Disrupted relationship between blood glucose and brain dopamine D2/3 receptor binding in patients with first-episode schizophrenia.

An elemental function of brain dopamine is to coordinate cognitive and motor resources for successful exploitation of environmental energy sources. Dopamine transmission, goal-directed behavior, and glucose homeostasis are altered in schizophrenia patients prior to and after initiation of pharmacological treatment. Thus, we investigated the relationship between blood glucose levels and brain dopamine signaling in drug-naïve patients with first-episode psychosis. We quantified blood glucose levels and binding of the dopamine D2/3 receptor agonist radioligand (+)-[11C]-PHNO in 15 medication-naïve patients and 27 healthy volunteers employing positron emission tomography. Whole-brain voxel-wise linear model analysis identified two clusters of significant interaction between blood glucose levels and diagnosis on (+)-[11C]-PHNO binding-potential values. We observed positive relationships between blood glucose levels and binding-potential values in healthy volunteers but negative ones in patients with first episode psychosis in a cluster surviving rigorous multiple testing correction located in the in the right ventral tegmental area. Another cluster of homologous behavior, however at a lower level of statistical significance, comprised the ventral striatum and pallidum. Extracellular dopamine levels are a major determinant of (+)-[11C]-PHNO binding in the brain. In line with the concept that increased dopamine signaling occurs when goal-directed behavior is needed for restoring energy supply, our data indicate that in healthy volunteers, extracellular dopamine levels are high when blood glucose levels are low and vice-versa. This relationship is reversed in patients with first-episode psychosis, possibly reflecting an underlying pathogenic alteration that links two seemingly unrelated aspects of the illness: altered dopamine signaling and dysfunctional glucose homeostasis.

Influence of escitalopram treatment on 5-HT 1A receptor binding in limbic regions in patients with anxiety disorders.

There is an increasing interest in the underlying mechanisms of the antidepressant and anxiolytic treatment effect associated with changes in serotonergic neurotransmission after treatment with selective serotonin (5-HT) reuptake inhibitors (SSRIs) in humans. The 5-HT(1A) receptor is known to play a crucial role in the pathophysiology of affective disorders, and altered 5-HT(1A) receptor binding has been found in anxiety patients. SSRI treatment raises the 5-HT level in the synaptic cleft and might change postsynaptic receptor densities. Therefore, our study in patients suffering from anxiety disorders investigated the effects of long-term treatment with escitalopram on the 5-HT(1A) receptor. A longitudinal positrone emission tomography (PET) study in 12 patients suffering from anxiety disorders was conducted. Two dynamic PET scans were performed applying the selective 5-HT(1A) receptor antagonist [carbonyl-(11)C]WAY-100635. Eight regions of interest were defined a priori (orbitofrontal cortex, amygdala, hippocampus, subgenual cortex, anterior and posterior cingulate cortex, dorsal raphe nucleus and cerebellum as reference). After the baseline PET scan, patients were administered escitalopram (average dose of 11.2+/-6.0 mg day(-1)) for a minimum of 12 weeks. A second PET scan was conducted after 109+/-27 days. 5-HT(1A) receptor binding potentials in 12 patients were assessed by PET applying the Simplified Reference Tissue Model.There was a significant reduction in the 5-HT(1A) receptor binding potential after a minimum of 12 weeks of escitalopram treatment in the hippocampus (P=0.006), subgenual cortex (P=0.017) and posterior cingulate cortex (P=0.034). The significance of the hippocampus region survived the Bonferroni-adjusted threshold for multiple comparisons. These PET data in humans in vivo demonstrate a reduction of the 5-HT(1A) binding potential after SSRI treatment.

Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression.

