Several structural deviances in the brain in "endogenous psychoses" have been described over the last decades. The enlargement of the lateral ventricles and the subtle structural deficits in temporobasal and orbital frontal structures (hypofrontality) are reasonably well established in the majority of schizophrenic patients. We examined the cytoarchitecture of these important central structures, namely the entorhinal region and the orbitofrontal cortex (Brodmann area 11), which have been under meticulous investigation in our laboratories over the last few decades. In a new series of schizophrenic patients and normal controls, we made serial cuts of the whole rostral entorhinal cortex on both sides. For this report, we selected two cases with very different psychopathologies, and present the serial cuts through both hemispheres and the malformations found. We report on the differing magnitude of the heterotopic malformations (for definition see page 103), either bilaterally or unilaterally.

Guidelines for biological Treatment of Schizophrenia, : Part 1: Acute Treatment of Schizophrenia and Part 2: Long-term Treatment of Schizophrenia

In the hippocampal formation of schizophrenics, the detailed morphology of Golgi-impregnated granule cells was examined. These granule cells of the dentate gyrus are interposed between the rostral entorhinal cortex and the hippocampus proper. In these limbic regions significant cytoarchitectural alterations in schizophrenics are reported, giving rise to the concept of a prenatal limbic maldevelopement in schizophrenia. Compared to controls, the frequency of dentate granule cells with basal dendrites was significantly increased in schizophrenics [43% (±3)] vs. [22% (±2) in the control group]. In epilepsy, dentate granule cells of epileptic patients also develop basal dendrites, which is explained as an adaptive process of plasticity. Similarly, the hippocampal alterations described in schizophrenics could be the sequela of primary entorhinal cytoarchitectural alterations. Since the increase in basal dendrites seems to reflect a process of continuous plasticity, suggesting an increased rate of postnatal granule cell generation, the synthesis of a prenatal limbic maldevelopement with an ongoing process of plasticity might, therefore, supersede the hypothesis of a neurodegeneration in schizophrenia.

The last decades have revealed several structural deviances in patients with so called "endogenous psychoses". Reasonably well established are the enlargement of the lateral ventricles and subtle structural deficits in temporobasal and orbital frontal structures (hypofrontality) in a majority of schizophrenic patients. It is the aim of this investigation to examine the cytoarchitecture of these important central structures, namely the entorhinal region and the orbitofrontal cortex (Brodmann area 11) which have been under meticulous investigation in our laboratories over decades (for review: Beckmann, 2000).

The concentrations of 17 substances were determined in the cerebrospinal fluid (CSF) of 28 paranoid schizophrenic patients and 16 controls. Results were standardized and simultaneously evaluated through Multidimensional Scaling (MDS). The full data set can be considered as a cloud of points consisting of the 44 subjects in the 17-dimensional parameter space. MDS seeks a two-dimensional representation of this 17-dimensional cloud of points, while retaining as much as possible the distances between the subjects. The two-dimensional reduction of the 17 CSF parameters correctly separated 15 of 16 controls from the schizophrenic subjects. This indicates that a biological heterogeneity between schizophrenic and nonschizophrenic subjects can be detected by the simultaneous analysis of the CSF concentrations of substances related directly or indirectly to the neuronal activity in the brain.

Summary: The concept of hebephrenia has undergone more changes than almost any other diagnostic category in clinical psychiatry. In the present article we want to outline these changes from Hecker's first description of hebephrenia to contemporary concepts mainly based on Bleuler's viewpoints. Due to rather heterogeneous and vaguely defined symptomatology, hebephrenia lost relevance as a diagnostic category in today's classification systems. As an alternative approach, Kleist and Leonhard see hebephrenias as forming distinct clinical entities with insidious beginning and a chronically progressive course leading to specific and stable residual syndromes, mainly featured by disturbed affectivity and, thus, initiative. As known up to now, hebephrenias within Leonhard's classification show poor prognosis, little response to treatment and low heredity. This concept of hebephrenia seems to be more appropriate to demarcate a homogeneous subtype which can be the subject of further promising research to clarify aetiology and nosology of schizophrenic spectrum psychoses.

Ein Konzept zur Realisierung einer effizienten SRM-Strategie sind SRM-Portale. SRM-Portale stellen im Internet/Extranet Funktionalitaten zur Verfugung, uber die Unternehmen samtliche Kommunikation mit ihren Lieferanten durchfuhren konnen. Sie bieten somit einen Ansatz zur Automatisierung der Lieferantenbeziehungen. In diesem Artikel wird die Architektur, Implementierung und der Betrieb eines SRM-Portals betrachtet (im Rahmen des Projektes E-START), welches fur die Prozessintegration zwischen Lieferant und Einkaufer steht. Daruber hinaus liefert das Portal Unterstutzung zur Aufbereitung elektronischer Produktdaten (Basis fur die Produktauswahl) sowie bei der Lieferantensuche.

