Long-term follow-up of patients with obsessive-compulsive disorder treated by anterior capsulotomy: a neuropsychological study.

BACKGROUND: For treatment-refractory Obsessive-Compulsive-Disorder (OCD) patients, anterior capsulotomy is a potential therapy. We investigated what kinds of cognitive deficits treatment-refractory patients have and how anterior capsulotomy modifies their clinical and cognitive profiles. METHODS: Ten treatment-refractory OCD patients were examined in two groups (operated and non-operated) with 5 participants in each group, matched for symptom severity, gender, age and education. The operated group was treated with anterior capsulotomy; the non-operated group was treated only with pharmaco- and psychotherapy. The Yale-Brown Obsessive-Compulsive Rating Scale (Y-BOCS) was used to measure OCD symptoms, and ten neuropsychological tests were used to measure cognitive functioning. RESULTS: In the operated group, the score of Y-BOCS score significantly decreased during the two-year follow-up period. Additionally, we found a significant increase in neuropsychological test scores on the Wechsler Intelligence Test (MAWI), California Sorting Test Part A (CST-A), Stroop Test Interference Score (STR-I), Verbal Fluency Test and Iowa Gambling Test. As a negative result, we observed intrusion errors in the Category Fluency Test. In the non-operated group significant improvement was found in Y-BOCS scores. At follow-up, we found significant differences between the operated and non-operated groups on three neuropsychological tests: Trail Making Test Part B, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Index and RBANS Language Index, with better performance in the non-operated group. CONCLUSIONS: Both treatment methods (i.e. anterior capsulotomy and pharmaco- and psychotherapy) seem effective in reducing OCD symptoms and cognitive deficits, but, importantly, to different degrees. The clinical and neuropsychological improvements were more impressive in the operated group.

Potential genetic markers of sporadic Alzheimer's dementia.

Polymorphisms within the genes encoding apolipoprotein E (ApoE), apolipoprotein CI (ApoCI), alpha1-antichymotrypsin (ACT), the low-density lipoprotein (LDL) receptor and lipoprotein lipase were investigated in patients suffering from Alzheimer's dementia and non-demented psychiatric patients as control subjects. The ApoE allele 4, well known as a risk factor in Alzheimer's disease, and the ApoCI allele A2, which is closely linked to the ApoE allele 4, were found elevated in the index group. Concerning the polymorphism within exon 8 of the LDL receptor (alanin/threonin), there was also a predominance of the allele carrying threonin in the index group, which barely missed significance. Distribution of the polymorphisms of ACT and lipoprotein lipase were similar in both groups investigated. We conclude that, apart from the ApoE allele 4, other genetically regulated factors like ApoCI and the LDL receptor modulate the individual risk for Alzheimer's disease.

Ciliary neurotrophic factor null mutation and schizophrenia in a Swedish population.

According to the maldevelopmental hypothesis, the neurotrophic factor system represents an important area which might be genetically and neurochemically involved in the etiopathogenesis of schizophrenic psychoses. Patients suffering from schizophrenic psychoses and control persons were genotyped for a null mutation of the ciliary neurotropic factor gene. There were no significant differences in the allelic and genotypic distributions in the total schizophrenic and control samples. However, there was a negative association with a family history of psychosis. Thus, it cannot be excluded that this genetic variant represents a vulnerability marker for specific schizophrenic subtypes. The development of valid diagnostic instruments based on biological criteria is crucial for schizophrenia research; more homogeneous subgroups are more likely to represent distinct nosological entities than the heterogenous group of diseases presently categorized as schizophrenia.

Variants in neurotrophic factor genes and schizophrenic psychoses: no associations in a Spanish population.

Possible associations between schizophrenic psychoses, a ciliary neurotrophic factor (CNTF) null mutation and a neurotrophin in 3 (NT3) bi-allele polymorphism were investigated in a Spanish population. The sample consisted of 107 patients suffering from schizophrenic psychoses and 100 healthy volunteers. There was no statistical difference in the frequencies of the mutant CNTF allele in the index and control groups (0.125 vs. 0.121). The frequency of the rare NT3 allele (Glu) was very low and similar in both groups (0.005). Previous findings supporting the involvement of these genetic markers in the pathogenesis of schizophrenic psychoses were thus not confirmed. In light of neurodevelopmental hypotheses of schizophrenia, however, genes coding for neurotrophic factors remain interesting susceptibility loci in schizophrenia research. Subsequent studies should not focus exclusively on genetic alterations but also take into account secondary changes of the neurotrophic factor system at the mRNA and protein levels. Further, the current unsatisfying operationalized classification of the heterogeneous syndrome 'schizophrenia' remains a crucial problem that could be partially resolved by introducing more differentiated diagnoses defined on the basis of neurobiological criteria.

[Biochemical and ultrasonic screening of chromosomal aneuploidies in the second trimester of pregnancy]. / Kromoszomális aneuploidiák biokémiai és ultrahangszürése a terhesség második trimeszterében.