Complex genetic disorders such as depression likely exhibit epistasis, but neural mechanisms of such gene-gene interactions are incompletely understood. 5-HTTLPR and BDNF VAL66MET, functional polymorphisms of the serotonin (5-HT) transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene, impact on two distinct, but interacting signaling systems, which have been related to depression and to the modulation of neurogenesis and plasticity of circuitries of emotion processing. Recent clinical studies suggest that the BDNF MET allele, which shows abnormal intracellular trafficking and regulated secretion, has a protective effect regarding the development of depression and in mice of social defeat stress. Here we show, using anatomical neuroimaging techniques in a sample of healthy subjects (n=111), that the BDNF MET allele, which is predicted to have reduced responsivity to 5-HT signaling, protects against 5-HTTLPR S allele-induced effects on a brain circuitry encompassing the amygdala and the subgenual portion of the anterior cingulate (rAC). Our analyses revealed no effect of the 5-HTTLPR S allele on rAC volume in the presence of BDNF MET alleles, whereas a significant volume reduction (P<0.001) was seen on BDNF VAL/VAL background. Interacting genotype effects were also found in structural connectivity between amygdala and rAC (P=0.002). These data provide in vivo evidence of biologic epistasis between SLC6A4 and BDNF in the human brain by identifying a neural mechanism linking serotonergic and neurotrophic signaling on the neural systems level, and have implications for personalized treatment planning in depression.

In vivo detection of cortical plaques by MR imaging in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: In vivo detection of cortical lesions in patients with multiple sclerosis (MS) by MR imaging is hampered by several factors. Among them is the low contrast between small cortical lesions and surrounding cortical gray matter offered by present techniques. METHODS: T1-weighted 3D spoiled gradient-recalled-echo (SPGR) volumes and 2D fluid-attenuated inversion recovery (FLAIR) sequences of 22 patients with MS who had 12 monthly brain MR imaging examinations at 1.5T, using a quadrature head coil, were retrospectively analyzed. These serial studies were coregistered and averaged to generate a single high signal-to-noise ratio (SNR) mean image, which was used to identify cortical lesions. The means of 12 FLAIRs and SPGRs from 14 age- and sex-matched healthy volunteers were analyzed as well. RESULTS: No cortical lesions were found on images of healthy subjects. Eighty-six cortical lesions were identified in 13 (59.1%) patients, predominantly in the frontal lobe (73.3%); 23.3% of cortical lesions lay entirely in the cortex, whereas the remaining lesions invaded the white matter underneath. CONCLUSION: Averaging multiple SPGRs created a single high SNR volume, allowing identification of cortical lesions. Because data were obtained monthly for 1 year, the average image does not account for transient lesion activity. However, for cortical lesions that remained stable during this time, the findings are valid in demonstrating the importance of high SNR images for detecting cortical brain abnormalities in MS.

In vivo 123I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol.

We investigated the degree of striatal dopamine-2 (D2) receptor occupancy in six schizophrenic patients receiving clinically effective antipsychotic treatment with olanzapine 10-25 mg/day in comparison to patients treated with clozapine 300-600 mg/day (n = 6) or haloperidol 5-20 mg/day (n = 10). 123I Iodobenzamide (IBZM) and single photon emission computerized tomography (SPECT) were used for the visualization of striatal D2 receptors. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to that in untreated healthy controls (n = 8) reported earlier. Olanzapine led to a mean striatal D2 receptor occupancy rate of 75% (range 63-85). Haloperidol-treated patients showed dose-dependently (Pearson r = 0.64; P < 0.05) a significantly higher (P < 0.05) mean occupancy rate of 84% (range 67-94). During clozapine treatment, the mean D2 receptor occupancy of 33% (range < 20-49) was significantly lower than with olanzapine (P < 0.005). The higher striatal D2 receptor occupancy of haloperidol was correlated with the incidence and severity of extrapyramidal motor side-effects (EPS). No clinical relevant EPS occurred during treatment with olanzapine or clozapine. There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.

The use of the antioxidant tirilazad mesylate in human liver transplantation: is there a therapeutic benefit?

