognitive disorder represents a rare complication of corticoid therapy involving memory, concentration, attention, or occupational performance. We observed the effects of a 20-day self-induced high-dose corticosteroid treatment on the cognitive functions in a 54-year-old patient. Having excluded dementia due to other organic causes, we examined the patient neuropsychologically immediately at the end of the steroid therapy and at follow-up (1, 2, 4, and 6 months). The initial tests showed seriously impaired functioning of concentration, attention, learning, and memory as well as of common ability to solve problems. The follow-up tests up to 6 months revealed an improvement of concentration and attention, but there were still serious deficits of the declarative memory with a high confabulating tendency. Our results confirm those of human experimental studies that exogenous steroids can cause serious persisting specific cognitive disorders especially of the declarative, hippocampus-dependent memory.

Objectives: We studied the effects of cardiac resynchronization therapy (CRT) on heart failure (HF) patients with central sleep apnea (CSA)., Background: Patients with advanced HF often suffer from CSA with Cheyne-Stokes respiration. Cardiac resynchronization therapy improves myocardial function and exercise capacity in HF patients with conduction disturbances. The relationship between CRT and CSA is currently unknown., Methods: Twenty-four patients (7 females; 62 +/- 11 years) with HF, a reduced left ventricular ejection fraction (24 +/- 6%), and left bundle branch block (QRS duration 173 +/- 22 ms) received a CRT device. The number of apneas and hypopneas per hour (apnea-hypopnea index [AHI]) and minimal oxygen saturation (SaO2min) were quantified by cardiorespiratory polygraphy. Fourteen patients showed CSA (AHI >5/h), and 10 patients had an AHI <5/h without CSA. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Data were evaluated before and after 17 +/- 7 weeks of CRT., Results: In patients with CSA, CRT led to a significant decrease in AHI (19.2 +/- 10.3 to 4.6 +/- 4.4, p < 0.001) and PSQI (10.4 +/- 1.6 to 3.9 +/- 2.4, p < 0.001) without Cheyne-Stokes respiration and to a significant increase in SaO2min (84 +/- 5% to 89 +/- 2%, p < 0.001). There was no significant change in AHI (1.7 +/- 0.7 to 1.5 +/- 1.6), PSQI (2.4 +/- 0.5 to 2.6 +/- 0.9), and SaO2min (90 +/- 2% to 91 +/- 1%) in patients without CSA., Conclusions: Cardiac resynchronization therapy leads to a reduction of CSA and to increased sleep quality in patients with HF and sleep-related breathing disorders. This may have prognostic implications in patients receiving CRT.

Various studies have indicated an impairment of sensory signal processing in schizophrenic patients. Anatomical and functional imaging studies have indicated morphological and metabolic abnormalities in the thalamus in schizophrenia. Other results give evidence for an additional role of cortical dysfunction in sensory processing in schizophrenia. Advanced analysis of human median nerve somatosensory evoked potentials (SEPs) reveals a brief oscillatory burst of low-amplitude and high-frequency activity ( approximately 600 Hz), the so-called high frequency oscillations (HFOs). The present study explores the behavior of HFOs in a cohort of schizophrenic patients in comparison to a group of controls. HFOs in the group of patients appeared with a delayed latency. In the low-frequency part of the SEPs an increase in amplitude was found. These results are interpreted to reflect a lack of somatosensory inhibition in the somatosensory pathway, either at a thalamic or a cortical level.

The concept "stalking" refers to willful, malicious, and repeated following or harassment of another person that threatens her or his security. Although there is nothing new about the occurrence of this conduct it has been discussed in psychiatry more intensely in recent years. As a result there are a few attempts at classification, without any claim of general validity. Patterns of stalking behaviour reflect a wide spectrum from aggressive actions in the course of conflicts in a relationship to schizophrenia. Thus, it is not adequate to classify this as a psychiatric disorder per se. Thorough diagnostic assessments are mandatory before introducing legal measures, whereas if these are omitted, the term "mental disorder" may be inappropriately used in a wider sense. This may entail unfavourable consequences to be discussed in this paper.

Human cortical somatosensory evoked potentials (SEPs), which are presumably generated in afferent thalamocortical and early cortical fibers, reveal a burst of superimposed early (N20) high-frequency oscillations (HFOs), around 600 Hz. There is increasing evidence of an imbalance of thalamocortical systems in schizophrenic patients. In order to assess correlations between somatosensory evoked oscillations and symptoms of schizophrenia, we investigated median nerve SEPs in 20 inpatients and their age-matched and gender-matched healthy controls using a multichannel EEG. Dipole source analysis and wavelet transformation were performed before and after application of a 450-Hz high-pass filter. In schizophrenics, the maximum HFOs occurred with a significantly prolonged latency. There was also a higher amplitude (energy) in the low-frequency range of the N20 component compared with the controls. Importantly, amplitudes (energy) of HFOs were inversely correlated with symptoms of formal thought disorder and delusions. Alterations of the thalamocortical somatosensory signal processing in schizophrenia with absence of an early HFO - assumed to be of inhibitory nature - could indicate a dysfunctional thalamic inhibition with increased amplitudes of N20, paralleled by enhanced positive schizophrenic symptoms., (Copyright 2004 S. Karger AG, Basel)

