The development concept of "endogenous psychoses".

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.

Increased frequency of dentate granule cells with basal dendrites in the hippocampal formation of schizophrenics.

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 maldevelopment 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 maldevelopment with an ongoing process of plasticity might, therefore, supersede the hypothesis of a neurodegeneration in schizophrenia.

Periodic catatonia: confirmation of linkage to chromosome 15 and further evidence for genetic heterogeneity.

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.

Postpartum psychoses: prognosis, risk factors, and treatment.

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.

The concept of hebephrenia over the course of time with particular reference to the Wernicke-Kleist-Leonhard School.

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.

Novel 5'-regulatory region polymorphisms of the 5-HT2C receptor gene: association study with panic disorder.

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.