Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls.

A genetic association between NOTCH4 and schizophrenia has previously been proposed. Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observation. These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia.

DAT1 gene polymorphism in alcoholism: a family-based association study.

BACKGROUND: The present study tests the hypothesis that the 9-repeat allele of the dopamine transporter gene (DAT1; SLC6A3) is more frequent in alcohol-dependent probands--and in particular those with severe withdrawal symptoms (seizures and/or delirium)--compared to nonalcoholics. METHODS: To avoid stratification effects, the family-based association approach of Falk and Rubinstein was used in our sample of 87 alcohol-dependent probands and their biological parents. RESULTS: By applying a family-based association approach, we were not able to detect significant association between allele 9 at DAT1 (SLC6A3) and alcoholism as well as between patients with or without severe withdrawal symptoms. CONCLUSIONS: Based on our data, the impact of the 9-repeat allele of the dopamine transporter gene in alcoholism and the severity of alcohol withdrawal symptoms is putatively not substantial.

Informative morphogenetic variants in patients with schizophrenia and alcohol-dependent patients: beyond the Waldrop Scale.

OBJECTIVE: The authors evaluated the presence or absence of informative morphogenetic variants in patients with schizophrenia compared with alcohol-dependent patients. METHODS: Taking into consideration the criticisms of the Waldrop Scale, which was widely used until recently to define the presence of informative morphogenetic variants, the authors evaluated the presence or absence of 56 informative morphogenetic variants in 50 consecutively admitted patients with schizophrenia and 50 consecutively admitted alcohol-dependent patients. They made a distinction between minor malformations (those developing during organogenesis) and phenogenetic variants (those developing after organogenesis). A kappa index above 75% was considered reliable. RESULTS: Thirty-four of the 56 informative morphogenetic variants met the authors' reliability criterion. Patients with schizophrenia had significantly higher rates of three minor malformations (furrowed tongue, multiple buccal frenula, and hemangioma) and two phenogenetic variants (protruding auricle and large tongue). CONCLUSIONS: The results suggest that using finer distinction in the evaluation of informative morphogenetic variants in schizophrenia may open new perspectives in the research of the neurodevelopmental background of schizophrenia.

Support for allelic association of a polymorphic site in the promoter region of the serotonin transporter gene with risk for alcohol dependence.

OBJECTIVE: An association between the 5-HTTLPR short variant polymorphism in the promoter region of the serotonin transporter gene and risk for alcohol dependence has been reported from case-control studies that are, however, prone to chance findings related to artifacts of population structure. The authors sought additional evidence for this association from a family-based study. METHOD: Ninety-two alcohol-dependent probands and their parents were tested for nonrandom transmission of alleles from heterozygous parents to affected probands. RESULTS: Preferential transmission of the short allele was found (65 of 102 transmissions from heterozygous parents). CONCLUSIONS: The results suggest allelic association between a variant in the promoter region of the serotonin transporter gene and the risk for alcohol dependence. However, it remains to be seen whether the functional properties of this variant are directly responsible for the increased risk to alcohol dependence.

Further evidence for a susceptibility locus on chromosome 10p14-p11 in 72 families with schizophrenia by nonparametric linkage analysis.

Recent reports on potential linkage by Faraone and the NIMH Genetics Initiative-Millennium Schizophrenia Consortium [1997: Am J Med Genet 74:557], and by Straub et al. [1997: Am J Med Genet 74:558], prompted us to study chromosome 10 in a sample of 72 families containing 2 or more affected sibs with schizophrenia for additional evidence of linkage. We obtained highest allele sharing for the two markers D10S582 (61.5% allele sharing, chi2 = 7.6, P = 0.0058) and D10S1423 (59% allele sharing, chi2 = 4.76, P = 0.029). D10S1423 is one of the markers with the highest lod scores in the study of Faraone and the NIMH Genetics Initiative-Millennium Schizophrenia Consortium [1997: Am J Med Genet 74:557]. GENEHUNTER analysis revealed a nonparametric lod score (NPL) of 3.2 (P = 0.0007) for the marker D10S1714, which lies in the same region. Multipoint affected sib-pair lod score analysis (identity by descent) calculated by ASPEX revealed a lod score of 1.72 for all possible sib-pair combinations (107) and of 2.13, when only independent sib-pairs (87) were counted. Our study provides further evidence for a potential susceptibility locus for schizophrenia on chromosome 10p.

Minor physical anomalies in schizophrenia and bipolar affective disorder.

OBJECTIVE: The prevalence of minor physical anomalies (MPAs) (prenatal errors of morphogenesis) was evaluated in patients with schizophrenia and bipolar affective disorder. METHOD: A new modification of the Waldrop-scale was used to detect the presence or absence of 57 MPAs in 30 patients with schizophrenia, 30 with bipolar disorder, and in 30 matched normal controls. RESULTS: Patients with schizophrenia compared to normal controls had significantly higher rates of three minor malformations (furrowed tongue, flat occiput, primitive shape of ears) and those of one phenogenetic variant (wide distance between toes 1 and 2), and they also had a significantly higher rate of one minor malformation (primitive shape of ears), as compared to patients with bipolar disorder. In patients with bipolar disorder, furrowed tongue was significantly more common than in controls. CONCLUSIONS: These results support an 'early' neuro-developmental model of schizophrenia.

