PCR-Based Detection of Cephalosporium gramineum in Winter Wheat.

A polymerase chain reaction (PCR) assay was developed amplifying a 496-bp fragment of the internal transcribed spacer region of Cephalosporium gramineum genomic DNA at concentrations of 100 fg/µl. Winter wheat seed and seedlings were collected from field plots where C. gramineum was present. Seed was tested by PCR using 20-seed samples bulked for DNA extraction. Estimates of seed infection, based on isolation of the pathogen on semiselective medium and PCR, were comparable at 0.18 and 0.13% of winter wheat 'Stephens' (P = 0.6042), and 0.45 and 0.58% of experimental line WA7970 (P = 0.5636), respectively. PCR differentiated between plants with well-developed symptoms of Cephalosporium stripe and noninoculated plants. Positive PCR was obtained from 22% of asymptomatic leaf blades from inoculated plants. We found no false positives when PCR and C. gramineum isolation on a semiselective medium were performed using tissue from the same leaf. The PCR assay has potential to diagnose Cephalosporium stripe disease prior to the appearance of symptoms. Negative PCR for some samples from which C. gramineum was isolated suggests that C. gramineum may be present below the level of detection in some asymptomatic leaves. This PCR assay may be useful for investigations into C. gramineum infection of wheat.

Neuroendocrine response to antipsychotics: effects of drug type and gender.

BACKGROUND: To study the influences of drug type and gender on the neuroendocrine response to neuroleptic treatment, we compared the endocrine actions of two neuroleptics with different receptor affinity profiles--a substituted benzamide, amisulpride, a selective D2-like dopamine antagonist; and a thioxanthene, flupenthixol, a mixed D1/D2-like antagonist also blocking serotonin, H1, and D1 receptors--on anterior pituitary hormone secretion in schizophrenic patients (DSM-III-R). METHODS: Blood was withdrawn at 15-min intervals to assess basal secretion of prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH). Four hundred micrograms of thyrotropin-releasing hormone (TRH) was injected i.v. to investigate drug effects on TRH-stimulated secretion of prolactin, TSH, and GH. RESULTS: Prolactin plasma levels were markedly elevated in both treatment groups. In female, but not in male patients, this elevation was significantly more pronounced under amisulpride than under flupenthixol. The prolactin response to TRH was significantly blunted by amisulpride only in male subjects. While basal TSH secretion was significantly increased by both compounds, TRH-stimulated TSH secretion was elevated only in patients treated with amisulpride. Low basal prolactin levels predicted improvement of negative symptoms in patients treated with amisulpride. CONCLUSIONS: Amisulpride's more pronounced endocrine effects may be a reflection of its distinguished pharmacology and pharmacokinetics.

Blood ethanol levels and adenylyl cyclase activity in lymphocytes of alcoholic patients.

BACKGROUND: The adenylyl cyclase (AC) signal transduction pathway is a target of acute and chronic ethanol actions. This study examined whether AC activity in lymphocyte membranes of male alcoholic patients correlated with blood concentrations of ethanol. METHODS: Patients (n = 13; mean age: 40 +/- 8 years) were studied on the day of admission (day 0) and 2 days later under detoxification. Moreover, 13 age-matched male healthy controls (mean age 40 +/- 9 years) were included. Lymphocyte membranes were prepared by differential centrifugation whereby blood ethanol was washed out. As a measure of AC activity the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate was determined without (basal activity) and with stimulation of the second messenger system by the guanosine triphosphate (GTP) analogue GTP gamma S (20 mumol/L) via the G-protein or by forskolin (100 mumol/L) acting directly on the AC enzyme. RESULTS: On day 0, when ethanol blood concentrations were 38-100 mmol/L, we found a significant negative correlation between ethanol blood levels and stimulated AC activities. On day 2, the negative correlation with blood ethanol levels of day 0 had disappeared. CONCLUSIONS: The consumption of ethanol affects the AC system in lymphocytes of alcohol-dependent patients by a persistent effect on the cAMP forming enzyme.

Roxindole, a dopamine autoreceptor agonist, in the treatment of positive and negative schizophrenic symptoms.