OBJECTIVES: To test the hypothesis whether in patients undergoing liver transplantation the antioxidant tirilazad mesylate can reduce hepatic ischaemia-reperfusion injury and improve postoperative outcome. DESIGN: Prospective, randomised, placebo controlled trial. SETTING: University hospital. PATIENTS: 20 patients were randomised to receive either tirilazad mesylate or placebo (saline). INTERVENTIONS: Patients in the tirilazad group (n = 10) received four intravenous infusions of tirilazad at 6-h intervals (men 3 mg/kg, women 3.75 mg/kg) after the induction of anaesthesia. The other patients (n = 10) served as controls. MEASUREMENTS AND RESULTS: Plasma levels of malonaldehyde (MDA) were determined after the induction of anaesthesia prior to the infusion of tirilazad (baseline), during the anhepatic period, and 5 min and 24 h after reperfusion. Postoperatively, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and serum cholinesterase were determined daily for 1 week. Compared to baseline, plasma MDA levels did not significantly change during the anhepatic period and after reperfusion and they did not differ between groups. Postoperative liver enzymes and prothrombin time did not differ between groups, but on the first (p = 0.03) and second (p = 0.01) postoperative day cholinesterase levels were significantly higher in tirilazad-treated patients than in control patients. For neither length of stay in the intensive care unit nor hospital stay were any differences observed between groups. CONCLUSIONS: In patients undergoing liver transplantation, tirilazad does not improve overall outcome. Whether the higher cholinesterase levels on the first 2 postoperative days in tirilazad treated patients indicates an earlier recovery of liver function remains to be tested.

Nutritional status, ICU duration and ICU mortality in lung transplant recipients.

OBJECTIVE: To determine the relation of malnutrition and underlying diagnosis to the length of stay in the Intensive Care Unit (ICU) and to mortality after lung transplantation (LTX). DESIGN: Retrospective ICU chart review. SETTING: Cardiothoracic ICU in a University hospital. PATIENTS: Fifty-one consecutive patients who suffered from end-stage lung disease from April 1992 to January 1994. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The median time spent in the ICU was 5 days (range, 2-123 days). Patients with an underlying diagnosis of obstructive lung disease had significantly shorter ICU stays (median 4 days; range, 2-28 days) than those with restrictive lung disease (median 7 days; range, 2-123 days) (p = 0.005) or pulmonary hypertension (median 10 days' range, 2-38 days) (p = 0.041). Significant differences in ICU duration were observed between patients after double lung transplantation (median 10 days; range, 2-123 days) and those after single lung transplantation (median 4 days; range, 2-36 days) (p = 0.004). No statistically significant difference in ICU duration was found between patients with different nutritional statuses. In those patients who could not be discharged from the ICU before the 5th day, a body mass index (BMI) below the 25th percentile was a statistically significant risk factor for ICU mortality (p = 0.05). CONCLUSIONS: We conclude that the type of transplant procedure and the underlying diagnosis are important predictive indicators of ICU duration. A poor nutritional status (BMI below the 25th percentile) is a risk factor for ICU mortality in cases of patients who stay for 5 days or longer in the ICU.

Buprenorphine versus methadone maintenance for the treatment of opioid dependence.

AIMS: To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks. DESIGN: Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study. SETTING: Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna. PARTICIPANTS: Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment. INTERVENTION: Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase. MEASUREMENT: Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis. FINDINGS: The retention rate was significantly better in the methadone maintained group (p < 0.05) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption (p = 0.04). CONCLUSION: The results support the superiority of methadone with respect to retention rate. However, they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a specific subgroup may be benefiting from buprenorphine. This is the first comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol.

Fluoxetine treatment in patients with recurrent brief depression.

