0000000000394601
AUTHOR
Margot Albus
A genome screen for genes predisposing to bipolar affective disorder detects a new susceptibility locus on 8q
Bipolar affective disorder (BPAD), also known as manic depressive illness, is a severe psychiatric disorder characterized by episodes of mania and depression. It has a lifetime prevalence of approximately 1% in all human populations. In order to identify chromosomal regions containing genes that play a role in determining susceptibility to this psychiatric condition, we have conducted a complete genome screen with 382 markers (average marker spacing of 9.3 cM) in a sample of 75 BPAD families which were recruited through an explicit ascertainment scheme. Pedigrees were of German, Israeli and Italian origin, respectively. Parametric and non-parametric linkage analysis was performed. The highe…
Drug treatment of panic disorder: early response to treatment as a predictor of final outcome
One of the core problems in clinical research is the detection of early changes in target symptoms that predict future therapeutic outcome. To analyze potential predictors of outcome, data of a multicenter study on patients with panic disorder were used. A total of 1010 patients were randomly allocated either to alprazolam, imipramine or placebo treatment. Early improvement in the number of spontaneous panic attacks within the first week of treatment predicted outcome exclusively in the alprazolam group. In contrast, placebo responders and nonresponders were differentiated by early changes in anticipatory anxiety intensity. For tricyclic antidepressants such as imipramine an evaluation peri…
Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families.
Previously reported linkage of bipolar affective disorder to DNA markers on chromosome 18 was reexamined in a large sample of German bipolar families. Twenty-three short tandem repeat markers were investigated in 57 families containing 103 individuals with bipolar I disorder (BPI), 26 with bipolar II disorder (BPII), nine with schizoaffective disorder of the bipolar type (SA/BP), and 38 individuals with recurrent unipolar depression (UPR). Evidence for linkage was tested with parametric and non-parametric methods under two definitions of the affected phenotype. Analysis of all 57 families revealed no robust evidence for linkage. Following previous reports we performed separate analyses afte…
A possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25--q26.
In an attempt to identify susceptibility loci for bipolar affective disorder, we are currently conducting a systematic genome screen with highly polymorphic microsatellite markers at an average marker spacing of 10 cM in a series of 75 families, comprising 66 families from Germany, eight families from Israel, and one family from Italy. The families were ascertained through index cases with bipolar affective disorder. The distribution of diagnoses is as follows: 126 individuals with bipolar I disorder, 40 with bipolar II disorder, 14 with schizoaffective disorder of the bipolar type, 40 individuals with recurrent unipolar depression, 51 with a minor psychiatric diagnosis, and two individuals…
Consistencies and discrepancies in self- and observer-rated anxiety scales. A comparison between the self- and observer-rated Marks-Sheehan scales.
The Marks-Sheehan anxiety scales are the only scales where self-ratings and observer ratings are perfectly matched by the number, the content and the scaling of the items. Therefore these scales are an excellent tool to investigate the compatibility and to study different structures in self- and observer ratings. This was done by using the data material on the Marks-Sheehan scales of the Cross National Collaborative Panic Study. In this study 1168 outpatients who met the DSM-III criteria for panic disorder were randomly allocated either to alprazolam, imipramine or placebo treatment. Our results show that the Marks-Sheehan scales are highly comparable to other established rating scales. Bot…
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 non-parametric method, sib pair analysis, a P value of 0.068 correspon…
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 D6…
Self- and observer assessment in anxiolytic drug trials: A comparison of their validity
Self-rating scales are considered to be less useful for comparing different treatments in anxiety patients than observer-rating scales. However, the empirical evidence for this assumption is not adequate. A self-rating inventory of 35 items related to anxiety was perfectly parallel with an observer-rating inventory. Both instruments were used in the Cross National Collaborative Panic Study to compare the efficacy of imipramine, alprazolam and placebo in an 8-week drug trial in a sample of 1168 outpatients. The variance of the self-rating assessments was about two times higher. Both scales were equally sensitive to change; however, the measurement of change by means of the self-rating scale …
The Panic-Associated Symptom Scale: measuring the severity of panic disorder.
The Panic-Associated Symptom Scale (PASS) is presented as a new measurement of the severity of the core symptoms of panic disorder. This first description addresses the rationale for its design and its scoring, score distributions, test-retest reliability, correlations within the PASS and with other scales, principal component structure, and response to drug therapy. Data are presented from a large study group of patients with panic disorder (n = 1168). Problems in measuring panic disorder are discussed.
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-HT{sub 1A} 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{prime} untranslated region of the 5-HT{sub 1A} gene. The region upstream to the coding sequence we investigated contains a …
Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia
Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT{sub 1F}) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T{r_arrow}A transversion in the third position of codon 261 (encoding isoleucine), a silent C{r_arrow}T transition in the third position of codon 176 (encoding histidine), and a C{r_arrow}T transition in position -78 upstream from the start codon. The lack of significan…
Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: Identification of two naturally occurring receptor variants and association analysis in schizophrenia
A statistically significant association between a silent mutation (102T/C) in the serotonin-2A (5-HT2A) receptor gene and schizophrenia has recently been reported in a sample of Japanese patients and healthy controls. This finding suggests that genetic predisposition to schizophrenia may be affected by a functional 5-HT2A receptor variant that is in linkage disequilibrium with 102T/C. In the present study, we have sought to identify genetic variation in the 5-HT2A receptor gene by screening genomic DNA samples from 91 unrelated subjects comprising 45 patients with schizophrenia and 46 healthy controls by using single-strand conformation analysis. We have identified four nucleotide sequence …