Twenty schizophrenic inpatients with either predominantly positive or predominantly negative symptoms were treated with the dopamine autoreceptor agonist roxindole in prospective open clinical trials. There was no antipsychotic effect in the subgroup with positive symptoms, whereas the subgroup with negative symptoms, especially those with the residual type of schizophrenia, showed a moderate but significant 20% reduction in total scores on the Scale for the Assessment of Negative Symptoms.

Effects of subchronic paroxetine administration on night-time endocrinological profiles in healthy male volunteers.

To evaluate the subchronic effects of paroxetine, a selective serotonin reuptake inhibitor, on nocturnal endocrinological profiles, eight healthy male volunteers with no personal or family history of a psychiatric or neurological disease were administered paroxetine (30 mg/day) or placebo in a double-blind cross-over design. Drugs were given as a single dose at 10:00 h for a period of 4 weeks each. Between days 21 and 28 of each treatment period, sleep EEG was registered for four consecutive nights from 23:00 to 07:00 h. During the last night, hormonal profiles for prolactin, growth hormone (GH), cortisol, corticotropin (ACTH), luteinizing hormone (LH), testosterone and melatonin were determined, and area-under-the-curve values were calculated. None of the endocrinological parameters revealed any statistically significant changes. A trend could be found for an increased cortisol production under paroxetine (P = 0.069). ACTH, LH, and melatonin showed slight and non-significant decreases. Prolactin release was only marginally elevated (+7%). The mean sleep onset GH release (as measured for a time period of 180 min after sleep onset) was decreased by about 30% under paroxetine. However, statistical significance could not be reached. For hGH, there was a delayed mean GH-peak under paroxetine. Nocturnal testosterone secretion remained almost unaltered. The lack of significant endocrinological alterations might be partially explained by both adaptational phenomena under subchronic treatment conditions and the extended time span between the single morning dose and the registration period, respectively.

Combination treatment with clomipramine and fluvoxamine: drug monitoring, safety, and tolerability data.

BACKGROUND: Combination treatment with tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors (SSRIs) is an increasingly employed strategy especially in depressed patients unresponsive to monotherapy. Comedications with SSRIs, however, may be hazardous owing to pharmacokinetic interactions that can result in elevated serum TCA levels. For the combinations, safety and tolerability data are lacking. METHOD: We report tolerability and safety of combined treatment with fluvoxamine and clomipramine (CMI) in 22 patients. Most patients suffered from depression and obsessive-compulsive symptoms. Diagnoses were made according to DSM-III-R criteria. Serum levels of CMI, N-desmethylclomipramine (DCMI), and 8-hydroxylated metabolites were determined. EEG, ECG, and laboratory parameters and adverse effects reported by the patients, as well as global clinical improvement, were assessed. RESULTS: Generally, fluvoxamine/clomipramine comedication was well tolerated. Serum CMI levels reached 500 to 1200 ng/mL in half of the patients, while corresponding levels for DCMI and 8-hydroxylated metabolites were low. Moreover, the ratios of N-demethylation DCMI:CMI calculated from the ratios of drug concentrations in serum were markedly lower under comedication than under CMI monotherapy. Alterations in EEG, ECG, and laboratory parameters that had clinical relevance were rarely observed and were reversible after dose reduction of CMI. However, 2 patients developed myoclonic jerks. A majority of patients improved clinically during combination treatment. Clinically relevant side effects were absent in patients with serum CMI and DCMI levels below 450 ng/mL and ratios of N-demethylation below 0.3. CONCLUSION: Our results suggest that comedication of fluvoxamine and clomipramine will result in markedly elevated serum clomipramine levels. Therefore, combination treatment with fluvoxamine and clomipramine should be carefully monitored by determination of serum levels of the TCA. Clinically, the pharmacokinetic interactions between fluvoxamine and clomipramine may be well tolerated in a majority of patients. However, in a few patients, higher serum levels may be associated with an increased risk of EEG changes and changes of intracardiac conductance. EEG and ECG should be used regularly to monitor comedicated patients.

Savoxepine: invalidation of an "atypical" neuroleptic response pattern predicted by animal models in an open clinical trial with schizophrenic patients.