Recurrent brief depression (RBD) fulfills DSM-IV criteria for major depression except duration. Depressive episodes last at least 2 days but less than 2 weeks occurring at least once a month for 12 consecutive months without association to the menstrual cycle. RBD has a high prevalence in the general population (approximately 10%). At present, there are few double-blind controlled studies indicating that selective serotonine reuptake inhibitors (SSRIs) might not be effective in treatment of RBD. However, most of those studies include patients with a history of frequent suicide attempts and depressive episodes lasting shorter 2 weeks. It has previously been shown that fluoxetine was effective in patients with RBD in an open-label study. The objective of our study was to reinvestigate these contradictory results concerning the effectiveness of fluoxetine in patients with RBD. Seventeen patients with RBD according to DSM-IV and ICD-10 diagnostic criteria, who had no history of major depression were treated with a dosage of 20-40 mg fluoxetine daily. Patients had to keep a diary in order to document psychopathological symptoms according to DSM-IV. We also used the 21-item Hamilton Depression Rating Scale (HAM-D), the Beck Depression Inventory (BDI) and the Clinical Global Impressions (CGI). Duration of the study was 8 weeks. The diaries of nine patients were observed for a clinical observation period of 20 weeks after the end of the study with continued fluoxetine treatment. Two patients who initially fulfilled diagnostic criteria for RBD suffered from depressive episodes that lasted longer than 2 weeks. Therefore, their data had to be excluded from primary analysis. In the remaining 15 patients, we showed statistically significant improvement of depressive episodes measured by patient's diary, HIAM-D, BDI and CGI that persisted over the clinical observation period. Frequency of depressive episodes showed a significant decrease during fluoxetine treatment. Duration and severity of the single depressive episodes also decreased but did not reach statistical significance. In accordance with previous studies, fluoxetine could be a treatment option for patients with RBD. Treatment of RBD with SSRIs has been discussed controversially in the literature. Our study shows the effectiveness of fluoxetine in this depressive disorder. To confirm these preliminary results, a double-blind controlled study is necessary.

Efficacy, cardiac safety and tolerability of sertindole: a drug surveillance.

Sertindole is a novel atypical antipsychotic, which has shown efficacy in the treatment of positive and negative symptoms of schizophrenia in phase II and III studies. Furthermore, these studies have demonstrated tolerability and a favourable side-effect profile. In contrast to classical antipsychotics, sertindole was not associated with extrapyramidal symptoms (EPS). We report drug surveillance data in 34 comorbid and comedicated sertindole treated patients suffering from different psychotic disorders. The drug surveillance consisted of two distinct phases: inpatient treatment and outpatient follow-up. Clinical global impression (severity and improvement of illness), psychotic symptoms, side-effects, and blood parameters have been carefully documented. With special respect to cardiac safety electrocardiograms (ECGs) have been recorded twice (during sertindole treatment and during treatment with an antipsychotic different from sertindole). Recommended ECG-parameters for assessment of the proarrhythmic risk of a drug have been calculated (QTc-, QTc2-interval; QT-, QTc-dispersion). The majority of patients (n = 29) have been treated previously with several typical and/or atypical antipsychotics. We observed a clinical response to sertindole treatment in 29 patients (85%). Both positive and negative symptoms improved with sertindole and no severe side-effects have been documented. EPS occurred at placebo level. A mean QTc-interval prolongation of 19.7 ms (4.7%) has been detected. None of the patients developed clinical or electrocardiographic evidence of cardiac dysrhythmia during sertindole treatment, or other clinical evidence of cardiac abnormalities. In summary, sertindole did show efficacy for positive and negative symptoms together with a favourable side-effect profile. No evidence for an increased proarrhythmic risk has been found.

Mirtazapine in recurrent brief depression.

Recurrent brief depression (RBD) has a high prevalence in the general population (approximately 10%). At present, data on the treatment of RBD are sparse. Results of treatment studies with selective serotonin reuptake inhibitors (fluoxetine, paroxetine) did not demonstrate superiority of the active drug over placebo in RBD. We report about two patients with RBD treated with mirtazapine over a period of 4 months. Mirtazapine is a noradrenergic with specific selective serotoninergic antidepressant. Patients had to keep a diary in order to document psychopathological symptoms of major depression according to DSM-IV. We showed a marked reduction of severity, duration and frequency of brief depressive episodes in two patients with RBD treated with 30 mg mirtazapine over a period of 4 months. Mirtazapine enhances serotonergic as well as noradrenergic neurotransmission. This dual mechanism of action may be necessary to improve RBD. Consequently, mirtazapine might be a treatment option for patients with RBD. However, our preliminary observations need to be substantiated in controlled studies.