Tuberculosis (TB) increasingly appears in a multidrug-resistant form (MDR-TB) in Europe, too. Treatment remains difficult due to various side effects of the multi-drug-regimens. Ciprofloxacin is widely used as one of the few TB-second-line drugs. We report on the course of a ciprofloxacin-induced acute psychosis in a patient with MDR(isoniazid, streptomycin)-TB which resolved after cessation of ciprofloxacin treatment and introduction of a novel oxazolidone. Careful treatment considerations particularly in patients with additional predisposing factors to neuropsychiatric symptoms are recommended in the potentially dangerous MDR-TB, thus creating an enormous therapeutic challenge.

Due to its low profile for extrapyramidal side-effects, quetiapine has become an alternative to clozapine in the treatment of dopamimetic psychosis in patients with Parkinson's disease (PD). We describe the case of a patient with PD who developed severe akathisia, a common complication with classical antipsychotics, with quetiapine., (Copyright 2003 Movement Disorder Society)

Dysfunction of central serotonergic activity has been assumed in patients with borderline personality disorder (BPD) characterized by a prominent impulsive behavioral style. Following the high serotonergic innervation of the primary auditory cortex, there is increasing evidence of the intensity dependence of auditory evoked potentials (AEP), especially the N1/P2 component, indicating serotonergic neurotransmission in animals and humans. 15 females who met the IPDE-criteria for BPD and a group of comparative healthy females (controls) completed extensive personality questionnaires which gave special regard to impulsiveness. We obtained event-related AEP through the application of various loudness stimuli. We examined the relevant N1/P2 amplitude of the tangential dipole of the auditory evoked response using dipole source analysis. The augmentation of the N1/P2 amplitude of tangential dipole source activity with rising stimulus intensity was significantly pronounced in BPD as opposed to controls, accompanied by a reduction in N1 and P2 latencies. The strong loudness dependency of AEP correlated with aspects of impulsiveness. These data imply reduced inhibiting control over cortical sensory processing in BPD. Our findings contribute a further argument to the hypothesis of low serotonergic neurotransmission in BDP and may point to a trait character of impulsiveness in this personality disorder.

Palinacousis is a rarely reported symptom of temporal lobe dysfunction. Especially in psychiatric patients it may be misdiagnosed if it is not differentiated from the auditory hallucinations of psychotic illness. We report the case of a 20-year-old patient with the previously established diagnosis of paranoid schizophrenia who presented with the symptom of palinacousis. She was not psychotic at that time, her only complaints being recurrent auditory sensations. Repeated EEG recordings showed a left temporal theta focus with spikes. The diagnosis of temporal lobe seizures was made. Treatment with carbamazepine led to complete recovery., (Copyright 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved.)

Objective: This paper reports the occurrence of ping-pong gaze, a neuro-ophthalmological syndrome usually related to severe structural brain damage, in a patient intoxicated with tranylcypromine, thioridazine, and clomipramine., Background: Although there have been some reports about the occurence of Ping-pong gaze after intoxications, it is usually related to severe bilateral hemispheric brain damage following stroke or traumatic injuries., Method: We report the case of a 56-year old woman who developed a neurotoxic syndrome with coma, hyperthermia, muscular rigidity, myoclonic jerks and tachycardia following an intoxication. Additionally rhythmic and pendular conjugate horizontal eye movements could be observed for three days, so that the diagnosis of ping-pong gaze was made., Results: A treatment with dantrolene lead to complete remission of the neurotoxic syndrome with no signs of neurological or physical deficits. At the stage of regaining consciousness the eye movements became normal., Conclusion: In our case the combined intoxication with an monoamine oxidase inhibitor, a neuroleptic and a tricyclic agent lead to a neurotoxic syndrome and the occurrence of a rare neuro-ophthalmological syndrome usually related to bilateral hemispheric brain dysfunction.

Neurotoxic damage of central serotonergic systems has been demonstrated in numerous animal studies after exposure to methylenedioxyamphetamines (ecstasy). A high intensity dependence of auditory evoked potentials and, particularly, of the tangential N1/P2 source activity has been associated with low levels of serotonergic neurotransmission in humans. We performed an auditory evoked potentials study in 28 abstinent recreational ecstasy users and two equally sized groups of cannabis users and nonusers. The ecstasy users exhibited an increase of the amplitude of the tangential N1/P2 source activity with higher stimulus intensities; whereas, both control groups failed to exhibit this feature. These data are in line with the hypothesis that abstinent ecstasy users present with diminished central serotonergic activity. This feature of information processing is probably related to the well-recognized neurotoxic potential of ecstasy. Our data indicate that recreational ecstasy use may cause long-term alterations in the function (and possibly structure) of the human brain.

Human immunodeficiency virus (HIV)-seropositive patients show involvement of the central and/or peripheral nervous system. We present here the results of electroencephalographic (EEG) findings in stage WR 1-5 HIV-seropositive hemophiliacs from a total of 184 who attended our clinic prior to October 1987.