The new tetracyclic compound savoxepine exhibits potent antidopaminergic effects with preferential activity in the hippocampus as compared to striatum in rat brain. As a result of behavioural animal models and regional differences in dopamine receptor binding characteristics, it has been suggested to possess an "atypical" neuroleptic response pattern. In an open clinical trial, savoxepine was administered to 12 in-patients suffering from paranoid schizophrenia and schizophreniform disorder (DSM-III). Eight patients were treated with a stable dose of 0.5 mg per day throughout the study, while in the remaining patients higher doses up to 20 mg/day were administered. Mean total BPRS scores and subscores demonstrated a moderate improvement of mainly positive schizophrenic symptoms. In contrast to animal test results, savoxepine in a broad dose range produced typical untoward extrapyramidal symptoms in the majority of patients. Our results indicate that savoxepine may not possess the expected "atypical" neuroleptic response pattern, and that the predictive validity of the animal models in question used to separate antipsychotic effects from extrapyramidal reactions may be ill-founded.

Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients.

Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients. A column switching technique combined with high performance liquid chromatography (HPLC) enabled automated analyses of plasma for simultaneous determination of fluvoxamine, tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run. The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine, clomipramine, amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine. In patients under fluvoxamine monotherapy before comedication, plasma concentrations of fluvoxamine increased after administration of a tricyclic antidepressant, thus indicating bidirectional drug interactions. The inhibitory effects of fluvoxamine on the metabolism of classical antidepressants disappeared after discontinuation of concomitant fluvoxamine treatment within at least 1-2 weeks. The reported alterations in drug metabolism observed in depressed patients who were under fluvoxamine/tricyclic antidepressant comedication suggested that careful supervision and regular drug monitoring are necessary in such patients.

Roxindole, a dopamine autoreceptor agonist, in the treatment of major depression.

Roxindole is a potent autoreceptor-"selective" dopamine agonist originally developed for the treatment of schizophrenic syndromes. The drug also inhibits 5-HT uptake and has 5-HT1A agonistic actions. In this open clinical trial 12 in-patients suffering from a major depressive episode (DSM-III-R) were treated with roxindole for 28 days in a fixed dosage of 15 mg per day. A reduction of at least 50% in HAMD-17 total scores was observed in 8 out of 12 patients after 4 weeks (mean HAMD-17 reduction of 56% in all patients), while 4 patients did not respond to roxindole treatment. Half of the patients showed a complete psychopathological remission (HAMD-17 < 8). Roxindole's onset of antidepressant action was remarkably rapid. Seven out of eight responders improved within the first 2 weeks of treatment (at least 50% decrease in HAMD-17 total score), and four patients were nearly asymptomatic within 1 week. Our results indicate that roxindole may possess potent antidepressant properties and that its efficacy should be further evaluated by double-blind controlled studies against reference drugs.

Seroquel (ICI 204 636), a putative "atypical" antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters.

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36.1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)

The neuroendocrinological profile of roxindole, a dopamine autoreceptor agonist, in schizophrenic patients.

Roxindole is a potent autoreceptor-selective dopamine agonist with additional properties as a serotonin reuptake inhibitor and 5-HT1A agonist. In order to get more insight into its mode of action in various psychiatric populations, we evaluated the effects of subchronic roxindole treatment on pituitary and adrenal hormone secretion, i.e. release of prolactin, thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and cortisol. Fifteen schizophrenic patients with positive and negative symptomatology, respectively, were treated with roxindole for 28 days. Both basal and thyrotropin releasing hormone (TRH) -induced prolactin secretion diminished significantly to 26.4% and 22.8% of baseline levels, respectively, under roxindole. Basal GH secretion was insignificantly elevated by 89%, whereas GH levels increased nearly 3-fold after stimulation by TRH. TSH levels decreased insignificantly to 57.5% of baseline levels, while TRH-induced TSH release was not affected by subchronic roxindole. Roxindole treatment influenced neither LH secretion nor cortisol release. Our results indicate that roxindole's dopaminergic actions might prevail over its serotonergic effects, at least as far as the regulation of anterior pituitary hormone secretion is concerned.

Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application.

Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t1/2 beta), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g t1/2 beta values were 5.5 and 4.7 h, respectively, mean-g tmax data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g Cmax maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag, tmax, and Cmax. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite "reduced benperidol" were found to be very low.

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.

RATIONALE: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors. OBJECTIVES: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. METHODS: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. RESULTS: A high occupancy of striatal D(2)-like DA receptors similar to that induced by typical neuroleptics was observed in all patients treated with EMD 57445. CONCLUSIONS: Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.

Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group.

The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.

Evaluation of standardized rater training for the Positive and Negative Syndrome Scale (PANSS).

The Positive and Negative Syndrome Scale (PANSS) is employed increasingly for the evaluation of therapeutic outcome in studies on schizophrenia. Rater training is important to improve the concordance and accuracy of ratings; however, there are no established guidelines for carrying out such training. We conducted rater training, under clinical conditions, of psychiatrists and clinical psychologists who were rather unfamiliar with the PANSS. Based on videotapes of PANSS interviews, all participants were trained during five successive standardized weekly sessions. The results were analyzed with respect to conventional criteria of concordance with standard expert ratings and interrater reliability. The main objective was to evaluate the number of training sessions which are necessary and sufficient to achieve acceptable PANSS rating results. Additionally, differences in training outcome for positive, negative and general psychopathological symptoms and between subgroups of different clinical and PANSS experience were considered. After three weekly sessions, satisfactory concordance of about 80% of clinicians on the PANSS total scale was obtained. However, in comparison with the positive and general psychopathological subscales, the PANSS negative-symptom subscale yielded somewhat less satisfactory results, with about 70% of the raters achieving sufficient accuracy. Intraclass correlations corroborated these findings. No substantial differences in training outcome were found between subgroups of different clinical and PANSS experience. We conclude that at least three standardized PANSS training sessions are recommended to obtain satisfactory accuracy of ratings.

Dimensionality of depression in acute schizophrenia: a methodological study using the Bech-Rafaelsen Melancholia Scale (BRMES).

Despite the great clinical importance of depressive symptoms in schizophrenia there is a lack of studies on the assessment and evaluation of depression in acutely psychotic patients. For the Bech-Rafaelsen Melancholia Scale (BRMES), among other advantages, the concept of unidimensionality was confirmed in patients with major depression by different methodological approaches including Rasch analysis. The present evaluation was designed to investigate the scale properties of the BRMES in acutely schizophrenic patients with particular emphasis on the dimensionality of the scale. Three different statistical approaches were used: principal component analysis in combination with computer simulation, polytomous Rasch analysis using advanced latent trait and latent class models and confirmatory factor analysis (CFA) by means of linear structure model approaches. The statistical methods were applied to BRMES baseline data of 132 acutely schizophrenic patients with predominantly positive symptoms participating in a multi-center pharmacological trial. The different methodological approaches revealed converging results indicating: (1) a substantial proportion of acutely ill schizophrenic patients showed depressive symptoms; (2) the hypothesis of unidimensionality of the BRMES had to be rejected for the sample of acutely schizophrenic patients and (3) a three-factorial model of depressive symptoms as measured by the BRMES ('retardation', 'depressive core symptoms', 'unspecific depressive symptoms') yielded the best fit of the present data. Depression in acutely psychotic patients has to be considered rather as a heterogeneous construct than as a well-defined syndrome. The differentiation of depressive symptomatology should facilitate treatment evaluation and help to clarify relationships between different symptom classes in further studies.

A randomized, double-blind comparison of a rapidly escalating dose of venlafaxine and imipramine in inpatients with major depression and melancholia.

A double-blind, randomized, parallel study in 167 hospitalized patients with major depression and melancholia was conducted to determine if rapidly escalated doses of venlafaxine produced an earlier response, compared with rapidly escalated doses of imipramine. The daily dose of venlafaxine was rapidly increased to 375 mg/day over a five-day period, was maintained at this level for 10 days, and then was reduced to 150 mg/day for the remainder of the study. The imipramine dose was rapidly increased to 200 mg/day over five days and was maintained at this level to the end of the study. The primary efficacy variables were time to response and time to sustained response on the HAM-D and MADRS. No differences in the response rates on the HAM-D or MADRS were observed between treatments. However, among patients who demonstrated a response on the HAM-D, there was a significantly faster onset of response (p = 0.036) and sustained response (p = 0.018) in the venlafaxine group. The median time to response on the HAM-D among responders was 14 days with venlafaxine and 21 days with imipramine. However, no differences between treatments were observed among responders on the MADRS (median time to response: 15 days for venlafaxine, 18 days for imipramine). Study events were reported in 69% of venlafaxine-treated patients and 76% of imipramine-treated patients. In severely depressed patients with melancholia, a faster onset of response was observed with venlafaxine on the HAM-D, but not the MADRS, and maximal tolerated doses of venlafaxine and imipramine were comparable for overall efficacy. These results confirm and extend previous observations and suggest that venlafaxine may have an early onset of action and may produce a rapid response in hospitalized patients with severe depression complicated by melancholia.