Cerebral CT findings in male opioid-dependent patients: stereological, planimetric and linear measurements.

Cerebrospinal fluid (CSF) space enlargement has been demonstrated in substance-related disorders like alcohol and cocaine dependence. Experimental animal studies showed a reduction in shape and size of mesolimbic dopaminergic neurons after chronic morphine administration. Other studies indicated a change of neurofilament and glial fibrillary acid proteins after chronic opiate administration. Furthermore, frequent overdosing and toxicological effects of 'street'-heroin may lead to CSF space enlargement in opioid dependence. In our study the pericortical and ventricular CSF space of 21 male opioid-dependent patients was compared with an age- and sex-matched normal control group. Considering serious problems with ratio and proportion measures, we used a battery of linear (cella media index, Huckman number, frontal horn index), planimetric (cortical atrophy score) and stereological volumetric measures in order to detect differences in cranial computerized tomography scans. We found a significant ventricular and cortical volume loss of the brain in opioid-dependent patients. A higher degree of frontal lobe volume loss seemed to be associated with a shorter period of abstinence before relapse. However, the etiology of volume loss of the brain in opioid-dependent patients is still unclear, but experimental animal studies provide some evidence that long-term, chronic opiate exposure is associated with visible changes of specific structures in the brain.

[Mirtazapine in inpatient treatment of depressed patients]. / Mirtazapin bei stationär behandelten depressiven Patienten.

Mirtazapine is a new antidepressant with a specific pharmacological profile which is different from all other currently available antidepressants. It is a so-called noradrenergic and specific serotonergic antidepressant (NaSSA). 46 in-patients were treated with mirtazapine. The mean dose was 56 mg mirtazapine per day (SD: 23; range: 15 to 90). The duration of treatment was 3.6 weeks (SD +/- 3.4). Patients presented with following diagnosis: 29 (= 63%) were diagnosed as having a unipolar depression, 26% (n = 12) suffered from a depression in the course of a bipolar disorder. 37% (n = 17) were moderately depressed, 52% (n = 24) were severely depressed. 2 patients (= 4%) met ICD-10 (international Classification of Diseases) criteria for a schizoaffective disorder, 2 patients (= 4%) suffered from dysthymia. 1 patient suffered from an organic depressive disorder. The efficacy of the treatment was evaluated with CGI (Clinical Global Impression), when patients were discharged from hospital. 68% of the patients were in partial or full remission (CGI 2, 3 and 4), 17% were unimproved (CGI 5 and 6), in 15% of the patients the treatment was stopped before. Our observations are indicative that mirtazapine is effective in the treatment of moderately and severely depressed patients and therefore confirm the data obtained in phase III-trials. Furthermore we found mirtazapine in either mono- or combination-therapy with various other antidepressants to be tolerated well. Side effects did not cause in a single patient a discontinuation in treatment.

[Central nervous system activation in opioid dependent patients, evaluation with Fourier analysis of pupillary oscillations]. / Zentralnervöse Aktiviertheit bei opioidabhängigen Patienten, evaluiert durch Fourieranalyse der Pupillenoszillationen.