The meaning of heterogeneity in schizophrenia and the impact of genetic and environmental factors on etiology are a matter of continuous debate in psychiatric research. Different clinical and birth history variables were investigated in a sample of 68 patients with chronic catatonic schizophrenia according to DSM III-R, classified into Leonhard's systematic schizophrenia (n = 32) and periodic catatonia (n = 36). Parental transmission of the disease was evident in 44% of the periodic catatonia cases compared to one case in systematic catatonia (3%; p = 0.0003). In systematic catatonia, 34% of the index cases were exposed to prenatal infections compared to 8% in periodic catatonia (p = 0.008). Using logistic regression analysis exposure to gestational maternal infections predicted diagnosis of systematic catatonia at p = 0.008, and parental psychosis predicted diagnosis of periodic catatonia in the index cases at p = 0.0001. The latter finding is substantiated by the recent mapping of a periodic catatonia-susceptibility locus on chromosome 15q15 with evidence for autosomal dominant transmission. These findings support the hypothesis that distinct schizophrenia phenotypes are based on different etiological mechanisms.

The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously.

We earlier reported significant evidence for linkage on chromosome 15q15 in periodic catatonia, a sub-phenotype of schizophrenic psychoses. The disorder is characterized by qualitative hyperkinetic and akinetic psychomotor disturbances through acute psychotic episodes and debilitating symptoms in the long term, with psychomotor weakness, grimacing facial movements and apathy. Here, we confirm mapping of a major gene locus on chromosome 15q15 in a second genome scan in a new set of four multiplex families. Non-parametric multipoint linkage analyses identified a broad region with a maximum peak of Z(all) =3.91 ( P=0.006) and Z(lr) =3.04 at D15S1234 ( P=0.001), satisfying conventional criteria for confirmed linkage. Parametric affected-only analyses under an autosomal dominant model gave a maximum HLOD score of 1.65 (D15S1234) with an estimated 47% of families being linked. Analysis of individual families showed that one large family showed linkage, whereas two others could be clearly excluded, confirming genetic heterogeneity. No other locus reached suggestive levels of significance. Haplotype analysis on chromosome 15 in this and previously linked families placed the susceptibility region to a 11-cM interval between marker D15S1042 and D15S659. Periodic catatonia is the first sub-phenotype of schizophrenic psychoses with confirmed linkage despite the existence of considerable genetic heterogeneity.

Puerperal psychoses do not represent a nosological entity, but rather a selection of puerperally triggered "ordinary" functional psychoses with cycloid psychoses predominating and schizophrenias occurring very rarely. The prognosis is basically favorable concerning symptom remission and social and occupational functioning. However, there is a considerable frequency of relapses and an increased suicide rate. The most important risk factors for an episode of a puerperal psychosis are being primiparous and having suffered a previous episode of a psychosis, particularly a cycloid psychosis. Controlled treatment studies up to now are absent. Case studies suggest in acute episodes the efficacy of a symptom-oriented pharmacologic treatment where ablactation is recommended. With respect to prophylactic treatment some authors propose to apply lithium in late pregnancy or immediately after delivery. Because of its possible teratogenic effects and the altogether rather sparse data, the authors however cannot recommend the use of lithium during pregnancy. Applying estradiol after delivery may be beneficial and safe, but further studies are necessary to clarify these issues.

Hintergrund: Methoden: Diskussion: Background: Methods: Conclusion:

The human calcium-activated potassium channel gene (hKCNN3, hSKCa3) contains two tandemly arranged, multiallelic CAG repeats located in exon 1 which result in short to moderate polyglutamine stretches of unknown functional significance. Case-control and family-based association studies suggested an association of hKCNN3 repeats with susceptibility for schizophrenia. Twelve multiplex pedigrees with periodic catatonia, a schizophrenia subtype with major gene effect and patterns of anticipation, were genotyped using the multiallelic hKCNN3 repeat polymorphism. Using a dominant model of inheritance with sex- and age-dependent penetrance classes, cumulative results showed exclusion of linkage of hKCNN3 to periodic catatonia under the assumption of genetic homogeneity with lod score of −48.01 at zero recombination fraction. Our results provide evidence that hKCNN3 is not the causative gene in the familial schizophrenia subtype of periodic catatonia. By fluorescent in situ hybridization we confirmed the assignment of hKCNN3 to chromosome 1q21 near the heterochromatin region. Linkage mapping showed segregation with marker DIS498 (θ=0.05) and placed hKCNN3 in the genetic linkage map in a cluster of genes near the centromeric region of chromosome 1.

