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Biomedical subjects

M Albus

Publications and source records attributed to M Albus.

At least 73 records · Page 4Linked to original sources
PubMed1995

Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene.

In the present study we sought to identify genetic variation in the 5-HT1A receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette's syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5' untranslated region of the 5-HT1A gene. The region upstream to the coding sequence we investigated contains a functional promoter. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A-->G) in nucleotide position 82 which leads to an amino acid exchange (Ile-->Val) in position 28 of the receptor protein and a silent mutation (C-->T) in nucleotide position 549. The occurrence of the Ile-28-Val substitution was studied in an extended sample of patients (n = 352) and controls (n = 210) but was found in similar frequencies in all groups. Thus, this mutation is unlikely to play a significant role in the genetic predisposition to the diseases investigated. In conclusion, our study does not provide evidence that the 5-HT1A gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipolar affective disorder, or Tourette's syndrome.

Base Sequence↗
PubMed1995

Potential linkage for schizophrenia on chromosome 22q12-q13: a replication study.

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al. [1994: Am J Med Genet 54:36-43], we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Zmax = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sib pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al. [1994: Am J Med Genet 54:36-43] and Coon et al. [1994: Am J Med Genet 54:72-79], is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point.

Chromosomes, Human, Pair 22↗
PubMed1995

Panic disorder with or without concomitant depression 5 years after treatment: a prospective follow-up.

50 patients with panic disorder (30 without and 20 with concomitant depression) were enrolled in a controlled treatment study using either imipramine or doxepin in addition to supportive psychotherapy and were then studied under naturalistic treatment conditions over a 5-year period. While patients with concomitant depression scored higher in overall measures of illness severity (as measured by HAMA, HAMD and GAS), no differences were detected between the groups with regard to panic disorder symptoms and degree of impairment. Our data suggest that comorbidity of panic disorder and depression is no prerequisite for poorer long-term outcome compared with panic disorder without depression.

Adult↗
PubMed1995

Lack of gender differences in age at onset in familial schizophrenia.

One of the most consistent findings in the epidemiology of schizophrenia is that males are younger at the onset of schizophrenia than females. However, the vast majority of studies focussing on gender differences have not considered the potential influence of genetic factors on age at onset. We investigated the impact of familial loading on gender differences in age at onset in families with at least two siblings with RDC/DSM-III-R schizophrenia or chronic schizoaffective disorder. A total of 106 sib pairs, including 38 male-male pairs, 29 female-female pairs and 39 mixed-sex pairs of siblings as well as 260 male and 221 female isolated cases with no relative of first, second or third degree suffering from psychotic or major affective illness were investigated. We found no gender differences in age at onset in familial cases. An earlier age at onset in males compared to females was observed only in isolated cases. Our data strongly support the assumption that gender differences in age at onset of schizophrenia is not consistent across all subgroups of schizophrenics.

Adolescent↗
PubMed1995

Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis.

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6S271), with a maximum lod score of 2.2 occurring near D6S274, located in 6p22. However, we obtained a lod score of -2 at D6S296, the locus found by others to provide the greatest linkage evidence. At D6S274, we report a positive lod score as do Straub et al. (individually non-significant). A combined total lod of 3.6-4.0 suggests the possibility of a susceptibility locus in this region. However, methodological differences between our studies makes a firm conclusion difficult.

Chromosome Mapping↗
PubMed1995

Identification of two novel polymorphisms and a rare deletion variant in the human dopamine D4 receptor gene.

We report two novel polymorphisms and a rare deletion variant in the human dopaine D4 receptor gene. The two polymorphisms are characterized by single base pair substitutions, namely a G-->C transversion changing codon 11 from GGG (encoding Gly) to CGG (encoding Arg) and a C-->T transition in position -11 upstream from the start codon. The Arg11 variant occurs at a frequency of about 1% and the C-->T transition at a frequency of about 7% in German control subjects (n = 148). Allele frequencies observed in patients suffering from schizophrenia (n = 256) and bipolar affective disorder (n = 99) were similar. The deletion variant is characterized by a 21 bp deletion affecting codons 36 to 42 coding for amino acids Ala-Ala-Leu-Val-Gly-Gly-Val located in the first transmembrane domain of the dopamine D4 receptor. The mutation was identified in a single individual suffering from obsessive-compulsive disorder and panic disorder. We were unable to detect the deletion in patients with schizophrenia and bipolar affective disorder, nor in healthy controls.