The aim of the present investigation was to determine whether Fourier analysis of pupillary oscillations permits detection of differences in the activation of the central nervous system of opioid-addicted patients. We analysed pupillary oscillations during the recording period of static pupillometry, which lasted 25.6 s. Using Fourier analysis, the spectrum was divided into five frequency bands (0.0-0.20, 0.21-0.40, 0.41-0.60, 0.61-0.80, 0.81-1.0 Hz); the total spectrum (0-1 Hz) was also assessed. Three groups of patients were selected: the group addicted to heroin (consuming exclusively heroin) consisted of 26 patients with a mean age of 25.0 +/- 6.3 years, the methadone substitution group of 20 patients with a mean age of 30.9 +/- 8.2 years, and the morphine substitution group of 20 patients with a mean age of 33.2 +/- 4.6 years. The 3 patient groups were compared with normal controls of similar age (25.1 +/- 4.6 years). In the frequency band of 0.0-0.20 Hz the morphine group showed significantly lower amplitudes than the heroin group. Also in the frequency band of 0.41-0.60 Hz the morphine group differed significantly from the other groups concerning lower amplitudes, reflecting deactivation. In the total spectrum of 0 to 1 Hz the differences between these two groups were significant. Comparison with normal controls also showed significant differences. The groups were further divided according to dose (high/low): Patients of the heroin group as well as those of the methadone and morphine groups who had consumed higher doses showed greater activation of the central nervous system. In conclusion the morphine group was more deactivated than the methadone and heroin group and patients who received higher doses of the substances showed greater central nervous activation. Thus, the measurement of central nervous activation by means of Fourier analysis of pupillary oscillations might be useful in monitoring substitution therapy.

[Pregnancy and drug dependence]. / Schwangerschaft und Drogenabhängigkeit.

A major problem in the treatment of opiate-dependent patients arises due to illicit drug abuse capted with drug dependence and pregnancy. Drug abuse during pregnancy involves a high risk for the mother as well as for the unborn child. Twenty-three pregnant, opiate-dependent women, were enrolled in a 19-month study of the outpatient clinic for drug addiction. The mean age of the subjects was 26.7 years (SD +/- 4.8; range: 20-37 years), the mean duration of opiate dependence was 61.8 months (SD +/- 47.5; range: 12-204 months). Seventeen women were enrolled in a methadone maintenance program and six women were treated with morphine. The babies mean weight at birth was 2746 g (SD +/- 830.1; range: 940-4370), they had no congenital anomalies and all the maintained babies showed an opiate withdrawal syndrome. The treatment yielded in five subjects to a drug-free condition at delivery. The application of morphine might be an alternative in opiate dependent pregnant women and might reduce the additional consumption of illicit drugs during pregnancy.

[Protein catabolism after lung transplantation and heart transplantation]. / Eiweisskatabolismus nach Lungentransplantation und Herztransplantation.

Any surgical intervention is associated with an activation of protein catabolism, the extent of which is dependent on the severity of surgical trauma. There is a paucity of reports on protein catabolism after transplantation of chest organs (lung transplantation (LTX) and heart transplantation (HTX)). The aim of the present study was to quantify and compare the extent of postoperative protein catabolism and associated metabolic perturbations in patients after LTX and HTX. Eighteen consecutive patients after LTX and 15 consecutive patients after HTX who required postoperative intensive care for more than 4 days, constituted the study population. The nitrogen balance (assessed on the basis of the urea nitrogen production rate and nitrogen intake) was assessed retrospectively and correlated with insulin requirements, immunosuppression and the clinical course. Within the first 5 days the nitrogen balance became progressively negative in both groups, reaching a maximum on the 5th day. Thereafter the nitrogen balance of patients following LTX remained negative, whereas the nitrogen balance of patients following HTX tended to improve. The evolution of nitrogen balance significantly differed between both groups (p < 0.01). The mean nitrogen loss was -0.29 +/- 0.17g/kg BW/day after LTX versus -0.22 +/- 0.12g/kg BW/day after HTX. Smaller amounts of glucocorticoids were used for immunosuppression in patients after HTX than in patients after LTX; nevertheless, heart transplant recipients required higher doses of insulin to maintain normoglycemia. A regression analysis revealed that the duration of stay at the intensive care unit (p < 0.001) and the amount of glucocorticoids (p < 0.01) negatively affected the nitrogen balance, whereas an increased protein intake (p < 0.001) exerted a positive effect. Compared to other major surgical procedures, protein catabolism is excessively elevated in patients after thoracic transplantation. Immunosuppressive therapy with glucocorticoids contributes to protein degradation; the nitrogen balance after LTX is more negative than that after HTX because of higher glucocorticoid requirements following LTX. More aggressive nutritional intervention and especially an increased nitrogen intake might help to reduce protein losses in these patients.