The nature of subtypes in schizophrenia and the meaning of heterogeneity in schizophrenia have been considered a principal controversy in psychiatric research. We addressed these issues in periodic catatonia, a clinical entity derived from Leonhard's classification of schizophrenias, in a genomewide linkage scan. Periodic catatonia is characterized by qualitative psychomotor disturbances during acute psychotic outbursts and by long-term outcome. On the basis of our previous findings of a lifetime morbidity risk of 26.9% of periodic catatonia in first-degree relatives, we conducted a genome scan in 12 multiplex pedigrees with 135 individuals, using 356 markers with an average spacing of 11 cM. In nonparametric multipoint linkage analyses (by GENEHUNTER-PLUS), significant evidence for linkage was obtained on chromosome 15q15 (P = 2.6 x 10(-5); nonparametric LOD score [LOD*] 3.57). A further locus on chromosome 22q13 with suggestive evidence for linkage (P = 1.8 x 10(-3); LOD* 1.85) was detected, which indicated genetic heterogeneity. Parametric linkage analysis under an autosomal dominant model (affecteds-only analysis) provided independent confirmation of nonparametric linkage results, with maximum LOD scores 2.75 (recombination fraction [theta].04; two-point analysis) and 2.89 (theta =.029; four-point analysis), at the chromosome 15q candidate region. Splitting the complex group of schizophrenias on the basis of clinical observation and genetic analysis, we identified periodic catatonia as a valid nosological entity. Our findings provide evidence that periodic catatonia is associated with a major disease locus, which maps to chromosome 15q15.

Candidate genes for association studies in panic disorder are often selected on the basis of molecular mechanisms of drugs utilized in challenge tests such as m-chlorophenylpiperazine (mCPP), a non-selective 5-HT2C receptor agonist. Two novel, adjacent polymorphisms [(GT)12-18 and (CT)4-5] in the 5'-regulatory region of the X-chromosomal 5-HT2C receptor gene have recently been reported. We determined the allele frequency of long vs. short polymorphism haplotypes in a German and an Italian sample (combined n = 211) of panic disorder patients (DSM-III-R) and compared it with allele frequencies in two ethnically matched control samples (combined n = 226). In the German sample, a comparison of female genotypes containing the short haplotype vs. female genotypes containing only long haplotypes showed a significant difference (p = 0.01, ?2 analysis). In the Italian sample, however, this observation could not be replicated (p = 0.54, ?2 analysis). This argues against a major role for these promoter-associated 5-HT2C receptor gene length polymorphisms in the aetiopathogenesis of panic disorder.

Naturally occurring benzodiazepines (BZDs) were first detected in mammalian tissues in 1986. They comprise a variety of 1,4-benzodiazepines corresponding to drugs commercially available for the treatment of anxiety disorders, sleep disturbances and epileptic seizures. Several biosynthetic pathways leading to the formation of BZDs are currently being discussed and have led to the proposition of possible precursor molecules.

The main reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conformity. This has not changed markedly following the introduction of modern operational diagnostic systems. Taking schizophrenia as a disease entity or assuming schizophrenia spectrum psychoses to represent a continuum of diseases without any clear dividing lines, the results of family and twin studies point to a multifactorial etiology based on a polygenic mode of transmission. Further, then it has to be assumed a familial continuum from schizophrenia to affective psychosis and other spectrum disorders. However, in family and twin studies based on Leonhard's classification, there is clearcut evidence that schizophrenic spectrum psychoses have to be divided into clinical and etiological subgroups with a completely different genetic background. For example, systematic catatonia is, for the most part, a sporadic disease, whereas periodic catatonia aggregates in families in a manner consistent with a major gene effect. Further, the results indicate that schizophrenic spectrum psychoses consist of three main valid categories: cycloid psychoses, unsystematic schizophrenias and systematic schizophrenias. In the case of cycloid psychosis and systematic schizophrenias, genetic loading seem to be very low, while "environmental" factors, for example, birth complications, may play an important etiological role. Unsystematic schizophrenias, however, are predominantly inherited and "environmental" factors are not very prominent.

In a polydiagnostic study, a systematically recruited collective of 34, women with a first-episode postpartum psychosis was reexamined after a period of 6-26 years (averaging 12.6 years) in order to establish lifetime-diagnoses according to ICD-10 and Leonhard's classification,and to determine course and outcome. According to ICD-10, unipolar depressive disorders (32%) and acute polymorphous psychotic disorders (28%) represented the most frequent diagnoses. Applying Leonhard's classification revealed a marked predominance of cycloid psychoses (62%) with the subform of motility psychosis being the most frequent diagnosis (38%). Schizophrenias occurred rarely according to both classifications.Investigating the long-term course,we found in 59% multiphasic disorders. The mean number of episodes per patient was 2.5 (range 2-6) with a mean duration of 9.8 weeks (SD = 5.2). 6 patients (18%) had undergone a monophasic course, in 4 cases (12%) the course was not determinable. 17 women (50%) had 19 further deliveries during the follow-up period. The frequency of relapses in connection with a further delivery was 47%. Administering the Strauss-Carpenter-Outcome-Scale revealed a favourable outcome with a mean value of 14.1 (SD = 2.83) for our total sam pie. Only 4 patients (12%) had never recovered fully since the onset of the illness.Our findings suggest that cycloid psychoses, in particular motility psychoses, account for the majority of postpartum psychoses, and do not support the hypothesis of a nosological independence of postpartum psychoses. They provide further evidence of a favourable prognosis of severe postpartum psychiatric disorder despite a relatively high rate of non-puerperal and especially puerperal relapses.