For prenatal screening of chromosomal aneuploidies (primarily the most frequent Down syndrome) maternal serum AFP screening in the second trimester of pregnancy has been supplemented by the determination of hCG in Hajdú-Bihar county. In pregnancies at risk on the basis of biochemical tests, a thorough, aimed ultrasound examination for the detection of minor and major anomalies characteristic for chromosomal abnormalities was carried out. If both biochemical and ultrasound examinations were suggestive of high risk prenatal karyotyping was offered. During a two-years prospective study 14328 pregnancies were screened. Authors could detect 38% of Down-syndrome cases prenatally, 5 cases in pregnant women at age under 35 years and at the same time the number of amniocenteses increased only by 70. It was concluded that 66% of all Down syndrome cases could have been prenatally diagnosed if prenatal chromosome test were performed in all cases at high risk on the basis of screening tests and maternal age.

The Gly/Glu polymorphism of the neurotrophin 3 gene: allele frequencies in a Caucasian population and relevance for psychiatric disorders.

Using a modified method for the determination of the genotype of the neurotrophin 3 Gly/Glu polymorphism by PCR, we investigated allele frequencies in patients suffering from different psychiatric diseases as well as in healthy controls. There was a much lower frequency of the allele Glu among Caucasians (0.006) than previously reported for a Japanese population (0.203). No homozygotes and only three heterozygotes for the rare allele could be detected: the latter belonged to the patient group and suffered from endogenous depression (two patients) and hebephrenia (one patient). Due to its very low frequency it seems unlikely that the allele Glu plays a decisive role in the aetiopathogenesis of schizophrenic psychoses or other psychiatric diseases. However, it cannot be excluded that it represents a risk or vulnerability factor.

A null mutation allele in the CNTF gene and schizophrenic psychoses.

The maldevelopmental theory postulates disturbances in neural development as crucial factors in the aetiopathogenesis of schizophrenia. Neurotrophic factors, including ciliary neurotrophic factor (CNTF), play a central role in the regulation of such development. A mutation has been described for the CNTF gene, whereby subjects homozygous for the mutation lack CNTF. The polymerase chain reaction was used to amplify the CNTF gene region containing this mutation in whole blood genomic DNA. The mutation was detected by analysis of restriction fragment length polymorphisms. Patients suffering from schizophrenic psychosis (ICD-10 criteria) (51 from Würzburg, 83 from Barcelona), and healthy controls (62 from Würzburg, 50 from Barcelona) were investigated. In the Würzburg group, the frequency of subjects homozygous or heterozygous for the mutation was significantly higher among schizophrenic patients than in controls. However, no difference could be detected in the Spanish sample; the possible reasons for the different allele distribution in the two patient groups is discussed. It is concluded that the CNTF null mutation may be relevant to the aetiopathogenesis of schizophrenia in some patients, but further work is required to identify specifically the patient group for which it is important.

Atrial dissociation. A case of unilateral slow atrial rhythm.

Atrial dissociation is a very rare, transient arrhythmia frequently associated with intractable congestive heart failure. A case of atrial dissociation in a 48-year-old woman was observed in the first 72 hours of her recent inferolateral and probably atrial infarction. The slow unilateral rhythm was registered in the presence of sinus rhythm, 2:1 AV block, advanced AV block and ventricular pacemaker stimulation, respectively. The simultaneous right atrial electrogram indicated the origin of the isolated slow rhythm as left atrial. After temporary pacemaker therapy the atrial dissociation disappeared within three days; on the fifth day the normal sinus rhythm was restored spontaneously.

Antenatally diagnosed thanatophoric dysplasia.

A case of antenatally diagnosed thanatophoric dysplasia is described. Other syndromes accompanied by chondrodysplastic tetramicromelia were excluded and diagnosis was based on the narrow thorax, secondary pulmonary hypoplasia and macrocephaly detected by ultrasound and on radiological findings of disturbed bone formation. At the mother's request labour was induced and radiological, anatomic and histological examination of the newborn confirmed the prenatal diagnosis. On basis of the literature, the possible aetiology of the disease is discussed and autosomal recessive heredity is suggested. Attention is focussed on the significant hydramnios which led to the suspicion of fetal malformation. The importance in pregnancy of routine ultrasound screening is emphasized, since such malformations can be detected as early as in midtrimester pregnancy.

The role of potassium-canrenoate on 3H-noradrenaline uptake and metabolism of the rat heart.

The influence of potassium-canrenoate (structurally related to spironolactones) on noradrenaline (NA) uptake and metabolism of the heart was studied in normal and hypopotassaemic rats. In normal rats spironolactone administration resulted in a marked increase of 3H-NA uptake in both the atrial and the ventricular tissues, but the NA content was unchanged. An increased myocardial NA uptake in the presence of an unchanged content suggested an increased rate of NA turnover under the influence of spironolactone. In saluretic pretreated animals, spironolactone normalized both the previously decreased NA uptake and the low intracellular potassium level of the heart tissue. The augmentation of catecholamine metabolism due to spironolactone may be involved in enhanced activity of adenyl cyclase and forms the basis of the compounds positive inotropic effect.