Antipsychotic use in pregnancy. What are the best treatment options?

Both the rapid emergence of new antipsychotic medications and the increasing fertility rate among women with psychotic disorders have contributed to the growing clinical importance of the treatment of pregnant women who have psychotic illnesses. The treatment of this patient population must always take into consideration the effect of that treatment on the fetus. With regard to the high risk of decompensation during pregnancy and postpartum, continuous antipsychotic medication is needed using the minimum effective dose. The use of high-potency agents appears to be preferable for first-line management, as there are few data regarding the use of atypical agents such as clozapine in pregnancy. Guidelines for treating pregnant women with psychoses vary little from those for nonpregnant patients. Clinicians must always carefully weigh up the risks and benefits for each patient on an individual basis.

Antipsychotics and breast-feeding: a review of the literature.

Many women with mental illnesses would like to breast feed their infants. In light of the limited but rapidly growing data, it seems that in some cases the possible physiological and psychological benefits may outweigh putative risks. All antipsychotics are secreted into breast milk but the concentrations and effects vary. There is a subgroup of mothers with mental illnesses who want to breast feed their infants and who are receiving a single established antipsychotic drug (principally, haloperidol or chlorpromazine) at the lowest possible clinically effective dose. As a tentative conclusion, this group could experience benefits from being able to nurse which would outweigh the risk of exposing their babies to very small amounts of antipsychotic drugs. However, larger study groups with longer follow-up periods would be required to confirm this tentative conclusion. Those mothers who require 2 or more antipsychotic drugs simultaneously and those taking one drug, but at the upper end of the recommended dose range, should not be advised to breast feed. Safety considerations suggest that women taking atypical antipsychotics would be advised not to breast feed because of the limited experience with these agents. When mothers taking antipsychotic drugs do nurse, it is desirable to monitor drug concentrations in breast milk and in the infants themselves. Close monitoring of the infant is essential.

[A case of psychotic couvade (psychodynamic analysis)]. / Pszichotikus couvade esete (Pszichodinamikai elemzés).

The authors analyse a case of a paranoid psychosis in a male during his wife's pregnancy. They emphasize the importance of oedipal fixation and of double identification. They deal with the clinical importance of the couvade-syndrome.

[The Ekbom symptom in schizophrenic psychoses]. / Az Ekbom-tünet megjelenéséröl schizophren pszichózisokban.

In connection with their schizophrenic cases, the authors analyse the nosological and psychodynamical characteristics of the phenomenon described by Ekbom. They emphasize the interaction between the psychotic process and object losses, which can be observed in the formation of secondary symptoms.

[Use of clozapine during pregnancy]. / Clozapine alkalmazásáról terhesség során.

The authors deal with the use of closapine during pregnancy. In their cases after the use of closapine during pregnancy, healthy children were born.

["Folie a deux hallucinatoire"--a new case of induced hallucinatory psychosis. A new entity?]. / "Folie a deux hallucinatoire"--indukált hallucinózis újabb esete. Uj entitás?

The authors in their case report show a case of induced hallucinatory psychosis induced in a wife of a patient with alcoholic hallucinosis. They deal with the nosological position of "folie a deux hallucinatoire" (induced hallucinatory psychosis) and integrate the consequences of the case to the general psychopathological theory of hallucinations.

[Olanzapine and pregnancy]. / Olanzapin és terhesség.

The appearance of psychosis during pregnancy means a challenge for clinicians, either untreated psychiatric disorders or pharmacological treatment of pregnant psychotic females increase risk of complications. Controlled clinical trials can't be evaluated because of ethical considerations, so case reports have higher scientific values than in other clinical issues. The authors inform about a delivery of a young psychotic female, who was treated with olanzapine (atypical antipsychotic) after the 25th weeks of her pregnancy. A healthy newborn was born in the observed case, the Apgar score was 7 at the first minute and 9 at fifth minute.

[A case of datura stramonium poisoning--general problems of differential diagnosis]. / Csattanómaszlag-mérgezés esete--a differenciáldiagnózis gyakorlati kérdései.

In past year drug abuse becomes more and more general in Hungary. In addition to consume traditional drugs, other substances are used frequently too. One of them is the Datura stramonium, which contains alkaloids (mostly atropine), and can result in hallucinations. Therefore Datura stramonium is seemingly becoming popular as a hallucinogenic drug. The consumption of any part of the plant causes atropine intoxication, thus anticholinergic delirium. Differential diagnosis of Datura intoxication can be difficult in the everyday medical practise. In our paper the symptomatology, diagnosis, differential diagnosis, and therapy of Datura intoxication are discussed and we report one of our cases.