Adult↗
PubMed1995

Fluctuation of symptoms and social functioning in panic disorder with or without concomitant depression. A 5-year prospective follow-up.

After controlled treatment with either imipramine or doxepin with additional psychotherapy, 30 patients with pure panic disorder and 20 with concomitant depression were followed under ordinary treatment conditions over a 5-year period. While the overall level of illness severity was mild in both groups (slightly worse in the group with comorbidity), social impairment as well as fluctuation of symptoms were similar in both groups. Therefore, comorbidity of panic disorder and depression does not necessarily imply a poorer outcome in a self-referred patient sample initially treated with psychotropic drugs combined with supportive psychotherapy.

Agoraphobia↗
PubMed1995

[Which factors modify drug-compliance?].

Since the extent of medication noncompliance in schizophrenic patients ranges between 50 and 60%, evaluation of factors that are associated with noncompliance has become an important issue. 197 schizophrenic patients have been interviewed with regard to numerous issues: Form and type of medication; information about side effects; attitude of patients towards illness and medication. Our data suggest that information about benefits and side effects, as well as the attitude of patients towards illness and medication play an important role in the adherence to the treatment regimen.

Adult↗
PubMed1994

Psychophysiological and biochemical changes in patients with panic attacks in a defined situational arousal.

A group of 27 patients with panic disorder with or without agoraphobia were compared with 10 control subjects before stress exposure. No statistically significant differences between patients and controls were found for the cardiovascular parameters. Skin conductance level and skin conductance reaction were significantly higher in the patient group. They also showed higher self-ratings in behavioural symptoms associated with anxiety. There were statistically significant higher venous plasma levels of norepinephrine in patients than in controls, although the epinephrine levels were similar. The number of binding sites of alpha 2-receptors and the affinity of 3H-yohimbine to the alpha 2-receptors on intact thrombocytes was statistically significantly lower in patients compared to controls. Significant differences between the gender groups of patients and controls were found for electrodermal activity and epinephrine levels. These data add further evidence to an overshooting activation of the noradrenergic pathway in patients with panic disorder, possibly based on a dysregulation of alpha 2-receptor.

Adult↗
PubMed1994

Prospective follow-up study lasting 2 years in patients with panic disorder with and without depressive disorders.

A group of 52 patients presenting at an outpatient unit for anxiety disorders were included consecutively in a prospective 2-year follow-up study. Patients were administered to a structured interview for DSM-III-R diagnoses, a follow-up interview (LIFE), and various other ratings. Sociodemographic and illness-history characteristics, levels of anxiety and depressive symptoms, as well as psychosocial impairment, were evaluated at baseline and follow-up and compared between patients with panic disorder only and patients with panic disorder and concomitant depressive disorders at index assessment. Cross-sectional and longitudinal differences between patients with panic disorder only and patients with panic disorder and concomitant depression have been found, indicating that patients with comorbid conditions are more severely ill and have a less favorable outcome. For the total sample, however, the 2-year outcome was better than that reported in many other follow-up studies.

Adolescent↗
PubMed1994

The impact of familial loading on gender differences in age at onset of schizophrenia.

To evaluate the impact of familial loading and gender on age at onset, 197 schizophrenic patients were investigated. Patients with familial loading had an earlier age at onset without gender differences. In contrast, an earlier age at onset for men was found in sporadic cases. These data support that both gender and familial loading contribute to the heterogeneity of schizophrenia.

Adult↗
PubMed1994

D2-dopamine receptor occupancy differs between patients with and without extrapyramidal side effects.

To investigate whether the occurrence of extrapyramidal side effects was related to D2 dopamine receptor occupancy, iodobenzamide single positron emission computed tomography was carried out in 27 schizophrenic patients and 10 controls. Eighteen patients were treated with haloperidol; 9 patients were treated with clozapine. Our data suggest a relationship between D2 receptor occupancy and extrapyramidal side effects as well as the existence of a neuroleptic threshold of a striatal:frontal cortex ratio of 1.2, below which drug-induced exptrapyramidal side effects can be expected.

Adult↗