Parsing the clinical phenotype of depression: the need to integrate brief depressive episodes.

OBJECTIVE: To expand the concept of recurrent brief depression (RBD) to brief depression (BD) and to test its clinical relevance. METHOD: Subjects (N = 591) were studied prospectively six times from ages 20/21 to 40/41 years. RBD was defined according to DSM-IV as episodes under 2 weeks with about monthly recurrence and work impairment. BD embraces RBD and brief depressive episodes with a frequency of 1-11 per year. RESULTS: Pure BD and pure major depressive episodes (MDE) did not differ in treatment rates, family history of mood and anxiety disorders or comorbidity with bipolar spectrum and anxiety disorders but they differed in work impairment, suicide attempt rates and distress self-ratings. The combination of BD + MDE identified a very severe group of MDE, comparable with combined depression (MDE + RBD) and double depression (MDE + dysthymia). CONCLUSION: Our data argue for the use of BD as a diagnostic specifier for severe MDE. RBD remains an important independent subgroup.

[Depression and anxiety]. / Depression und Angst.

Depression and anxiety disorders are among the most common psychiatric disorders in the general population and in daily practice of a general practitioner. Only a few years ago these disorders have been diagnosed either as "depression" or as "neurosis" in case of anxiety disorders. Since standardised diagnostic manuals have been available, it has been possible to differentiate between several depressive and anxiety disorders, which need a specific treatment. This change in the psychiatric diagnostic system is basing on psychiatric research results in the field of clinical diagnostics, biological psychiatry and epidemiology. This article provides guidance in diagnosis, differential diagnosis of depression and anxiety disorders and their therapy basing on international accepted treatment algorithms. Reviewed topics should make easy recognition and therapy possible for the general practitioner.

[Recurrent brief depressive episodes. Epidemiology, clinical aspects, diagnosis and therapy]. / Rezidivierende kurze depressive Episoden. Epidemiologie, Klinik, Diagnostik und Therapie.

Recurrent brief depression (RBD), an affective disorder with a similarly high risk of suicidal behavior as major depression (MD), is characterized by depressive episodes occurring about once a month that last only a few days. The combination of RBD and MD, called combined depression (CD), increases the risk of suicidal behavior enormously. Whereas patients with CD are usually in the care of psychiatrists or neurologists, epidemiological data demonstrate that RBD patients usually see only general practitioners and are not recognized as suffering from an affective disorder. Diagnostic criteria for RBD can be found in the ICD-10 and are helpful in both research and clinical routine. Recurrent brief psychiatric syndromes should be taken into differential diagnostic consideration and are discussed in detail in this review. However, the possibility of prospective diagnostic confirmation of RBD and the way of evaluating drug responses in prophylactic intervention of RBD differ essentially from those in treatment of MD and are more related to clinical procedures used in treating migraine or epilepsy. Differences in the courses of RBD and MD are responsible for different requirements in the design of drug treatment studies. Denial of special methodological needs and highly selected patient samples have probably been responsible for false negative results in double-blind, placebo-controlled treatment studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, no treatment algorithm can be given. Future treatment studies without the limitations of previous studies are clearly needed in the field of RBD.

Successful treatment of recurrent brief depression with reboxetine -- a single case analysis.

Recurrent Brief Depression (RBD) is a prevalent condition among the depressive illnesses, and is characterized by depressive episodes of a few days' duration occurring almost every month that are unrelated to the menstruation cycle. So far, RBD has not been shown to respond to antidepressive treatment in controlled clinical trials with citalopram, fluoxetine, flupenthixol, paroxetine, or mianserin using a "classical" parallel group design. However, successful RBD treatment on about sixty patients has so far been reported in one open trial with fluoxetine and in several cases with lithium, mirtazapine, and tranylcypromine. Furthermore, successful treatment of RBD has been reported in a few patients with carbamazepine, nimodipine, and verapamil in controlled double-blind single-case analyses using a flexible cross-over design.