Acute antagonism of dopamine D2-like receptors by amisulpride: effects on hormone secretion in healthy volunteers.

Amisulpride is a selective D2-like dopamine receptor antagonist with a high affinity for the cloned D2 and D3 receptors. At low doses it may improve depressive and negative schizophrenic symptoms whereas antipsychotic effects on positive schizophrenic symptomatology require higher dosages. Acute endocrine effects were studied for two doses of amisulpride with regard to the daytime secretion of prolactin, thyroidea stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH) and cortisol. Amisulpride was administered i.v. to eight healthy male volunteers in a single-blind trial under a randomized cross-over, placebo-controlled design using doses of 20 mg or 100 mg, or saline. The drug was injected at 09:00 h, and plasma samples were withdrawn from 08:30 h to 16:00 h at intervals of 15 and 30 min, respectively. At both dosages, prolactin was significantly elevated to the eight- to ten-fold of baseline levels. Likewise, a significant 50% elevation of TSH concentrations with a trend to a greater increase under the 100 mg dose was observed. Plasma levels of LH and cortisol were not significantly affected by amisulpride. With regard to GH secretion, there was a trend to a decrease only with the 20 mg dose. These results indicate that the neuroendocrinological side-effect profile of acute amisulpride administration may be similar to conventional neuroleptics, and that there are only minor dose-dependent differential effects on hormone secretion in the dose range investigated.

Primary enduring negative symptoms in schizophrenia and major depression.

Primary enduring negative symptoms (PENS) were studied in 26 patients with DSM-III-R schizophrenia and in 94 patients with unipolar major depressive episodes 5 years after the index episode. PENS were assessed with the Schedule for Deficit Syndrome (SDS). Negative symptoms were also assessed with the Scale for Assessment of Negative Symptoms (SANS) and subclassified into primary and secondary according to the SDS. The frequency of PENS did not differ significantly between schizophrenics and non-schizophrenic patients. Enduring negative symptoms (regardless of whether primary or not) were more frequently observed in schizophrenia (65% according to the SDS, and 88% according to the SANS) than in patients who had major depressive episodes (29% according to the SDS and 32% according to the SANS). By applying the SDS criteria for PENS, their frequency decreased in a manner which would probably affect the availability of patients samples for testing antinegative drugs. The results suggest that neither the negative symptomatology nor the primary enduring subtype ("deficit") is specific for schizophrenia. This finding might imply potential advantages of non-nosological, functional approaches for research into PENS.

The Calgary Depression Rating Scale for Schizophrenia: development and interrater reliability of a German version (CDSS-G).

A German version of the Calgary Depression Rating Scale for Schizophrenia (CDSS-G) approved by the author of the original scale is presented comprising a semi-structured interview for 9 items to sensitively and specifically assess depression in schizophrenia and related disorders. The process of translation is outlined and the finally derived CDSS-G was investigated with respect to interrater reliability in three studies. To keep comparability with the CDSS source version a standard procedure was used. Two trained raters jointly assessed ten schizophrenic patients (study I). In a second study, videotapes with the CDSS-G were presented to clinically inexperienced raters (study II, N = 14/15) to test the agreement on the CDSS-G in this sample. Finally, in a third study clinically experienced researchers participated in a rater training (study III, N = 34). They carried out CDSS ratings on three patients with mild depressive symptoms. The dependence of interrater reliability on depression severity was investigated for all studied patients. Both intraclass correlation coefficients (ICC) and weighted kappa coefficients (kappa(w)) were calculated. The results revealed a high ICC = 0.97 in study I for the total CDSS-G score. Single item ICC values were all above 0.70. The results of study II revealed somewhat lower agreement on CDSS-G items and total scores in psychiatric novices with however acceptable values of kappa(w)>0.50 for the total scores. Study III yielded satisfactory results (0.66